Publications by authors named "Sung-Hyun Kim"

539 Publications

Myeloid-specific PTP1B deficiency attenuates inflammation- and ovariectomy-induced bone loss in mice by inhibiting osteoclastogenesis.

J Bone Miner Res 2021 Nov 23. Epub 2021 Nov 23.

Department of Biochemistry and Institute for Hard Tissue and Bone Regeneration, School of Dentistry, Kyungpook National University, Daegu, South Korea.

The differentiation and activity of bone-resorbing osteoclasts are tightly regulated to maintain the homeostasis of healthy bones. In this study, the role of protein tyrosine phosphatase 1B (PTP1B) during osteoclastogenesis was studied in myeloid-specific Ptpn1-deficient (cKO) mice. The mRNA and protein expression of PTP1B increased during the formation of mature osteoclasts from mouse bone macrophages on stimulation with macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor kB ligand (RANKL). The Ptpn1 cKO mice exhibited increased femoral trabecular bone volume with a decreased number and activity of osteoclasts compared with control mice. The in vitro culture of osteoclast precursors corroborated the inhibition of osteoclastogenesis in cKO cells compared with control, with concomitantly decreased RANKL-dependent proliferation, lower osteoclast marker gene expression, reduced nuclear expression of nuclear factor of activated T cells cytoplasmic 1 (NFATc1), diminished intracellular Ca oscillations, and increased phosphorylation of Src on inhibitory tyrosine residue. In a ligature-induced periodontitis model, Ptpn1 cKO mice exhibited attenuated osteoclastogenesis and alveolar bone loss following the induction of inflammation. The Ptpn1-deficient mice were similarly protected from ovariectomy-induced bone loss compared with control mice. These results provide a novel regulatory role of PTP1B in osteoclastogenesis and suggest a potential as a therapeutic target for bone-lytic diseases. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jbmr.4478DOI Listing
November 2021

Six-well plate-based colony-forming efficacy assay and Co-Culture application to assess toxicity of metal oxide nanoparticles.

Regul Toxicol Pharmacol 2021 Nov 17;128:105085. Epub 2021 Nov 17.

Lab of Toxicology, Department of Health Sciences, The Graduate School of Dong-A University, 37, Nakdong-daero 550 Beon-gil, Saha-gu, Busan, 49315, Republic of Korea. Electronic address:

The development of a universal, label-free, and reliable in vitro toxicity testing method for nanoparticles is urgent because most nanoparticles can interfere with toxicity assays. In this regard, the colony-forming efficacy (CFE) assay has been suggested as a suitable in vitro toxicity assay for testing nanoparticles without such interference. Recently, the Organisation for Economic Co-operation and Development (OECD) developed a 60 × 15 mm Petri dish-based CFE assay for testing nanoparticles in MDCK-1 cells. However, further investigations are needed, including testing with other cell types, at a smaller scale for greater efficiency, and the application of the co-culture technique. In this study, we selected TiO, CuO, CeO, and SiO as test nanoparticles and successfully developed a 6-well plate-based CFE assay using HepG2 and A549 cells and a co-culture assay for combinations of HepG2 cells and THP-1 macrophages or A549 cells and THP-1 monocytes. The results suggest that the 6-wellplate-based CFE assay for HepG2 and A549 cells can be applied to nanoparticles, but the co-culture CFE assay has limitations in that it is not different from the single culture study, and it inhibits colony-formation by A549 cells in the presence of macrophages; this warrant further study.
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http://dx.doi.org/10.1016/j.yrtph.2021.105085DOI Listing
November 2021

Molecular approaches for detection and quantification of Vibrio scophthalmi based on recA.

J Fish Dis 2021 Nov 14. Epub 2021 Nov 14.

Department of Aquatic Life Medicine, College of Fisheries Science, Pukyong National University, Busan, Korea.

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http://dx.doi.org/10.1111/jfd.13551DOI Listing
November 2021

Prediction of genetic alteration of phospholipase C isozymes in brain disorders: Studies with deep learning.

Adv Biol Regul 2021 Oct 29;82:100833. Epub 2021 Oct 29.

Korea Brain Research Institute, 41062, Daegu, Republic of Korea. Electronic address:

Genetic mutations leading to the development of various diseases, such as cancer, diabetes, and neurodegenerative disorders, can be attributed to multiple mechanisms and exposure to diverse environments. These disorders further increase gene mutation rates and affect the activity of translated proteins, both phenomena associated with cellular responses. Therefore, maintaining the integrity of genetic and epigenetic information is critical for disease suppression and prevention. With the advent of genome sequencing technologies, large-scale genomic data-based machine learning tools, including deep learning, have been used to predict and identify somatic inactivation or negative dominant expression of target genes in various diseases. Although deep learning studies have recently been highlighted for their ability to distinguish between the genetic information of diseases, conventional wisdom is also necessary to explain the correlation between genotype and phenotype. Herein, we summarize the current understanding of phosphoinositide-specific phospholipase C isozymes (PLCs) and an overview of their associations with genetic variation, as well as their emerging roles in several diseases. We also predicted and discussed new findings of cryptic PLC splice variants by deep learning and the clinical implications of the PLC genetic variations predicted using these tools.
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http://dx.doi.org/10.1016/j.jbior.2021.100833DOI Listing
October 2021

Early Diagnostic Ability of Human Complement Factor B in Pancreatic Cancer Is Partly Linked to Its Potential Tumor-Promoting Role.

J Proteome Res 2021 Nov 12. Epub 2021 Nov 12.

Yonsei Proteome Research Center, Yonsei University, 50 Yonsei-ro, Seodaemoon-ku, Seoul 03722, South Korea.

