1.Sex-Specific Susceptibility Loci Associated With Coronary Artery Aneurysms in Patients With Kawasaki Disease
Jae-Jung KIM ; Young Mi HONG ; Sin Weon YUN ; Kyung-Yil LEE ; Kyung Lim YOON ; Myung-Ki HAN ; Gi Beom KIM ; Hong-Ryang KIL ; Min Seob SONG ; Hyoung Doo LEE ; Kee Soo HA ; Hyun Ok JUN ; Jeong Jin YU ; Gi Young JANG ; Jong-Keuk LEE ;
Korean Circulation Journal 2024;54(9):577-586
Background and Objectives:
Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20–25% of untreated children with KD and 3–5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients.
Methods:
A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases).
Results:
Six male-specific susceptibility loci, PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ (odds ratios [ORs], 2.25–9.98; p=0.00204–1.96×10−6 ), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD.
Conclusions
A sex-stratified GWAS identified 6 male-specific (PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ) and 2 female-specific (SMAD3 and IL1RAPL1) CAA susceptibility loci in patients with KD.
2.Sex-Specific Susceptibility Loci Associated With Coronary Artery Aneurysms in Patients With Kawasaki Disease
Jae-Jung KIM ; Young Mi HONG ; Sin Weon YUN ; Kyung-Yil LEE ; Kyung Lim YOON ; Myung-Ki HAN ; Gi Beom KIM ; Hong-Ryang KIL ; Min Seob SONG ; Hyoung Doo LEE ; Kee Soo HA ; Hyun Ok JUN ; Jeong Jin YU ; Gi Young JANG ; Jong-Keuk LEE ;
Korean Circulation Journal 2024;54(9):577-586
Background and Objectives:
Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20–25% of untreated children with KD and 3–5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients.
Methods:
A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases).
Results:
Six male-specific susceptibility loci, PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ (odds ratios [ORs], 2.25–9.98; p=0.00204–1.96×10−6 ), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD.
Conclusions
A sex-stratified GWAS identified 6 male-specific (PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ) and 2 female-specific (SMAD3 and IL1RAPL1) CAA susceptibility loci in patients with KD.
3.Sex-Specific Susceptibility Loci Associated With Coronary Artery Aneurysms in Patients With Kawasaki Disease
Jae-Jung KIM ; Young Mi HONG ; Sin Weon YUN ; Kyung-Yil LEE ; Kyung Lim YOON ; Myung-Ki HAN ; Gi Beom KIM ; Hong-Ryang KIL ; Min Seob SONG ; Hyoung Doo LEE ; Kee Soo HA ; Hyun Ok JUN ; Jeong Jin YU ; Gi Young JANG ; Jong-Keuk LEE ;
Korean Circulation Journal 2024;54(9):577-586
Background and Objectives:
Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20–25% of untreated children with KD and 3–5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients.
Methods:
A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases).
Results:
Six male-specific susceptibility loci, PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ (odds ratios [ORs], 2.25–9.98; p=0.00204–1.96×10−6 ), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD.
Conclusions
A sex-stratified GWAS identified 6 male-specific (PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ) and 2 female-specific (SMAD3 and IL1RAPL1) CAA susceptibility loci in patients with KD.
4.Sex-Specific Susceptibility Loci Associated With Coronary Artery Aneurysms in Patients With Kawasaki Disease
Jae-Jung KIM ; Young Mi HONG ; Sin Weon YUN ; Kyung-Yil LEE ; Kyung Lim YOON ; Myung-Ki HAN ; Gi Beom KIM ; Hong-Ryang KIL ; Min Seob SONG ; Hyoung Doo LEE ; Kee Soo HA ; Hyun Ok JUN ; Jeong Jin YU ; Gi Young JANG ; Jong-Keuk LEE ;
Korean Circulation Journal 2024;54(9):577-586
Background and Objectives:
Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20–25% of untreated children with KD and 3–5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients.
Methods:
A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases).
Results:
Six male-specific susceptibility loci, PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ (odds ratios [ORs], 2.25–9.98; p=0.00204–1.96×10−6 ), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD.
Conclusions
A sex-stratified GWAS identified 6 male-specific (PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ) and 2 female-specific (SMAD3 and IL1RAPL1) CAA susceptibility loci in patients with KD.
