1.Low-Density Lipoprotein Cholesterol Level, the Lower the Better? Analysis of Korean Patients in the Treat Stroke to Target Trial
Hanim KWON ; Jae-Chan RYU ; Jae-Kwan CHA ; Sang Min SUNG ; Tae-Jin SONG ; Kyung Bok LEE ; Eung-Gyu KIM ; Yong-Won KIM ; Ji Hoe HEO ; Man Seok PARK ; Kyusik KANG ; Byung-Chul LEE ; Keun-Sik HONG ; Oh Young BANG ; Jei KIM ; Jong S. KIM
Journal of Stroke 2025;27(2):228-236
Background:
and Purpose The Treat Stroke to Target (TST) was a randomized clinical trial involving French and Korean patients demonstrating that a lower low-density lipoprotein cholesterol (LDL-C, <70 mg/dL) target group (LT) experienced fewer cerebro-cardiovascular events than a higher target (90–110 mg/dL) group (HT). However, whether these results can be applied to Asian patients with different ischemic stroke subtypes remains unclear.
Methods:
Patients from 14 South Korean centers were analyzed separately. Patients with ischemic stroke or transient ischemic attack with evidence of atherosclerosis were randomized into LT and HT groups. The primary endpoint was a composite of ischemic stroke, myocardial infarction, coronary or cerebral revascularization, and cardiovascular death.
Results:
Among 712 enrolled patients, the mean LDL-C level was 71.0 mg/dL in 357 LT patients and 86.1 mg/dL in 355 HT patients. The primary endpoint occurred in 24 (6.7%) of LT and in 31 (8.7%) of HT group patients (adjusted hazard ratio [HR]=0.78; 95% confidence interval [CI]=0.45–1.33, P=0.353). Cardiovascular events alone occurred significantly less frequently in the LT than in the HT group (HR 0.26, 95% CI 0.09–0.80, P=0.019), whereas there were no significant differences in ischemic stroke events (HR 1.12, 95% CI 0.60–2.10, P=0.712). The benefit of LT was less apparent in patients with small vessel disease and intracranial atherosclerosis than in those with extracranial atherosclerosis.
Conclusion
In contrast to the French TST, the outcomes in Korean patients were neutral. Although LT was more effective in preventing cardiovascular diseases, it was not so in stroke prevention, probably attributed to the differences in stroke subtypes. Further studies are needed to elucidate the efficacy of statins and appropriate LDL-C targets in Asian patients with stroke.
2.Low-Density Lipoprotein Cholesterol Level, the Lower the Better? Analysis of Korean Patients in the Treat Stroke to Target Trial
Hanim KWON ; Jae-Chan RYU ; Jae-Kwan CHA ; Sang Min SUNG ; Tae-Jin SONG ; Kyung Bok LEE ; Eung-Gyu KIM ; Yong-Won KIM ; Ji Hoe HEO ; Man Seok PARK ; Kyusik KANG ; Byung-Chul LEE ; Keun-Sik HONG ; Oh Young BANG ; Jei KIM ; Jong S. KIM
Journal of Stroke 2025;27(2):228-236
Background:
and Purpose The Treat Stroke to Target (TST) was a randomized clinical trial involving French and Korean patients demonstrating that a lower low-density lipoprotein cholesterol (LDL-C, <70 mg/dL) target group (LT) experienced fewer cerebro-cardiovascular events than a higher target (90–110 mg/dL) group (HT). However, whether these results can be applied to Asian patients with different ischemic stroke subtypes remains unclear.
Methods:
Patients from 14 South Korean centers were analyzed separately. Patients with ischemic stroke or transient ischemic attack with evidence of atherosclerosis were randomized into LT and HT groups. The primary endpoint was a composite of ischemic stroke, myocardial infarction, coronary or cerebral revascularization, and cardiovascular death.