Although plasma complement factor B (CFB, NX_P00751), both alone and in combination with CA19-9 (i.e., the ComB-CAN), previously exhibited a reliable diagnostic ability for pancreatic cancer (PC), its detectability of the early stages and the cancer detection mechanism remained elusive. We first evaluated the diagnostic accuracy of ComB-CAN using plasma samples from healthy donors (HDs), patients with chronic pancreatitis (CP), and patients with different PC stages (I/II vs III/IV). An analysis of the area under the curve (AUC) by PanelComposer using logistic regression revealed that ComB-CAN has a superior diagnostic ability for early-stage PC (97.1.% [95% confidence interval (CI): (97.1-97.2)]) compared with CFB (94.3% [95% CI: 94.2-94.4]) or CA19-9 alone (34.3% [95% CI: 34.1-34.4]). In the comparisons of all stages of patients with PC vs CP and HDs, the AUC values of ComB-CAN, CFB, and CA19-9 were 0.983 (95% CI: 0.983-0.983), 0.950 (95% CI: 0.950-0.951), and 0.873 (95% CI: 0.873-0.874), respectively. We then investigated the molecular mechanism underlying the detection of early-stage PC by using stable cell lines of knockdown and overexpression. A global transcriptomic analysis coupled to cell invasion assays of both -modulated cell lines suggested that plays a tumor-promoting role in PC, which likely initiates the PI3K-AKT cancer signaling pathway. Thus our study establishes ComB-CAN as a reliable early diagnostic marker for PC that can be clinically applied for early PC screening in the general public.
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http://dx.doi.org/10.1021/acs.jproteome.1c00805DOI Listing
November 2021

Identifying New COVID-19 Receptor Neuropilin-1 in Severe Alzheimer's Disease Patients Group Brain Using Genome-Wide Association Study Approach.

Front Genet 2021 21;12:741175. Epub 2021 Oct 21.

Neurodegenerative Disease Research Group, Korea Brain Research Institute, Daegu, South Korea.

Recent preclinical studies show that Neuropilin-1 (NRP1), which is a transmembrane protein with roles in neuronal development, axonal outgrowth, and angiogenesis, also plays a role in the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus, we hypothesize that NRP1 may be upregulated in Alzheimer's disease (AD) patients and that a correlation between AD and SARS-CoV-2 NRP1-mediated infectivity may exist as angiotensin converting enzyme 2 (ACE2). We used an AD mouse model that mimics AD and performed high-throughput total RNA-seq with brain tissue and whole blood. For quantification of NRP1 in AD, brain tissues and blood were subjected to Western blotting and real-time quantitative PCR (RT-qPCR) analysis. analysis for NRP1 expression in AD patients has been performed on human hippocampus data sets. Many cases of severe symptoms of COVID-19 are concentrated in an elderly group with complications such as diabetes, degenerative disease, and brain disorders. Total RNA-seq analysis showed that the gene was commonly overexpressed in the AD model. Similar to ACE2, the NRP1 protein is also strongly expressed in AD brain tissues. Interestingly, analysis revealed that the level of expression for NRP1 was distinct at age and AD progression. Given that NRP1 is highly expressed in AD, it is important to understand and predict that NRP1 may be a risk factor for SARS-CoV-2 infection in AD patients. This supports the development of potential therapeutic drugs to reduce SARS-CoV-2 transmission.
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http://dx.doi.org/10.3389/fgene.2021.741175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566993PMC
October 2021

Development of a nutritional index to evaluate the effectiveness of total parenteral nutrition during the early postoperative period after pancreaticoduodenectomy.

Gland Surg 2021 Sep;10(9):2622-2630

Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea.

Background: Malnutrition leads to adverse effects on the short- and long-term prognosis in patients with periampullary diseases who underwent surgery. Nutritional risk indicators based on albumin and body weight have been developed to evaluate nutritional status and nutritional therapy efficacy, but no standard objective measurement has been devised to evaluate nutritional status during the early period after pancreaticoduodenectomy (PD). Therefore, this study aimed to assess the efficacy of total parenteral nutrition (TPN) during the early postoperative period after PD.

Methods: We analyzed 28 patients with a periampullary disease-common bile duct cancer, ampulla of Vater cancer, pancreatic head cancer, neuroendocrine tumor, chronic pancreatitis-who have undergone PD from Jan. 1, 2012 to Dec. 31, 2016. For all the patients, TPN was administered from postoperative day (POD) 1 at 25 Kcal/kg ideal body weight. Various nutritional indicators were measured such as Body mass index, nutritional risk index, protein, albumin, prealbumin, C-reactive protein. The volume of skeletal muscle area, muscle density, visceral and subcutaneous fat areas were assessed two times, preoperatively and on POD 7 by CT scan at the 3rd lumbar spine (L3) level.

Results: Average age of the 28 study subjects (18 males and 10 females) was 63.5±9.7 years. Although there is no difference in BMI between preoperative result and POD 7, protein, albumin, and prealbumin levels were significantly lower POD 7 the preoperative (P<0.001), but CRP was higher (P<0.001), and prealbumin and CRP levels were negatively correlated (R=-0.682, P<0.01). Muscle mass increased postoperatively (P=0.02), but the amount of visceral fat decreased (P=0.00). Based on CRP, and muscle density results, muscle, visceral and subcutaneous fat masses did not change after PD.

Conclusions: In order to evaluate the nutritional status accurately after the hepato-biliary radical surgery, we suggest the muscle and fat mass measurement that can adjust the degree of inflammation during the early postoperative period.
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http://dx.doi.org/10.21037/gs-20-390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514298PMC
September 2021

Comparison of postoperative complications and long-term oncological outcomes in minimally invasive versus open pancreatoduodenectomy for distal cholangiocarcinoma: A propensity score-matched analysis.

J Hepatobiliary Pancreat Sci 2021 Oct 30. Epub 2021 Oct 30.

Department of Hepatobiliary and Pancreatic Surgery, Yonsei University College of Medicine, Seoul, Korea.

Background: Pancreatoduodenectomy (PD) is the only curative therapy for distal cholangiocarcinoma (dCC). There has been no study to compare outcomes between minimally invasive pancreatoduodenectomy (MIPD) and open pancreatoduodenectomy (OPD) for dCC. The aim of the study is to compare the two operation types for dCC in terms of postoperative and oncologic outcomes.

Methods: Data from 426 patients who underwent MIPD (n = 91) or OPD (n = 335) for dCC from January 2012 to December 2019 at two tertiary hospitals were retrospectively reviewed. After 1:2 propensity score matching, postoperative and oncologic outcomes were compared.

