1.Lazertinib versus Gefitinib as First-Line Treatment for EGFR-mutated Locally Advanced or Metastatic NSCLC: LASER301 Korean Subset
Ki Hyeong LEE ; Byoung Chul CHO ; Myung-Ju AHN ; Yun-Gyoo LEE ; Youngjoo LEE ; Jong-Seok LEE ; Joo-Hang KIM ; Young Joo MIN ; Gyeong-Won LEE ; Sung Sook LEE ; Kyung-Hee LEE ; Yoon Ho KO ; Byoung Yong SHIM ; Sang-We KIM ; Sang Won SHIN ; Jin-Hyuk CHOI ; Dong-Wan KIM ; Eun Kyung CHO ; Keon Uk PARK ; Jin-Soo KIM ; Sang Hoon CHUN ; Jangyoung WANG ; SeokYoung CHOI ; Jin Hyoung KANG
Cancer Research and Treatment 2024;56(1):48-60
Purpose:
This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC).
Materials and Methods:
Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS).
Results:
In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib.
Conclusion
Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.
2.Clinical Outcomes of Clipping and Coil Embolization for Ruptured Intracranial Aneurysms Categorized by Region and Hospital Size: A Nationwide Cohort Study in Korea
Yu Deok WON ; Hyoung Soo BYOUN ; Tae Won CHOI ; Sang Hyo LEE ; Young Deok KIM ; Seung Pil BAN ; Jae Seung BANG ; O-Ki KWON ; Chang Wan OH ; Si Un LEE
Journal of Korean Medical Science 2024;39(23):e188-
Background:
To analyze the outcomes of clipping and coiling for ruptured intracranial aneurysms (RIAs) based on data from the National Health Insurance Service in South Korea, with a focus on variations according to region and hospital size.
Methods:
This study analyzed the one-year mortality rates for patients with RIAs who underwent clipping or coiling in 2018. Coiling was further categorized into non-stent assisted coiling (NSAC) and stent assisted coiling (SAC). Hospitals were classified as tertiary referral general hospitals (TRGHs), general hospitals (GHs), or semi-general hospitals (sGHs) based on size. South Korea’s administrative districts were divided into 15 regions for analysis.
Results:
In 2018, there were 2,194 (33.1%) clipping procedures (TRGH, 985; GH, 827; sGH, 382) and 4,431 (66.9%) coiling procedures (TRGH, 1,642; GH, 2076; sGH, 713) performed for RIAs treatment. Among hospitals performing more than 20 treatments, the one-year mortality rates following clipping or coiling were 11.2% and 16.0%, respectively, with no significant difference observed. However, there was a significant difference in one-year mortality between NSAC and SAC (14.3% vs. 19.5%, P = 0.034), with clipping also showing significantly lower mortality compared to SAC (P = 0.019). No significant differences in other treatment modalities were observed according to hospital size, but clipping at TRGHs had significantly lower mortality than at GHs (P = 0.042). While no significant correlation was found between the number of treatments and outcomes at GHs, at TRGHs, a higher volume of clipping procedures was significantly associated with lower total mortality (P = 0.023) and mortality after clipping (P = 0.022).
Conclusion
Using Korea NHIS data, mortality rates for RIAs showed no significant variation by hospital size due to coiling’s prevalence. However, differences in clipping outcomes by hospital size and volume in TRGH highlight the need for national efforts to improve clipping skills and standardization. Additionally, the higher mortality rate with SAC emphasizes the importance of precise indications for its application.
3.Standardized Database of 12-Lead Electrocardiograms with a Common Standard for the Promotion of Cardiovascular Research: KURIAS-ECG
Hakje YOO ; Yunjin YUM ; Soo Wan PARK ; Jeong Moon LEE ; Moonjoung JANG ; Yoojoong KIM ; Jong-Ho KIM ; Hyun-Joon PARK ; Kap Su HAN ; Jae Hyoung PARK ; Hyung Joon JOO
Healthcare Informatics Research 2023;29(2):132-144
Objectives:
Electrocardiography (ECG)-based diagnosis by experts cannot maintain uniform quality because individual differences may occur. Previous public databases can be used for clinical studies, but there is no common standard that would allow databases to be combined. For this reason, it is difficult to conduct research that derives results by combining databases. Recent commercial ECG machines offer diagnoses similar to those of a physician. Therefore, the purpose of this study was to construct a standardized ECG database using computerized diagnoses.