Results:
Among 712 enrolled patients, the mean LDL-C level was 71.0 mg/dL in 357 LT patients and 86.1 mg/dL in 355 HT patients. The primary endpoint occurred in 24 (6.7%) of LT and in 31 (8.7%) of HT group patients (adjusted hazard ratio [HR]=0.78; 95% confidence interval [CI]=0.45–1.33, P=0.353). Cardiovascular events alone occurred significantly less frequently in the LT than in the HT group (HR 0.26, 95% CI 0.09–0.80, P=0.019), whereas there were no significant differences in ischemic stroke events (HR 1.12, 95% CI 0.60–2.10, P=0.712). The benefit of LT was less apparent in patients with small vessel disease and intracranial atherosclerosis than in those with extracranial atherosclerosis.
Conclusion
In contrast to the French TST, the outcomes in Korean patients were neutral. Although LT was more effective in preventing cardiovascular diseases, it was not so in stroke prevention, probably attributed to the differences in stroke subtypes. Further studies are needed to elucidate the efficacy of statins and appropriate LDL-C targets in Asian patients with stroke.
3.Low-Density Lipoprotein Cholesterol Level, the Lower the Better? Analysis of Korean Patients in the Treat Stroke to Target Trial
Hanim KWON ; Jae-Chan RYU ; Jae-Kwan CHA ; Sang Min SUNG ; Tae-Jin SONG ; Kyung Bok LEE ; Eung-Gyu KIM ; Yong-Won KIM ; Ji Hoe HEO ; Man Seok PARK ; Kyusik KANG ; Byung-Chul LEE ; Keun-Sik HONG ; Oh Young BANG ; Jei KIM ; Jong S. KIM
Journal of Stroke 2025;27(2):228-236
Background:
and Purpose The Treat Stroke to Target (TST) was a randomized clinical trial involving French and Korean patients demonstrating that a lower low-density lipoprotein cholesterol (LDL-C, <70 mg/dL) target group (LT) experienced fewer cerebro-cardiovascular events than a higher target (90–110 mg/dL) group (HT). However, whether these results can be applied to Asian patients with different ischemic stroke subtypes remains unclear.
Methods:
Patients from 14 South Korean centers were analyzed separately. Patients with ischemic stroke or transient ischemic attack with evidence of atherosclerosis were randomized into LT and HT groups. The primary endpoint was a composite of ischemic stroke, myocardial infarction, coronary or cerebral revascularization, and cardiovascular death.
Results:
Among 712 enrolled patients, the mean LDL-C level was 71.0 mg/dL in 357 LT patients and 86.1 mg/dL in 355 HT patients. The primary endpoint occurred in 24 (6.7%) of LT and in 31 (8.7%) of HT group patients (adjusted hazard ratio [HR]=0.78; 95% confidence interval [CI]=0.45–1.33, P=0.353). Cardiovascular events alone occurred significantly less frequently in the LT than in the HT group (HR 0.26, 95% CI 0.09–0.80, P=0.019), whereas there were no significant differences in ischemic stroke events (HR 1.12, 95% CI 0.60–2.10, P=0.712). The benefit of LT was less apparent in patients with small vessel disease and intracranial atherosclerosis than in those with extracranial atherosclerosis.
Conclusion
In contrast to the French TST, the outcomes in Korean patients were neutral. Although LT was more effective in preventing cardiovascular diseases, it was not so in stroke prevention, probably attributed to the differences in stroke subtypes. Further studies are needed to elucidate the efficacy of statins and appropriate LDL-C targets in Asian patients with stroke.
4.Clinical Characteristics, Diagnosis, and Treatment of Thyroid Stimulating Hormone-Secreting Pituitary Neuroendocrine Tumor (TSH PitNET): A Single-Center Experience
Jung HEO ; Yeon-Lim SUH ; Se Hoon KIM ; Doo-Sik KONG ; Do-Hyun NAM ; Won-Jae LEE ; Sung Tae KIM ; Sang Duk HONG ; Sujin RYU ; You-Bin LEE ; Gyuri KIM ; Sang-Man JIN ; Jae Hyeon KIM ; Kyu Yeon HUR
Endocrinology and Metabolism 2024;39(2):387-396
Background:
Thyroid-stimulating hormone (TSH)-secreting pituitary neuroendocrine tumor (TSH PitNET) is a rare subtype of PitNET. We investigated the comprehensive characteristics and outcomes of TSH PitNET cases from a single medical center. Also, we compared diagnostic methods to determine which showed superior sensitivity.
