1.Identification of signature gene set as highly accurate determination of metabolic dysfunction-associated steatotic liver disease progression
Sumin OH ; Yang-Hyun BAEK ; Sungju JUNG ; Sumin YOON ; Byeonggeun KANG ; Su-hyang HAN ; Gaeul PARK ; Je Yeong KO ; Sang-Young HAN ; Jin-Sook JEONG ; Jin-Han CHO ; Young-Hoon ROH ; Sung-Wook LEE ; Gi-Bok CHOI ; Yong Sun LEE ; Won KIM ; Rho Hyun SEONG ; Jong Hoon PARK ; Yeon-Su LEE ; Kyung Hyun YOO
Clinical and Molecular Hepatology 2024;30(2):247-262
Background/Aims:
Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression.
Methods:
Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD.
Results:
After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort.
Conclusions
We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.
2.Telemedicine Protocols for the Management of Patients with Acute Spontaneous Intracerebral Hemorrhage in Rural and Medically Underserved Areas in Gangwon State : Recommendations for Doctors with Less Expertise at Local Emergency Rooms
Hyo Sub JUN ; Kuhyun YANG ; Jongyeon KIM ; Jin Pyeong JEON ; Sun Jeong KIM ; Jun Hyong AHN ; Seung Jin LEE ; Hyuk Jai CHOI ; In Bok CHANG ; Jeong Jin PARK ; Jong-Kook RHIM ; Sung-Chul JIN ; Sung Min CHO ; Sung-Pil JOO ; Seung Hun SHEEN ; Sang Hyung LEE ;
Journal of Korean Neurosurgical Society 2024;67(4):385-396
Previously, we reported the concept of a cloud-based telemedicine platform for patients with intracerebral hemorrhage (ICH) at local emergency rooms in rural and medically underserved areas in Gangwon state by combining artificial intelligence and remote consultation with a neurosurgeon. Developing a telemedicine ICH treatment protocol exclusively for doctors with less ICH expertise working in emergency rooms should be part of establishing this system. Difficulties arise in providing appropriate early treatment for ICH in rural and underserved areas before the patient is transferred to a nearby hub hospital with stroke specialists. This has been an unmet medical need for decade. The available reporting ICH guidelines are realistically possible in university hospitals with a well-equipped infrastructure. However, it is very difficult for doctors inexperienced with ICH treatment to appropriately select and deliver ICH treatment based on the guidelines. To address these issues, we developed an ICH telemedicine protocol. Neurosurgeons from four university hospitals in Gangwon state first wrote the guidelines, and professors with extensive ICH expertise across the country revised them. Guidelines and recommendations for ICH management were described as simply as possible to allow more doctors to use them easily. We hope that our effort in developing the telemedicine protocols will ultimately improve the quality of ICH treatment in local emergency rooms in rural and underserved areas in Gangwon state.
3.Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia: The Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia Study
Keun-Sik HONG ; Sun Uck KWON ; Jong-Ho PARK ; Jae-Kwan CHA ; Jin-Man JUNG ; Yong-Jae KIM ; Kyung Bok LEE ; Sung Il SOHN ; Yong-Seok LEE ; Joung-Ho RHA ; Jee-Hyun KWON ; Sang Won HAN ; Bum Joon KIM ; Jaseong KOO ; Jay Chol CHOI ; Sang Min SUNG ; Soo Joo LEE ; Man-Seok PARK ; Seong Hwan AHN ; Oh Young BANG ; Yang-Ha HWANG ; Hyo Suk NAM ; Jong-Moo PARK ; Hee-Joon BAE ; Eung Gyu KIM ; Kyung-Yul LEE ; Mi Sun OH
Journal of Clinical Neurology 2021;17(3):344-353
Background:
and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia.
Methods:
This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293).
Results:
Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event.
Conclusions
Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.
4.Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia: The Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia Study
Keun-Sik HONG ; Sun Uck KWON ; Jong-Ho PARK ; Jae-Kwan CHA ; Jin-Man JUNG ; Yong-Jae KIM ; Kyung Bok LEE ; Sung Il SOHN ; Yong-Seok LEE ; Joung-Ho RHA ; Jee-Hyun KWON ; Sang Won HAN ; Bum Joon KIM ; Jaseong KOO ; Jay Chol CHOI ; Sang Min SUNG ; Soo Joo LEE ; Man-Seok PARK ; Seong Hwan AHN ; Oh Young BANG ; Yang-Ha HWANG ; Hyo Suk NAM ; Jong-Moo PARK ; Hee-Joon BAE ; Eung Gyu KIM ; Kyung-Yul LEE ; Mi Sun OH
Journal of Clinical Neurology 2021;17(3):344-353
Background:
and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia.
Methods:
This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293).
Results:
Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event.