Results: Minimally invasive pancreatoduodenectomy group showed more favorable results than OPD group in terms of blood loss (MIPD vs OPD, 250 [150-400] vs 400 [200-600], mL, P < .001), and length of hospital stay (19.8 ± 11.3 vs 26.6 ± 14.3 days, P < .001). OPD group showed more favorable results than MIPD group in terms of operation time (MIPD vs OPD, 457 ± 70 vs 398 ± 85 min, P < .001) and harvested lymph nodes (14.9 ± 7.8 vs 20.7 ± 11.5, P < .001). There was no statistical difference between the two groups in the R0 resection rate and complications. In long-term survival analysis, there was no significant difference between the two groups.

Conclusion: Minimally invasive pancreatoduodenectomy showed comparable postoperative complications and long-term oncologic survival with OPD in the treatment of dCC.
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http://dx.doi.org/10.1002/jhbp.1067DOI Listing
October 2021

Efficacy and Safety of CT-P10 Versus Rituximab in Untreated Low-Tumor-Burden Follicular Lymphoma: Final Results of a Randomized Phase III Study.

Clin Lymphoma Myeloma Leuk 2021 Aug 28. Epub 2021 Aug 28.

Institute of Experimental Cancer Research, Comprehensive Cancer Center Ulm, University Hospital of Ulm, 89081 Ulm, Germany. Electronic address:

Introduction: This double-blind, parallel-group, active-controlled phase III trial (NCT02260804) assessed CT-P10 and rituximab safety and efficacy in patients with previously untreated low-tumor-burden follicular lymphoma (LTBFL), including after a single switch from rituximab to CT-P10.

Patients And Methods: LTBFL patients were randomized (1:1) to receive CT-P10 or rituximab (375 mg/m intravenously; day 1 of 4 7-day cycles). Patients achieving disease control entered a 2-year maintenance period. CT-P10 or rituximab were administered every 8 weeks (6 cycles) in year 1; all patients could receive CT-P10 (every 8 weeks; 6 cycles) in year 2. Secondary endpoints (reported here) were overall response rate (ORR) during the study period, progression-free survival (PFS), time to progression (TTP), and overall survival (OS). Safety and immunogenicity were evaluated.

Results: Between  November 9, 2015 and  January 4, 2018, 258 patients were randomized (130 for CT-P10; 128 for rituximab). ORR was similar between groups over the study period (CT-P10: 88%; rituximab: 87%). After 29.2 months' median follow-up, median PFS, TTP, and OS were not estimable; 24-month Kaplan-Meier estimates suggested similarity between groups. Overall, 114 (CT-P10: 88%), and 104 (rituximab: 81%) patients experienced treatment-emergent adverse events. The single switch was well tolerated.

Conclusion: These updated data support therapeutic similarity of CT-P10 and rituximab and support the use of CT-P10 monotherapy for previously untreated LTBFL.
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http://dx.doi.org/10.1016/j.clml.2021.08.005DOI Listing
August 2021

Safety and feasibility of laparoscopic pancreaticoduodenectomy in octogenarians.

Asian J Surg 2021 Oct 11. Epub 2021 Oct 11.

Department of Hepatobiliary and Pancreatic Surgery, Yonsei University College of Medicine, Seoul, South Korea; Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul, South Korea. Electronic address:

Introduction: With continued technical advances in surgical instruments and growing surgical expertise, many laparoscopic pancreaticoduodenectomies (LPDs) have been safely performed with favorable outcomes, and this approach is being used more frequently. With an increase in the life expectancy, interest in treatments for elderly patients has increased. In this study, we investigated the safety and feasibility of LPD in octogenarians.

Methods: From September 2005 to February 2020, resectable/borderline resectable periampullary tumors (PATs) were diagnosed in 71 octogenarians at Sincheon Severance Hospital and CHA Bundang Medical Center. Patients were divided into two groups: those who underwent surgery (PD, N = 38) and those who did not (NPD, N = 33). The group that underwent surgery was further divided into two groups: those who underwent open PD (OPD, N = 19), and those who underwent LPD (LPD, N = 19). Perioperative outcomes, including long-term survival, were retrospectively compared between these groups.

Results: There was no significant difference in age, sex, comorbidities, diagnosis, and chemo-radiotherapy between the surgery and non-surgery groups. The PD group had a better survival rate than the NPD group (p < 0.05). The baseline characteristics and postoperative outcomes were not significantly different between the OPD and LPD groups. Only three and two patients in the OPD and LPD groups had a biochemical leak (p > 0.999). There was no significant difference in overall survival and disease-free survival between the OPD and LPD groups (p = 0.816, p = 0.446, respectively).

Conclusions: LPD is a good alternative for octogenarians with PAT requiring PD.
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http://dx.doi.org/10.1016/j.asjsur.2021.09.021DOI Listing
October 2021

Non-invasive ultrasonic inspection of sludge accumulation in a pipe.

Ultrasonics 2022 Feb 29;119:106602. Epub 2021 Sep 29.

Institute of Advanced Machines and Design, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea; Department of Mechanical Engineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea. Electronic address:

Sludge accumulated inside a fluid-flowing pipe used in a chemical or semiconductor processing factory should be periodically removed to avoid flow blockage that increases undesirable pressure inside the pipe. Accordingly, it is common practice to periodically dismantle a pipe system, clean up the accumulate sludge, and reassemble. Therefore, an accurate estimation of sludge accumulation in the pipe is important to minimize the halting time of a chemical process using the system. Considering the lack of a practically efficient, non-invasive method to estimate the severity of sludge accumulation without interrupting the on-going chemical process, we propose an ultrasonic, non-invasive, real-time inspection method using a pair of ultrasonic wedge transducers installed circumferentially on the outer wall of a pipe at the same axial coordinate. To detect lowly accumulated sludge, an ultrasonic wave path from a transmitting transducer via a test pipe with accumulated sludge to a receiving transducer is carefully designed. The severity of sludge accumulation can then be determined by the amplitude of the longitudinal wave picked up by another transducer installed on the other side of the wall. We performed a series of experiments with steel and PVC pipes that are partially filled with water and sludge of different heights. The experimental results confirmed the effectiveness and practical viability of the proposed inspection method.
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http://dx.doi.org/10.1016/j.ultras.2021.106602DOI Listing
February 2022

Computer-aided automatic measurement of leg length on full leg radiographs.