Methods:
The constructed database was standardized using Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) and Observational Medical Outcomes Partnership–common data model (OMOP-CDM), and data were then categorized into 10 groups based on the Minnesota classification. In addition, to extract high-quality waveforms, poor-quality ECGs were removed, and database bias was minimized by extracting at least 2,000 cases for each group. To check database quality, the difference in baseline displacement according to whether poor ECGs were removed was analyzed, and the usefulness of the database was verified with seven classification models using waveforms.
Results:
The standardized KURIAS-ECG database consists of high-quality ECGs from 13,862 patients, with about 20,000 data points, making it possible to obtain more than 2,000 for each Minnesota classification. An artificial intelligence classification model using the data extracted through SNOMED-CT showed an average accuracy of 88.03%.
Conclusions
The KURIAS-ECG database contains standardized ECG data extracted from various machines. The proposed protocol should promote cardiovascular disease research using big data and artificial intelligence.
4.Clinical Outcomes of Coil Embolization for Unruptured Intracranial Aneurysms Categorized by Region and Hospital Size : A Nationwide Cohort Study in Korea
Bong-Gyu RYU ; Si Un LEE ; Hwan Seok SHIM ; Jeong-Mee PARK ; Yong Jae LEE ; Young-Deok KIM ; Tackeun KIM ; Seung Pil BAN ; Hyoung Soo BYOUN ; Jae Seung BANG ; O-ki KWON ; Chang Wan OH
Journal of Korean Neurosurgical Society 2023;66(6):690-702
Objective:
: To analyze the outcomes of coil embolization (CE) for unruptured intracranial aneurysm (UIA) according to region and hospital size based on National Health Insurance Service data in South Korea.
Methods:
: The incidence of complications, including intracranial hemorrhage (ICRH) and cerebral infarction (CI), occurring within 3 months and the 1-year mortality rates in UIA patients who underwent CE in 2018 were analyzed. Hospitals were classified as tertiary referral general hospitals (TRGHs), general hospitals (GHs) or semigeneral hospitals (sGHs) according to their size, and the administrative districts of South Korea were divided into 15 regions.
Results:
: In 2018, 8425 (TRGHs, 4438; GHs, 3617; sGHs, 370) CEs were performed for UIAs. Complications occurred in 5.69% of patients seen at TRGHs, 13.48% at GHs, and 20.45% at sGHs. The complication rate in TRGHs was significantly lower than that in GHs (p=0.039) or sGHs (p=0.005), and that in GHs was significantly lower than that in sGHs (p=0.030). The mortality rates in TRGHs, GHs, and sGHs were 0.81%, 2.16%, and 3.92%, respectively, with no significant difference. Despite no significant difference in the mortality rates, the complication rate significantly increased as the number of CE procedures per hospital decreased (p=0.001; rho=-0.635). Among the hospitals where more than 30 CEs were performed for UIAs, the incidence of CIs (p=0.096, rho=-0.205) and the mortality rates (3 months, p=0.048, rho=-0.243; 1 year, p=0.009, rho=-0.315) significantly decreased as the number of CEs that were performed increased and no significant difference in the incidence of post-CE ICRH was observed.
Conclusion
: The complication rate in patients who underwent CE for UIA increased as the hospital size and physicians’ experience in conducting CEs decreased. We recommend nationwide quality control policies CEs for UIAs.
5.Increased risk of gastric cancer in workers with occupational dust exposure
Mo-Yeol KANG ; Jiyoun JUNG ; Jung-Wan KOO ; Inah KIM ; Hyoung-Ryoul KIM ; Jun-Pyo MYONG
The Korean Journal of Internal Medicine 2021;36(Suppl 1):S18-S26
Background/Aims:
Workers who are exposed to dust in the workplace tend to show a higher incidence of gastric cancer. Nevertheless, scientific evidence to support an association between dust exposure and the risk of gastric cancer is inadequate. This study aimed to investigate whether or not occupational dust exposure influences the risk of gastric cancer.
