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.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.
3.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.
4.Nation-Wide Retrospective Analysis of Allogeneic Stem Cell Transplantation in Patients with Multiple Myeloma: A Study from Korean Multiple Myeloma Working Party (KMM1913)
Ho-Jin SHIN ; Do-Young KIM ; Kihyun KIM ; Chang-Ki MIN ; Je-Jung LEE ; Yeung-Chul MUN ; Won-Sik LEE ; Sung-Nam LIM ; Jin Seok KIM ; Joon Ho MOON ; Da Jung KIM ; Soo-Mee BANG ; Jong-Ho WON ; Jae-Cheol JO ; Young Il KOH
Cancer Research and Treatment 2024;56(3):956-966
Purpose:
The role of allogeneic stem cell transplantation (alloSCT) in multiple myeloma (MM) treatment remains controversial. We conducted a retrospective, multicenter, nationwide study in Korea to evaluate the outcomes of alloSCT in Asian patients with MM.
Materials and Methods:
Overall, 109 patients with MM who underwent alloSCT between 2003 and 2020 were included in this study. Data were collected from the Korean Multiple Myeloma Working Party Registry.
Results:
The overall response rate and stringent complete response plus complete response (CR) rates were 67.0 and 46.8%, respectively, after alloSCT. At a median follow-up of 32.5 months, the 3-year probability of progression-free survival (PFS) and overall survival (OS) rates were 69.3% and 71.8%, respectively. The 3-year probabilities of OS rates in the upfront alloSCT, tandem auto-alloSCT, and later alloSCT groups were 75.0%, 88.9%, and 61.1%, respectively. Patients who achieved CR before or after alloSCT had significantly longer OS (89.8 vs. 18 months and 89.8 vs. 15.2 months, respectively). Even though patients who did not achieve CR prior to alloSCT, those who achieve CR after alloSCT had improved PFS and OS compared to those who had no achievement of CR both prior and after alloSCT. Patients who underwent alloSCT with 1-2 prior treatment lines had improved PFS (22.4 vs. 4.5 months) and OS (45.6 vs. 15.3 months) compared to those with three or more prior treatment lines.
Conclusion
AlloSCT may be a promising therapeutic option especially for younger, chemosensitive patients with earlier implementation from relapse.
5.Management of immune thrombocytopenia: 2022 update of Korean experts recommendations
Young Hoon PARK ; Dae-Young KIM ; Seongkoo KIM ; Young Bae CHOI ; Dong-Yeop SHIN ; Jin Seok KIM ; Won Sik LEE ; Yeung-Chul MUN ; Jun Ho JANG ; Jong Wook LEE ; Hoon KOOK ;
Blood Research 2022;57(1):20-28
Despite the availability of therapies to treat patients with immune thrombocytopenia (ITP), there is currently little data from randomized trials to assist clinicians in managing patients. The evidence-based guidelines of the Korean Society of Hematology Aplastic Anemia Working Party (KSHAAWP) are intended to support patients and physicians in the management of ITP. Experts from the KSHAAWP discussed and described this guideline according to the current treatment situation for ITP in Korea and finalized the guidelines. The expert panel recommended the management of ITP in adult and pediatric patients with newly diagnosed, persistent, and chronic disease refractory to first-line therapy with minor bleeding. Management approaches include observation and administration of corticosteroids, intravenous immunoglobulin, anti-D immunoglobulin, and thrombopoietin receptor agonists. Currently, evidence supporting strong recommendations for various management approaches is lacking. Therefore, a large focus was placed on shared decision-making, especially regarding second-line treatment.
