1.Low-Dose Radiotherapy Attenuates Experimental Autoimmune Arthritis by Inducing Apoptosis of Lymphocytes and Fibroblast-Like Synoviocytes
Bo-Gyu KIM ; Hoon Sik CHOI ; Yong-ho CHOE ; Hyun Min JEON ; Ji Yeon HEO ; Yun-Hong CHEON ; Ki Mun KANG ; Sang-Il LEE ; Bae Kwon JEONG ; Mingyo KIM
Immune Network 2024;24(4):e32-
Low-dose radiotherapy (LDRT) has been explored as a treatment option for various inflammatory diseases; however, its application in the context of rheumatoid arthritis (RA) is lacking. This study aimed to elucidate the mechanism underlying LDRT-based treatment for RA and standardize it. LDRT reduced the total numbers of immune cells, but increased the apoptotic CD4+ T and B220+ B cells, in the draining lymph nodes of collagen induced arthritis and K/BxN models. In addition, it significantly reduced the severity of various pathological manifestations, including bone destruction, cartilage erosion, and swelling of hind limb ankle. Post-LDRT, the proportion of apoptotic CD4+ T and CD19 + B cells increased significantly in the PBMCs derived from human patients with RA. LDRT showed a similar effect in fibroblast-like synoviocytes as well. In conclusion, we report that LDRT induces apoptosis in immune cells and fibro-blast-like synoviocytes, contributing to attenuation of arthritis.
2.Cohort profile: Multicenter Networks for Ideal Outcomes of Rare Pediatric Endocrine and Metabolic Diseases in Korea (OUTSPREAD study)
Yun Jeong LEE ; Chong Kun CHEON ; Junghwan SUH ; Jung-Eun MOON ; Moon Bae AHN ; Seong Hwan CHANG ; Jieun LEE ; Jin Ho CHOI ; Minsun KIM ; Han Hyuk LIM ; Jaehyun KIM ; Shin-Hye KIM ; Hae Sang LEE ; Yena LEE ; Eungu KANG ; Se Young KIM ; Yong Hee HONG ; Seung YANG ; Heon-Seok HAN ; Sochung CHUNG ; Won Kyoung CHO ; Eun Young KIM ; Jin Kyung KIM ; Kye Shik SHIM ; Eun-Gyong YOO ; Hae Soon KIM ; Aram YANG ; Sejin KIM ; Hyo-Kyoung NAM ; Sung Yoon CHO ; Young Ah LEE
Annals of Pediatric Endocrinology & Metabolism 2024;29(6):349-355
Rare endocrine diseases are complex conditions that require lifelong specialized care due to their chronic nature and associated long-term complications. In Korea, a lack of nationwide data on clinical practice and outcomes has limited progress in patient care. Therefore, the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Disease (OUTSPREAD) study was initiated. This study involves 30 centers across Korea. The study aims to improve the long-term prognosis of Korean patients with rare endocrine diseases by collecting comprehensive clinical data, biospecimens, and patient-reported outcomes to identify complications and unmet needs in patient care. Patients with childhood-onset pituitary, adrenal, or gonadal disorders, such as craniopharyngioma, congenital adrenal hyperplasia (CAH), and Turner syndrome were prioritized. The planned enrollment is 1,300 patients during the first study phase (2022–2024). Clinical, biochemical, and imaging data from diagnosis, treatment, and follow-up during 1980–2023 were retrospectively reviewed. For patients who agreed to participate in the prospective cohort, clinical data and biospecimens will be prospectively collected to discover ideal biomarkers that predict the effectiveness of disease control measures and prognosis. Patient-reported outcomes, including quality of life and depression scales, will be evaluated to assess psychosocial outcomes. Additionally, a substudy on CAH patients will develop a steroid hormone profiling method using liquid chromatography-tandem mass spectrometry to improve diagnosis and monitoring of treatment outcomes. This study will address unmet clinical needs by discovering ideal biomarkers, introducing evidence-based treatment guidelines, and ultimately improving long-term outcomes in the areas of rare endocrine and metabolic diseases.