Methods:
We collected the electronic data from the Pneumoconiosis Health Examination (PHE) program, provided by the Ministry of Employment and Labor and the Korea Workers’ Compensation and Welfare Service from 2002 to 2017. The PHE database was linked to the National Health Insurances databases. The age-standardized incidence ratio (SIR) and 95% confidence intervals (CIs) of the risk of gastric cancers were evaluated in workers with occupational dust exposure, and the results were compared to those in the general population.
Results:
From 2004 to 2015, 1,543 cases of gastric cancer were observed in the male participants, as compared with 1,174 of expected cases, which yielded an SIR of 1.314 (95% CI, 1.249 to 1.380). Under dust exposure, the risk of gastric cancer was increased 23.9% in the male participants (95% CI, 19.9 to 27.5), and the degree of impairment of lung function was inversely related to the risk of gastric cancer.
Conclusions
Workers with occupational dust exposure were at higher risk of developing gastric cancer than the general population. Thus, future efforts for the prevention of gastric cancer are necessary for dust exposed workers.
6.Clinical Outcomes of Clipping and Coiling in Elderly Patients with Unruptured Cerebral Aneurysms: a National Cohort Study in Korea
Sang Hyo LEE ; Si Un LEE ; O-Ki KWON ; Jae Seung BANG ; Seung Pil BAN ; Tackeun KIM ; Young Deok KIM ; Hyoung Soo BYOUN ; Chang Wan OH
Journal of Korean Medical Science 2021;36(26):e178-
Background:
We aimed to analyze outcomes of clipping and coiling in treating unruptured intracranial aneurysms (UIAs) in elderly patients and to identify the age at which perioperative risk increases based on national cohort data in South Korea.
Methods:
The incidence of perioperative intracranial hemorrhage (ICRH), perioperative cerebral infarction (CI), mortality, and moderate to severe disability data of the patients who underwent coiling or clipping for UIAs were retrieved. Estimated breakpoint (EBP) was calculated to identify the age at which the risk of treatment increases.
Results:
A total of 38,207 patients were treated for UIAs. Among these, 22,093 (57.8%) patients underwent coiling and 16,114 (42.2%) patients underwent clipping. The incidence of ICRH, requiring a secondary operation, within 3 months in patients ≥ 65 years that underwent coiling and clipping was 1.13% and 4.81%, respectively, and that of both groups assessed were significantly higher in patients ≥ 75 years (coiling, P = 0.013, relative risk (RR) 1.81; clipping, P = 0.015) than younger patients. The incidence of CI within 3 months in patients aged ≥ 65 was 13.90% and 9.19% in the coiling and clipping groups, respectively. The incidence of CI after coiling in patients aged ≥ 75 years (P < 0.001, RR 1.96) and after clipping in patients aged ≥ 70 years (P < 0.001, RR 1.76) was significantly higher than that in younger patients. The mortality rates within 1 year in patients with perioperative ICRH or CI were 2.41% and 3.39% for coiling and clipping groups, respectively, in patients ≥ 65. These rates increased significantly at age 70 in the coiling group and at age 75 for the clipping group (P = 0.012 and P < 0.001, respectively).
Conclusion
The risk of treatment increases with age, and this risk increases dramatically in patients aged ≥ 70 years. Therefore, the treatment decisions in patients aged ≥ 70 years should be made with utmost care.
7.Clinical Outcomes of Clipping and Coiling in Elderly Patients with Unruptured Cerebral Aneurysms: a National Cohort Study in Korea
Sang Hyo LEE ; Si Un LEE ; O-Ki KWON ; Jae Seung BANG ; Seung Pil BAN ; Tackeun KIM ; Young Deok KIM ; Hyoung Soo BYOUN ; Chang Wan OH
Journal of Korean Medical Science 2021;36(26):e178-
Background:
We aimed to analyze outcomes of clipping and coiling in treating unruptured intracranial aneurysms (UIAs) in elderly patients and to identify the age at which perioperative risk increases based on national cohort data in South Korea.
Methods:
The incidence of perioperative intracranial hemorrhage (ICRH), perioperative cerebral infarction (CI), mortality, and moderate to severe disability data of the patients who underwent coiling or clipping for UIAs were retrieved. Estimated breakpoint (EBP) was calculated to identify the age at which the risk of treatment increases.