Methods:
A total of 17 patients diagnosed with TSH PitNET after surgery between 2002 and 2022 in Samsung Medical Center was retrospectively reviewed. Data on comprehensive characteristics and treatment outcomes were collected. The sensitivities of diagnostic methods were compared.
Results:
Seven were male (41%), and the median age at diagnosis was 42 years (range, 21 to 65); the median follow-up duration was 37.4 months. The most common (59%) initial presentation was hyperthyroidism-related symptoms. Hormonal co-secretion was present in four (23%) patients. Elevated serum alpha-subunit (α-SU) showed the greatest diagnostic sensitivity (91%), followed by blunted response at thyrotropin-releasing hormone (TRH) stimulation (80%) and elevated sex hormone binding globulin (63%). Fourteen (82%) patients had macroadenoma, and a specimen of one patient with heavy calcification was negative for TSH. Among 15 patients who were followed up for more than 6 months, 10 (67%) achieved hormonal and structural remission within 6 months postoperatively. A case of growth hormone (GH)/TSH/prolactin (PRL) co-secreting mixed gangliocytoma-pituitary adenoma (MGPA) was discovered.
Conclusion
The majority of the TSH PitNET cases was macroadenoma, and 23% showed hormone co-secretion. A rare case of GH/TSH/PRL co-secreting MGPA was discovered. Serum α-SU and TRH stimulation tests showed great diagnostic sensitivity. Careful consideration is needed in diagnosing TSH PitNET. Achieving remission requires complete tumor resection. In case of nonremission, radiotherapy or medical therapy can improve the long-term remission rate.
5.Early Prediction of Mortality for Septic Patients Visiting Emergency Room Based on Explainable Machine Learning: A Real-World Multicenter Study
Sang Won PARK ; Na Young YEO ; Seonguk KANG ; Taejun HA ; Tae-Hoon KIM ; DooHee LEE ; Dowon KIM ; Seheon CHOI ; Minkyu KIM ; DongHoon LEE ; DoHyeon KIM ; Woo Jin KIM ; Seung-Joon LEE ; Yeon-Jeong HEO ; Da Hye MOON ; Seon-Sook HAN ; Yoon KIM ; Hyun-Soo CHOI ; Dong Kyu OH ; Su Yeon LEE ; MiHyeon PARK ; Chae-Man LIM ; Jeongwon HEO ; On behalf of the Korean Sepsis Alliance (KSA) Investigators
Journal of Korean Medical Science 2024;39(5):e53-
Background:
Worldwide, sepsis is the leading cause of death in hospitals. If mortality rates in patients with sepsis can be predicted early, medical resources can be allocated efficiently. We constructed machine learning (ML) models to predict the mortality of patients with sepsis in a hospital emergency department.
Methods:
This study prospectively collected nationwide data from an ongoing multicenter cohort of patients with sepsis identified in the emergency department. Patients were enrolled from 19 hospitals between September 2019 and December 2020. For acquired data from 3,657 survivors and 1,455 deaths, six ML models (logistic regression, support vector machine, random forest, extreme gradient boosting [XGBoost], light gradient boosting machine, and categorical boosting [CatBoost]) were constructed using fivefold cross-validation to predict mortality. Through these models, 44 clinical variables measured on the day of admission were compared with six sequential organ failure assessment (SOFA) components (PaO 2 /FIO 2 [PF], platelets (PLT), bilirubin, cardiovascular, Glasgow Coma Scale score, and creatinine).The confidence interval (CI) was obtained by performing 10,000 repeated measurements via random sampling of the test dataset. All results were explained and interpreted using Shapley’s additive explanations (SHAP).
Results:
Of the 5,112 participants, CatBoost exhibited the highest area under the curve (AUC) of 0.800 (95% CI, 0.756–0.840) using clinical variables. Using the SOFA components for the same patient, XGBoost exhibited the highest AUC of 0.678 (95% CI, 0.626–0.730). As interpreted by SHAP, albumin, lactate, blood urea nitrogen, and international normalization ratio were determined to significantly affect the results. Additionally, PF and PLTs in the SOFA component significantly influenced the prediction results.