Skeletal Radiol 2021 Sep 30. Epub 2021 Sep 30.

Division of AI Computer Science and Engineering, Kyonggi University, 154-42, Gwanggyosan-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do, 16227, Republic of Korea.

Objectives: To develop and evaluate a deep learning (DL)-based system for measuring leg length on full leg radiographs of diverse patients, including those with orthopedic hardware implanted for surgical treatment.

Methods: This study retrospectively assessed 2767 X-ray scanograms of 2767 patients who did or did not have orthopedic hardware implanted between January 2016 and December 2019. A cascaded DL model was developed to localize the relevant landmarks on the pelvis, knees, and ankles required for measuring leg length. Statistical analysis was performed using the correlation coefficient analysis and Bland-Altman plots to assess the agreement between the reference standard and DL-calculated lengths.

Results: Testing data comprised 400 radiographs from 400 patients. Of these radiographs, 100 were from patients with orthopedic hardware implanted in their pelvis, knees, or ankles. For all testing data, leg lengths derived from the DL-based measurement system, with or without internal fixation devices, showed excellent agreement with the reference standard (femoral length, r = 0.99 (P < .001); root mean square error (RMSE) = 0.17 cm; mean difference, - 0.01 ± 0.17 cm; 95% limit of agreement (LoA), - 0.35 to 0.34; tibial length, r = 0.99 (P < .001); RMSE = 0.17 cm; mean difference, - 0.02 ± 0.17 cm, 95% LoA, - 0.34 to 0.31; and full leg length, r = 1.0 (P < .001); RMSE = 0.19 cm; mean difference, 0.05 ± 0.18 cm; 95% LoA, - 0.31 to 0.40). The mean time for leg length measurement for each patient using the DL-based system was 8.68 ± 0.18 s.

Conclusion: The DL-based leg length measurement system could provide similar performance to radiologists in terms of accuracy and reliability for a diverse group of patients.
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http://dx.doi.org/10.1007/s00256-021-03928-zDOI Listing
September 2021

Safety, Virologic Efficacy, and Pharmacokinetics of CT-P59, a Neutralizing Monoclonal Antibody Against SARS-CoV-2 Spike Receptor-Binding Protein: Two Randomized, Placebo-Controlled, Phase I Studies in Healthy Individuals and Patients With Mild SARS-CoV-2 Infection.

Clin Ther 2021 10 23;43(10):1706-1727. Epub 2021 Aug 23.

Division of Infectious Diseases, Chungnam National University School of Medicine, Daejeon, Republic of Korea. Electronic address:

Purpose: Neutralizing antibodies can reduce SARS-CoV-2 cellular entry, viral titers, and pathologic damage. CT-P59 (regdanvimab), a SARS-CoV-2 neutralizing monoclonal antibody, was examined in 2 randomized, double-blind, placebo-controlled, single ascending dose, Phase I studies.

Methods: In study 1.1, healthy adults were sequentially enrolled to receive CT-P59 10, 20, 40, or 80 mg/kg or placebo. In study 1.2, adult patients with mild SARS-CoV-2 infection were enrolled to receive CT-P59 20, 40, or 80 mg/kg or placebo. Primary objectives of both studies were safety and tolerability up to day 14 after infusion. Secondary end points included pharmacokinetic properties. Study 1.2 also measured virology and clinical efficacy.

Findings: Thirty-two individuals were randomized to study 1.1 (6 per CT-P59 dose cohort and 8 in the placebo cohort). By day 14 after infusion, adverse events (AEs) were reported in 2 individuals receiving CT-P59 20 mg/kg (headache and elevated C-reactive protein levels) and 1 receiving CT-P59 40 mg/kg (pyrexia) (all Common Terminology Criteria for Adverse Events grade 1). In study 1.2, 18 patients were randomized (5 per dose cohort and 3 in the placebo cohort). Sixteen AEs were reported in 10 patients receiving CT-P59. No AEs in either study led to study discontinuation. Greater reductions in viral titers were reported with CT-P59 than placebo in those with maximum titers >10 copies/mL. Mean time to recovery was 3.39 versus 5.25 days.

Implications: CT-P59 exhibited a promising safety profile in healthy individuals and patients with mild SARS-CoV-2 infection, with potential antiviral and clinical efficacy in patients with mild SARS-CoV-2 infection. ClinicalTrials.gov identifier: NCT04525079 (study 1.1) and NCT04593641 (study 1.2).
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http://dx.doi.org/10.1016/j.clinthera.2021.08.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380488PMC
October 2021

Four Unrecorded Species from the Rhizosphere Soil in South Korea.

Mycobiology 2021 6;49(4):346-354. Epub 2021 Jul 6.

School of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul, Republic of Korea.

The genus is commonly isolated from various marine and terrestrial environments; however, only a few species have been studied in rhizosphere soil. As part of the Korean indigenous fungal excavation project, we investigated fungal diversity from rhizosphere soil, focusing on species. A total of 13 strains were isolated from the rhizosphere soil of three different plants. Based on phylogenetic analysis of β-tubulin and calmodulin and morphological characteristics, we identified five species. . and . were commonly isolated from the rhizosphere soil. Four species were confirmed as unrecorded species in Korea: . , . , . , and . . The detailed morphological descriptions of these unrecorded species are provided.
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http://dx.doi.org/10.1080/12298093.2021.1944461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409969PMC
July 2021

The Association Between Sagittal Plane Alignment and Disc Space Narrowing of Lumbar Spine in Farmers.

Ann Rehabil Med 2021 Aug 30;45(4):294-303. Epub 2021 Aug 30.

Human Medical Imaging and Intervention Center, Seoul, Korea.

Objective: To investigate whether lumbar lordosis (LL) and lumbar segmental lordosis (LSL) are related to sex, age, low back pain (LBP), and lumbar disc space narrowing (DSN).

Methods: A total of 569 farmers were recruited. In lateral spine radiograph, LL (L1-L5) and LSL (L1, L2, L3, L4, and L5) were measured using Cobb's method. The differences in LSL values (ΔLSL) according to the presence or absence of a DSN were calculated as LSLDSN - LSLnoDSN for each DSN level.

