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.Serotype Distribution and Antimicrobial Resistance of Streptococcus pneumoniae Causing Invasive Pneumococcal Disease in Korea Between 2017 and 2019 After Introduction of the 13-Valent Pneumococcal Conjugate Vaccine
Gyu Ri KIM ; Eun-Young KIM ; Si Hyun KIM ; Hae Kyung LEE ; Jaehyeon LEE ; Jong Hee SHIN ; Young Ree KIM ; Sae Am SONG ; Joseph JEONG ; Young UH ; Yu Kyung KIM ; Dongeun YONG ; Hyun Soo KIM ; Sunjoo KIM ; Young Ah KIM ; Kyeong Seob SHIN ; Seok Hoon JEONG ; Namhee RYOO ; Jeong Hwan SHIN
Annals of Laboratory Medicine 2023;43(1):45-54
Background:
Streptococcus pneumoniae is a serious pathogen causing various infections in humans. We evaluated the serotype distribution and antimicrobial resistance of S. pneumoniae causing invasive pneumococcal disease (IPD) after introduction of pneumococcal conjugate vaccine (PCV)13 in Korea and investigated the epidemiological characteristics of multidrug-resistant (MDR) isolates.
Methods:
S. pneumoniae isolates causing IPD were collected from 16 hospitals in Korea between 2017 and 2019. Serotyping was performed using modified sequential multiplex PCR and the Quellung reaction. Antimicrobial susceptibility tests were performed using the broth microdilution method. Multilocus sequence typing was performed on MDR isolates for epidemiological investigations.
Results:
Among the 411 S. pneumoniae isolates analyzed, the most prevalent serotype was 3 (12.2%), followed by 10A (9.5%), 34 (7.3%), 19A (6.8%), 23A (6.3%), 22F (6.1%), 35B (5.8%), 11A (5.1%), and others (40.9%). The coverage rates of PCV7, PCV10, PCV13, and pneumococcal polysaccharide vaccine (PPSV)23 were 7.8%, 7.8%, 28.7%, and 59.4%, respectively. Resistance rates to penicillin, ceftriaxone, erythromycin, and levofloxacin were 13.1%, 9.2%, 80.3%, and 4.1%, respectively. MDR isolates accounted for 23.4% of all isolates. Serotypes 23A, 11A, 19A, and 15B accounted for the highest proportions of total isolates at 18.8%, 16.7%, 14.6%, and 8.3%, respectively. Sequence type (ST)166 (43.8%) and ST320 (12.5%) were common among MDR isolates.
Conclusions
Non-PCV13 serotypes are increasing among invasive S. pneumoniae strains causing IPD. Differences in antimicrobial resistance were found according to the specific serotype. Continuous monitoring of serotypes and antimicrobial resistance is necessary for the appropriate management of S. pneumoniae infections.
7.Effects of Sexual Rehabilitation on Sexual Dysfunction in Patients with Cardiovascular Disease: A Systematic Review and Meta-Analysis
Jae Joon PARK ; Seung Whan DOO ; Allison KWON ; Do Kyung KIM ; Won Jae YANG ; Yun Seob SONG ; Sung Ryul SHIM ; Jae Heon KIM
The World Journal of Men's Health 2023;41(2):330-341
Purpose:
Cardiovascular disease (CVD) is one of the leading causes of death, accounting for one-third of all deaths worldwide. Patients with CVD are three times more likely to complain of sexual dysfunction than healthy people. Causes of sexual dysfunction in patients with CVD include physical/mental changes and drug side effects. The prevalence of sexual dysfunction in patients with CVD has been estimated to be up to 89%. Ordinary treatments such as pharmacotherapy cannot effectively reduce sexual problems. Therefore, sexual rehabilitation has a broad spectrum, including exercise therapy such as pelvic floor muscle treatment, appropriate counseling, a multidisciplinary approach, and partner rehabilitation. In this study, systematic review and meta-analysis was performed to investigate the effect of sexual rehabilitation on sexual problems in patients with CVD.
Materials and Methods:
Comprehensive literature searches were conducted using MEDLINE, Cochrane Library electronic database, and EMBASE through June 2022. Questionnaire scores at the end point as outcomes of the study were recorded as were standardized mean difference (SMD) with their 95% confidence intervals (CIs). Meta-regression analysis was conducted for each moderator. We performed a risk of bias evaluation for included studies using the RoB 2 tool.