5.Contribution of Enhanced Locoregional Control to Improved Overall Survival with Consolidative Durvalumab after Concurrent Chemoradiotherapy in Locally Advanced Non–Small Cell Lung Cancer: Insights from Real-World Data
Jeong Yun JANG ; Si Yeol SONG ; Young Seob SHIN ; Ha Un KIM ; Eun Kyung CHOI ; Sang-We KIM ; Jae Cheol LEE ; Dae Ho LEE ; Chang-Min CHOI ; Shinkyo YOON ; Su Ssan KIM
Cancer Research and Treatment 2024;56(3):785-794
Purpose:
This study aimed to assess the real-world clinical outcomes of consolidative durvalumab in patients with unresectable locally advanced non–small cell lung cancer (LA-NSCLC) and to explore the role of radiotherapy in the era of immunotherapy.
Materials and Methods:
This retrospective study assessed 171 patients with unresectable LA-NSCLC who underwent concurrent chemoradiotherapy (CCRT) with or without consolidative durvalumab at Asan Medical Center between May 2018 and May 2021. Primary outcomes included freedom from locoregional failure (FFLRF), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS).
Results:
Durvalumab following CCRT demonstrated a prolonged median PFS of 20.9 months (p=0.048) and a 3-year FFLRF rate of 57.3% (p=0.008), compared to 13.7 months and 38.8%, respectively, with CCRT alone. Furthermore, the incidence of in-field recurrence was significantly greater in the CCRT-alone group compared to the durvalumab group (26.8% vs. 12.4%, p=0.027). While median OS was not reached with durvalumab, it was 35.4 months in patients receiving CCRT alone (p=0.010). Patients positive for programmed cell death ligand 1 (PD-L1) expression showed notably better outcomes, including FFLRF, DMFS, PFS, and OS. Adherence to PACIFIC trial eligibility criteria identified 100 patients (58.5%) as ineligible. The use of durvalumab demonstrated better survival regardless of eligibility criteria.
Conclusion
The use of durvalumab consolidation following CCRT significantly enhanced locoregional control and OS in patients with unresectable LA-NSCLC, especially in those with PD-L1–positive tumors, thereby validating the role of durvalumab in standard care.
6.Newly Developed Sex-Specific Z Score Model for Coronary Artery Diameter in a Pediatric Population
Jeong Jin YU ; Hee Joung CHOI ; Hwa Jin CHO ; Sung Hye KIM ; Eun Jung CHEON ; Gi Beom KIM ; Lucy Youngmin EUN ; Se Yong JUNG ; Hyun Ok JUN ; Hyang-Ok WOO ; Sin-Ae PARK ; Soyoung YOON ; Hoon KO ; Ji-Eun BAN ; Jong-Woon CHOI ; Min Seob SONG ; Ji Whan HAN
Journal of Korean Medical Science 2024;39(16):e144-
Background:
This study aimed to generate a Z score calculation model for coronary artery diameter of normal children and adolescents to be adopted as the standard calculation method with consensus in clinical practice.
Methods:
This study was a retrospective, multicenter study that collected data from multiple institutions across South Korea. Data were analyzed to determine the model that best fit the relationship between the diameter of coronary arteries and independent demographic parameters. Linear, power, logarithmic, exponential, and square root polynomial models were tested for best fit.
Results:
Data of 2,030 subjects were collected from 16 institutions. Separate calculation models for each sex were developed because the impact of demographic variables on the diameter of coronary arteries differs according to sex. The final model was the polynomial formula with an exponential relationship between the diameter of coronary arteries and body surface area using the DuBois formula.
Conclusion
A new coronary artery diameter Z score model was developed and is anticipated to be applicable in clinical practice. The new model will help establish a consensus-based Z score model.
7.Exploratory evaluation of the role of cardiac troponin on the clinical outcome of patients visiting emergency department with or without chronic kidney disease
Minseok SONG ; Eun-Jin KANG ; Taerim KIM ; Jong Eun PARK ; Gun Tak LEE ; Hee YOON ; Sung Yeon HWANG ; Won Chul CHA ; Tae Gun SHIN ; Min Seob SIM ; Ik Joon JO ; Jin-Ho CHOI
Journal of the Korean Society of Emergency Medicine 2021;32(6):548-560
Objective:
Elevated levels of cardiac troponin in chronic kidney disease (CKD) patients admitted to the emergency department (ED) is not well understood and is often ignored. This study aimed to investigate the impact of cardiac troponin I (TnI) levels on the clinical outcome of patients visiting the ED with or without CKD.
