1.Association between Congestive Heart Failure and Ossification of the Posterior Longitudinal Ligament in Korea: A Nationwide Longitudinal Cohort Study
Dong Soon JANG ; Hakyung KIM ; Seung Hun SHEEN ; Inbo HAN ; Soo Hyun LEE ; Woo Seok CHOI ; Je Beom HONG ; Min Jai CHO ; Seil SOHN
The Nerve 2024;10(1):19-24
Objective:
The objective of this nationwide, long-term follow-up study was to explore the connection between congestive heart failure (CHF) and ossification of the posterior longitudinal ligament (OPLL) in Korea.
Methods:
Patient information was collected from the Health Screening cohort of the National Health Insurance Service. Individuals diagnosed with OPLL were identified using specific International Classification of Diseases, 10th revision codes (M48.8, M48.81, M48.82, and M48.83). A total of 1,289 OPLL patients and 6,445 controls were included in the study, selected through 1:5 age and sex matching. The data spanned from January 1, 2004 to July 31, 2015. To compute the incidence rate of CHF in each group, the Kaplan-Meier method was employed. Additionally, Cox proportional-hazards regression analysis was utilized to estimate the hazard ratio of CHF.
Results:
CHF was present in 19 patients (1.47%) in the OPLL group and 71 patients (1.10%) in the control group. After accounting for age and sex, the hazard ratio for CHF in the OPLL group was 3.164 (95% confidence interval [CI], 1.867-5.360). When additionally considering income and underlying diseases, the hazard ratio for CHF within the OPLL group was 3.355 (95% CI, 1.977-5.694). All subgroups of OPLL patients exhibited an increased risk ratio for CHF across parameters such as sex, age, diabetes, hypertension, and dyslipidemia.
Conclusion
According to this nationwide longitudinal study, an elevated incidence rate of CHF was associated with OPLL.
2.Effect of Kaempferol on Modulation of Vascular Contractility Mainly through PKC and CPI-17 Inactivation
Hyuk-Jun YOON ; Heui Woong MOON ; Young Sil MIN ; Fanxue JIN ; Joon Seok BANG ; Uy Dong SOHN ; Hyun Dong JE
Biomolecules & Therapeutics 2024;32(3):361-367
In this study, we investigated the efficacy of kaempferol (a flavonoid found in plants and plant-derived foods such as kale, beans, tea, spinach and broccoli) on vascular contractibility and aimed to clarify the detailed mechanism underlying the relaxation. Isometric contractions of divested muscles were stored and linked with western blot analysis which was carried out to estimate the phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) and phosphorylation-dependent inhibitory protein for myosin phosphatase (CPI-17) and to estimate the effect of kaempferol on the RhoA/ROCK/CPI-17 pathway. Kaempferol conspicuously impeded phorbol ester-, fluoride- and a thromboxane mimetic-derived contractions regardless of endothelial nitric oxide synthesis, indicating its direct effect on smooth muscles. It also conspicuously impeded the fluoride-derived elevation in phospho-MYPT1 rather than phospho-CPI-17 levels and phorbol 12,13-dibutyrate-derived increase in phospho-CPI-17 and phospho-ERK1/2 levels, suggesting the depression of PKC and MEK activities and subsequent phosphorylation of CPI-17 and ERK1/2. Taken together, these outcomes suggest that kaempferol-derived relaxation incorporates myosin phosphatase retrieval and calcium desensitization, which appear to be modulated by CPI-17 dephosphorylation mainly through PKC inactivation.
3.Brain Frailty and Outcomes of Acute Minor Ischemic Stroke With Large-Vessel Occlusion
Je-Woo PARK ; Joon-Tae KIM ; Ji Sung LEE ; Beom Joon KIM ; Joonsang YOO ; Jung Hoon HAN ; Bum Joon KIM ; Chi Kyung KIM ; Jae Guk KIM ; Sung Hyun BAIK ; Jong-Moo PARK ; Kyusik KANG ; Soo Joo LEE ; Hyungjong PARK ; Jae-Kwan CHA ; Tai Hwan PARK ; Kyungbok LEE ; Jun LEE ; Keun-Sik HONG ; Byung-Chul LEE ; Dong-Eog KIM ; Jay Chol CHOI ; Jee-Hyun KWON ; Dong-Ick SHIN ; Sung Il SOHN ; Sang-Hwa LEE ; Wi-Sun RYU ; Juneyoung LEE ; Hee-Joon BAE
Journal of Clinical Neurology 2024;20(2):175-185
Background:
and Purpose The influence of imaging features of brain frailty on outcomes were investigated in acute ischemic stroke patients with minor symptoms and large-vessel occlusion (LVO).
