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.Radiological and Pathological Challenges in Diagnosing Pleomorphic Lobular Carcinoma In Situ With Focal Invasion: A Case Report
Hyo-jae LEE ; Chan PARK ; Won Gi JEONG ; Ji Shin LEE ; Min Ho PARK ; Hyo Soon LIM
Journal of Breast Disease 2024;12(2):33-36
Pleomorphic lobular carcinoma in situ (PLCIS) is a relatively uncommon subtype of lobular neoplasia, characterized by large pleomorphic discohesive cells exhibiting marked nuclear atypia, frequent central comedo-necrosis, and microcalcifications. Owing to these features, PLCIS is difficult to distinguish using radiological and histological analyses with high-grade ductal carcinoma in situ. This report presents a case in which breast PLCIS was initially misdiagnosed as invasive ductal carcinoma based on core-needle biopsy and radiological findings. However, further investigation confirmed the diagnosis of PLCIS with invasive lobular carcinoma, measuring only 1.04 mm. This case illustrates the diagnostic challenges of PLCIS, which mimics invasive ductal carcinoma, causing unnecessarily aggressive treatment. Notably, this warrants careful pathological and radiological evaluations for accurate diagnosis and guides appropriate management.
4.Radiological and Pathological Challenges in Diagnosing Pleomorphic Lobular Carcinoma In Situ With Focal Invasion: A Case Report
Hyo-jae LEE ; Chan PARK ; Won Gi JEONG ; Ji Shin LEE ; Min Ho PARK ; Hyo Soon LIM
Journal of Breast Disease 2024;12(2):33-36
Pleomorphic lobular carcinoma in situ (PLCIS) is a relatively uncommon subtype of lobular neoplasia, characterized by large pleomorphic discohesive cells exhibiting marked nuclear atypia, frequent central comedo-necrosis, and microcalcifications. Owing to these features, PLCIS is difficult to distinguish using radiological and histological analyses with high-grade ductal carcinoma in situ. This report presents a case in which breast PLCIS was initially misdiagnosed as invasive ductal carcinoma based on core-needle biopsy and radiological findings. However, further investigation confirmed the diagnosis of PLCIS with invasive lobular carcinoma, measuring only 1.04 mm. This case illustrates the diagnostic challenges of PLCIS, which mimics invasive ductal carcinoma, causing unnecessarily aggressive treatment. Notably, this warrants careful pathological and radiological evaluations for accurate diagnosis and guides appropriate management.
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.Radiological and Pathological Challenges in Diagnosing Pleomorphic Lobular Carcinoma In Situ With Focal Invasion: A Case Report
Hyo-jae LEE ; Chan PARK ; Won Gi JEONG ; Ji Shin LEE ; Min Ho PARK ; Hyo Soon LIM
Journal of Breast Disease 2024;12(2):33-36
Pleomorphic lobular carcinoma in situ (PLCIS) is a relatively uncommon subtype of lobular neoplasia, characterized by large pleomorphic discohesive cells exhibiting marked nuclear atypia, frequent central comedo-necrosis, and microcalcifications. Owing to these features, PLCIS is difficult to distinguish using radiological and histological analyses with high-grade ductal carcinoma in situ. This report presents a case in which breast PLCIS was initially misdiagnosed as invasive ductal carcinoma based on core-needle biopsy and radiological findings. However, further investigation confirmed the diagnosis of PLCIS with invasive lobular carcinoma, measuring only 1.04 mm. This case illustrates the diagnostic challenges of PLCIS, which mimics invasive ductal carcinoma, causing unnecessarily aggressive treatment. Notably, this warrants careful pathological and radiological evaluations for accurate diagnosis and guides appropriate management.
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.Neutrophil Migration Is Mediated by VLA-6 in the Inflamed Adipose Tissue
Hyunseo LIM ; Young Ho CHOE ; Jaeho LEE ; Gi Eun KIM ; Jin Won HYUN ; Young-Min HYUN
Immune Network 2024;24(3):e23-
Adipose tissue, well known for its endocrine function, plays an immunological role in the body. The inflamed adipose tissue under LPS-induced systemic inflammation is characterized by the dominance of pro-inflammatory immune cells, particularly neutrophils.Although migration of macrophages toward damaged or dead adipocytes to form a crownlike structure in inflamed adipose tissue has been revealed, the neutrophilic interaction with adipocytes or the extracellular matrix remains unknown. Here, we demonstrated the involvement of adhesion molecules, particularly integrin α6β1, of neutrophils in adipocytes or the extracellular matrix of inflamed adipose tissue interaction. These results suggest that disrupting the adhesion between adipose tissue components and neutrophils may govern the accumulation of excessive neutrophils in inflamed tissues, a prerequisite in developing antiinflammatory therapeutics by inhibiting inflammatory immune cells.
9.The Profile of Early Sedation Depth and Clinical Outcomes of Mechanically Ventilated Patients in Korea
Dong-gon HYUN ; Jee Hwan AHN ; Ha-Yeong GIL ; Chung Mo NAM ; Choa YUN ; Jae-Myeong LEE ; Jae Hun KIM ; Dong-Hyun LEE ; Ki Hoon KIM ; Dong Jung KIM ; Sang-Min LEE ; Ho-Geol RYU ; Suk-Kyung HONG ; Jae-Bum KIM ; Eun Young CHOI ; JongHyun BAEK ; Jeoungmin KIM ; Eun Jin KIM ; Tae Yun PARK ; Je Hyeong KIM ; Sunghoon PARK ; Chi-Min PARK ; Won Jai JUNG ; Nak-Jun CHOI ; Hang-Jea JANG ; Su Hwan LEE ; Young Seok LEE ; Gee Young SUH ; Woo-Sung CHOI ; Keu Sung LEE ; Hyung Won KIM ; Young-Gi MIN ; Seok Jeong LEE ; Chae-Man LIM
Journal of Korean Medical Science 2023;38(19):e141-
Background:
Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known.
Methods:
From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation–Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups.
Results:
Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence inter val [CI], 0.55– 0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% 0.56–0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79–1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65–2.17; P = 0.582).
Conclusion
In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.
10.Malignant Apocrine Lesions of the Breast: Multimodality Imaging Findings and Biologic Features
Hyo-jae LEE ; Seung Wan KANG ; Jong Eun LEE ; Won Gi JEONG ; Ji Shin LEE ; Min Ho PARK ; Hyo Soon LIM
Journal of Breast Cancer 2022;25(6):513-521
The apocrine morphology of the breast is observed in a broad pathological spectrum, ranging from benign cysts to invasive carcinomas. However, the number of clinical research investigating malignant apocrine lesions is limited. This study retrospectively reviewed the data of patients with malignant apocrine lesions admitted in a tertiary center between January 2004 and December 2021, based on the radiology-pathology correlation and the recent advances in their status to enhance the therapeutic implications of androgen receptor (AR). Among the 37 patients with lesions, 27 (73.0%) had triple-negative subtypes with predominant AR expression. The radiological features of malignant apocrine lesions did not differ from those of typical invasive ductal carcinoma or ductal carcinoma in situ. This study demonstrated that knowledge on the imaging features of malignant apocrine lesions and their histological basis could enhance the adoption of new targeted therapies in patients with this particular type of breast cancer.

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