6.Risk Factors for Coronavirus Disease 2019 (COVID-19)-Associated Pulmonary Aspergillosis in Critically Ill Patients: A Nationwide, Multicenter, Retrospective Cohort Study
Si-Ho KIM ; Jin Yeong HONG ; Seongman BAE ; Hojin LEE ; Yu Mi WI ; Jae-Hoon KO ; Bomi KIM ; Eun-Jeong JOO ; Hyeri SEOK ; Hye Jin SHI ; Jeong Rae YOO ; Miri HYUN ; Hyun ah KIM ; Sukbin JANG ; Seok Jun MUN ; Jungok KIM ; Min-Chul KIM ; Dong-Sik JUNG ; Sung-Han KIM ; Kyong Ran PECK
Journal of Korean Medical Science 2022;37(18):e134-
Background:
Coronavirus disease 2019 (COVID-19) is often accompanied by secondary infections, such as invasive aspergillosis. In this study, risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA) and their clinical outcomes were evaluated.
Methods:
This multicenter retrospective cohort study included critically ill COVID-19 patients from July 2020 through March 2021. Critically ill patients were defined as patients requiring high-flow respiratory support or mechanical ventilation. CAPA was defined based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. Factors associated with CAPA were analyzed, and their clinical outcomes were adjusted by a propensity score-matched model.
Results:
Among 187 eligible patients, 17 (9.1%) developed CAPA, which is equal to 33.10 per 10,000 patient-days. Sixteen patients received voriconazole-based antifungal treatment. In addition, 82.4% and 53.5% of patients with CAPA and without CAPA, respectively, received early high-dose corticosteroids (P = 0.022). In multivariable analysis, initial 10-day cumulative steroid dose > 60 mg of dexamethasone or dexamethasone equivalent dose) (adjusted odds ratio [OR], 3.77; 95% confidence interval [CI], 1.03–13.79) and chronic pulmonary disease (adjusted OR, 4.20; 95% CI, 1.26–14.02) were independently associated with CAPA. Tendencies of higher 90-day overall mortality (54.3% vs. 35.2%, P= 0.346) and lower respiratory support-free rate were observed in patients with CAPA (76.3% vs. 54.9%, P = 0.089).
Conclusion
Our study showed that the dose of corticosteroid use might be a risk factor for CAPA development and the possibility of CAPA contributing to adverse outcomes in critically ill COVID-19 patients.
7.The Pattern of Care for Brain Metastasis from Breast Cancer over the Past 10 Years in Korea: A Multicenter Retrospective Study (KROG 16-12)
Jae Sik KIM ; Kyubo KIM ; Wonguen JUNG ; Kyung Hwan SHIN ; Seock-Ah IM ; Hee-Jun KIM ; Yong Bae KIM ; Jee Suk CHANG ; Jee Hyun KIM ; Doo Ho CHOI ; Yeon Hee PARK ; Dae Yong KIM ; Tae Hyun KIM ; Byung Ock CHOI ; Sea-Won LEE ; Suzy KIM ; Jeanny KWON ; Ki Mun KANG ; Woong-Ki CHUNG ; Kyung Su KIM ; Ji Ho NAM ; Won Sup YOON ; Jin Hee KIM ; Jihye CHA ; Yoon Kyeong OH ; In Ah KIM
Cancer Research and Treatment 2022;54(4):1121-1129
Purpose:
We aimed to investigate manifestations and patterns of care for patients with brain metastasis (BM) from breast cancer (BC) and compared their overall survival (OS) from 2005 through 2014 in Korea.
Materials and Methods:
We retrospectively reviewed 600 BC patients with BM diagnosed between 2005 and 2014. The median follow-up duration was 12.5 months. We categorized the patients into three groups according to the year when BM was initially diagnosed (group I [2005-2008], 98 patients; group II [2009-2011], 200 patients; and group III [2012-2014], 302 patients).
Results:
Over time, the median age at BM diagnosis increased by 2.2 years (group I, 49.0 years; group II, 48.3 years; and group III, 51.2 years; p=0.008). The percentage of patients with extracranial metastasis was 73.5%, 83.5%, and 86.4% for group I, II, and III, respectively (p=0.011). The time interval between BC and BM was prolonged in patients with stage III primary BC (median, 2.4 to 3 years; p=0.029). As an initial brain-directed treatment, whole-brain radiotherapy alone decreased from 80.0% in 2005 to 41.1% in 2014. Meanwhile, stereotactic radiosurgery or fractionated stereotactic radiotherapy alone increased from 13.3% to 34.7% during the same period (p=0.005). The median OS for group I, II, and III was 15.6, 17.9, and 15.0 months, respectively, with no statistical significance.