Methods:
This was a retrospective analysis of a prospective, multicenter, nationwide registry of consecutive patients with acute (within 24 h) minor (National Institutes of Health Stroke Scale score=0–5) ischemic stroke with anterior circulation LVO (acute minor LVO). Brain frailty was stratified according to the presence of an advanced white-matter hyperintensity (WMH) (Fazekas grade 2 or 3), silent/old brain infarct, or cerebral microbleeds. The primary outcome was a composite of stroke, myocardial infarction, and all-cause mortality within 1 year.
Results:
In total, 1,067 patients (age=67.2±13.1 years [mean±SD], 61.3% males) were analyzed. The proportions of patients according to the numbers of brain frailty burdens were as follows: no burden in 49.2%, one burden in 30.0%, two burdens in 17.3%, and three burdens in 3.5%. In the Cox proportional-hazards analysis, the presence of more brain frailty burdens was associated with a higher risk of 1-year primary outcomes, but after adjusting for clinically relevant variables there were no significant associations between burdens of brain frailty and 1-year vascular outcomes. For individual components of brain frailty, an advanced WMH was independently associated with an increased risk of 1-year primary outcomes (adjusted hazard ratio [aHR]=1.33, 95% confidence interval [CI]=1.03–1.71) and stroke (aHR=1.32, 95% CI=1.00–1.75).
Conclusions
The baseline imaging markers of brain frailty were common in acute minor ischemic stroke patients with LVO. An advanced WMH was the only frailty marker associated with an increased risk of vascular events. Further research is needed into the association between brain frailty and prognosis in patients with acute minor LVO.
4.The Effect of Luteolin on the Modulation of Vascular Contractility via ROCK and CPI-17 Inactivation
Hyuk-Jun YOON ; Dae Hong KANG ; Fanxue JIN ; Joon Seok BANG ; Uy Dong SOHN ; Hyun Dong JE
Biomolecules & Therapeutics 2023;31(2):193-199
In this investigation, we made a study of the efficacy of luteolin (a flavonoid found in plants such as vegetables, herbs and fruits) on vascular contractibility and to elucidate the mechanism underlying the relaxation. Isometric contractions of denuded muscles were stored and combined with western blot analysis which was conducted to assess the phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) and phosphorylation-dependent inhibitory protein for myosin phosphatase (CPI-17) and to examine the effect of luteolin on the RhoA/ROCK/CPI-17 pathway. Luteolin significantly alleviated phorbol ester-, fluoride- and thromboxane mimetic-elicited contractions regardless of endothelial nitric oxide synthesis, implying its direct effect on smooth muscle. It also significantly alleviated the fluoride-elicited elevation in pCPI-17 and pMYPT1 levels and phorbol 12,13-dibutyrate-elicited in-crease in pERK1/2 level, suggesting depression of ROCK and PKC/MEK activity and ensuing phosphorylation of MYPT1, CPI-17 and ERK1/2. Taken together, these results suggest that luteolin-elicited relaxation includes myosin phosphatase reactivation and calcium desensitization, which seems to be arbitrated by CPI-17 dephosphorylation via ROCK/PKC inhibition.
5.Clinical Significance of bZIP In-Frame CEBPA-Mutated Normal Karyotype Acute Myeloid Leukemia
Seo-Yeon AHN ; TaeHyung KIM ; Mihee KIM ; Ga-Young SONG ; Sung-Hoon JUNG ; Deok-Hwan YANG ; Je-Jung LEE ; Mi Yeon KIM ; Chul Won JUNG ; Jun-Ho JANG ; Hee Je KIM ; Joon Ho MOON ; Sang Kyun SOHN ; Jong-Ho WON ; Sung-Hyun KIM ; Hyeoung-Joon KIM ; Jae-Sook AHN ; Dennis Dong Hwan KIM
Cancer Research and Treatment 2023;55(3):1011-1022
Purpose:
We evaluated the characteristics of CCAAT/enhancer-binding protein α (CEBPA) mutations and the significance of a basic leucine zipper in-frame mutation (bZIPin-f) of CEBPA in patients with acute myeloid leukemia with a normal karyotype.
