Publications by authors named "Joon Ho Moon"

185 Publications

Characterization of the novel DQA1*01:01:09 allele by next-generation sequencing.

HLA 2021 Mar 21. Epub 2021 Mar 21.

Department of Clinical Pathology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

HLA-DQA1*01:01:09 differs from HLA-DQA1*01:01:01:01 by one nucleotide substitution in codon-12 in exon 1.
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http://dx.doi.org/10.1111/tan.14264DOI Listing
March 2021

Maternal Hyperglycemia during Pregnancy Increases Adiposity of Offspring.

Diabetes Metab J 2021 Feb 22. Epub 2021 Feb 22.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

Background: The effect of intrauterine hyperglycemia on fat mass and regional fat proportion of the offspring of mothers with gestational diabetes mellitus (OGDM) remains to be determined.

Methods: The body composition of OGDM (n=25) and offspring of normoglycemic mothers (n=49) was compared using dualenergy X-ray absorptiometry at age 5 years. The relationship between maternal glucose concentration during a 100 g oral glucose tolerance test (OGTT) and regional fat mass or proportion was analyzed after adjusting for maternal prepregnancy body mass index (BMI).

Results: BMI was comparable between OGDM and control (median, 16.0 kg/m2 vs. 16.1 kg/m2 ). Total, truncal, and leg fat mass were higher in OGDM compared with control (3,769 g vs. 2,245 g, P=0.004; 1,289 g vs. 870 g, P=0.017; 1,638 g vs. 961 g, P=0.002, respectively), whereas total lean mass was lower in OGDM (15,688 g vs. 16,941 g, P=0.001). Among OGDM, total and truncal fat mass were correlated with fasting and 3-hour glucose concentrations of maternal 100 g OGTT during pregnancy (total fat mass, r=0.49, P=0.018 [fasting], r=0.473, P=0.023 [3-hour]; truncal fat mass, r=0.571, P=0.004 [fasting], r=0.558, P=0.006 [3-hour]), but there was no correlation between OGDM leg fat mass and maternal OGTT during pregnancy. Regional fat indices were not correlated with concurrent maternal 75 g OGTT values.

Conclusion: Intrauterine hyperglycemia is associated with increased fat mass, especially truncal fat, in OGDM aged 5 years.
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http://dx.doi.org/10.4093/dmj.2020.0154DOI Listing
February 2021

Prognostic impact of F-FDG PET/CT in patients with multiple myeloma presenting with renal impairment.

Int J Hematol 2021 Jan 21. Epub 2021 Jan 21.

Departments of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea.

Renal insufficiency (RI) is a frequent manifestation of multiple myeloma (MM) at time of diagnosis but there is no reliable prognostic factor for patients with MM presenting with RI. This study investigated the prognostic impact of F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) in patients with MM with RI at diagnosis. The records of 209 patients with MM between June 2011 and November 2018 were retrospectively analyzed. PET/CT positivity was defined as the presence of more than three focal lesions or the presence of extramedullary disease. Of 209 patients, 90 (43.1%) had RI and showed similar survival outcomes to patients who had normal renal function. In total, 113 patients (54.0%) were PET/CT-positive, and 46.6% of patients with RI were PET/CT-positive at baseline. In patients with RI, those who were PET/CT-positive showed significantly inferior survival outcomes to those who were PET/CT-negative [progression-free survival (PFS), 12.7 vs. 34.0 months, P < 0.001; overall survival (OS), 42.2 months vs. not reached, P = 0.001]. On multivariate analysis, PET/CT positivity was significantly associated with PFS and OS in patients with RI. In conclusion, PET/CT is a reliable imaging technique for predicting survival outcomes in patients with MM with RI.
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http://dx.doi.org/10.1007/s12185-021-03079-wDOI Listing
January 2021

Cell-Laden Gelatin Methacryloyl Bioink for the Fabrication of Z-Stacked Hydrogel Scaffolds for Tissue Engineering.

Polymers (Basel) 2020 Dec 17;12(12). Epub 2020 Dec 17.

Department of Stem Cell and Regenerative Biotechnology, KU Convergence Science and Technology Institute, Konkuk University, Seoul 05029, Korea.

Hydrogel-based scaffolds have been widely used to fabricate artificial tissues capable of replacing tissues and organs. However, several challenges inherent in fabricating tissues of large size and complex morphology using such scaffolds while ensuring cell viability remain. To address this problem, we synthesized gelatin methacryloyl (GelMA) based bioink with cells for fabricating a scaffold with superior characteristics. The bioink was grafted onto a Z-stacking bioprinter that maintained the cells at physiological temperature during the printing process, without exerting any physical pressure on the cells. Various parameters, such as the bioink composition and light exposure time, were optimized. The printing accuracy of the scaffolds was evaluated using photorheological studies. The internal morphology of the scaffolds at different time points was analyzed using electron microscopy. The Z-stacked scaffolds were fabricated using high-speed printing, with the conditions optimized to achieve high model reproducibility. Stable adhesion and high proliferation of cells encapsulated within the scaffold were confirmed. We introduced various strategies to improve the accuracy and reproducibility of Z-stack GelMA bioprinting while ensuring that the scaffolds facilitated cell adhesion, encapsulation, and proliferation. Our results demonstrate the potential of the present method for various applications in tissue engineering.
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http://dx.doi.org/10.3390/polym12123027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767119PMC
December 2020

Allogeneic transplant can abrogate the risk of relapse in the patients of first remission acute myeloid leukemia with detectable measurable residual disease by next-generation sequencing.

Bone Marrow Transplant 2020 Dec 5. Epub 2020 Dec 5.

Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.

In patients with acute myeloid leukemia (AML) consolidation treatment options are between allogeneic hematopoietic stem cell transplantation (HCT) and chemotherapy, based on disease risk at the time of initial presentation and age. Measurable residual disease (MRD) following induction chemotherapy could be incorporated as a useful parameter for treatment decisions. The present study evaluated treatment outcomes according to the next-generation sequencing (NGS)-based MRD status and the type of consolidation therapy in patients with normal karyotype (NK)-AML. By sequencing 278 paired samples collected at diagnosis and first remission (CR1), we identified 361 mutations in 124 patients at diagnosis and tracked these at CR1. After excluding mutations associated with age-related clonal hematopoiesis, 82 mutations in 50 of the 124 patients (40.3%) were detected at CR1. Survival benefit was observed in favor of allogeneic HCT over chemotherapy consolidation in the MRD subgroup with respect to overall survival (HR 0.294, p = 0.003), relapse-free survival (HR 0.376, p = 0.015) and cumulative incidence of relapse (HR 0.279, p = 0.004) in multivariate analysis, but not in the MRD subgroup. In summary, these data support allogeneic HCT in NK-AML patients with detectable MRD by NGS in CR1. Randomized clinical trials will be required to confirm this observation.
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http://dx.doi.org/10.1038/s41409-020-01165-xDOI Listing
December 2020

Open-label, single arm, multicenter phase II study of VIDL induction chemotherapy followed by upfront autologous stem cell transplantation in patients with advanced stage extranodal NK/T-cell lymphoma.

Bone Marrow Transplant 2020 Dec 4. Epub 2020 Dec 4.

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

The clinical outcome of advanced-stage Extranodal NK/T cell lymphoma (ENKTL) patients using conventional chemotherapy is extremely poor. The aim of this study was to investigate the outcomes of advanced-stage ENKTL patients treated with non-anthracycline-based chemotherapy followed by upfront autologous stem cell transplant (ASCT). From 8 institutions, 27 patients were recruited from February 2016 to May 2019. Patients were treated with 4 cycles of VIDL induction chemotherapy. Patients who achieved complete response (CR) or partial response (PR) underwent upfront ASCT. This study is registered with clinicaltrial.gov, # NCT02544425. Twenty patients (74.1%) completed 4 cycles of VIDL induction. The overall response rate of VIDL was 74.1%, including 17 (63.0%) with CR and 3 (11.1%) with PR. Primary toxicity of the induction regimen was grade 3 or 4 neutropenia, and no treatment-related mortality was reported. Seventeen patients proceeded with upfront ASCT, and 9 patients relapsed after ASCT, among whom, 4 was central nervous system (CNS) relapse. The median duration of response was 15.2 months (95% CI, 6.3-24.1 months). This study suggested that VIDL induction chemotherapy followed by upfront ASCT is feasible and effective for the treatment of advanced-stage ENKTL. However, CNS relapse prevention is needed in the treatment of advanced-stage ENKTL.
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http://dx.doi.org/10.1038/s41409-020-01160-2DOI Listing
December 2020

Clonal hematopoiesis is associated with risk of severe Covid-19.

medRxiv 2020 Nov 27. Epub 2020 Nov 27.

Acquired somatic mutations in hematopoietic stem and progenitor cells (clonal hematopoiesis or CH) are associated with advanced age, increased risk of cardiovascular and malignant diseases, and decreased overall survival. These adverse sequelae may be mediated by altered inflammatory profiles observed in patients with CH. A pro-inflammatory immunologic profile is also associated with worse outcomes of certain infections, including SARS-CoV-2 and its associated disease Covid-19. Whether CH predisposes to severe Covid-19 or other infections is unknown. Among 515 individuals with Covid-19 from Memorial Sloan Kettering (MSK) and the Korean Clonal Hematopoiesis (KoCH) consortia, we found that CH was associated with severe Covid-19 outcomes (OR=1.9, 95%=1.2-2.9, p=0.01). We further explored the relationship between CH and risk of other infections in 14,211 solid tumor patients at MSK. CH was significantly associated with risk of (HR=2.0, 95% CI: 1.2-3.3, p=6×10 ) and infections (HR=1.5, 95% CI=1.1-2.1, p=5×10 ). These findings suggest a relationship between CH and risk of severe infections that warrants further investigation.
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http://dx.doi.org/10.1101/2020.11.25.20233163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709186PMC
November 2020

RNA sequencing as an alternative tool for detecting measurable residual disease in core-binding factor acute myeloid leukemia.

Sci Rep 2020 11 18;10(1):20119. Epub 2020 Nov 18.

Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada.

DNA sequencing-based measurable residual disease (MRD) detection has shown to be clinically relevant in AML. However, the same methodology cannot be applied to fusion gene-driven subtypes of AML such as core-binding factor AML (CBF-AML). Here in this study, we evaluated the effectiveness of using DNA and RNA sequencing in MRD detection and in tracking clonal dynamics in CBF-AML. Using RNA-seq, we were able to quantify expression levels of RUNX1-RUNX1T1 and CBFB-MYH11 at diagnosis and their levels of reduction during remission (P < 6.3e-05 and P < 2.2e-13). The level of reduction of RUNX1-RUNX1T1 as measured by RNA-seq and qPCR were highly correlated (R = 0.74, P < 5.4e-05). A decision tree analysis, based on 3-log reduction of RUNX1-RUNX1T1 and cKIT-D816 at diagnosis, stratified RUNX1-RUNX1T1 AML patients into three subgroups. These three subgroups had 2-year overall survival rates at 87%, 74%, and 33% (P < 0.08) and 2-year relapse incidence rates at 13%, 42%, and 67% (P < 0.05). On the other hand, although low residual allelic burden was common, it was not associated with long-term outcome, indicating that mutation clearance alone cannot be interpreted as MRD-negative. Overall, our study demonstrates that the clinical utility of RNA sequencing as a potential tool for MRD monitoring in fusion gene-driven AML such as RUNX1-RUNX1T1 AML.
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http://dx.doi.org/10.1038/s41598-020-76933-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674449PMC
November 2020

Validation of a wearable cuff-less wristwatch-type blood pressure monitoring device.

