1.Therapeutic Outcomes and Electrophysiological Biomarkers in Anti-Myelin-Associated Glycoprotein Neuropathy:A Multicenter Cohort Study in South Korea
Young Gi MIN ; Hee-Jo HAN ; Ha Young SHIN ; Jong-Gyu BAEK ; Jun-Soon KIM ; Kyung-Seok PARK ; Seol-Hee BAEK ; Ilhan YOO ; So-Young HUH ; Young Nam KWON ; Seok-Jin CHOI ; Sung-Min KIM ; Yoon-Ho HONG ; Jung-Joon SUNG
Journal of Clinical Neurology 2024;20(1):50-58
Background:
and Purpose Unlike other immune-mediated neuropathies, anti-myelin-associated glycoprotein (MAG) neuropathy is often refractory to immunotherapy. It is necessary to compare the relative efficacies of various immunotherapies and develop objective biomarkers in order to optimize its clinical management.
Methods:
This study recruited 91 patients with high anti-MAG antibody titers from 7 tertiary hospitals in South Korea. We analyzed the baseline characteristics, therapeutic outcomes, and nerve conduction study (NCS) findings of 68 patients and excluded 23 false positive cases.
Results:
The rate of positive responses to treatment was highest using zanubrutinib (50%) and rituximab (36.4%), followed by corticosteroids (16.7%), immunosuppressants (9.5%), intravenous immunoglobulin (5%), and plasma exchange (0%). Disability and weakness were significantly associated with multiple NCS parameters at the time of diagnosis, especially distal compound muscle action potential (CMAP) amplitudes. Moreover, the longitudinal trajectory of the average CMAP amplitudes paralleled the clinical courses, with a 16.2 percentile decrease as an optimal cutoff for predicting a clinical exacerbation (area under the receiver operating characteristic curve=0.792).
Conclusions
Our study supports the use of NCS as an objective marker for estimating disease burden and tracking clinical changes in patients with anti-MAG neuropathy. We have described the beneficial effects of rituximab and a new drug, zanubrutinib, compared with conventional immunotherapies.
2.Temporal Trend of the Incidence and Characteristics of Renal Infarction:Korean Nationwide Population Study
Dong-Eon KIM ; Inki MOON ; Suyeong PARK ; Minae PARK ; Sojeong PARK ; Seong Soon KWON ; Min Gyu KONG ; Hyun Woo PARK ; Hyung Oh CHOI ; Hye-Sun SEO ; Yoon Haeng CHO ; Nae Hee LEE ; Jon SUH
Journal of Korean Medical Science 2023;38(31):e239-
Background:
Large-scale studies about epidemiologic characteristics of renal infarction (RI) are few. In this study, we aimed to analyze the incidence and prevalence of RI with comorbidities in the South Korean population.
Methods:
We investigated the medical history of the entire South Korean adult population between 2013 and 2019 using the National Health Insurance Service database (n = 51,849,591 in 2019). Diagnosis of RI comorbidities were confirmed with International Classification of Disease, Tenth Revision, Clinical Modification codes. Epidemiologic characteristics, distribution of comorbidities according to etiologic mechanisms, and trend of antithrombotic agents were estimated.
Results:
During the 7-years, 10,496 patients were newly diagnosed with RI. The incidence rate increased from 2.68 to 3.06 per 100,000 person-years during the study period.The incidence rate of RI increased with age peaking in the 70s with 1.41 times male predominance. The most common comorbidity was hypertension, followed by dyslipidemia and diabetes mellitus. Regarding etiologic risk factor distribution, high embolic risk group, renovascular disease group, and hypercoagulable state group accounted for 16.6%, 29.1%, and 13.7% on average, respectively. For the antithrombotic treatment of RI, the prescription of antiplatelet agent gradually decreased from 17.0% to 13.0% while that of anticoagulation agent was maintained around 35%. The proportion of non-vitamin K antagonist oral anticoagulants remarkably increased from only 1.4% to 17.6%.
Conclusion
Considering the progressively increasing incidence of RI and high prevalence of coexisting risk factors, constant efforts to raise awareness of the disease are necessary. The current epidemiologic investigation of RI would be the stepping-stone to establishing future studies about clinical outcomes and optimal treatment strategies.