Materials and Methods:
Based on updated knowledge of CEBPA mutations, we conducted next-generation sequencing analyses in a previously established real-world cohort.
Results:
Among 78 of a total of 395 patients (19.7%), 50 had bZIPin-f CEBPA, and 28 had non-bZIPin-f CEBPA. In the multivariate analysis, patients with NPM1mut, those with bZIPin-f CEBPA, and those who underwent allogeneic hematopoietic cell transplantation (allo-HCT) had favorable overall survival (OS), but FLT3-ITDmut was a poor prognostic indicator. For relapse-free survival (RFS) and cumulative incidence of relapse, bZIPin-f CEBPA, and allo-HCT were associated with favorable outcomes; FLT3-ITDpos was associated with worse outcomes. In the CEBPA double-mutated group (CEBPAdm), bZIPin-f CEBPA was associated with superior outcomes in terms of OS (p=0.007) and RFS (p=0.007) compared with non-bZIPin-f CEBPA. Of 50 patients with bZIPin-f CEBPA, 36 patients had at least one mutation. When grouped by the presence of mutations in chromatic/DNA modifiers (C), cohesion complex (C), and splicing genes (S) (CCS mutations), CCS-mutated bZIPin-f CEBPA was associated with poor OS (p=0.044; hazard ratio [HR], 2.419) and a trend in inferior RFS (p=0.186; HR, 1.838).
Conclusion
Only bZIPin-f CEBPA was associated with favorable outcomes in patients with CEBPAdm. However, some mutations accompanying bZIPin-f CEBPA showed inferior OS; thus, further studies with larger numbers of patients are required for clear conclusions of the significance of bZIPin-f CEBPA.
6.Association between ischemic stroke and pyogenic spondylitis in Korea: Nationwide longitudinal cohort study
Soo Hyun LEE ; Hakyung KIM ; In-bo HAN ; Seung Hun SHEEN ; Je Beom HONG ; Seil SOHN
Journal of Cerebrovascular and Endovascular Neurosurgery 2023;25(2):143-149
Objective:
The purpose of this nationwide age- and sex- matched longitudinal study was to determine the pyogenic spondylitis (PS) increases the incidence of ischemic stroke (IS) in Korea.
Methods:
From the National Health Insurance Service (NHIS), we collected the patient data for the period from January 1, 2004 to December 31, 2015. PS was classified according to the International Classification of Disease codes M46.2-M46.8, M49.2, and M49.3. By using a 1:5 age- and sex- stratified matching, a total of 628 patients and 3140 control subjects were included in the study. The IS incidence rates in PS and control group was calculated by using the Kaplan-Meier method. The outcome of hazard ratio of IS was estimated by Cox proportional hazards regression analyses. This study did not exclude PS as a result of postoperative complications.
Results:
According to the study, 51 patients (8.12%) in the PS group and 201 patients (6.4%) in the control group experienced IS. The adjusted hazard ratio of IS in the PS group was 3.419 (95% CI: 2.473-4.729) after adjusting individual medical condition and demographics. Following the results of subgroup analysis, the risk ratio of IS was greater in most of the subgroup categories (male, female, age <65, age >65, non-diabetic, hypertensive, non-hypertensive, dyslipidemic and non-dyslipidemic subgroup). However, the risk of IS did not differ significantly in diabetic subgroup (95% CI: 0.953-4.360).
Conclusions
The risk rate of IS increased in patient with pyogenic spondylitis.