Sci Rep 2020 11 4;10(1):19015. Epub 2020 Nov 4.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.

Ambulatory blood pressure (BP) monitoring is recommended to improve the management of hypertension. Here, we investigated the accuracy of BP estimated using a wearable cuff-less device, InBodyWATCH, compared with BP measured using a manual sphygmomanometer. Thirty-five adults were enrolled (age 57.1 ± 17.9 years). The BP was estimated using InBodyWATCH with an individualized estimation based on a neural network model. Three paired sets of BPs from the two devices were compared using correlation analysis and Bland-Altman plots (n = 105 paired BP readings). The correlations for both systolic and diastolic BP (SBP and DBP) between the two devices were high (r = 0.964 and 0.939, both P < 0.001). The mean difference was 2.2 ± 6.1 mmHg for SBP and -0.2 ± 4.2 mmHg for DBP; these were not significant (P = 0.472 for SBP and P = 0.880 for DBP). The proportions of estimated SBP/DBP obtained from the InBodyWATCH within ± 5 mmHg of manual SBP/DBP were 71.4%/83.8%; within ± 10 mmHg they were 86.7%/98.1%; and within ± 15 mmHg they were 97.1%/99.0%. The estimated BP from this wearable cuff-less device correlated highly with the manual BP and showed good accuracy, suggesting its potential to be used in ambulatory BP monitoring.
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http://dx.doi.org/10.1038/s41598-020-75892-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642418PMC
November 2020

Hypomethylating agent-based post-transplant strategies to maximize the outcome of high-risk acute myeloid leukemia after allogeneic stem cell transplantation.

Expert Rev Hematol 2020 09 14;13(9):959-969. Epub 2020 Aug 14.

Department of Hematology/Oncology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University , Daegu, South Korea.

Introduction: Clinical outcomes of patients diagnosed with high-risk acute myeloid leukemia (AML) are poor, and relapse or refractoriness is main cause of treatment failure, even in those who underwent standard allogeneic stem cell transplantation (allo-SCT). Therefore, innovative or additional approaches are necessary to overcome refractoriness to the graft-versus-leukemia (GVL) effect immediately after allo-SCT.

Areas Covered: Hypomethylating agents (HMA) present a feasible option that can be adopted during the post-transplant phase. Moreover, combination strategies based on HMA may induce a synergistic effect by promoting anti-leukemic effects that overcome residual leukemic burden, and it is a well-tolerated therapeutic option for high-risk disease. Relevant literatures published in the last 30 years were searched from PubMed to review the topic of AML, allo-SCT, and HMAs.

Expert Opinion: Post-transplant therapy is strongly needed to improve the outcomes of allogeneic transplantation for certain AML patients classified with high-risk disease. In that sense, prophylactic and preemptive HMAs are a promising additive therapy for allogeneic recipients.
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http://dx.doi.org/10.1080/17474086.2020.1804355DOI Listing
September 2020

Optimizing Preparative Regimen for Umbilical Cord Blood Transplantation in Adult Acute Leukemia Patients: Acute Lymphoblastic Leukemia Requires Myeloablative Conditioning but Not Acute Myeloid Leukemia.

J Clin Med 2020 Jul 21;9(7). Epub 2020 Jul 21.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, 101, Daehak-ro, Jongro-gu, Seoul 03080, Korea.

Cord blood transplantation (CBT) is a valuable alternative to bone marrow transplantation in adults without readily available donors. We conducted this study to investigate the feasibility of CBT for adult patients with acute leukemia with regards to impact of different conditioning and graft-versus-host disease (GVHD) prophylaxis regimens on clinical outcomes. From 16 centers in Korea, 41 acute myeloid leukemia (AML) and 29 ALL (acute lymphoblastic leukemia) patients undergoing CBT were enrolled. For AML patients, the neutrophil engraftment was observed in 87.5% of reduced intensity conditioning (RIC) and 72.0% of myeloablative conditioning (MAC) ( = 0.242). The median RFS was 5 months and OS 7 months. Conditioning regimen did not affect relapse free survival (RFS) or overall survival (OS). GVHD prophylaxis using calcineurin inhibitors (CNI) plus methotrexate was associated with better RFS compared to CNI plus ATG ( = 0.032). For ALL patients, neutrophil engraftment was observed in 55.6% of RIC and 90.0% of MAC ( = 0.034). The median RFS was 5 months and OS 19 months. MAC regimens, especially total body irradiation (TBI)-based regimen, were associated with both longer RFS and OS compared to other conditioning regimens. In conclusion, individualized conditioning regimens will add value in terms of enhancing safety and efficacy of CBT.
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http://dx.doi.org/10.3390/jcm9072310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408460PMC
July 2020

Prognostic significance of interim PET/CT response for the treatment of advanced-stage marginal zone lymphoma in the post-rituximab era.

Sci Rep 2020 07 15;10(1):11649. Epub 2020 Jul 15.

Chonnam National University Hwasun Hospital, Hwasun, Jeollanam-do, Republic of Korea.