3.Combination Therapy of the Active KRAS-Targeting Antibody inRas37 and a PI3K Inhibitor in Pancreatic Cancer
Ji Eun LEE ; Min Gyu WOO ; Kyung Hee JUNG ; Yeo Wool KANG ; Seung-Min SHIN ; Mi Kwon SON ; Zhenghuan FANG ; Hong Hua YAN ; Jung Hee PARK ; Young-Chan YOON ; Yong-Sung KIM ; Soon-Sun HONG
Biomolecules & Therapeutics 2022;30(3):274-283
KRAS activating mutations, which are present in more than 90% of pancreatic cancers, drive tumor dependency on the RAS/ mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. Therefore, combined targeting of RAS/MAPK and PI3K/AKT signaling pathways may be required for optimal therapeutic effect in pancreatic cancer.However, the therapeutic efficacy of combined MAPK and PI3K/AKT signaling target inhibitors is unsatisfactory in pancreatic cancer treatment, because it is often accompanied by MAPK pathway reactivation by PI3K/AKT inhibitor. Therefore, we developed an inRas37 antibody, which directly targets the intra-cellularly activated GTP-bound form of oncogenic RAS mutation and investigated its synergistic effect in the presence of the PI3K inhibitor BEZ-235 in pancreatic cancer. In this study, inRas37 remarkably increased the drug response of BEZ-235 to pancreatic cancer cells by inhibiting MAPK reactivation. Moreover, the co-treatment synergistically inhibited cell proliferation, migration, and invasion and exhibited synergistic anticancer activity by inhibiting the MAPK and PI3K pathways. The combined administration of inRas37and BEZ-235 significantly inhibited tumor growth in mouse models. Our results demonstrated that inRas37 synergistically increased the antitumor activity of BEZ-235 by inhibiting MAPK reactivation, suggesting that inRas37 and BEZ-235 co-treatment could be a potential treatment approach for pancreatic cancer patients with KRAS mutations.
4.Results of Hip Arthroplasty Using a COREN Stem at a Minimum of Ten Years
Joon Soon KANG ; Yoon Cheol NAM ; Dae Gyu KWON ; Dong Jin RYU
Hip & Pelvis 2022;34(4):211-218
Purpose:
We report on the 10-year clinical hip function and radiologic outcomes of patients who underwent hip arthroplasty using a COREN stem.
Materials and Methods:
A consecutive series of 224 primary cementless hip arthroplasty implantations were performed using a COREN stem between 2009 and 2011; among these, evaluation of 128 hips was performed during a minimum follow-up period of 10 years. The mean age of patients was 65.4 years (range, 40-82 years) and the mean duration of follow-up was 10.8 years (range, 10-12 years). Evaluation of clinical hip function and radiologic implant outcomes was performed according to clinical score, thigh pain, and radiologic analysis.
Results:
Dramatic improvement of the mean Harris hip score (HHS) from 59.4 preoperatively to 93.5 was observed at the final follow-up (P≤0.01). Stable fixation was demonstrated for all implants with no change in position except for one case of Vancouver type B2 periprosthetic femur fracture. A radiolucent line (RLL) was observed in 16 hips (12.5%). Thigh pain was observed in only two hips (1.6%) at the final follow-up. There were no cases of osteolysis around the stem. The survival rate for the COREN stem was 97.7%.
Conclusion
Good long-term survival with excellent clinical and radiological outcomes can be achieved using the COREN femoral stem regardless of Dorr type.
5.Prognostic Value of Alpha-Fetoprotein in Patients Who Achieve a Complete Response to Transarterial Chemoembolization for Hepatocellular Carcinoma
Jae Seung LEE ; Young Eun CHON ; Beom Kyung KIM ; Jun Yong PARK ; Do Young KIM ; Sang Hoon AHN ; Kwang-Hyub HAN ; Wonseok KANG ; Moon Seok CHOI ; Geum-Youn GWAK ; Yong-Han PAIK ; Joon Hyeok LEE ; Kwang Cheol KOH ; Seung Woon PAIK ; Hwi Young KIM ; Tae Hun KIM ; Kwon YOO ; Yeonjung HA ; Mi Na KIM ; Joo Ho LEE ; Seong Gyu HWANG ; Soon Sun KIM ; Hyo Jung CHO ; Jae Youn CHEONG ; Sung Won CHO ; Seung Ha PARK ; Nae-Yun HEO ; Young Mi HONG ; Ki Tae YOON ; Mong CHO ; Jung Gil PARK ; Min Kyu KANG ; Soo Young PARK ; Young Oh KWEON ; Won Young TAK ; Se Young JANG ; Dong Hyun SINN ; Seung Up KIM ;
Yonsei Medical Journal 2021;62(1):12-20
Purpose:
Alpha-fetoprotein (AFP) is a prognostic marker for hepatocellular carcinoma (HCC). We investigated the prognostic value of AFP levels in patients who achieved complete response (CR) to transarterial chemoembolization (TACE) for HCC.
Materials and Methods:
Between 2005 and 2018, 890 patients with HCC who achieved a CR to TACE were recruited. An AFP responder was defined as a patient who showed elevated levels of AFP (>10 ng/mL) during TACE, but showed normalization or a >50% reduction in AFP levels after achieving a CR.
Results:
Among the recruited patients, 569 (63.9%) with naïve HCC and 321 (36.1%) with recurrent HCC after complete resection were treated. Before TACE, 305 (34.3%) patients had multiple tumors, 219 (24.6%) had a maximal tumor size >3 cm, and 22 (2.5%) had portal vein tumor thrombosis. The median AFP level after achieving a CR was 6.36 ng/mL. After a CR, 473 (53.1%) patients experienced recurrence, and 417 (46.9%) died [median progression-free survival (PFS) and overall survival (OS) of 16.3 and 62.8 months, respectively]. High AFP levels at CR (>20 ng/mL) were independently associated with a shorter PFS [hazard ratio (HR)=1.403] and OS (HR=1.284), together with tumor multiplicity at TACE (HR=1.518 and 1.666, respectively). AFP non-responders at CR (76.2%, n=359 of 471) showed a shorter PFS (median 10.5 months vs. 15.5 months, HR=1.375) and OS (median 41.4 months vs. 61.8 months, HR=1.424) than AFP responders (all p=0.001).