Conclusion
Newly established ML-based models achieved good prediction of mortality in patients with sepsis. Using several clinical variables acquired at the baseline can provide more accurate results for early predictions than using SOFA components. Additionally, the impact of each variable was identified.
6.The Oncologic Implications of Tumor Multiplicity in Intrahepatic Cholangiocarcinoma: Its Prognostic Value Might Be Underestimated
So Jeong YOON ; Sunghae PARK ; Hongbeom KIM ; Sang Hyun SHIN ; Jin Seok HEO ; Jinsoo RHU ; Gyu-Seong CHOI ; Jong Man KIM ; Jae-Won JOH ; In Woong HAN
Cancer Research and Treatment 2023;55(3):948-955
Purpose:
In the latest staging system of the American Joint Committee on Cancer for intrahepatic cholangiocarcinoma (IHCCC), solitary tumors with vascular invasion and multiple tumors are grouped together as T2. However, recent studies report that multifocal IHCCC has a worse prognosis than a single lesion. This study aimed to investigate the risk factors for IHCCC and explore the prognostic significance of multiplicity after surgical resection.
Materials and Methods:
A total of 257 patients underwent surgery for IHCCC from 2010 to 2019 and the clinicopathological data were retrospectively reviewed. Risk factor analysis was performed to identify variables associated with survival after resection. Survival outcomes were compared between patients with solitary and multiple tumors.
Results:
In multivariable analysis, the presence of preoperative symptoms, tumor size, lymph node ratio, multiplicity, and tumor differentiation were identified as risk factors for survival. Among 82 patients with T2, overall survival was significantly longer in patients with solitary tumors (sT2) than in those with multiple tumors (mT2) (p=0.017). Survival was compared among patients with stage II-sT2, stage II-mT2, and stage III. The stage II-sT2 group showed prolonged survival when compared with stage II-mT2 or stage III. Survivals of stage II-mT2 and stage III patients were not statistically different.
Conclusion
Tumor multiplicity was an independent risk factor for overall survival of IHCCC after surgical resection. Patients with multiple tumors showed poorer survival than patients with a single tumor. The oncologic significance of multiplicity in IHCCC should be reappraised and reflected in the next staging system update.
7.Stroke-Specific Predictors of Major Bleeding in Anticoagulated Patients With Stroke and Atrial Fibrillation: A Nationwide Multicenter Registry-Based Study
Darda CHUNG ; Tae-Jin SONG ; Bum Joon KIM ; Sung Hyuk HEO ; Jin-Man JUNG ; Kyungmi OH ; Chi Kyung KIM ; Sungwook YU ; Kwang Yeol PARK ; Jeong-Min KIM ; Jong-Ho PARK ; Man-Seok PARK ; Joon-Tae KIM ; Yang-Ha HWANG ; Yong-Jae KIM ; Jong-Won CHUNG ; Oh Young BANG ; Gyeong-Moon KIM ; Woo-Keun SEO ; Jay Chol CHOI
Journal of Clinical Neurology 2023;19(5):429-437
Background:
and Purpose The congestive heart failure, hypertension, age, diabetes, previous stroke/transient ischemic attack (CHA2DS2-VASc) and hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol (HAS-BLED) scores have been validated in estimating the risks of ischemic stroke and major bleeding, respectively, in patients with atrial fibrillation (AF). This study investigated stroke-specific predictors of major bleeding in patients with stroke and AF who were taking oral anticoagulants (OACs).
Methods:
Subjects were selected from patients enrolled in the Korean ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts (K-ATTENTION) nationwide multicenter registry between 2013 and 2015. Patients were excluded if they were not taking OACs, had no brain imaging data, or had intracranial bleeding directly related to the index stroke. Major bleeding was defined according to International Society of Thrombosis and Haemostasis criteria. Cox regression analyses were performed to assess the associations between clinical variables and major bleeding and Kaplan-Meier estimates were performed to analyze event-free survival.