There are still controversies about the use of interim positron emission tomography/computed tomography (PET/CT) in indolent non-Hodgkin lymphoma due to the variable fluorodeoxyglucose (FDG) avidity. Therefore, this study aimed to evaluate the roles of interim PET/CT in marginal zone lymphoma (MZL), a representative indolent lymphoma. We analyzed the data of 146 MZL patients. All were treated with rituximab-containing immunochemotherapy. Interim PET/CT scan was performed after 2-3 cycles of therapy, and the response was assessed using the Deauville 5-point scales (5-PS) and a semi-quantitative assessment using the SUVmax reduction rate (ΔSUVmax). Progression-free survival (PFS) was well stratified according to a visual assessment of interim PET/CT using 5-PS (p < 0.001). Particularly, there was a significant difference in PFS between patients with interim score 1-2 and those with score 3. However, ΔSUVmax did not predict the survival outcome using 59.8% of the optimal cutoff value. In the multivariate analysis, failure to achievement of grade 1-2 in interim PET/CT was significantly associated with inferior PFS (HR, 2.154; 95% CI 1.071-4.332; p = 0.031). The interim PET/CT response based on the 5-PS is useful for predicting PFS of patients with MZL in the post-rituximab era.
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http://dx.doi.org/10.1038/s41598-020-68310-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363857PMC
July 2020

Quantitative Assessment of Interim PET/CT Could Have More Prognostic Relevance than Visual Assessment for Predicting Clinical Outcome of Extranodal Diffuse Large B Cell Lymphoma.

In Vivo 2020 Jul-Aug;34(4):2127-2134

Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, School of Medicine, Chonnam National University, Hwasun, Republic of Korea

Background/aim: The present study retrospectively investigated the predictive accuracy of interim positron emission tomography/computed tomography (iPET/CT) based on the Deauville 5-point scale (5-PS) and a quantitative SUV-based assessment in patients with extranodal (EN) diffuse large B cell lymphoma (DLBCL).

Patients And Methods: The Deauville 5-PS and the SUVmax reduction (ΔSUVmax) assessment for interpreting the response to iPET/CT were used.

Results: A total of 163 patients were enrolled in this study. With a median follow-up of 52.5 months, ΔSUVmax successfully predicted the survival outcomes of patients with one extranodal (EN) involvement in terms of overall survival (OS) (p=0.012) and progression-free survival (PFS) (p<0.001). Visual assessment using the Deauville 5-PS did not predict survival outcomes in patients with one or more EN involvements in terms of OS and PFS.

Conclusion: The quantitative SUV-based assessment with iPET/CT was a significant prognosticator for long-term survival outcomes, especially in patients with one EN involvement.
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http://dx.doi.org/10.21873/invivo.12018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439899PMC
March 2020

Intravenous busulfan and melphalan versus high-dose melphalan as a conditioning regimen for early autologous stem cell transplantation in patients with multiple myeloma: a propensity score-matched analysis.

Leuk Lymphoma 2020 11 25;61(11):2714-2721. Epub 2020 Jun 25.

Seoul National University Hospital, Seoul, Republic of Korea.

We compared the efficacy and toxicity of busulfan and melphalan (BUMEL) and those of high-dose melphalan (HDMEL) as conditioning regimens for autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM) through a propensity score-matched analysis. No significant difference in the complete response and overall response rate after ASCT was observed between BUMEL and HDMEL. After a median follow-up of 37.3 months in the BUMEL group and 50.8 months in the HDMEL group, the median progression-free survival was calculated to be 32.9 months and 25.2 months ( = 0.995). With respect to non-hematologic toxicities, infections were more frequently reported in the BUMEL group ( < 0.001). Three patients who received BUMEL developed veno-occlusive disease (VOD), and all of them recovered without administration of defibrotide. In conclusion, BUMEL is an effective alternative conditioning regimen in terms of efficacy, but attention should be paid to toxicities.
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http://dx.doi.org/10.1080/10428194.2020.1783448DOI Listing
November 2020

Reduced-Intensity Conditioning with Busulfan and Fludarabine for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Lymphoblastic Leukemia.

Yonsei Med J 2020 Jun;61(6):452-459

Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Korea.

Purpose: Allogeneic hematopoietic stem cell transplantation (HSCT) with optimal conditioning has helped better long-term survival in acute lymphoblastic leukemia (ALL). This study investigated the efficacy and safety of reduced-intensity conditioning (RIC) with busulfan and fludarabine in adult ALL patients unfit for myeloablation.

Materials And Methods: Records of 78 patients who underwent HSCT with RIC consisting of 3.2 mg/kg/day of busulfan for 2 or 3 days and 30 mg/m²/day of fludarabine for 5 or 6 days were analyzed.

Results: The median age at diagnosis was 49 years. Over a median follow-up of 22 months, 2-year estimates of relapse-free survival (RFS) and overall survival were 57.4% and 68.7%, respectively. Multivariate analysis showed a trend of improved RFS in patients with chronic graft-versus-host disease (GVHD) (hazard ratio, 0.53; 95% confidence interval, 0.26-1.08; =0.080). The cumulative incidences of relapse and non-relapse mortality were 42.9% and 19.6%, respectively and one case of central nervous system relapse was noted. No hepatic veno-occlusive disease was reported. Grade II-IV acute GVHD and any grade chronic GVHD occurred in 21.1% and 41.7%, respectively.

Conclusion: RIC with busulfan and fludarabine is an effective and safe conditioning regimen for adult ALL patients unfit for myeloablation.
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http://dx.doi.org/10.3349/ymj.2020.61.6.452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256005PMC
June 2020

Apparent diffusion coefficient as a valuable quantitative parameter for predicting clinical outcomes in patients with newly diagnosed primary CNS lymphoma.