Conclusions
Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.
5.Efficacy and Safety of Letibotulinum Toxin A for the Treatment of Essential Blepharospasm
Ji Hyun KIM ; Doh Hoon CHUNG ; Sung Eun KIM ; Ji Sun PAIK ; Namju KIM ; Tae Yoon LA ; Jun Hyuk SON ; Hee Bae AHN ; Jae Wook YANG ; Kyung In WOO ; Helen LEW ; Jin Sook YOON ; Sang Un LEE ; Sung Bok LEE ; Jeong Kyu LEE ; Jae Woo JANG ; Ho Kyung CHOUNG ; Mijung CHI ; Suk Woo YANG
Journal of the Korean Ophthalmological Society 2020;61(3):227-234
PURPOSE: To evaluate the efficacy and safety of BOTULAX® in subjects with essential blepharospasm.METHODS: In this study, a total of 250 subjects with essential blepharospasm were enrolled at 15 investigational sites and a total of 220 subjects completed the study. The efficacy and safety were evaluated at weeks 4 and 16 after treatment compared with baseline. In total, 240 subjects were enrolled, treated with the investigational product, and evaluable for the primary efficacy assessment at week 4 after treatment; these subjects were included in the intention-to-treat (ITT) population. With the ITT set as the main efficacy set, efficacy assessment included Jankovic rating scale (JRS), functional disability score, investigator evaluation of global response and quality of life. Safety assessment including the incidence of adverse events was also performed.RESULTS: In terms of the primary efficacy endpoint (i.e., change in JRS total score at week 4 after treatment from baseline [ITT set]), mean change indicated a statistically significant reduction (p < 0.0001) and demonstrated the non-inferiority of the test drug to similar drugs. In terms of the secondary efficacy endpoints, mean change in JRS total score at week 16 after treatment and mean change in functional disability score at weeks 4 and 16 after treatment both exhibited a statistically significant reduction compared with baseline (p < 0.0001 for all). Among the 249 subjects treated with the investigational product in this study, 44 (17.67%) experienced 76 treatment emergent adverse events but no serious adverse events were observed.CONCLUSIONS: Based on the study results, BOTULAX® is considered to be an effective and safe treatment for essential blepharospasm.
6.Comparison of the accuracy of intraoral scanner by three-dimensional analysis in single and 3-unit bridge abutment model: In vitro study
Mei Yang HUANG ; Keunbada SON ; Wan Sun LEE ; Kyu Bok LEE
The Journal of Korean Academy of Prosthodontics 2019;57(2):102-109
PURPOSE: The purpose of this study was to evaluate the accuracy of three types of intraoral scanners and the accuracy of the single abutment and bridge abutment model. MATERIALS AND METHODS: In this study, a single abutment, and a bridge abutment with missing first molar was fabricated and set as the reference model. The reference model was scanned with an industrial three-dimensional scanner and set as reference scan data. The reference model was scanned five times using the three intraoral scanners (CS3600, CS3500, and EZIS PO). This was set as the evaluation scan data. In the three-dimensional analysis (Geomagic control X), the divided abutment region was selected and analyzed to verify the scan accuracy of the abutment. Statistical analysis was performed using SPSS software (α = .05). The accuracy of intraoral scanners was compared using the Kruskal-Wallis test and post-test was performed using the Pairwise test. The accuracy difference between the single abutment model and the bridge abutment model was analyzed by the Mann-Whitney U test. RESULTS: The accuracy according to the intraoral scanner was significantly different (P < .05). The trueness of the single abutment model and the bridge abutment model showed a statistically significant difference and showed better trueness in the single abutment (P < .05). There was no significant difference in the precision (P = .616). CONCLUSION: As a result of comparing the accuracy of single and bridge abutments, the error of abutment scan increased with increasing scan area, and the accuracy of bridge abutment model was clinically acceptable in three types of intraoral scanners.