Results:
Of a total of 3,213 patients, 1,414 subjects (mean age of 72.6 years, 52.5% males) were enrolled in this study. Major bleeding was reported in 34 patients during the median follow-up period of 1.73 years. Multivariable analysis demonstrated that initial National Institutes of Health Stroke Scale scores (hazard ratio [HR] 1.07, p=0.006), hypertension (HR 3.18, p=0.030), persistent AF type (HR 2.51, p=0.016), and initial hemoglobin level (HR 0.74, p=0.001) were independently associated with major bleeding risk. Except for hypertension, these associations remained significant after adjusting for the HAS-BLED score. Intracranial atherosclerosis presented a trend of association without statistical significance (HR 2.21, p=0.050).
Conclusions
This study found that major bleeding risk was independently associated with stroke-specific factors in anticoagulated patients with stroke and AF. This has the clinical implication that baseline characteristics of patients with stroke and AF should be considered in secondary prevention, which would bring the net clinical benefit of balancing recurrent stroke prevention with minimal bleeding complications.
8.Initiation of Guideline-Matched Oral Anticoagulant in Atrial Fibrillation-Related Stroke
Mi-Yeon EUN ; Jae-Young KIM ; Yang-Ha HWANG ; Man-Seok PARK ; Joon-Tae KIM ; Kang-Ho CHOI ; Jin-Man JUNG ; Sungwook YU ; Chi Kyung KIM ; Kyungmi OH ; Tae-Jin SONG ; Yong-Jae KIM ; Bum Joon KIM ; Sung Hyuk HEO ; Kwang-Yeol PARK ; Jeong-Min KIM ; Jong-Ho PARK ; Jay Chol CHOI ; Jong-Won CHUNG ; Oh Young BANG ; Gyeong-Moon KIM ; Woo-Keun SEO
Journal of Stroke 2021;23(1):113-123
Background:
and Purpose To evaluate the outcome events and bleeding complications of the European Society of Cardiology (ESC) guideline-matched oral anticoagulant therapy for patients with acute ischemic stroke and atrial fibrillation (AF).
Methods:
Patients with acute ischemic stroke and AF from a nationwide multicenter registry (Korean ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts [K-ATTENTION]) between January 2013 and December 2015 were included in the study. Patients were divided into the ESC guideline-matched and the non-matched groups. The primary outcome was recurrence of any stroke during the 90-day follow-up period. Secondary outcomes were major adverse cerebrovascular and cardiovascular events, ischemic stroke, intracranial hemorrhage, acute coronary syndrome, allcause mortality, and major hemorrhage. Propensity score matching and logistic regression analyses were performed to assess the effect of the treatments administered.
Results:
Among 2,321 eligible patients, 1,126 patients were 1:1 matched to the ESC guidelinematched and the non-matched groups. As compared with the non-matched group, the ESC guideline-matched group had a lower risk of any recurrent stroke (1.4% vs. 3.4%; odds ratio [OR], 0.41; 95% confidence interval [CI], 0.18 to 0.95). The risk of recurrent ischemic stroke was lower in the ESC guideline-matched group than in the non-matched group (0.9% vs. 2.7%; OR, 0.32; 95% CI, 0.11 to 0.88). There was no significant difference in the other secondary outcomes between the two groups.
Conclusions
ESC guideline-matched oral anticoagulant therapy was associated with reduced risks of any stroke and ischemic stroke as compared with the non-matched therapy.
9.Pediatric Adenocarcinoma in Korea: A Multicenter Study
Hee-Beom YANG ; Jung-Man NAMGOONG ; Ki Hoon KIM ; Dae Yeon KIM ; Jinyoung PARK ; Hyun Beak SHIN ; Joong Kee YOUN ; Sanghoon LEE ; Ji Won LEE ; Sung Eun JUNG ; Jae Hee CHUNG ; Yun-Mee CHOE ; Tae Gil HEO ; In Geol HO ; Hyun-Young KIM
Cancer Research and Treatment 2020;52(1):117-127
Purpose:
Adenocarcinoma is an extremely rare malignancy in the pediatric population. Research regarding pediatric adenocarcinoma is very rare in Korea. This study aimed to investigate the clinical features of pediatric adenocarcinomas of various primary organ sites in Korea.
Materials and Methods:
Pediatric patients under 18 years, diagnosed with adenocarcinoma of various sites between January 1995 and December 2016, were included. We retrospectively reviewed patient and tumor characteristics and calculated survival estimates, reported as 5-year survival rate and 95% confidence interval.