Blood Res 2020 Jun;55(2):99-106

Department of Hematology/Oncology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea.

Background: This study attempted to identify novel prognostic factors in patients with newly diagnosed primary central nervous system lymphoma (PCNSL) using magnetic resonance imaging (MRI).

Methods: We retrospectively evaluated 67 patients diagnosed with central nervous system (CNS) tumors. The enrollment criteria were as follows: i) pathologic diagnosis of CNS lymphoma, ii) no evidence of systemic involvement, iii) no evidence of human immunodeficiency virus-1 infection or other immunodeficiencies, and iv) MRI scans available at diagnosis. Fifty-two patients met these criteria and were enrolled.

Results: The 3-year overall survival (OS) and failure-free survival rates were 69.7% and 45.6%, respectively, with a median follow-up duration of 36.2 months. OS of patients with low apparent diffusion coefficient (ADC) was lower than those with higher ADC. Multivariate analysis revealed that old age (>60 yr) [hazard ratio (HR), 20.372; =0.001], Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 (HR, 10.429; < 0.001), higher lactate dehydrogenase (LDH) levels (HR, 7.408; =0.001), and low ADC (HR, 0.273; =0.009) were associated with lower OS. We modified the conventional prognostic scoring system using low ADC, old age (>60 yr), ECOG PS ≥2, and higher LDH. The risk of death was categorized as high (score 3-4), intermediate-2 (score 2), intermediate- 1 (score 1), and low (score 0), with three-year OS rates of 33.5%, 55.4%, 88.9%, and 100%, respectively.

Conclusion: ADC demonstrated significant prognostic value for long-term survival in patients with newly diagnosed PCNSL. Low ADC was an independent unfavorable prognostic factor, suggesting that ADC obtained from MRI can improve the current prognostic scoring system.
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http://dx.doi.org/10.5045/br.2020.2020032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343555PMC
June 2020

COVID-19 transmission and blood transfusion: A case report.

J Infect Public Health 2020 Nov 13;13(11):1678-1679. Epub 2020 May 13.

Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; Department of Hematology/Oncology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. Electronic address:

The recent outbreak of the novel coronavirus disease 2019 (COVID-19) has been labelled as a pandemic by the World Health Organization. Although person-to-person transmission of the etiologic agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been confirmed, it is not known whether COVID-19 may be transmitted by blood transfusion. Notwithstanding the urgent requirement of blood, it is critical to know whether the SARS-CoV-2 virus can be transmitted by blood transfusion because many individuals may be asymptomatic carriers and may donate blood. Several cases in which specific viral RNA could be detected in the serum from patients with COVID-19 have already been reported; these findings suggest that blood donation may be an unexplored route of transmission. However, the American Association of Blood Banks and Centers for Disease Control and Prevention have not recommended any specific SARS-CoV-2-related actions to be taken at blood collection centres at this time. In this report, we describe a case of a 21-year-old man with very severe aplastic anaemia who received apheresis platelet transfusion from an individual who was subsequently diagnosed with COVID-19. Our patient tested negative for COVID-19 and is awaiting allogeneic stem cell transplantation.
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http://dx.doi.org/10.1016/j.jiph.2020.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218366PMC
November 2020

Lactation improves pancreatic β cell mass and function through serotonin production.

Sci Transl Med 2020 04;12(541)

Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea.

Pregnancy imposes a substantial metabolic burden on women through weight gain and insulin resistance. Lactation reduces the risk of maternal postpartum diabetes, but the mechanisms underlying this benefit are unknown. Here, we identified long-term beneficial effects of lactation on β cell function, which last for years after the cessation of lactation. We analyzed metabolic phenotypes including β cell characteristics in lactating and non-lactating humans and mice. Lactating and non-lactating women showed comparable glucose tolerance at 2 months after delivery, but after a mean of 3.6 years, glucose tolerance in lactated women had improved compared to non-lactated women. In humans, the disposition index, a measure of insulin secretory function of β cells considering the degree of insulin sensitivity, was higher in lactated women at 3.6 years after delivery. In mice, lactation improved glucose tolerance and increased β cell mass at 3 weeks after delivery. Amelioration of glucose tolerance and insulin secretion were maintained up to 4 months after delivery in lactated mice. During lactation, prolactin induced serotonin production in β cells. Secreted serotonin stimulated β cell proliferation through serotonin receptor 2B in an autocrine and paracrine manner. In addition, intracellular serotonin acted as an antioxidant to mitigate oxidative stress and improved β cell survival. Together, our results suggest that serotonin mediates the long-term beneficial effects of lactation on female metabolic health by increasing β cell proliferation and reducing oxidative stress in β cells.
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http://dx.doi.org/10.1126/scitranslmed.aay0455DOI Listing
April 2020

Serotonergic regulation of energy metabolism in peripheral tissues.

J Endocrinol 2020 04;245(1):R1-R10

Graduate School of Medical Science and Engineering, KAIST, Daejeon, Republic of Korea.