In Vitro Techniques
;
Molar
7.Executive Summary of Stroke Statistics in Korea 2018: A Report from the Epidemiology Research Council of the Korean Stroke Society
Jun Yup KIM ; Kyusik KANG ; Jihoon KANG ; Jaseong KOO ; Dae Hyun KIM ; Beom Joon KIM ; Wook Joo KIM ; Eung Gyu KIM ; Jae Guk KIM ; Jeong Min KIM ; Joon Tae KIM ; Chulho KIM ; Hyun Wook NAH ; Kwang Yeol PARK ; Moo Seok PARK ; Jong Moo PARK ; Jong Ho PARK ; Tai Hwan PARK ; Hong Kyun PARK ; Woo Keun SEO ; Jung Hwa SEO ; Tae Jin SONG ; Seong Hwan AHN ; Mi Sun OH ; Hyung Geun OH ; Sungwook YU ; Keon Joo LEE ; Kyung Bok LEE ; Kijeong LEE ; Sang Hwa LEE ; Soo Joo LEE ; Min Uk JANG ; Jong Won CHUNG ; Yong Jin CHO ; Kang Ho CHOI ; Jay Chol CHOI ; Keun Sik HONG ; Yang Ha HWANG ; Seong Eun KIM ; Ji Sung LEE ; Jimi CHOI ; Min Sun KIM ; Ye Jin KIM ; Jinmi SEOK ; Sujung JANG ; Seokwan HAN ; Hee Won HAN ; Jin Hyuk HONG ; Hyori YUN ; Juneyoung LEE ; Hee Joon BAE
Journal of Stroke 2019;21(1):42-59
Despite the great socioeconomic burden of stroke, there have been few reports of stroke statistics in Korea. In this scenario, the Epidemiologic Research Council of the Korean Stroke Society launched the “Stroke Statistics in Korea” project, aimed at writing a contemporary, comprehensive, and representative report on stroke epidemiology in Korea. This report contains general statistics of stroke, prevalence of behavioral and vascular risk factors, stroke characteristics, pre-hospital system of care, hospital management, quality of stroke care, and outcomes. In this report, we analyzed the most up-to-date and nationally representative databases, rather than performing a systematic review of existing evidence. In summary, one in 40 adults are patients with stroke and 232 subjects per 100,000 experience a stroke event every year. Among the 100 patients with stroke in 2014, 76 had ischemic stroke, 15 had intracerebral hemorrhage, and nine had subarachnoid hemorrhage. Stroke mortality is gradually declining, but it remains as high as 30 deaths per 100,000 individuals, with regional disparities. As for stroke risk factors, the prevalence of smoking is decreasing in men but not in women, and the prevalence of alcohol drinking is increasing in women but not in men. Population-attributable risk factors vary with age. Smoking plays a role in young-aged individuals, hypertension and diabetes in middle-aged individuals, and atrial fibrillation in the elderly. About four out of 10 hospitalized patients with stroke are visiting an emergency room within 3 hours of symptom onset, and only half use an ambulance. Regarding acute management, the proportion of patients with ischemic stroke receiving intravenous thrombolysis and endovascular treatment was 10.7% and 3.6%, respectively. Decompressive surgery was performed in 1.4% of patients with ischemic stroke and in 28.1% of those with intracerebral hemorrhage. The cumulative incidence of bleeding and fracture at 1 year after stroke was 8.9% and 4.7%, respectively. The direct costs of stroke were about ₩1.68 trillion (KRW), of which ₩1.11 trillion were for ischemic stroke and ₩540 billion for hemorrhagic stroke. The great burden of stroke in Korea can be reduced through more concentrated efforts to control major attributable risk factors for age and sex, reorganize emergency medical service systems to give patients with stroke more opportunities for reperfusion therapy, disseminate stroke unit care, and reduce regional disparities. We hope that this report can contribute to achieving these tasks.
Adult
;
Aged
;
Alcohol Drinking
;
Ambulances
;
Atrial Fibrillation
;
Cerebral Hemorrhage
;
Emergency Medical Services
;
Emergency Service, Hospital
;
Epidemiology
;
Female
;
Hemorrhage
;
Hope
;
Humans
;
Hypertension
;
Incidence
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Korea
;
Male
;
Mortality
;
Prevalence
;
Reperfusion
;
Risk Factors
;
Smoke
;
Smoking
;
Stroke
;
Subarachnoid Hemorrhage
;
Writing
8.Fistula Formation Between the Disc and Dura after Percutaneous Endoscopic Lumbar Discectomy: A Case Report
Hak Sun KIM ; Hyoung Bok KIM ; Hoon Jae CHUNG ; Jea Ho YANG
Journal of Korean Society of Spine Surgery 2018;25(4):180-184
OBJECTIVES:
To document fistula formation between the disc and dura by an unrecognized dural tear after percutaneous endoscopic lumbar discectomy (PELD).SUMMARY OF LITERATURE REVIEW: The risk of durotomy is relatively low with PELD, but cases of unrecognized durotomies have been reported. An effective diagnostic tool for such situations has not yet been identified.
MATERIALS AND METHODS:
A patient twice underwent transforaminal PELD under the diagnosis of a herniated lumbar disc at L4-5. She still complained of intractable pain and motor weakness around the left lower extremity at 6 months postoperatively. Magnetic resonance imaging showed no specific findings suggestive of violation of the nerve root. However, L5 and S1 nerve root injury was noted on electromyography. An exploratory operation was planned to characterize damage to the neural structures.