3.Cohort profile: Multicenter Networks for Ideal Outcomes of Rare Pediatric Endocrine and Metabolic Diseases in Korea (OUTSPREAD study)
Yun Jeong LEE ; Chong Kun CHEON ; Junghwan SUH ; Jung-Eun MOON ; Moon Bae AHN ; Seong Hwan CHANG ; Jieun LEE ; Jin Ho CHOI ; Minsun KIM ; Han Hyuk LIM ; Jaehyun KIM ; Shin-Hye KIM ; Hae Sang LEE ; Yena LEE ; Eungu KANG ; Se Young KIM ; Yong Hee HONG ; Seung YANG ; Heon-Seok HAN ; Sochung CHUNG ; Won Kyoung CHO ; Eun Young KIM ; Jin Kyung KIM ; Kye Shik SHIM ; Eun-Gyong YOO ; Hae Soon KIM ; Aram YANG ; Sejin KIM ; Hyo-Kyoung NAM ; Sung Yoon CHO ; Young Ah LEE
Annals of Pediatric Endocrinology & Metabolism 2024;29(6):349-355
Rare endocrine diseases are complex conditions that require lifelong specialized care due to their chronic nature and associated long-term complications. In Korea, a lack of nationwide data on clinical practice and outcomes has limited progress in patient care. Therefore, the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Disease (OUTSPREAD) study was initiated. This study involves 30 centers across Korea. The study aims to improve the long-term prognosis of Korean patients with rare endocrine diseases by collecting comprehensive clinical data, biospecimens, and patient-reported outcomes to identify complications and unmet needs in patient care. Patients with childhood-onset pituitary, adrenal, or gonadal disorders, such as craniopharyngioma, congenital adrenal hyperplasia (CAH), and Turner syndrome were prioritized. The planned enrollment is 1,300 patients during the first study phase (2022–2024). Clinical, biochemical, and imaging data from diagnosis, treatment, and follow-up during 1980–2023 were retrospectively reviewed. For patients who agreed to participate in the prospective cohort, clinical data and biospecimens will be prospectively collected to discover ideal biomarkers that predict the effectiveness of disease control measures and prognosis. Patient-reported outcomes, including quality of life and depression scales, will be evaluated to assess psychosocial outcomes. Additionally, a substudy on CAH patients will develop a steroid hormone profiling method using liquid chromatography-tandem mass spectrometry to improve diagnosis and monitoring of treatment outcomes. This study will address unmet clinical needs by discovering ideal biomarkers, introducing evidence-based treatment guidelines, and ultimately improving long-term outcomes in the areas of rare endocrine and metabolic diseases.
4.Low-Dose Radiotherapy Attenuates Experimental Autoimmune Arthritis by Inducing Apoptosis of Lymphocytes and Fibroblast-Like Synoviocytes
Bo-Gyu KIM ; Hoon Sik CHOI ; Yong-ho CHOE ; Hyun Min JEON ; Ji Yeon HEO ; Yun-Hong CHEON ; Ki Mun KANG ; Sang-Il LEE ; Bae Kwon JEONG ; Mingyo KIM
Immune Network 2024;24(4):e32-
Low-dose radiotherapy (LDRT) has been explored as a treatment option for various inflammatory diseases; however, its application in the context of rheumatoid arthritis (RA) is lacking. This study aimed to elucidate the mechanism underlying LDRT-based treatment for RA and standardize it. LDRT reduced the total numbers of immune cells, but increased the apoptotic CD4+ T and B220+ B cells, in the draining lymph nodes of collagen induced arthritis and K/BxN models. In addition, it significantly reduced the severity of various pathological manifestations, including bone destruction, cartilage erosion, and swelling of hind limb ankle. Post-LDRT, the proportion of apoptotic CD4+ T and CD19 + B cells increased significantly in the PBMCs derived from human patients with RA. LDRT showed a similar effect in fibroblast-like synoviocytes as well. In conclusion, we report that LDRT induces apoptosis in immune cells and fibro-blast-like synoviocytes, contributing to attenuation of arthritis.