Results: In male, the lateral spine radiograph showed significantly greater L4-LSL and L5-LSL and smaller L1-LSL and L2-LSL compared to female. LLs in the 50-59 and ≥60 years age groups were significantly smaller compared to those in the <50 years age group. In subjects with LBP, LL and L4-LSL were significantly smaller than in those without. The ΔLSLs at the disc level with DSN showed the greatest decrease: L1-ΔLSL (Δ-3.99°), L2-ΔLSL (Δ-3.31°), L3-ΔLSL (Δ-2.87°), L4-ΔLSL (Δ-3.31°), and L5-ΔLSL (Δ-4.44°) in L1/2, L2/3, L3/4, L4/5, and L5/S1 DSN, respectively. Conversely, distant ΔLSLs were inversely increased: L1-LSL (Δ0.75°) with L4/5 DSN and L2-LSL (Δ0.94°) with L5/S1 DSN.

Conclusion: Sagittal plane alignment was significantly associated with sex, age, LBP, and DSN. LSLs around the levels of DSN were decreased, and there was compensational increase of LSL distant to the DSN to maintain the overall LL.
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http://dx.doi.org/10.5535/arm.21037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435469PMC
August 2021

Multicenter, phase II study of response-adapted lenalidomide-based therapy for transplant-ineligible patients with newly diagnosed multiple myeloma without high-risk features.

Curr Probl Cancer 2021 Aug 21:100788. Epub 2021 Aug 21.

Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea. Electronic address:

Lenalidomide and low-dose dexamethasone (Rd) are a standard treatment for older adults with multiple myeloma (MM). Lenalidomide monotherapy has rarely been evaluated for newly diagnosed transplant-ineligible MM patients. This multicenter phase II trial evaluated a response-adapted strategy for elderly patients with newly diagnosed MM without high-risk features. Patients were administered single-agent lenalidomide for the first 21 days of two 28-day cycles. Patients with progressive disease received Rd. The primary endpoint was progression-free survival using the uniform response assessment from the International Myeloma Working Group . Of the 34 enrolled patients, 28 were included in the efficacy analysis. The overall response rate (ORR, ≥ partial response [PR]) to single-agent lenalidomide or lenalidomide plus prednisone was 64.3%. Ten patients received Rd after disease progression, with an Rd ORR of 70%. The ORR of response-adapted lenalidomide-based therapy was 75%. After the median follow-up of 35.6 months, the median progression-free survival was 33.5 months (95% confidence interval [CI], 16.9-50.2), and the median overall survival was 51.8 months (95% CI, 22.0-81.6). The most common adverse event was neutropenia (46.7%), and 17 patients (56.7%) experienced infection including pneumonia. Response-adapted lenalidomide-based therapy was feasible in newly diagnosed, transplant-ineligible MM patients without high-risk features.
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http://dx.doi.org/10.1016/j.currproblcancer.2021.100788DOI Listing
August 2021

Skin Sensitization Potential and Cellular ROS-Induced Cytotoxicity of Silica Nanoparticles.

Nanomaterials (Basel) 2021 Aug 22;11(8). Epub 2021 Aug 22.

Division of Toxicological Research, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Osong, Cheongju 28159, Korea.

Nowadays, various industries using nanomaterials are growing rapidly, and in particular, as the commercialization and use of nanomaterials increase in the cosmetic field, the possibility of exposure of nanomaterials to the skin of product producers and consumers is increasing. Due to the unique properties of nanomaterials with a very small size, they can act as hapten and induce immune responses and skin sensitization, so accurate identification of toxicity is required. Therefore, we selected silica nanomaterials used in various fields such as cosmetics and biomaterials and evaluated the skin sensitization potential step-by-step according to in-vitro and in-vivo alternative test methods. KeratinoSens cells of modified keratinocyte and THP-1 cells mimicking dendritic-cells were treated with silica nanoparticles, and their potential for skin sensitization and cytotoxicity were evaluated, respectively. We also confirmed the sensitizing ability of silica nanoparticles in the auricle-lymph nodes of BALB/C mice by in-vivo analysis. As a result, silica nanoparticles showed high protein binding and reactive oxygen species (ROS) mediated cytotoxicity, but no significant observation of skin sensitization indicators was observed. Although more studies are needed to elucidate the mechanism of skin sensitization by nanomaterials, the results of this study showed that silica nanoparticles did not induce skin sensitization.
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http://dx.doi.org/10.3390/nano11082140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399877PMC
August 2021

Evaluation of the feasibility of explainable computer-aided detection of cardiomegaly on chest radiographs using deep learning.

Sci Rep 2021 08 19;11(1):16885. Epub 2021 Aug 19.

Division of AI Computer Science and Engineering, Kyonggi University, 154-42, Gwanggyosan-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16227, Republic of Korea.

We examined the feasibility of explainable computer-aided detection of cardiomegaly in routine clinical practice using segmentation-based methods. Overall, 793 retrospectively acquired posterior-anterior (PA) chest X-ray images (CXRs) of 793 patients were used to train deep learning (DL) models for lung and heart segmentation. The training dataset included PA CXRs from two public datasets and in-house PA CXRs. Two fully automated segmentation-based methods using state-of-the-art DL models for lung and heart segmentation were developed. The diagnostic performance was assessed and the reliability of the automatic cardiothoracic ratio (CTR) calculation was determined using the mean absolute error and paired t-test. The effects of thoracic pathological conditions on performance were assessed using subgroup analysis. One thousand PA CXRs of 1000 patients (480 men, 520 women; mean age 63 ± 23 years) were included. The CTR values derived from the DL models and diagnostic performance exhibited excellent agreement with reference standards for the whole test dataset. Performance of segmentation-based methods differed based on thoracic conditions. When tested using CXRs with lesions obscuring heart borders, the performance was lower than that for other thoracic pathological findings. Thus, segmentation-based methods using DL could detect cardiomegaly; however, the feasibility of computer-aided detection of cardiomegaly without human intervention was limited.
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http://dx.doi.org/10.1038/s41598-021-96433-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376868PMC
August 2021

Determination of Toxic Elements and Arsenic Species in Salted Foods and Sea Salt by ICP-MS and HPLC-ICP-MS.

ACS Omega 2021 Aug 19;6(30):19427-19434. Epub 2021 Jul 19.