Serotonin is a biogenic amine synthesized from the essential amino acid tryptophan. Because serotonin cannot cross the blood-brain barrier, it functions differently in neuronal and non-neuronal tissues. In the CNS, serotonin regulates mood, behavior, appetite, and energy expenditure. Although most serotonin in the body is synthesized at the periphery, its biological roles have not been well elucidated. Older studies using chemical agonists and antagonists yielded conflicting results, because the complexity of serotonin receptors and the low selectivity of agonists and antagonists were not known. Several recent studies using specific knock-out of serotonin receptors have been performed to assess the role of peripheral serotonin in regulating energy metabolism. This review discusses (1) the tissue-specific roles of peripheral serotonin in regulating energy metabolism, (2) the mechanism by which dysfunctional peripheral serotonin signaling can progress to metabolic diseases, and (3) how peripheral serotonin signaling could be a therapeutic target for metabolic diseases.
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http://dx.doi.org/10.1530/JOE-19-0546DOI Listing
April 2020

Clinical Effects of Hypomethylating Agents in Patients with Newly Diagnosed Myelodysplastic Syndrome Who Received DNA-Damaging Chemotherapy for Metastatic Breast Cancer.

J Breast Cancer 2019 Dec 5;22(4):647-652. Epub 2019 Nov 5.

Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, Kyungpook National University Cancer Research Institute, Kyungpook National University School of Medicine, Daegu, Korea.

The cumulative risk of therapy-related myelodysplastic syndrome (t-MDS) in breast cancer patients exposed to chemotherapy and/or radiotherapy is significantly high compared to that in other cancer patients. This report reviews the use of hypomethylating agents (HMAs) to treat a 57-year-old woman newly diagnosed with MDS during palliative chemotherapy for metastatic breast cancer. Over a period of 6 years, the patient received several DNA-damaging chemotherapeutics including doxorubicin, cyclophosphamide, and paclitaxel. Repeated thrombocytopenia was the main reason for suspecting secondary hematologic malignancy. She was diagnosed with t-MDS based on bone marrow examination and her treatment history for breast cancer. While azacitidine was originally administered to stabilize MDS, it also stabilized the patient's lung and lymph node metastases without any major toxicity. Therefore, the current case highlights the promising effects of HMAs for treating t-MDS following heavily pretreated breast cancer.
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http://dx.doi.org/10.4048/jbc.2019.22.e50DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933035PMC
December 2019

Correction to: Clinical outcomes in patients with diffuse large B cell lymphoma with a partial response to first-line R-CHOP chemotherapy: prognostic value of secondary International Prognostic Index scores and Deauville scores.

Ann Hematol 2020 01;99(1):213

Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, 50-1 Yonsei-ro, Seoul, Seodaemun-gu, 03722, South Korea.

An additional affiliation for the first author was not indicated. Hyewon Lee is also affiliated with: Department of Internal Medicine, Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul, South Korea.
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http://dx.doi.org/10.1007/s00277-019-03868-8DOI Listing
January 2020

Serotonin Regulates Adult β-Cell Mass by Stimulating Perinatal β-Cell Proliferation.

Diabetes 2020 02 5;69(2):205-214. Epub 2019 Dec 5.

Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea

A sufficient β-cell mass is crucial for preventing diabetes, and perinatal β-cell proliferation is important in determining the adult β-cell mass. However, it is not yet known how perinatal β-cell proliferation is regulated. Here, we report that serotonin regulates β-cell proliferation through serotonin receptor 2B (HTR2B) in an autocrine/paracrine manner during the perinatal period. In β-cell-specific knockout ( βKO) mice, perinatal β-cell proliferation was reduced along with the loss of serotonin production in β-cells. Adult βKO mice exhibited glucose intolerance with decreased β-cell mass. Disruption of in β-cells also resulted in decreased perinatal β-cell proliferation and glucose intolerance in adulthood. Growth hormone (GH) was found to induce serotonin production in β-cells through activation of STAT5 during the perinatal period. Thus, our results indicate that GH-GH receptor-STAT5-serotonin-HTR2B signaling plays a critical role in determining the β-cell mass by regulating perinatal β-cell proliferation, and defects in this pathway affect metabolic phenotypes in adults.
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http://dx.doi.org/10.2337/db19-0546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971487PMC
February 2020

Favorable long-term survival using consolidation chemotherapy without allogeneic hematopoietic cell transplantation for acute myeloid leukemia with wild-type without -ITD.

Blood Res 2019 Sep 25;54(3):189-197. Epub 2019 Sep 25.

Department of Hematology/Oncology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea.

Background: The role of allogeneic hematopoietic cell transplantation (allo-HCT) compared with consolidation chemotherapy alone in intermediate-risk acute myeloid leukemia (AML) patients with wild-type nucleophosmin/negative or a low level of Fms related tyrosine kinase 3 internal tandem duplication (/-ITD) has not yet been elucidated.

Methods: In this study, we retrospectively investigated 88 patients newly diagnosed with AML who received intensive induction chemotherapy at Kyungpook National University Hospital from March 2015 to July 2017. The selection criteria included the presence of results on genetic abnormalities including and -ITD.

Results: According to the European LeukemiaNet (ELN) risk classification, 25 patients (28%) were categorized as favorable, 44 (50%) as intermediate, and 19 (22%) as adverse risk. Among the intermediate-risk patients, 40 were identified as /-ITD. Among the patients with /-ITD, complete remission (CR) was achieved in 26 patients out of 40 (65%). One-year overall survival (OS) rate was 100% in the favorable-risk group and 87.9% in the /-ITD group (=0.233). Among the intermediate-risk /-ITD patients, there was no survival benefit with allo-HCT (N=19) compared to consolidation chemotherapy (N=21; =0.372). In the multivariate analysis, the ELN risk group [hazard ratio (HR), 6.36; =0.019] and the achievement of CR (HR, 2.95; =0.017) were both identified as factors affecting OS of patients with newly diagnosed AML.