7.Rituximab plus multiagent chemotherapy for newly diagnosed CD20-positive acute lymphoblastic leukemia: a prospective phase II study
Dong Won BAEK ; Han-Seung PARK ; Sang Kyun SOHN ; Dae Young KIM ; Inho KIM ; Jae-Sook AHN ; Young Rok DO ; Se Ryeon LEE ; Hyeon-Seok EOM ; Won-Sik LEE ; Sung-Hyun KIM ; Ho Sup LEE ; Yoo Jin LEE ; Joon Ho MOON ; Je-Hwan LEE ;
The Korean Journal of Internal Medicine 2023;38(5):734-746
Background/Aims:
We performed a prospective study to determine the efficacy and safety of rituximab including chemotherapy in CD20-positive acute lymphoblastic leukemia (ALL).
Methods:
Patients with newly diagnosed ALL, aged ≥ 15 years, were eligible for the study if their leukemic blast cells in bone marrow expressed CD20 ≥ 20% at the time of diagnosis. Patients received multiagent chemotherapy with rituximab. After achieving complete remission (CR), patients received five cycles of consolidation with concomitant rituximab. Rituximab was administered monthly from day 90 of transplantation for patients who received allogeneic hematopoietic cell transplantation.
Results:
In patients with Philadelphia (Ph)-negative ALL, 39 of 41 achieved CR (95.1%), the 2- and 4-year relapse-free survival (RFS) rates were 50.4% and 35.7%, and the 2- and 4-year overall survival (OS) rates were 51.5% and 43.2%, respectively. In the group with Ph-positive ALL, all 32 patients achieved CR, the 2- and 4-year RFS rates were 60.7% and 52.1%, and the 2- and 4-year OS rates were 73.3% and 52.3%, respectively. In the Ph-negative ALL group, patients with higher CD20 positivity experienced more favorable RFS (p < 0.001) and OS (p = 0.06) than those with lower CD20 positivity. Patients who received ≥ 2 cycles of rituximab after transplantation had significantly improved RFS (hazard ratio [HR], 0.31; p = 0.049) and OS (HR, 0.29; p = 0.021) compared with those who received < 2 cycles.
Conclusions
The addition of rituximab to conventional chemotherapy for CD20-positive ALL is effective and tolerable (Clinicaltrials. gov NCT01429610).
8.The Effect of Galangin on the Regulation of Vascular Contractility via the Holoenzyme Reactivation Suppressing ROCK/CPI-17 rather than PKC/CPI-17
Hyuk-Jun YOON ; Won Pill JUNG ; Young Sil MIN ; Fanxue JIN ; Joon Seok BANG ; Uy Dong SOHN ; Hyun Dong JE
Biomolecules & Therapeutics 2022;30(2):145-150
In this study, we investigated the influence of galangin on vascular contractibility and to determine the mechanism underlying the relaxation. Isometric contractions of denuded aortic muscles were recorded and combined with western blot analysis which was performed to measure the phosphorylation of phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17) and myosin phosphatase targeting subunit 1 (MYPT1) and to evaluate the effect of galangin on the RhoA/ROCK/CPI-17 pathway.Galangin significantly inhibited phorbol ester-, fluoride- and thromboxane mimetic-induced vasoconstrictions regardless of endothelial nitric oxide synthesis, suggesting its direct effect on vascular smooth muscle. Galangin significantly inhibited the fluoridedependent increase in pMYPT1 and pCPI-17 levels and phorbol 12,13-dibutyrate-dependent increase in pERK1/2 level, suggesting repression of ROCK and MEK activity and subsequent phosphorylation of MYPT1, CPI-17 and ERK1/2. Taken together, these results suggest that galangin-induced relaxation involves myosin phosphatase reactivation and calcium desensitization, which appears to be mediated by CPI-17 dephosphorylation via not PKC but ROCK inactivation.
9.Early diagnosis of Gaucher disease in Korean patients with unexplained splenomegaly: a multicenter observational study
Young Rok DO ; Yunsuk CHOI ; Mi Hwa HEO ; Jin Seok KIM ; Jae-ho YOON ; Je-Hwan LEE ; Joon Seong PARK ; Sang Kyun SOHN ; Sung Hyun KIM ; Sungnam LIM ; Joo Seop CHUNG ; Deog-Yeon JO ; Hyeon Seok EOM ; Hawk KIM ; So Yeon JEON ; Jong-Ho WON ; Hee Jeong LEE ; Jung Won SHIN ; Jun-Ho JANG ; Sung-Soo YOON
Blood Research 2022;57(3):207-215
Background:
Gaucher disease (GD) is an autosomal recessive disorder characterized by excessive accumulation of glucosylceramide in multiple organs. This study was performed to determine the detection rate of GD in a selected patient population with unexplained splenomegaly in Korea.