Results:
Of 80 patients (median age, 15 years; range, 10 to 17 years), 37 (46.3%) were men, and 24 (30%) had a family history of cancer or underlying disease relevant to malignancy. The cancer locations were the colon and rectum (n=32), ovaries (n=18), stomach (n=15), lung (n=4), small bowel (n=1), and other sites (n=10). Totally, 54.8% patients (42/77) had stage 3 or 4 disease. The median follow-up period was 2.0 years (range, 0 to 20.4). The 5-year overall survival estimate for all patients, and for those with stomach, colorectal, ovarian, and other cancer sites were 57.9%±11.5%, 58.2%±25.7%, 41.5%±18.2%, 87.5%±16.2%, and 64.0%±34.4%, respectively. The 5-year survival rate differed significantly between categories of adenocarcinomas into gastrointestinal (GI) (44.7%) and non-GI adenocarcinomas (78.8%) (p=0.007). The 5-year survival rate also differed significantly according to carcinoembryonic antigen level (69.3% in < 3 ng/mL, 23.8% in > 3 ng/mL; p < 0.001).
Conclusion
In pediatric patients, adenocarcinomas arise from various organs and are often diagnosed at advanced stages. Large, prospective studies for their accurate clinical characteristics and prognostic factors are needed.
10.Long-Term Outcomes of Real-World Korean Patients with Atrial-Fibrillation-Related Stroke and Severely Decreased Ejection Fraction
Jin Man JUNG ; Yong Hyun KIM ; Sungwook YU ; Kyungmi O ; Chi Kyung KIM ; Tae Jin SONG ; Yong Jae KIM ; Bum Joon KIM ; Sung Hyuk HEO ; Kwang Yeol PARK ; Jeong Min KIM ; Jong Ho PARK ; Jay Chol CHOI ; Man Seok PARK ; Joon Tae KIM ; Kang Ho CHOI ; Yang Ha HWANG ; Jong Won CHUNG ; Oh Young BANG ; Gyeong moon KIM ; Woo Keun SEO
Journal of Clinical Neurology 2019;15(4):545-554
BACKGROUND AND PURPOSE: The clinical implications of echocardiography findings for long-term outcomes in atrial fibrillation (AF)-related stroke patients are unknown. METHODS: This was a substudy of the Korean ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts (K-ATTENTION), which is a multicenter-based cohort comprising prospective stroke registries from 11 tertiary centers. Stroke survivors who underwent two-dimensional transthoracic echocardiography during hospitalization were enrolled. Echocardiography markers included the left-ventricle (LV) ejection fraction (LVEF), the left atrium diameter, and the ratio of the peak transmitral filling velocity to the mean mitral annular velocity during early diastole (E/e′ ratio). LVEF was categorized into normal (≥55%), mildly decreased (>40% and <55%), and severely decreased (≤40%). The E/e′ ratio associated with the LV filling pressure was categorized into normal (<8), borderline (≥8 and <15), and elevated (≥15). Kaplan-Meier and Cox regression analyses were performed for recurrent stroke, major adverse cardiac events, and all-cause death. RESULTS: This study finally included 1,947 patients. Over a median follow-up of 1.65 years (interquartile range, 0.42–2.87 years), the rates of recurrent stroke, major adverse cardiac events, and all-cause death were 35.1, 10.8, and 69.6 cases per 1,000 person-years, respectively. Multivariable analyses demonstrated that severely decreased LVEF was associated with a higher risks of major adverse cardiac events [hazard ratio (HR), 3.91; 95% confidence interval (CI), 1.58–9.69] and all-cause death (HR, 1.95; 95% CI, 1.23–3.10). The multivariable fractional polynomial plot indicated that recurrent stroke might be associated with a lower LVEF. CONCLUSIONS: Severe LV systolic dysfunction could be a determinant of long-term outcomes in AF-related stroke.
Atrial Fibrillation
;
Cohort Studies
;
Diastole
;
Echocardiography
;
Follow-Up Studies
;
Heart Atria
;
Hospitalization
;
Humans
;
Prospective Studies
;
Registries
;
Stroke
;
Survivors

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