Conclusion: Among the AML patients, intermediate-risk /-ITD patients and favorable-risk patients showed similar OS rates. Our results suggested that allo-HCT might have limited clinical benefit for the intermediate-risk /-ITD patients. Well controlled studies are needed to confirm the current results.
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http://dx.doi.org/10.5045/br.2019.54.3.189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779939PMC
September 2019

Benefits of additional cycles of bortezomib/thalidomide/dexamethasone (VTD) induction therapy compared to four cycles of VTD for newly diagnosed multiple myeloma.

Bone Marrow Transplant 2019 12 29;54(12):2051-2059. Epub 2019 Jul 29.

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

Bortezomib/thalidomide/dexamethasone (VTD) induction therapy followed by autologous stem cell transplantation (ASCT) is one of the standard therapies for newly diagnosed multiple myeloma (NDMM). However, the appropriate depth of response to induction therapy and timing of upfront ASCT are still debated. We investigated if two additional cycles of VTD (VTD6) improved the responses and progression-free survival (PFS) compared with four cycles of VTD (VTD4). We retrospectively reviewed outcomes of 190 NDMM patients treated with at least four cycles of VTD followed by ASCT between September 2014 and August 2017 [VTD4, n = 129 (67.9%); VTD6, n = 61 (32.1%)]. The VTD6 group had a higher pre-ASCT complete response (CR) rate than the VTD4 group (31.1% versus 10.1%, P < 0.001), but, the pre- and post-ASCT ≥ very good partial response (VGPR), and 2-year PFS were similar. Multivariate analysis revealed age, β-microglobulin, and pre-ASCT CR as important factors for PFS. Two additional cycles of VTD prolonged PFS in patients with PR only after VTD4 [Hazard ratio (HR) = 0.29, P = 0.016] or those with Revised International Staging System stage I/II (HR = 0.36, P = 0.039). In conclusion, two additional VTD cycles may be helpful for patients with PR only after VTD4 but high risk MM needs the other treatment options.
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http://dx.doi.org/10.1038/s41409-019-0629-7DOI Listing
December 2019

Lenalidomide as a second-line therapy after failure of hypomethylating agents in patients with myelodysplastic syndrome.

Br J Haematol 2019 09 9;186(5):e151-e155. Epub 2019 Jun 9.

Department of Haematology, Catholic Haematology Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

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http://dx.doi.org/10.1111/bjh.15991DOI Listing
September 2019

Favorable Outcomes With Tumor Burden Reduction Following Administration of Hypomethylating Agents Before Allogeneic Hematopoietic Cell Transplantation in Patients With Higher Risk Myelodysplastic Syndrome.

Clin Lymphoma Myeloma Leuk 2019 07 11;19(7):e367-e373. Epub 2019 Apr 11.

Department of Hematology/Oncology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. Electronic address:

Introduction: The clinical significance of tumor burden reduction following administration of hypomethylating agents (HMAs) for transplant-eligible patients with higher risk myelodysplastic syndrome (MDS) was evaluated.

Patients And Methods: Data of 79 transplant-eligible patients (< 65 years) diagnosed with higher-risk MDS between July 2002 and March 2013 were retrospectively analyzed. Among 79 patients, 30 (38%) underwent allogeneic hematopoietic cell transplantation (HCT group), and 49 (62%) were treated with HMA alone (non-HCT group).

Results: The median follow-up duration was 732 days (range, 28-1952 days), and the 3-year overall survival (OS) rate of all patients was 30.6%. In the HCT group, early HCT showed a better 3-year OS rate than late HCT (67.1% vs. 25.7%; P = .035). In multivariate analysis, time/performance of allogenic transplant (no HCT vs. early HCT, hazard ratio, 0.18; 95% confidence interval, 0.04-0.81; P = .026) and follow-up higher risk International Prognostic Scoring System (hazard ratio, 6.22; 95% confidence interval, 2.09-18.51; P = .001) were significantly correlated with OS.

Conclusion: To predict the clinical outcomes of patients with higher risk MDS, the optimal time for tumor burden evaluation is prior to follow-up rather than at the time of initial diagnosis. Patients with lower International Prognostic Scoring System risk groups after HMA treatment or early HCT had favorable OS.
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http://dx.doi.org/10.1016/j.clml.2019.03.016DOI Listing
July 2019

Thermogenesis-independent metabolic benefits conferred by isocaloric intermittent fasting in ob/ob mice.

Sci Rep 2019 02 21;9(1):2479. Epub 2019 Feb 21.

Translational Medicine Program, The Hospital for Sick Children, Toronto, Ontario, Canada.

Intermittent fasting (IF) is an effective dietary intervention to counteract obesity-associated metabolic abnormalities. Previously, we and others have highlighted white adipose tissue (WAT) browning as the main underlying mechanism of IF-mediated metabolic benefits. However, whether IF retains its efficacy in different models, such as genetically obese/diabetic animals, is unknown. Here, leptin-deficient ob/ob mice were subjected to 16 weeks of isocaloric IF, and comprehensive metabolic phenotyping was conducted to assess the metabolic effects of IF. Unlike our previous study, isocaloric IF-subjected ob/ob animals failed to exhibit reduced body weight gain, lower fat mass, or decreased liver lipid accumulation. Moreover, isocaloric IF did not result in increased thermogenesis nor induce WAT browning in ob/ob mice. These findings indicate that isocaloric IF may not be an effective approach for regulating body weight in ob/ob animals, posing the possible limitations of IF to treat obesity. However, despite the lack of improvement in insulin sensitivity, isocaloric IF-subjected ob/ob animals displayed improved glucose tolerance as well as higher postprandial insulin level, with elevated incretin expression, suggesting that isocaloric IF is effective in improving nutrient-stimulated insulin secretion. Together, this study uncovers the insulinotropic effect of isocaloric IF, independent of adipose thermogenesis, which is potentially complementary for the treatment of type 2 diabetes.
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http://dx.doi.org/10.1038/s41598-019-39380-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385507PMC
February 2019

Production of Transgenic Porcine Embryos Reconstructed with Induced Pluripotent Stem-Like Cells Derived from Porcine Endogenous Factors Using piggyBac System.