Results:
A total of 38,207 patients were treated for UIAs. Among these, 22,093 (57.8%) patients underwent coiling and 16,114 (42.2%) patients underwent clipping. The incidence of ICRH, requiring a secondary operation, within 3 months in patients ≥ 65 years that underwent coiling and clipping was 1.13% and 4.81%, respectively, and that of both groups assessed were significantly higher in patients ≥ 75 years (coiling, P = 0.013, relative risk (RR) 1.81; clipping, P = 0.015) than younger patients. The incidence of CI within 3 months in patients aged ≥ 65 was 13.90% and 9.19% in the coiling and clipping groups, respectively. The incidence of CI after coiling in patients aged ≥ 75 years (P < 0.001, RR 1.96) and after clipping in patients aged ≥ 70 years (P < 0.001, RR 1.76) was significantly higher than that in younger patients. The mortality rates within 1 year in patients with perioperative ICRH or CI were 2.41% and 3.39% for coiling and clipping groups, respectively, in patients ≥ 65. These rates increased significantly at age 70 in the coiling group and at age 75 for the clipping group (P = 0.012 and P < 0.001, respectively).
Conclusion
The risk of treatment increases with age, and this risk increases dramatically in patients aged ≥ 70 years. Therefore, the treatment decisions in patients aged ≥ 70 years should be made with utmost care.
8.Association of Low Blood Pressure with White Matter Hyperintensities in Elderly Individuals with Controlled Hypertension
Jun Sung KIM ; Subin LEE ; Seung Wan SUH ; Jong Bin BAE ; Ji Hyun HAN ; Seonjeong BYUN ; Ji Won HAN ; Jae Hyoung KIM ; Ki Woong KIM
Journal of Stroke 2020;22(1):99-107
Background:
and Purpose Both hypertension and hypotension increase cerebral white matter hyperintensities. However, the effects of hypotension in individuals with treated hypertension are unknown. We analyzed the association of low blood pressure with the location and amount of white matter hyperintensities between elderly individuals with controlled hypertension and those without hypertension.
Methods:
We enrolled 505 community-dwelling, cognitively normal elderly individuals from the participants of the Korean Longitudinal Study on Cognitive Aging and Dementia. We measured blood pressure three times in a sitting position using a mercury sphygmomanometer and defined low systolic and diastolic blood pressure as ≤110 and ≤60 mm Hg, respectively. We segmented and quantified the periventricular and deep white matter hyperintensities from 3.0 Tesla fluid-attenuated inversion recovery magnetic resonance images.
Results:
Low systolic blood pressure was independently associated with larger volume of periventricular white matter hyperintensity (P=0.049). The interaction between low systolic blood pressure and hypertension was observed on the volume of periventricular white matter hyperintensity (P=0.005). Low systolic blood pressure was associated with the volume of periventricular white matter hyperintensity in individuals with controlled hypertension (F1,248=6.750, P=0.010), but not in those without hypertension (P=0.380). Low diastolic blood pressure was not associated with the volumes of white matter hyperintensities regardless of presence of controlled hypertension.
Conclusions
Low systolic blood pressure seems to be associated with larger volume of periventricular white matter hyperintensity in the individuals with a historyof hypertension but not in those without hypertension.
9.Clinical outcomes of submucosal colorectal cancer diagnosed after endoscopic resection: a focus on the need for surgery
Yun Sik CHOI ; Wan Soo KIM ; Sung Wook HWANG ; Sang Hyoung PARK ; Dong-Hoon YANG ; Byong Duk YE ; Seung-Jae MYUNG ; Suk-Kyun YANG ; Jeong-Sik BYEON
Intestinal Research 2020;18(1):96-106
Background/Aims:
We aimed to investigate the proportion of and risk factors for residual cancer and/or lymph node metastasis after surgery was performed because of high-risk pathological features in endoscopic resection specimen of suspected superficial submucosal colorectal cancer (SSMC).
Methods:
We reviewed medical records of 497 patients (58.8 ± 9.8 years, 331 males) undergoing endoscopic resection of suspected SSMC. High-risk pathological features included: deep submucosal cancer invasion ≥ 1,000 μm; positive lymphovascular and/or perineural invasion; poorly differentiated adenocarcinoma; and positive resection margin. We investigated the occurrence of additional surgery and residual cancer and/or lymph node involvement in the surgical specimen.