Methods:
In this retrospective single-center cohort study, we enrolled patients visiting the ED without a diagnosis of coronary artery disease (CAD). Elevated cardiac TnI was defined as being ≥99th percentile of the normal population (Siemens ADVIA Centaur TnI-Ultra≥0.040 ng/mL). The clinical outcomes of patients with CKD stage≤2 and CKD stage ≥3 were compared. The primary endpoint was the 180-day all-cause death, including cardiovascular and non-cardiovascular deaths.
Results:
Among a total of 30,472 patients (median age, 61 years; male sex, 54.3%), elevated TnI was found in 4,377 patients (14.4%). There were 3,634 deaths (11.9%) including 584 cardiovascular (1.9%) and 3,050 non-cardiovascular deaths (10.0%). The risk of all-cause death increased in patients with elevated TnI in both CKD stage≤2 (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.9-2.3) and CKD stage≥3 (HR, 1.5; 95% CI, 1.4-1.7), and so did the risks of cardiovascular and non-cardiovascular death (HR, 1.2-4.7) (P<0.05, all). The association of elevated TnI with death risk was consistent in multivariate analyses and in most clinical subgroup analyses.
Conclusion
Elevated TnI was associated with higher 180-day mortality irrespective of renal function among patients visiting the ED without documented CAD. CKD patients visiting the ED with elevated TnI may warrant additional evaluation or careful follow-up even without the presence of CAD.
8.Monitoring Radiation Doses during Diagnostic and Therapeutic Neurointerventional Procedures: Multicenter Study for Establishment of Reference Levels
Yon-Kwon IHN ; Bum-soo KIM ; Hae Woong JEONG ; Sang Hyun SUH ; Yoo Dong WON ; Young-Jun LEE ; Dong Joon KIM ; Pyong JEON ; Chang-Woo RYU ; Sang-il SUH ; Dae Seob CHOI ; See Sung CHOI ; Sang Heum KIM ; Jun Soo BYUN ; Jieun RHO ; Yunsun SONG ; Woo Sang JEONG ; Noah HONG ; Sung Hyun BAIK ; Jeong Jin PARK ; Soo Mee LIM ; Jung-Jae KIM ; Woong YOON
Neurointervention 2021;16(3):240-251
Purpose:
To assess patient radiation doses during diagnostic and therapeutic neurointerventional procedures from multiple centers and propose dose reference level (RL).
Materials and Methods:
Consecutive neurointerventional procedures, performed in 22 hospitals from December 2020 to June 2021, were retrospectively studied. We collected data from a sample of 429 diagnostic and 731 therapeutic procedures. Parameters including dose-area product (DAP), cumulative air kerma (CAK), fluoroscopic time (FT), and total number of image frames (NI) were obtained. RL were calculated as the 3rd quartiles of the distribution.
Results:
Analysis of 1160 procedures from 22 hospitals confirmed the large variability in patient dose for similar procedures. RLs in terms of DAP, CAK, FT, and NI were 101.6 Gy·cm2, 711.3 mGy, 13.3 minutes, and 637 frames for cerebral angiography, 199.9 Gy·cm2, 3,458.7 mGy, 57.3 minutes, and 1,000 frames for aneurysm coiling, 225.1 Gy·cm2, 1,590 mGy, 44.7 minutes, and 800 frames for stroke thrombolysis, 412.3 Gy·cm2, 4,447.8 mGy, 99.3 minutes, and 1,621.3 frames for arteriovenous malformation (AVM) embolization, respectively. For all procedures, the results were comparable to most of those already published. Statistical analysis showed male and presence of procedural complications were significant factors in aneurysmal coiling. Male, number of passages, and procedural combined technique were significant factors in stroke thrombolysis. In AVM embolization, a significantly higher radiation dose was found in the definitive endovascular cure group.
Conclusion
Various RLs introduced in this study promote the optimization of patient doses in diagnostic and therapeutic interventional neuroradiology procedures. Proposed 3rd quartile DAP (Gy·cm2) values were 101.6 for diagnostic cerebral angiography, 199.9 for aneurysm coiling, 225.1 for stroke thrombolysis, and 412.3 for AVM embolization. Continual evolution of practices and technologies requires regular updates of RLs.