Strategy and Planning Division/SME Service Department, World Institute of Kimchi, Gwangju 61755, Republic of Korea.

Toxic elements (Cd, Pb, and As) accumulate into the environment by industrialization and natural phenomena and then pass to organisms. Analysis of toxic elements in food must be accurately carried out on a regular basis so as to avoid any adverse impact. Salted foods are difficult samples and accurate analysis of As is not easy due to salt interference. In this study, analysis of As was carried without influence of salts in three types of salted foods via an analytical method, which was validated using spiking recovery experiments and by analyzing certified reference materials. As a result, toxic elements were detected in all samples but none of these exceeded the World Health Organization recommended limits. Among the As species, arsenobetaine (AsB) was the most abundant, while inorganic As was below the detection limit in all samples. All the analyzed salted food samples appeared to be safe for consumption. In addition, the analysis of sea shrimp, freshwater shrimp, and seawater verified As bioaccumulation in these organisms from the environment.
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http://dx.doi.org/10.1021/acsomega.1c01273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340090PMC
August 2021

Anticancer effects of oleanolic acid on human melanoma cells.

Chem Biol Interact 2021 Sep 5;347:109619. Epub 2021 Aug 5.

Department of Companion and Laboratory Animal Science, Kongju National University, Yesan, Chungcheongnam, 32439, Republic of Korea. Electronic address:

Owing to the ineffectiveness of the currently used therapies against melanoma, there has been a shift in focus toward alternative therapies involving the use of natural compounds. This study assessed the anticancer effects of oleanolic acid (OA) and its ability to induce apoptosis in A375SM and A375P melanoma cells in vivo. Compared to the control group, viability of A375P and A375SM cells decreased following OA treatment. In OA-treated A375SM and A375P cells, 4',6-diamidino-2-phenylindole staining showed an increase in the apoptotic body, and flow cytometry revealed increased number of apoptotic cells compared to that in the control group. OA-treated A375SM cells exhibited an increased expression of the apoptotic proteins, cleaved poly (ADP-ribose) polymerase (PARP) and B-cell lymphoma (Bcl)-2-associated X protein (Bax) as well as decreased expression of the antiapoptotic protein Bcl-2 compared to that in the control group. In OA-treated A375P cells, expression patterns of cleaved PARP and Bcl-2 were similar to those in OA-treated A375SM cells; however, no difference was reported in the expression of Bax compared to that in the control group. Additionally, OA-treated melanoma cells showed decreased expression of phospho-nuclear factor-κB (p-NF-κB), phospho-inhibitor of nuclear factor-κBα (p-IκBα), and phospho-IκB kinase αβ than that in the control group. Moreover, immunohistochemistry showed a comparatively decreased level of p-NF-κB in the OA-treated group than that in the control group. Xenograft analysis confirmed the in vivo anticancer effects of OA against A375SM cells. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay revealed an increased number of TUNEL-positive cells in the OA-treated group compared to that in the control group. In conclusion, the study results suggest that OA induces apoptosis of A375SM and A375P cells in vitro and apoptosis of A375SM cells in vivo. Furthermore, the in vitro and in vivo anticancer effects were mediated by the NF-κB pathway.
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http://dx.doi.org/10.1016/j.cbi.2021.109619DOI Listing
September 2021

Costunolide Induces Apoptosis via the Reactive Oxygen Species and Protein Kinase B Pathway in Oral Cancer Cells.

Int J Mol Sci 2021 Jul 13;22(14). Epub 2021 Jul 13.

Department of Animal Science and Biotechnology, ITRD, Kyungpook National University, Sangju 37224, Korea.

Oral cancer (OC) has been attracted research attention in recent years as result of its high morbidity and mortality. Costunolide (CTD) possesses potential anticancer and bioactive abilities that have been confirmed in several types of cancers. However, its effects on oral cancer remain unclear. This study investigated the potential anticancer ability and underlying mechanisms of CTD in OC in vivo and in vitro. Cell viability and anchorage-independent colony formation assays were performed to examine the antigrowth effects of CTD on OC cells; assessments for migration and invasion of OC cells were conducted by transwell; Cell cycle and apoptosis were investigated by flow cytometry and verified by immunoblotting. The results revealed that CTD suppressed the proliferation, migration and invasion of oral cancer cells effectively and induced cell cycle arrest and apoptosis; regarding the mechanism, CTD bound to AKT directly by binding assay and repressed AKT activities through kinase assay, which thereby downregulating the downstream of AKT. Furthermore, CTD remarkably promotes the generation of reactive oxygen species by flow cytometry assay, leading to cell apoptosis. Notably, CTD strongly suppresses cell-derived xenograft OC tumor growth in an in vivo mouse model. In conclusion, our results suggested that costunolide might prevent progression of OC and promise to be a novel AKT inhibitor.
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http://dx.doi.org/10.3390/ijms22147509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305390PMC
July 2021

Flow cytometric evaluation of the potential of metal oxide nanoparticles for skin sensitization using 5-Bromo-2-deoxyuridine.

Toxicol Res 2021 Jul 4;37(3):369-377. Epub 2021 Jan 4.

Division of Toxicological Research, Ministry of Food and Drug Safety, National Institute of Food and Drug Safety Evaluation, 187, Osongsaengmyeong 2-ro, Osong-eup, Cheongju-si, Chungcheongbuk-do 28159 Korea.

Although skin sensitization potential of various chemicals has been extensively studied, there are only a few reports on nanoparticles induced skin sensitization. Aiming to fill this lacuna, in this study we evaluated the potential of metal oxide nanoparticles (NPs) to induce skin sensitization with flow cytometry. Seven different metal oxide NPs, including copper oxide, cobalt oxide, nickel oxide, titanium oxide, cerium oxide, iron oxide, and zinc oxide were applied to Balb/c mice. After selecting the proper vehicle, the NPs were applied, and the skin sensitization potential were assessed using 5-bromo-2-deoxyuridine with flow cytometry. Physiochemical properties such as hydrodynamic size, polydispersity, and zeta potential were measured for the NPs prior to the tests. All the seven metal oxide NPs studied showed negative responses for skin sensitization potential. These results suggest that the OECD TG 442B using 5-bromo-2-deoxyuridine with flow cytometry can be applied to evaluate the potential of NPs for skin sensitization.
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http://dx.doi.org/10.1007/s43188-020-00073-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249504PMC
July 2021

ABCG1 and ABCG4 as key transporters in the development of pulmonary alveolar proteinosis by nanoparticles.