Results:
En bloc resection was performed in 447 patients (89.9%). High-risk pathological features were detected in 372 patients (74.8%). Additional surgery was performed in 336 of 372 patients with high-risk pathological features. Of these, 47 surgical specimens (14.0%) showed residual cancer and/or lymph node metastasis. Piecemeal resection was more common in those with residual cancer and/or lymph node involvement than those without (9/47 [19.1%] vs. 24/289 [8.3%], P= 0.032). Positive resection margin was also significantly associated with positive residual cancer and/or lymph node involvement. As the number of high-risk pathological features increased, the risk of regional lymph node metastasis increased proportionally (P= 0.002).
Conclusions
High-risk pathological features were frequently detected after endoscopic resection of suspected SSMC while residual cancer and/or lymph node metastasis were not commonly present in the additional surgical specimen. Further optimized strategy for proper endoscopic management of suspected SSMC is necessary.
10.Urinary Angiotensinogen in addition to Imaging Classification in the Prediction of Renal Outcome in Autosomal Dominant Polycystic Kidney Disease
Hayne Cho PARK ; Juhee KIM ; AJin CHO ; Do Hyoung KIM ; Young-Ki LEE ; Hyunjin RYU ; Hyunsuk KIM ; Kook-Hwan OH ; Yun Kyu OH ; Young-Hwan HWANG ; Kyu-Beck LEE ; Soo Wan KIM ; Yeong Hoon KIM ; Joongyub LEE ; Curie AHN ;
Journal of Korean Medical Science 2020;35(22):e165-
Background:
Intrarenal renin-angiotensin system (RAS) is known to play the major role in the development of hypertension and renal progression in autosomal dominant polycystic kidney disease (ADPKD). Urinary angiotensinogen to creatinine ratio (AGT/Cr) was suggested as a novel biomarker to reflect intrarenal RAS activity. This study was performed to evaluate urinary AGT/Cr as a predictive biomarker for renal function decline in addition to imaging classification in a prospective ADPKD cohort.
Methods:
From 2011 to 2016, a total of 364 ADPKD patients were enrolled in the prospective cohort called the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). Among them, a total of 207 subjects in chronic kidney disease stage 1–4 with baseline urinary AGT and total kidney volume and subsequent renal function follow-up data over more than 1 year were included in the analysis. Patients were defined as slow progressors (SP) if they are classified as 1A or 1B by imaging classification whereas rapid progressors (RP) if they are classified as 1C–1E. Patients were divided according to AGT/Cr quartiles and annual estimated glomerular filtration rate (eGFR) slope was compared among highest quartile (hAGT group) and the rest of quartiles (lAGT group). Patients were divided into 4 groups to evaluate the predictive value of urinary AGT/Cr in addition to imaging classification: SP/lAGT, SP/hAGT, RP/lAGT, and RP/hAGT. The Cox regression model was used to evaluate the hazard ratio (HR) between groups.
Results:
The mean age was 45.9 years and 88.9% had hypertension. Baseline eGFR was 79.0 ± 28.4 mL/min/1.73 m2 and median height-adjusted total kidney volume was 788.2 (471.2;1,205.2) mL/m. The patients in the hAGT group showed lower eGFR (72.4 ± 24.8 vs. 81.1 ± 29.2 mL/min/1.73 m2, P = 0.039), lower plasma hemoglobin (13.0 ± 1.4 vs. 13.7 ± 1.6 g/dL, P = 0.007), higher urinary protein to creatinine ratio (0.14 [0.09, 0.38] vs. 0.07 [0.04, 0.12] g/g, P = 0.007) compared to the lAGT group. The hAGT group was an independent risk factor for faster eGFR decline after adjusting for gender, RP, baseline eGFR, and other known risk factors. During median follow-up duration of 4.6 years, a total of 29 renal events (14.0%) occurred. The SP/hAGT group showed significantly higher risk of developing renal outcome compared to SP/lAGT group (HR, 13.4; 95% confidence interval, 1.282–139.324; P = 0.03).
Conclusion
Urinary AGT/Cr can be a useful predictive marker in the patients with relatively small ADPKD. Various biomarkers should be considered to define RP when implementing novel treatment in the patients with ADPKD.

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