Results:
The overall SMD in the meta-analysis for sexual rehabilitation versus no-sexual rehabilitation was 0.430 (95% CI, 0.226–0.633). There was a statistical difference between groups. SMD changes were 0.674 (95% CI, 0.308–1.039) at one month and 0.320 (95% CI, 0.074–0.565) at six months. The regression analysis with all variables (number of patients, study duration, and questionnaire types) revealed no significance.
Conclusions
This study indicates that sexual rehabilitation is an effective method with high therapeutic potential for sexual dysfunction of patients with CVD. However, for clinical application, well-designed studies with many patients should be conducted in the future and the standardization of rehabilitation protocols is required.
8.Outcome of dose-escalated intensity-modulated radiotherapy for limited disease small cell lung cancer
Eunyeong YANG ; Young Seob SHIN ; Ji Hyeon JOO ; Wonsik CHOI ; Su Ssan KIM ; Eun Kyung CHOI ; Jaeha LEE ; Si Yeol SONG
Radiation Oncology Journal 2023;41(3):199-208
Purpose:
An optimal once-daily radiotherapy (RT) regimen is under investigation for definitive concurrent chemoradiotherapy (CCRT) in limited disease small cell lung cancer (LD-SCLC). We compared the efficacy and safety of dose escalation with intensity-modulated radiotherapy (IMRT).
Materials and Methods:
Between January 2016 and March 2021, patients treated with definitive CCRT for LD-SCLC with IMRT were retrospectively reviewed. Patients who received a total dose <50 Gy or those with a history of thoracic RT or surgery were excluded. The patients were divided into two groups (standard and dose-escalated) based on the total biologically effective dose (BED, α/β = 10) of 70 Gy. The chemotherapeutic regimen comprised four cycles of etoposide and cisplatin.
Results:
One hundred and twenty-two patients were analyzed and the median follow-up was 27.8 months (range, 4.4 to 76.9 months). The median age of the patients was 63 years (range, 35 to 78 years) and the majority had a history of smoking (86.0%). The 1- and 3-year overall survival rates of the escalated dose group were significantly higher than those of the standard group (93.5% and 50.5% vs. 76.7% and 33.3%, respectively; p = 0.008), as were the 1- and 3-year freedom from in-field failure rates (91.4% and 66.5% vs. 73.8% and 46.9%, respectively; p = 0.018). The incidence of grade 2 or higher acute and late pneumonitis was not significantly different between the two groups (p = 0.062, 0.185).
Conclusion
Dose-escalated once-daily CCRT with IMRT led to improved locoregional control and survival, with no increase in toxicity.
9.Clinical Outcome of Stereotactic Body Radiotherapy in Patients with Early-Stage Lung Cancer with Ground-Glass Opacity Predominant Lesions: A Single Institution Experience
Jeong Yun JANG ; Su Ssan KIM ; Si Yeol SONG ; Young Seob SHIN ; Sei Won LEE ; Wonjun JI ; Chang-Min CHOI ; Eun Kyung CHOI
Cancer Research and Treatment 2023;55(4):1181-1189
Purpose:
The detection rate of early-stage lung cancer with ground-glass opacity (GGO) has increased, and stereotactic body radiotherapy (SBRT) has been suggested as an alternative to surgery in inoperable patients. However, reports on treatment results are limited. Therefore, we performed a retrospective study to investigate the clinical outcome after SBRT in patients with early-stage lung cancer with GGO-predominant tumor lesions at a single institution.
Materials and Methods:
This study included 89 patients with 99 lesions who were treated with SBRT for lung cancer with GGO-predominant lesions that had a consolidation-to-tumor ratio of ≤0.5 at Asan Medical Center between July 2016 and July 2021. A median total dose of 56.0 Gy (range, 48.0–60.0) was delivered using 10.0–15.0 Gy per fraction.
Results:
The overall follow-up period for the study was median 33.0 months (range, 9.9 to 65.9 months). There was 100% local control with no recurrences in any of the 99 treated lesions. Three patients had regional recurrences outside of the radiation field, and three had distant metastasis. The 1-year, 3-year, and 5-year overall survival rates were 100.0%, 91.6%, and 82.8%, respectively. Univariate analysis revealed that advanced age and a low level of diffusing capacity of the lungs for carbon monoxide were significantly associated with overall survival. There were no patients with grade ≥3 toxicity.
Conclusion
SBRT is a safe and effective treatment for patients with GGO-predominant lung cancer lesions and is likely to be considered as an alternative to surgery.
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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