J Hazard Mater 2021 10 7;420:126595. Epub 2021 Jul 7.

Lab of Toxicology, Department of Health Sciences, The Graduate School of Dong-A University, 37, Nakdong-daero 550 beon-gil Saha-gu, Busan 49315, Republic of Korea. Electronic address:

Pulmonary alveolar proteinosis (PAP) has been reported in rodents treated with nanoparticles (NPs). However, little is known about the type of NPs producing PAP and their toxicity mechanisms. Here, we assembled seven PAP-inducing NPs and TiO NPs as a negative control. At 1 and 6 months after a single intratracheal instillation in rats, pulmonary inflammation and the gene expression of ATP-binding cassette (ABC) transporters and related genes were evaluated in separated alveolar macrophages (AMs). One month after intratracheal instillation, seven NPs (EuO, InO, PrO, SmO, TbO, and NiO) caused PAP, but only InO NPs caused persistent PAP at 6 months after treatment. The levels of phospholipids, indicators of PAP, showed good correlations with the gene expression profile of five transporters (ABCA1, ABCB4, ABCB8, ABCG1, and ABCG4), which effluxing phospholipids in AMs. Among them, ABCG1 and ABCG4 might be key transporters involved in PAP development because both showed a negative correlation with the magnitude of PAP, while others might be compensatory transporters for PAP recovery, as they showed a positive correlation. In conclusion, the identification of seven PAP-producing NPs implies that PAP may be an emerging occupational disease and that ABCG1 and ABCG4 may be therapeutic targets for PAP.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126595DOI Listing
October 2021

Infliximab Biosimilar CT-P13 Observational Studies for Rheumatoid Arthritis, Inflammatory Bowel Diseases, and Ankylosing Spondylitis: Pooled Analysis of Long-Term Safety and Effectiveness.

Adv Ther 2021 08 12;38(8):4366-4387. Epub 2021 Jul 12.

Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-Gu, Seoul, 137-701, Republic of Korea.

Introduction: Long-term, real-world safety and effectiveness data are required to support biosimilar use. This analysis pooled 5-year findings from observational studies of infliximab biosimilar CT-P13 treatment in patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and ankylosing spondylitis (AS).

Methods: Patients enrolled in the CT-P13 4.2, 4.3, or 4.4 Korea/European Union registries were analysed if they had initiated infliximab treatment with CT-P13 (CT-P13 group) or had switched from reference infliximab to CT-P13 (switched to CT-P13 group). The primary objective was to investigate long-term safety by evaluating adverse events of special interest (AESIs) per the CT-P13 risk-management plan. Incidence rates per 100 patient-years (PYs) were calculated. Additional long-term safety endpoints, immunogenicity (assessments optional), and effectiveness were evaluated.

Results: Overall, 736 patients (642 CT-P13; 94 switched to CT-P13) were analysed. Median (range) exposure to CT-P13 was 19.433 (0.03-63.11) months overall. The incidence of treatment-emergent adverse events was 69.0% (CT-P13 group) and 60.6% (switched to CT-P13 group). Infusion-related reaction/hypersensitivity/anaphylactic reaction was the most frequent AESI overall, with an incidence of 4.3828 per 100 PY (95% confidence interval: 3.3603-5.6185). For most AESIs, incidence rates per 100 PY were broadly comparable between treatment groups, considering overlapping 95% confidence intervals. At baseline, 42/445 (9.4%) and 21/59 (35.6%) evaluable patients in the CT-P13 and switched to CT-P13 groups, respectively, were antidrug antibody (ADA)-positive. After CT-P13 treatment during the study, 188/425 (44.2%) evaluable patients had ≥ 1 ADA-positive result, including 147/425 (34.6%) patients with negative or no ADA results reported at baseline. Effectiveness tended to increase over time for all indications.

Conclusion: The analysis did not identify any new safety findings for patients with RA, IBD, and AS treated with CT-P13 for up to 5 years in those who were infliximab-naïve at CT-P13 initiation, or those who had switched from reference infliximab to CT-P13.

Trial Registration: ClinicalTrials.gov identifiers: NCT02557295 (CT-P13 4.2; retrospectively registered on 23 September 2015); NCT02326155 (CT-P13 4.3; retrospectively registered on 25 December 2014); NCT02557308 (CT-P13 4.4; retrospectively registered on 23 September 2015).
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http://dx.doi.org/10.1007/s12325-021-01834-3DOI Listing
August 2021

Surface plasmonic resonance tunable nanocomposite thin films applicable to color filters, heat mirrors, semi-transparent electrodes, and electromagnetic-shields.

Nanoscale 2021 Jul 9;13(28):12260-12270. Epub 2021 Jul 9.

Chemical Materials Solutions Center, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea.

This study proposes a plasmonic resonance-tunable nanocomposite thin film, which applies to a color filter, heat mirror, semi-transparent color electrode, and electromagnetic shield, given that the size and structure of nanoclusters can be controlled by a sputtering power density. The structural and functional properties of silver/plasma-polymer-fluorocarbon (Ag/PPFC) nanocomposite thin films, which were sputtered by ternary composite targets, were investigated with various compositions and sputtering power densities. The growth of Ag nanoclusters of the thin film was suppressed as the sputtering power density increased due to the rich functional group of -CF- fluorine. As a result, a continuous color change from blue to yellow could be expressed on films given the precise control of the surface plasmonic resonance phenomenon. Grazing-incidence small-angle scattering (GISAXS) analysis indicated that the sputtering power density had a significant effect on the size, distribution, and orientation of the Ag nanoclusters in the thin film. For low sputtering power densities, Ag nanoclusters were forming aggregations along the out-of-plane direction, but as the sputtering power density increased, the nanoclusters showed random distribution instead of large aggregates. We also demonstrated applications of Ag/PPFC nanocomposite thin films to a color filter, heat mirror, semi-transparent electrode, and electromagnetic shield. In addition, the fabrication of a large-area film (400 × 700 mm) showed that the approach applies highly to industries.
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http://dx.doi.org/10.1039/d1nr02363bDOI Listing
July 2021

FRETboard: Semisupervised classification of FRET traces.

