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.Successful treatment of adjunctive teriparatide therapy for medicationrelated osteonecrosis of the jaw: a report of two cases
Ra-yeon KIM ; Sung ok HONG ; Jae-woong JUNG ; Mu-hang LEE ; Young-kee LEE ; Yu-jin JEE
Journal of the Korean Association of Oral and Maxillofacial Surgeons 2024;50(5):285-291
Medication-related osteonecrosis of the jaw (MRONJ) is a refractory disease that can lead to severe destruction of the jaw. As there is no standard protocol for treating MRONJ, various treatments have been studied. Teriparatide has been used as an adjunct therapy for MRONJ. However, its effectiveness has not been sufficiently demonstrated for use as a standard treatment for MRONJ. This study aimed to demonstrate the efficacy of teriparatide in treating MRONJ by presenting two successfully treated cases. Each patient received teriparatide therapy with surgical intervention. The appropriateness of teriparatide use was evaluated based on the patient’s systemic condition, and the administration of teriparatide was supervised by a physician.Complete resolution of the lesion was observed clinically and radiographically in both patients. The first patient underwent implant placement at the lesion site. Due to its anabolic properties and ability to stimulate bone remodeling, teriparatide is an effective adjunctive pharmacological treatment for bone healing before and after surgery with associated beneficial effects on bone and mucosal healing.
4.Successful treatment of adjunctive teriparatide therapy for medicationrelated osteonecrosis of the jaw: a report of two cases
Ra-yeon KIM ; Sung ok HONG ; Jae-woong JUNG ; Mu-hang LEE ; Young-kee LEE ; Yu-jin JEE
Journal of the Korean Association of Oral and Maxillofacial Surgeons 2024;50(5):285-291
Medication-related osteonecrosis of the jaw (MRONJ) is a refractory disease that can lead to severe destruction of the jaw. As there is no standard protocol for treating MRONJ, various treatments have been studied. Teriparatide has been used as an adjunct therapy for MRONJ. However, its effectiveness has not been sufficiently demonstrated for use as a standard treatment for MRONJ. This study aimed to demonstrate the efficacy of teriparatide in treating MRONJ by presenting two successfully treated cases. Each patient received teriparatide therapy with surgical intervention. The appropriateness of teriparatide use was evaluated based on the patient’s systemic condition, and the administration of teriparatide was supervised by a physician.Complete resolution of the lesion was observed clinically and radiographically in both patients. The first patient underwent implant placement at the lesion site. Due to its anabolic properties and ability to stimulate bone remodeling, teriparatide is an effective adjunctive pharmacological treatment for bone healing before and after surgery with associated beneficial effects on bone and mucosal healing.
5.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.
6.Successful treatment of adjunctive teriparatide therapy for medicationrelated osteonecrosis of the jaw: a report of two cases
Ra-yeon KIM ; Sung ok HONG ; Jae-woong JUNG ; Mu-hang LEE ; Young-kee LEE ; Yu-jin JEE
Journal of the Korean Association of Oral and Maxillofacial Surgeons 2024;50(5):285-291
Medication-related osteonecrosis of the jaw (MRONJ) is a refractory disease that can lead to severe destruction of the jaw. As there is no standard protocol for treating MRONJ, various treatments have been studied. Teriparatide has been used as an adjunct therapy for MRONJ. However, its effectiveness has not been sufficiently demonstrated for use as a standard treatment for MRONJ. This study aimed to demonstrate the efficacy of teriparatide in treating MRONJ by presenting two successfully treated cases. Each patient received teriparatide therapy with surgical intervention. The appropriateness of teriparatide use was evaluated based on the patient’s systemic condition, and the administration of teriparatide was supervised by a physician.Complete resolution of the lesion was observed clinically and radiographically in both patients. The first patient underwent implant placement at the lesion site. Due to its anabolic properties and ability to stimulate bone remodeling, teriparatide is an effective adjunctive pharmacological treatment for bone healing before and after surgery with associated beneficial effects on bone and mucosal healing.
7.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.
8.Pioneering PGC-1αα–boosted secretome: a novel approach to combating liver fibrosis
Chang Ho SEO ; Gun Hyung NA ; Dosang LEE ; Jung Hyun PARK ; Tae Ho HONG ; Ok-Hee KIM ; Sang Chul LEE ; Kee-Hwan KIM ; Ho Joong CHOI ; Say-June KIM
Annals of Surgical Treatment and Research 2024;106(3):155-168
Purpose:
Liver fibrosis is a critical health issue with limited treatment options. This study investigates the potential of PGC-Sec, a secretome derived from peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)-overexpressing adipose-derived stem cells (ASCs), as a novel therapeutic strategy for liver fibrosis.
Methods:
Upon achieving a cellular confluence of 70%–80%, ASCs were transfected with pcDNA-PGC-1α. PGC-Sec, obtained through concentration of conditioned media using ultrafiltration units with a 3-kDa cutoff, was assessed through in vitro assays and in vitro mouse models.