5.Cohort profile: Multicenter Networks for Ideal Outcomes of Rare Pediatric Endocrine and Metabolic Diseases in Korea (OUTSPREAD study)
Yun Jeong LEE ; Chong Kun CHEON ; Junghwan SUH ; Jung-Eun MOON ; Moon Bae AHN ; Seong Hwan CHANG ; Jieun LEE ; Jin Ho CHOI ; Minsun KIM ; Han Hyuk LIM ; Jaehyun KIM ; Shin-Hye KIM ; Hae Sang LEE ; Yena LEE ; Eungu KANG ; Se Young KIM ; Yong Hee HONG ; Seung YANG ; Heon-Seok HAN ; Sochung CHUNG ; Won Kyoung CHO ; Eun Young KIM ; Jin Kyung KIM ; Kye Shik SHIM ; Eun-Gyong YOO ; Hae Soon KIM ; Aram YANG ; Sejin KIM ; Hyo-Kyoung NAM ; Sung Yoon CHO ; Young Ah LEE
Annals of Pediatric Endocrinology & Metabolism 2024;29(6):349-355
Rare endocrine diseases are complex conditions that require lifelong specialized care due to their chronic nature and associated long-term complications. In Korea, a lack of nationwide data on clinical practice and outcomes has limited progress in patient care. Therefore, the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Disease (OUTSPREAD) study was initiated. This study involves 30 centers across Korea. The study aims to improve the long-term prognosis of Korean patients with rare endocrine diseases by collecting comprehensive clinical data, biospecimens, and patient-reported outcomes to identify complications and unmet needs in patient care. Patients with childhood-onset pituitary, adrenal, or gonadal disorders, such as craniopharyngioma, congenital adrenal hyperplasia (CAH), and Turner syndrome were prioritized. The planned enrollment is 1,300 patients during the first study phase (2022–2024). Clinical, biochemical, and imaging data from diagnosis, treatment, and follow-up during 1980–2023 were retrospectively reviewed. For patients who agreed to participate in the prospective cohort, clinical data and biospecimens will be prospectively collected to discover ideal biomarkers that predict the effectiveness of disease control measures and prognosis. Patient-reported outcomes, including quality of life and depression scales, will be evaluated to assess psychosocial outcomes. Additionally, a substudy on CAH patients will develop a steroid hormone profiling method using liquid chromatography-tandem mass spectrometry to improve diagnosis and monitoring of treatment outcomes. This study will address unmet clinical needs by discovering ideal biomarkers, introducing evidence-based treatment guidelines, and ultimately improving long-term outcomes in the areas of rare endocrine and metabolic diseases.
6.Low-Dose Radiotherapy Attenuates Experimental Autoimmune Arthritis by Inducing Apoptosis of Lymphocytes and Fibroblast-Like Synoviocytes
Bo-Gyu KIM ; Hoon Sik CHOI ; Yong-ho CHOE ; Hyun Min JEON ; Ji Yeon HEO ; Yun-Hong CHEON ; Ki Mun KANG ; Sang-Il LEE ; Bae Kwon JEONG ; Mingyo KIM
Immune Network 2024;24(4):e32-
Low-dose radiotherapy (LDRT) has been explored as a treatment option for various inflammatory diseases; however, its application in the context of rheumatoid arthritis (RA) is lacking. This study aimed to elucidate the mechanism underlying LDRT-based treatment for RA and standardize it. LDRT reduced the total numbers of immune cells, but increased the apoptotic CD4+ T and B220+ B cells, in the draining lymph nodes of collagen induced arthritis and K/BxN models. In addition, it significantly reduced the severity of various pathological manifestations, including bone destruction, cartilage erosion, and swelling of hind limb ankle. Post-LDRT, the proportion of apoptotic CD4+ T and CD19 + B cells increased significantly in the PBMCs derived from human patients with RA. LDRT showed a similar effect in fibroblast-like synoviocytes as well. In conclusion, we report that LDRT induces apoptosis in immune cells and fibro-blast-like synoviocytes, contributing to attenuation of arthritis.