9.Development and Validation of a Symptom-Focused Quality of Life Questionnaire (KOQUSS-40) for Gastric Cancer Patients after Gastrectomy
Bang Wool EOM ; Joongyub LEE ; In Seob LEE ; Young-Gil SON ; Keun Won RYU ; Sung Geun KIM ; Hyoung-Il KIM ; Young-Woo KIM ; Seong-Ho KONG ; Oh Kyoung KWON ; Ji-Ho PARK ; Ji Yeong AN ; Chang Hyun KIM ; Byoung-Jo SUH ; Hong Man YOON ; Myoung Won SON ; Ji Yeon PARK ; Jong-Min PARK ; Sang-Ho JEONG ; Moon-Won YOO ; Geum Jong SONG ; Han-Kwang YANG ; Yun-Suhk SUH ; Ki Bum PARK ; Sang-Hoon AHN ; Dong Woo SHIN ; Ye Seob JEE ; Hye-Seong AHN ; Sol LEE ; Jae Seok MIN ; Haejin IN ; Ahyoung KIM ; Hoon HUR ; Hyuk-Joon LEE ;
Cancer Research and Treatment 2021;53(3):763-772
Purpose:
Patients who have undergone gastrectomy have unique symptoms that are not appropriately assessed using currently available tools. This study developed and validated a symptom-focused quality of life (QoL) questionnaire for patients who have received gastrectomy for gastric cancer. Materials and Methods Based on a literature review, patient interviews, and expert consultation by the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS), the initial item pool was developed. Two large-scale developmental studies were then sequentially conducted for exploratory factor analyses for content validity and item reduction. The final item pool was validated in a separate cohort of patients and assessed for internal consistency, test-retest reliability, construct validity, and clinical validity.
Results
The initial questionnaire consisted of 46-items in 12 domains. Data from 465 patients at 11 institutions, followed by 499 patients at 13 institutions, were used to conduct item reduction and exploratory factor analyses. The final questionnaire (KOQUSS-40) comprised 40 items within 11 domains. Validation of KOQUSS-40 was conducted on 413 patients from 12 hospitals. KOQUSS-40 was found to have good model fit. The mean summary score of the KOQUSS-40 was correlated with the EORTC QLQ-C30 and STO22 (correlation coefficients, 0.821 and 0.778, respectively). The KOQUSS-40 score was also correlated with clinical factors, and had acceptable internal consistency (> 0.7). Test-retest reliability was greater than 0.8. Conclusion The KOQUSS-40 can be used to assess QoL of gastric cancer patients after gastrectomy and allows for a robust comparison of surgical techniques in clinical trials.
10.IgA Levels Are Associated with Coronary Artery Lesions in Kawasaki Disease
Jae-Jung KIM ; Hea-Ji KIM ; Jeong Jin KIM ; Sin Weon YUN ; Kyung-Yil LEE ; Kyung Lim YOON ; Hong-Ryang KIL ; Gi Beom KIM ; Myung-Ki HAN ; Min Seob SONG ; Hyoung Doo LEE ; Hyun Ok JUN ; Kee Soo HA ; Young Mi HONG ; Gi Young JANG ; Jong-Keuk LEE ;
Korean Circulation Journal 2021;51(3):267-278
Background and Objectives:
Kawasaki disease (KD) is an acute systemic vasculitis that affects the coronary arteries. Abnormal immune reactions are thought to contribute to disease pathogenesis. The effect of immunoglobulin (Ig) isotype (IgG, IgA, IgM, and IgE) on inflammatory data and clinical outcomes of patients with KD was examined.
Methods:
Ig levels in 241 patients with KD were measured during the acute, subacute, convalescent, and normal phases of the disease.
Results:
Compared with reference Ig values, IgG, IgA, and IgM levels were significantly higher in the subacute phase, while IgE levels were elevated in 73.9% (178/241) of patients with KD in all clinical phases. However, high IgE levels were not associated with clinical outcomes, including intravenous immunoglobulin unresponsiveness and coronary artery lesions (CALs).Significantly more CALs were observed in the high IgA group than in the normal IgA group (44.7% vs. 20.8%, respectively; p<0.01). In addition, IgA levels in the acute phase (p=0.038) were 2.2-fold higher, and those in the subacute phase were 1.7-fold higher (p <0.001), in the CAL group than in the non-CAL group. IgA concentrations increased along with the size of the coronary artery aneurysm (p <0.001). Furthermore, there was a strong correlation between IgA levels and CAL size (r=0.435, p<0.001), with a high odds ratio of 2.58 (p=0.022).
Conclusions
High IgA levels in patients with KD are prognostic for the risk of CALs.

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