Methods:
This was a multicenter, observational study conducted at 18 sites in Korea between December 2016 and February 2020. Adult patients with unexplained splenomegaly were enrolled and tested for β-glucosidase enzyme activity on dried blood spots (DBS) and in peripheral blood leukocytes. Mutation analysis was performed if the test was positive or indeterminate for the enzyme assay. The primary endpoint was the percentage of patients with GD in patients with unexplained splenomegaly.
Results:
A total of 352 patients were enrolled in this study (male patients, 199; mean age, 48.42 yr). Amongst them, 14.77% of patients had concomitant hepatomegaly. The most common sign related to GD was splenomegaly (100%), followed by thrombocytopenia (44.32%) and, anemia (40.91%). The β-glucosidase activity assay on DBS and peripheral leukocytes showed abnormal results in sixteen and six patients, respectively. Eight patients were tested for the mutation, seven of whom were negative and one patient showed a positive mutation analysis result. One female patient who presented with splenomegaly and thrombocytopenia was diagnosed with type 1 GD. The detection rate of GD was 0.2841% (exact 95% CI, 0.0072‒).
Conclusion
The detection rate of GD in probable high-risk patients in Korea was lower than expected.However, the role of hemato-oncologists is still important in the diagnosis of GD.
10.Clinical Guidance for Point-of-Care Ultrasound in the Emergency and Critical Care Areas after Implementing Insurance Coverage in Korea
Wook Jin CHOI ; Young Rock HA ; Je Hyeok OH ; Young Soon CHO ; Won Woong LEE ; You Dong SOHN ; Gyu Chong CHO ; Chan Young KOH ; Han Ho DO ; Won Joon JEONG ; Seung Mok RYOO ; Jae Hyun KWON ; Hyung Min KIM ; Su Jin KIM ; Chan Yong PARK ; Jin Hee LEE ; Jae Hoon LEE ; Dong Hyun LEE ; Sin Youl PARK ; Bo Seung KANG
Journal of Korean Medical Science 2020;35(7):54-
Point-of-care ultrasound (POCUS) is a useful tool that is widely used in the emergency and intensive care areas. In Korea, insurance coverage of ultrasound examination has been gradually expanding in accordance with measures to enhance Korean National Insurance Coverage since 2017 to 2021, and which will continue until 2021. Full coverage of health insurance for POCUS in the emergency and critical care areas was implemented in July 2019. The National Health Insurance Act classified POCUS as a single or multiple-targeted ultrasound examination (STU vs. MTU). STU scans are conducted of one organ at a time, while MTU includes scanning of multiple organs simultaneously to determine each clinical situation. POCUS can be performed even if a diagnostic ultrasound examination is conducted, based on the physician's decision. However, the Health Insurance Review and Assessment Service plans to monitor the prescription status of whether the POCUS and diagnostic ultrasound examinations are prescribed simultaneously and repeatedly. Additionally, MTU is allowed only in cases of trauma, cardiac arrest, shock, chest pain, and dyspnea and should be performed by a qualified physician. Although physicians should scan all parts of the chest, heart, and abdomen when they prescribe MTU, they are not required to record all findings in the medical record. Therefore, appropriate prescription, application, and recording of POCUS are needed to enhance the quality of patient care and avoid unnecessary cut of medical budget spending. The present article provides background and clinical guidance for POCUS based on the implementation of full health insurance coverage for POCUS that began in July 2019 in Korea.
Abdomen
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Budgets
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Chest Pain
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Critical Care
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Dyspnea
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Emergencies
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Heart
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Heart Arrest
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Insurance Coverage
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Insurance
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Insurance, Health
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Korea
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Medical Records
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National Health Programs
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Patient Care
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Point-of-Care Systems
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Prescriptions
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Shock
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Thorax
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Ultrasonography

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