7.Neovascularization in Outer Membrane of Chronic Subdural Hematoma : A Rationale for Middle Meningeal Artery Embolization
Hyun KIM ; Yoori CHOI ; Youngsun LEE ; Jae-Kyung WON ; Sung Ho LEE ; Minseok SUH ; Dong Soo LEE ; Hyun-Seung KANG ; Won-Sang CHO ; Gi Jeong CHEON
Journal of Korean Neurosurgical Society 2024;67(2):146-157
Objective:
: Chronic subdural hematomas (cSDHs) are generally known to result from traumatic tears of bridging veins. However, the causes of repeat spontaneous cSDHs are still unclear. We investigated the changes in vasculature in the human dura mater and outer membrane (OM) of cSDHs to elucidate the cause of their spontaneous repetition.
Methods:
: The dura mater was obtained from a normal control participant and a patient with repeat spontaneous cSDHs. The pathological samples from the patient included the dura mater and OM tightly adhered to the inner dura. The samples were analyzed with a particular focus on blood and lymphatic vessels by immunohistochemistry, 3-dimensional imaging using a transparent tissue clearing technique, and electron microscopy.
Results:
: The dural border cell (DBC) layer of the dura mater and OM were histologically indistinguishable. There were 5.9 times more blood vessels per unit volume of tissue in the DBC layer and OM in the patient than in the normal control. The DBC layer and OM contained pathological sinusoidal capillaries not observed in the normal tissue; these capillaries were connected to the middle meningeal arteries via penetrating arteries. In addition, marked lymphangiogenesis in the periosteal and meningeal layers was observed in the patient with cSDHs.
Conclusion
: Neovascularization in the OM seemed to originate from the DBC layer; this is a potential cause of repeat spontaneous cSDHs. Embolization of the meningeal arteries to interrupt the blood supply to pathological capillaries via penetrating arteries may be an effective treatment option.
8.Alterations in Plasma Cytokine Levels in Korean Children with Autism Spectrum Disorder
Songjoo SHIM ; Sungji HA ; Juli CHOI ; Ho-Keun KWON ; Keun-Ah CHEON
Yonsei Medical Journal 2024;65(2):70-77
Purpose:
Numerous studies have supported the role of the immune dysfunction in the pathogenesis of autism spectrum disorder (ASD); however, to our knowledge, no study has been conducted on plasma cytokine levels in children with ASD in South Korea. In this study, we aimed to analyze the immunological characteristics of Korean children with ASD through plasma cytokine analysis.
Materials and Methods:
Blood samples were collected from 94 ASD children (mean age 7.1; 81 males and 13 females) and 48 typically developing children (TDC) (mean age 7.3; 30 males and 18 females). Plasma was isolated from 1 mL of blood by clarifying with centrifugation at 8000 rpm at 4°C for 10 min. Cytokines in plasma were measured with LEGENDplex HU Th cytokine panel (BioLegend, 741028) and LEGENDplex HU cytokine panel 2 (BioLegend, 740102).
Results:
Among 25 cytokines, innate immune cytokine [interleukin (IL)-33] was significantly decreased in ASD children compared with TDC. In acute phase proteins, tumor necrosis factor α (TNF-α) was significantly increased, while IL-6, another inflammation marker, was decreased in ASD children compared with TDC. The cytokines from T cell subsets, including interferon (IFN)-γ, IL-5, IL-13, and IL-17f, were significantly decreased in ASD children compared to TDC. IL-10, a major anti-inflammatory cytokine, and IL-9, which modulates immune cell growth and proliferation, were also significantly decreased in ASD children compared to TDC.