Cell Reprogram 2019 02;21(1):26-36

1 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Research Institute of Veterinary Science, Seoul National University, Seoul, Republic of Korea.

The potential of induced pluripotent stem (iPS) cells, which have self-renewal ability and can differentiate into three germ layers, led us to hypothesize that iPS cells in pigs can be useful and suitable source for producing transgenic pigs. In this study, we generated iPS-like cells using doxycycline-inducible piggyBac (PB) expression vectors encoding porcine 4 transcription factors. After transfection, transfected cells were cultured until the formation of outgrowing colonies taking least of 7-10 days. The iPS-like cells demonstrated pluripotent characteristics such as self-renewal, high proliferation, expression of pluripotent markers, and aggregation ability. The embryo development through somatic cell nuclear transfer (SCNT), cleavage rate, and blastocyst formation rate did not show any significant differences. However, the total cell number of blastocysts was significantly increased with the established cell line. In conclusion, the iPS-like cell line, generated from porcine transcriptional factors using the PB transposon system, demonstrated pluripotency with the capacity for unlimited self-renewal, and could be used as donor cells to produce cloned embryos by SCNT. These cells will be suitable for gene modification and would contribute to the stability or safety of pig models in biomedical research.
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http://dx.doi.org/10.1089/cell.2018.0036DOI Listing
February 2019

Clinical impact of anti-thymocyte globulin on survival and graft-versus-host disease in patients undergoing human leukocyte antigen mismatched allogeneic stem cell transplantation.

Korean J Intern Med 2020 03 10;35(2):429-437. Epub 2019 Jan 10.

Department of Internal Medicine, Kosin University Gospel Hospital, Busan, Korea.

Background/aims: Rabbit anti-thymocyte globulin (ATG) is usually incorporated in hematopoietic stem cell transplantation (HSCT) to reduce the incidence of graft-versus-host disease (GVHD). This study aimed to find optimal ATG doses in patients undergoing human leukocyte antigen (HLA)-mismatched allogeneic HSCT.

Methods: We retrospectively collected medical records from 352 consecutive patients with acute myeloid leukemia (n = 214), acute lymphoblastic leukemia (n = 62), or myelodysplastic syndrome (n = 76) in eight centers of Korea between 2005 and 2015. All patients received busulfan-based conditioning without total body irradiation (TBI) and received stem cells from HLA-mismatched donors.

Results: In the current study, 5-year overall survival rates of patients receiving low to medium doses of ATG (2.5 to 7.5 mg/kg) were higher than those receiving other doses of ATG (hazard ratio [HR], 0.528; 95% confidence interval [CI], 0.311 to 0.897; p = 0.018). The incidence rates of extensive chronic GVHD (ecGVHD) after administration of low to medium doses of ATG were lower than those after other doses of ATG (HR, 0.447; 95% CI, 0.224 ton 0.889; p = 0.022).

Conclusion: The low to medium doses of ATG may be associated with improving survival outcomes and reducing incidence of ecGVHD without enhancing the chances of relapse in patients with acute leukemia or myelodysplastic syndrome undergoing non-TBI-based HLA-mismatched allogeneic HSCT.
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http://dx.doi.org/10.3904/kjim.2018.317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061010PMC
March 2020

Oral Glucose Tolerance Testing Allows Better Prediction of Diabetes in Women with a History of Gestational Diabetes Mellitus.

Diabetes Metab J 2019 06 7;43(3):342-349. Epub 2018 Dec 7.

Department of Preventive Medicine, Ajou University School of Medicine, Suwon, Korea.

Background: We aimed to identify the postpartum metabolic factors that were associated with the development of diabetes in women with a history of gestational diabetes mellitus (GDM). In addition, we examined the role of the oral glucose tolerance test (OGTT) in the prediction of future diabetes.

Methods: We conducted a prospective study of 179 subjects who previously had GDM but did not have diabetes at 2 months postpartum. The initial postpartum examination including a 75-g OGTT and the frequently sampled intravenous glucose tolerance test (FSIVGTT) was performed 12 months after delivery, and annual follow-up visits were made thereafter.

Results: The insulinogenic index (IGI30) obtained from the OGTT was significantly correlated with the acute insulin response to glucose (AIRg) obtained from the FSIVGTT. The disposition indices obtained from the OGTT and FSIVGTT were also significantly correlated. Women who progressed to diabetes had a lower insulin secretory capacity including IGI30, AIRg, and disposition indices obtained from the FSIVGTT and OGTT compared with those who did not. However, the insulin sensitivity indices obtained from the OGTT and FSIVGTT did not differ between the two groups. Multivariate logistic regression analysis showed that the 2-hour glucose and disposition index obtained from the FSIVGTT were significant postpartum metabolic risk factors for the development of diabetes.

Conclusion: We identified a crucial role of β-cell dysfunction in the development of diabetes in Korean women with previous GDM. The 2-hour glucose result from the OGTT is an independent predictor of future diabetes. Therefore, the OGTT is crucial for better prediction of future diabetes in Korean women with previous GDM.
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http://dx.doi.org/10.4093/dmj.2018.0086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581542PMC
June 2019