Biophys J 2021 08 6;120(16):3253-3260. Epub 2021 Jul 6.

Bioinformatics Group, Wageningen University, Wageningen.

Förster resonance energy transfer (FRET) is a useful phenomenon in biomolecular investigations, as it can be leveraged for nanoscale measurements. The optical signals produced by such experiments can be analyzed by fitting a statistical model. Several software tools exist to fit such models in an unsupervised manner but lack the flexibility to adapt to different experimental setups and require local installations. Here, we propose to fit models to optical signals more intuitively by adopting a semisupervised approach, in which the user interactively guides the model to fit a given data set, and introduce FRETboard, a web tool that allows users to provide such guidance. We show that our approach is able to closely reproduce ground truth FRET statistics in a wide range of simulated single-molecule scenarios and correctly estimate parameters for up to 11 states. On in vitro data, we retrieve parameters identical to those obtained by laborious manual classification in a fraction of the required time. Moreover, we designed FRETboard to be easily extendable to other models, allowing it to adapt to future developments in FRET measurement and analysis.
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http://dx.doi.org/10.1016/j.bpj.2021.06.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391082PMC
August 2021

Antioxidant, Anti-Obesity, and Anti-Aging Activities of Citrus Blended Vinegar.

Foods 2021 Jun 22;10(7). Epub 2021 Jun 22.

SME Service Department, Strategy and Planning Division, World Institute of Kimchi, Nam-Gu, Gwangju 61755, Korea.

Various types of vinegars have been developed as interest in their health benefits has increased. In this study, we prepared citrus blended vinegars (CBVs) by mixing premature mandarin vinegar and mandarin vinegar, with mandarin vinegar used as a control. The physicochemical properties of the vinegars, including pH, total acidity, and sugar content was determined. Moreover, antioxidant, anti-obesity, and anti-aging activities of the vinegars were investigated. Physicochemical analysis revealed that the CBVs had a pH similar to that of mandarin vinegar, whereas CBVs with relatively high premature mandarin vinegar content showed higher acidity and lower sugar content ( < 0.05). Moreover, the antioxidant activities and phenol contents of CBVs were significantly higher than those of mandarin vinegar ( < 0.05). Meanwhile, CBVs showed significantly decreased intracellular triglyceride, lipid accumulation, and anti-obesity related gene levels ( < 0.05), thereby highlighting their anti-obesity activity. In addition, CBVs showed anti-aging activity by increasing cell viability and cell lifespan, while decreasing the expression of senescence-related genes under HO-induced oxidative stress. Therefore, CBVs may be useful as a functional food with antioxidant, anti-obesity, and anti-aging effects in various food fields.
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http://dx.doi.org/10.3390/foods10071441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306124PMC
June 2021

Lenalidomide for anemia correction in lower-risk del(5q) myelodysplastic syndrome patients of Asian ethnicity.

Blood Res 2021 Jun;56(2):102-108

University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

Background: To estimate real-world outcomes in East Asian populations, we conducted a nationwide retrospective analysis of the efficacy and safety of lenalidomide for del(5q) myelodysplastic syndrome (MDS) patients with transfusion-dependent anemia in Korea.

Methods: Patients aged ≥19 years who had received lenalidomide for the treatment of lower-risk, red blood cell (RBC) transfusion-dependent del(5q) MDS were selected. A filled case report form (CRF) with information from electronic medical records was requested from members of the acute myeloid leukemia (AML)/MDS Working Party of the Korean Society of Hematology. All the CRFs were gathered and analyzed.

Results: A total of 31 patients were included in this study. Of 28 evaluable patients, 19 (67.9%) achieved RBC transfusion independence (RBC-TI). Female sex and the development of thrombocytopenia during treatment were associated with achieving RBC-TI. The most common non-hematologic toxicities were pruritus, fatigue, and rashes. All non-hematologic toxicities of grades ≥3 were limited to rash (12.9%) and pruritus (6.5%). Dose reduction was required in 15 of the 19 responders (78.9%). The most common final stable dosing schedule for the responders was 5 mg once every other day (31.6%).

Conclusion: Lenalidomide efficacy and tolerability were similar in the Asian del(5q) MDS patients and western patients. Dose reduction during treatment was common, but it was not associated with inferior outcomes.
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http://dx.doi.org/10.5045/br.2021.2021086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246035PMC
June 2021

Clinical characteristics and prognostic factors of acquired haemophilia A in Korea.

Haemophilia 2021 Sep 22;27(5):e609-e616. Epub 2021 Jun 22.

Division of Hematology,  Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Introduction: Acquired haemophilia A (AHA) treatment involves the haemostatic treatment for acute haemorrhage and immunosuppressive therapy (IST) to eradicate FVIII inhibitory antibodies.

Aim: We assessed the clinical features of AHA and analysed treatment outcomes in Korea. We further identified prognostic factors affecting treatment outcomes.

Methods: Medical records of 55 patients with AHA from 18 institutions were reviewed retrospectively. Logistic and Cox regression analyses were performed to elucidate clinical factors affecting the achievement of complete remission (CR). The primary endpoint was time to CR after IST, and secondary endpoints were time to haemostasis, the achievement of CR, and overall survival (OS).

Results: Among the 55 patients, 50 (91%) had bleeding symptoms. Bleeding was severe in 74% of patients. Thirty-six (72%) patients received haemostatic therapy. Of the 42 patients who received IST, 23 (52%) received steroid alone, with a 52% response rate, and 10 (25%) received a combination of steroid and cyclophosphamide, with an 83% response rate. Five (16%) patients relapsed after a median duration of 220 days. There were eight deaths. In the Cox regression analysis, the FVIII inhibitor titre ≥ 20 BU/mL was the only significant prognostic factor affecting time to CR and haemostasis. No significant difference was observed in OS based on the inhibitor titre.

Conclusion: The present study demonstrated the demographic data of AHA in Korea and showed that FVIII inhibitory antibody titre was a predictor of time to achieve CR after IST.
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http://dx.doi.org/10.1111/hae.14370DOI Listing
September 2021
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