Conclusion
High AFP levels and AFP non-responders were independently associated with poor outcomes after TACE. AFP holds clinical implications for detailed risk stratification upon achieving a CR after TACE.
6.The Similarity of Biomarkers Level between Direct Nasal Fluid and Nasal Lavage Fluid in Allergic Rhinitis Patients
Jae Soon KIM ; Su Jin HAN ; Jung Min PARK ; Sung Wan KIM ; Young-Gyu EUN ; Oh Eun KWON
Journal of Rhinology 2021;28(2):89-93
Background and Objectives:
Biomarkers of allergic rhinitis (AR) have been studied; however, little is known regarding their practical application in the diagnosis of AR. Previous studies collected samples using saline lavage, nasal brushing, or nasal biopsy. To utilize nasal fluid as a diagnostic tool, we need to standardize the method of sample collection. Therefore, this study aimed to evaluate the difference in concentration of biomarkers depending on the method of nasal fluid collection.Materials and Method: Forty-five AR patients who had greater than moderate AR symptoms and who had positive results on skin prick test and serum-specific IgE tests were enrolled in this study. Nasal fluid was collected using the direct method or saline lavage method. The concentration of each biomarker was analyzed using enzyme-linked immunosorbent assay and the values compared.
Results:
Nasal fluid samples were collected directly from 14 patients and were collected via saline lavage in 31 patients. No significant differences were found in the median value of each biomarker between the two methods of nasal sample collection.
Conclusion
Nasal fluid collection method does not significantly affect biomarker concentration.
7.The Similarity of Biomarkers Level between Direct Nasal Fluid and Nasal Lavage Fluid in Allergic Rhinitis Patients
Jae Soon KIM ; Su Jin HAN ; Jung Min PARK ; Sung Wan KIM ; Young-Gyu EUN ; Oh Eun KWON
Journal of Rhinology 2021;28(2):89-93
Background and Objectives:
Biomarkers of allergic rhinitis (AR) have been studied; however, little is known regarding their practical application in the diagnosis of AR. Previous studies collected samples using saline lavage, nasal brushing, or nasal biopsy. To utilize nasal fluid as a diagnostic tool, we need to standardize the method of sample collection. Therefore, this study aimed to evaluate the difference in concentration of biomarkers depending on the method of nasal fluid collection.Materials and Method: Forty-five AR patients who had greater than moderate AR symptoms and who had positive results on skin prick test and serum-specific IgE tests were enrolled in this study. Nasal fluid was collected using the direct method or saline lavage method. The concentration of each biomarker was analyzed using enzyme-linked immunosorbent assay and the values compared.
Results:
Nasal fluid samples were collected directly from 14 patients and were collected via saline lavage in 31 patients. No significant differences were found in the median value of each biomarker between the two methods of nasal sample collection.
Conclusion
Nasal fluid collection method does not significantly affect biomarker concentration.
8.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.
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Insurance, Health
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Korea
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National Health Programs
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Thorax
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Ultrasonography
9.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):e54-
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.
10.Mesenchymal Stem Cell-Mediated Therapy of Peripheral Artery Disease Is Stimulated by a Lamin A-Progerin Binding Inhibitor
Soon Chul HEO ; Yang Woo KWON ; Gyu Tae PARK ; Sang Mo KWON ; Sun Sik BAE ; Bum-Joon PARK ; Jae Ho KIM
Journal of Lipid and Atherosclerosis 2020;9(3):460-473
Objective:
Human adipose tissue-derived mesenchymal stem cells (ASCs) have been reported to promote angiogenesis and tissue repair. However, poor survival and engraftment efficiency of transplanted ASCs are the major bottlenecks for therapeutic application. The present study aims to improve the therapeutic efficacy of ASCs for peripheral artery diseases.
Methods:
Hydrogen peroxide (H2O2) was used to induce apoptotic cell death in ASCs.To measure apoptosis, we used flow cytometry-based apoptosis analysis and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. A murine hindlimb ischemia model was established to measure the ASC-mediated therapeutic angiogenesis and in vivo survival ability of ASCs.
Results:
We identified that the inhibitor of lamin A-progerin binding, JH4, protects ASCs against H2O2-induced oxidative stress and apoptosis. Co-administration of ASCs with JH4 improved ASC-mediated blood reperfusion recovery and limb salvage compared to that of the control group in a mouse hind limb ischemia model. Immunofluorescence showed that JH4 treatment potentiated ASC-mediated vascular regeneration via reducing ASC apoptosis post transplantation.
Conclusion
JH4 exerts anti-apoptotic effects in ASCs in conditions of oxidative stress, and contributes to the repair of ischemic hind limb injury by improving cell survival.

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