Results:
In vitro, PGC-Sec significantly reduced LX2 human hepatic stellate cell proliferation and mitigated mitochondrial oxidative stress compared to the control-secretome. In an in vivo mouse model, PGC-Sec treatment led to notable reductions in hepatic enzyme activity, serum proinflammatory cytokine concentrations, and fibrosis-related marker expression. Histological analysis demonstrated improved liver histology and reduced fibrosis severity in PGC-Sec–treated mice. Immunohistochemical staining confirmed enhanced expression of PGC-1α, optic atrophy 1 (a mitochondrial function marker), and peroxisome proliferator-activated receptor alpha (an antifibrogenic marker) in the PGC-Sec–treated group, along with reduced collagen type 1A expression (a profibrogenic marker).
Conclusion
These findings highlight the therapeutic potential of PGC-Sec in combating liver fibrosis by enhancing mitochondrial biogenesis and function, and promoting antifibrotic processes. PGC-Sec holds promise as a novel treatment strategy for liver fibrosis.
9.Long-term Outcomes of Protocol-Based Treatment for Newly Diagnosed Medulloblastoma
Won Kee AHN ; Seung Min HAHN ; Hong In YOON ; Jeongshim LEE ; Eun Kyung PARK ; Kyu Won SHIM ; Dong Seok KIM ; Chang-Ok SUH ; Se Hoon KIM ; Chuhl Joo LYU ; Jung Woo HAN
Cancer Research and Treatment 2024;56(2):652-664
Purpose:
The Korean Society of Pediatric Neuro-Oncology (KSPNO) conducted treatment strategies for children with medulloblastoma (MB) by using alkylating agents for maintenance chemotherapy or tandem high-dose chemotherapy (HDC) with autologous stem cell rescue (ASCR) according to the risk stratification. The purpose of the study was to assess treatment outcomes and complications based on risk-adapted treatment and HDC.
Materials and Methods:
Fifty-nine patients diagnosed with MB were enrolled in this study. Patients in the standard-risk (SR) group received radiotherapy (RT) after surgery and chemotherapy using the KSPNO M051 regimen. Patients in the high-risk (HR) group received two and four chemotherapy cycles according to the KSPNO S081 protocol before and after reduced RT for age following surgery and two cycles of tandem HDC with ASCR consolidation treatment.
Results:
In the SR group, 24 patients showed 5-year event-free survival (EFS) and overall survival (OS) estimates of 86.7% (95% confidence interval [CI], 73.6 to 100) and 95.8% (95% CI, 88.2 to 100), respectively. In the HR group, more infectious complications and mortality occurred during the second HDC than during the first. In the HR group, the 5-year EFS and OS estimates were 65.5% (95% CI, 51.4 to 83.4) and 72.3% (95% CI, 58.4 to 89.6), respectively.
Conclusion
High intensity of alkylating agents for SR resulted in similar outcomes but with a high incidence of hematologic toxicity. Tandem HDC with ASCR for HR induced favorable EFS and OS estimates compared to those reported previously. However, infectious complications and treatment-related mortalities suggest that a reduced chemotherapy dose is necessary, especially for the second HDC.
10.Etiology and Risk Factors of Community-Acquired Pneumonia in Hospitalized Children During the COVID-19 Pandemic in South Korea
Hae Min KANG ; Seung Ha SONG ; Bin AHN ; Ji Young PARK ; Hyunmi KANG ; Byung Ok KWAK ; Dong Hyun KIM ; Joon Kee LEE ; Soo-Han CHOI ; Jae Hong CHOI ; Eun Hwa CHOI ; Ki Wook YUN
Pediatric Infection & Vaccine 2023;30(1):20-32
Purpose:
This study aimed to identify the etiology and risk factors of community-acquired pneumonia (CAP) requiring hospitalization in Korean children during the coronavirus disease 2019 (COVID-19) pandemic.
Methods:
Clinical information of children admitted with CAP to Seoul National University Children’s Hospital (SNUCH) between January 1, 2021, and February 28, 2022, was retrospectively collected and analyzed. In addition, the etiologic diagnosis and demographic data of children with CAP who were discharged at the other seven hospitals between January and February 2022 were collected. Pneumonia was diagnosed using strict criteria comprising clinical symptoms, physical examination findings, and chest radiographic findings.
Results:
Among 91 children hospitalized with CAP at SNUCH during the 14-month period, 68.4% were aged <5 years and 79.1% had underlying diseases. Among the 95 CAP cases, respiratory assistance was required in 70.5%, and the use of a ventilator was required in 20.0%.A total of five patients expired, all of whom were either immunocompromised or had underlying neurological diseases. Neurological diseases and immunosuppression were significantly correlated with respiratory assistance (P=0.003) and death (P=0.014). A total of 55% of the detected respiratory pathogens were viruses, the most common of which was rhinovirus at 35.9%. Among the 169 children hospitalized for CAP at the eight institutions, ≥1 respiratory virus was detected in 92.3%, among which respiratory syncytial virus (79.8%) was the most prevalent.
Conclusions
Even during the COVID-19 pandemic, Korean children were hospitalized with CAP caused by seasonal respiratory viral pathogens. Although atypical and pyogenic bacteria were not detected, continuous clinical monitoring and further prospective studies should be conducted.

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