RESULTS:
In the exploration, a dural tear was found at the previous operative site, along with a fistula between the disc and dura was also found at the dural tear site. The durotomy site was located on the ventrolateral side of the dura and measured approximately 5 mm. The durotomy site was repaired with Nylon 5-0 and adhesive sealants. The patient's preoperative symptoms diminished considerably.
CONCLUSIONS
Fistula formation between the disc and dura can be caused by an unrecognized dural tear after PELD. Discography is a reliable diagnostic tool for fistulas formed by an unrecognized durotomy.
9.Fistula Formation Between the Disc and Dura after Percutaneous Endoscopic Lumbar Discectomy: A Case Report
Hak Sun KIM ; Hyoung Bok KIM ; Hoon Jae CHUNG ; Jea Ho YANG
Journal of Korean Society of Spine Surgery 2018;25(4):180-184
STUDY DESIGN: Case report OBJECTIVES: To document fistula formation between the disc and dura by an unrecognized dural tear after percutaneous endoscopic lumbar discectomy (PELD). SUMMARY OF LITERATURE REVIEW: The risk of durotomy is relatively low with PELD, but cases of unrecognized durotomies have been reported. An effective diagnostic tool for such situations has not yet been identified. MATERIALS AND METHODS: A patient twice underwent transforaminal PELD under the diagnosis of a herniated lumbar disc at L4-5. She still complained of intractable pain and motor weakness around the left lower extremity at 6 months postoperatively. Magnetic resonance imaging showed no specific findings suggestive of violation of the nerve root. However, L5 and S1 nerve root injury was noted on electromyography. An exploratory operation was planned to characterize damage to the neural structures. RESULTS: In the exploration, a dural tear was found at the previous operative site, along with a fistula between the disc and dura was also found at the dural tear site. The durotomy site was located on the ventrolateral side of the dura and measured approximately 5 mm. The durotomy site was repaired with Nylon 5-0 and adhesive sealants. The patient's preoperative symptoms diminished considerably. CONCLUSIONS: Fistula formation between the disc and dura can be caused by an unrecognized dural tear after PELD. Discography is a reliable diagnostic tool for fistulas formed by an unrecognized durotomy.
Adhesives
;
Diagnosis
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Diskectomy
;
Electromyography
;
Fistula
;
Humans
;
Lower Extremity
;
Magnetic Resonance Imaging
;
Nylons
;
Pain, Intractable
;
Tears
10.Quality of Anticoagulation with Warfarin in Korean Patients with Atrial Fibrillation and Prior Stroke: A Multicenter Retrospective Observational Study.
Keun Sik HONG ; Yang Ki KIM ; Hee Joon BAE ; Hyo Suk NAM ; Sun U KWON ; Oh Young BANG ; Jae Kwan CHA ; Byung Woo YOON ; Joung Ho RHA ; Byung Chul LEE ; Jong Moo PARK ; Man Seok PARK ; Jun LEE ; Jay Chol CHOI ; Dong Eog KIM ; Kyung Bok LEE ; Tai Hwan PARK ; Ji Sung LEE ; Seong Eun KIM ; Juneyoung LEE
Journal of Clinical Neurology 2017;13(3):273-280
BACKGROUND AND PURPOSE: The quality of anticoagulation is critical for ensuring the benefit of warfarin, but this has been less well studied in Korean ischemic stroke patients with atrial fibrillation (AF). METHODS: This study retrospectively analyzed the data of patients who had an AF-related ischemic stroke and were treated with long-term warfarin therapy in 16 Korean centers. The quality of warfarin therapy was primarily assessed by the time in therapeutic range [TTR; international normalized ratio (INR), 2.0–3.0] and additionally by the proportion of INR values within the therapeutic range. RESULTS: The long-term warfarin-treated cohort comprised 1,230 patients. They were aged 70.1±9.7 years (mean±SD), 42.5% were female, and their CHA₂DS₂-VASc score was 4.75±1.41. The TTR analysis included 33,941 INR measurements for 27,487 months: per patients, 27.6 (SD, 22.4) INR measurements for 22.4 (SD, 12.9) months. The mean TTR of individual patients was 49.1% (95% confidence interval, 47.9–50.3%), and the TTR quartiles were <34.5, 34.5–49.1, 49.1–64.5%, and >64.5%. None of the 16 centers achieved a mean TTR of >60%. Of all INR measurements, 44.6% were within the therapeutic range, 41.7% were <2.0, and 13.7% were >3.0. CONCLUSIONS: In Korean ischemic stroke patients who had AF, the quality of warfarin therapy was low and might be inadequate to effectively prevent recurrent stroke or systemic embolism.
Atrial Fibrillation*
;
Cohort Studies
;
Embolism
;
Female
;
Humans
;
International Normalized Ratio
;
Observational Study*
;
Retrospective Studies*
;
Stroke*
;
Warfarin*

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