Conclusion
We confirmed that Korean children with ASD showed altered immune function and unique cytokine expression patterns distinct from TDC.
9.Revised Clinical Practice Guidelines of the Korean Pancreatobiliary Association for Acute Pancreatitis
Sang Hyub LEE ; Jung Wan CHOE ; Young Koog CHEON ; Miyoung CHOI ; Min Kyu JUNG ; Dong Kee JANG ; Jung Hyun JO ; Jae Min LEE ; Eui Joo KIM ; Sung Yong HAN ; Young Hoon CHOI ; Hyung-Il SEO ; Dong Ho LEE ; Hong Sik LEE
Gut and Liver 2023;17(1):34-48
Acute pancreatitis can range from a mild, self-limiting disease requiring no more than supportive care, to severe disease with life-threatening complications. With the goal of providing a recommendation framework for clinicians to manage acute pancreatitis, and to contribute to improvements in national health care, the Korean Pancreatobiliary Association (KPBA) established the Korean guidelines for acute pancreatitis management in 2013. However, many challenging issues exist which often lead to differences in clinical practices. In addition, with newly obtained evidence regarding acute pancreatitis, there have been great changes in recent knowledge and information regarding this disorder. Therefore, the KPBA committee underwent an extensive revision of the guidelines. The revised guidelines were developed using the Delphi method, and the main topics of the guidelines include the following: diagnosis, severity assessment, initial treatment, nutritional support, convalescent treatment, and the treatment of local complications and necrotizing pancreatitis. Specific recommendations are presented, along with the evidence levels and recommendation grades.
10.Deep Learning-Based Computed Tomography Image Standardization to Improve Generalizability of Deep Learning-Based Hepatic Segmentation
Seul Bi LEE ; Youngtaek HONG ; Yeon Jin CHO ; Dawun JEONG ; Jina LEE ; Soon Ho YOON ; Seunghyun LEE ; Young Hun CHOI ; Jung-Eun CHEON
Korean Journal of Radiology 2023;24(4):294-304
Objective:
We aimed to investigate whether image standardization using deep learning-based computed tomography (CT) image conversion would improve the performance of deep learning-based automated hepatic segmentation across various reconstruction methods.
Materials and Methods:
We collected contrast-enhanced dual-energy CT of the abdomen that was obtained using various reconstruction methods, including filtered back projection, iterative reconstruction, optimum contrast, and monoenergetic images with 40, 60, and 80 keV. A deep learning based image conversion algorithm was developed to standardize the CT images using 142 CT examinations (128 for training and 14 for tuning). A separate set of 43 CT examinations from 42 patients (mean age, 10.1 years) was used as the test data. A commercial software program (MEDIP PRO v2.0.0.0, MEDICALIP Co. Ltd.) based on 2D U-NET was used to create liver segmentation masks with liver volume. The original 80 keV images were used as the ground truth. We used the paired t-test to compare the segmentation performance in the Dice similarity coefficient (DSC) and difference ratio of the liver volume relative to the ground truth volume before and after image standardization. The concordance correlation coefficient (CCC) was used to assess the agreement between the segmented liver volume and ground-truth volume.
Results:
The original CT images showed variable and poor segmentation performances. The standardized images achieved significantly higher DSCs for liver segmentation than the original images (DSC [original, 5.40%–91.27%] vs. [standardized, 93.16%–96.74%], all P < 0.001). The difference ratio of liver volume also decreased significantly after image conversion (original, 9.84%–91.37% vs. standardized, 1.99%–4.41%). In all protocols, CCCs improved after image conversion (original, -0.006–0.964 vs. standardized, 0.990–0.998).
Conclusion
Deep learning-based CT image standardization can improve the performance of automated hepatic segmentation using CT images reconstructed using various methods. Deep learning-based CT image conversion may have the potential to improve the generalizability of the segmentation network.

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