Conclusion
The manifestations of BM from BC and the pattern of care have changed from 2005 to 2014 in Korea. However, the OS has remained relatively unchanged over the 10 years.
8.Clinically Significant Monocyte Biomarker for Differential Diagnosis of COVID-19 Pneumonia in the Emergency Department
Hyo-Won KIM ; Jae Cheon JEON ; Woo Ik CHOI ; Ji Yeon LEE ; Yong Sik KWON ; Mi Jin LEE ; Jae Wan CHO ; Gyunmoo KIM ; You Ho MUN ; Sang-Hun LEE
Keimyung Medical Journal 2021;40(1):26-31
Objectives:
To determine basic patient characteristics and biomarkers to help in the early diagnosis of Coronavirus disease 2019 (COVID-19) pneumonia in patients with pneumonia who visited the emergency department (ED).
Methods:
This retrospective study evaluated patients diagnosed with community-acquired pneumonia (CAP) or COVID-19 pneumonia in ED at four tertiary medical centers between February 1 and March 31, 2020. Parameters related to the differential diagnosis between CAP and COVID-19 were investigated. Clinical characteristics and laboratory results of biomarkers were analyzed.
Results:
In total, 81 patients presented to the ED with COVID-19 pneumonia. Multivariate logistic regression analysis showed that monocyte count [odds ratio (OR): 0.996; 95% confidence interval (CI): 0.994–0.999] and pneumonia severity index (PSI) [OR: 1.025; 95% CI: 1.002–1.049] were associated with diagnosis of COVID-19 pneumonia. The area under the curve comprising the combination of monocyte and PSI was 0.789.
Conclusion
Differential diagnosis of COVID-19 pneumonia from pneumonia patients who visited the emergency room can be made by monocyte count and PSI score.
9.Clinically Significant Monocyte Biomarker for Differential Diagnosis of COVID-19 Pneumonia in the Emergency Department
Hyo-Won KIM ; Jae Cheon JEON ; Woo Ik CHOI ; Ji Yeon LEE ; Yong Sik KWON ; Mi Jin LEE ; Jae Wan CHO ; Gyunmoo KIM ; You Ho MUN ; Sang-Hun LEE
Keimyung Medical Journal 2021;40(1):26-31
Objectives:
To determine basic patient characteristics and biomarkers to help in the early diagnosis of Coronavirus disease 2019 (COVID-19) pneumonia in patients with pneumonia who visited the emergency department (ED).
Methods:
This retrospective study evaluated patients diagnosed with community-acquired pneumonia (CAP) or COVID-19 pneumonia in ED at four tertiary medical centers between February 1 and March 31, 2020. Parameters related to the differential diagnosis between CAP and COVID-19 were investigated. Clinical characteristics and laboratory results of biomarkers were analyzed.
Results:
In total, 81 patients presented to the ED with COVID-19 pneumonia. Multivariate logistic regression analysis showed that monocyte count [odds ratio (OR): 0.996; 95% confidence interval (CI): 0.994–0.999] and pneumonia severity index (PSI) [OR: 1.025; 95% CI: 1.002–1.049] were associated with diagnosis of COVID-19 pneumonia. The area under the curve comprising the combination of monocyte and PSI was 0.789.
Conclusion
Differential diagnosis of COVID-19 pneumonia from pneumonia patients who visited the emergency room can be made by monocyte count and PSI score.
10.Reduced-Intensity Conditioning with Busulfan and Fludarabine for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Lymphoblastic Leukemia
Seung-Shin LEE ; Sung-Hoon JUNG ; Young Rok DO ; Dae Sik KIM ; Ji Hyun LEE ; Han-Seung PARK ; Joon Ho MOON ; Jun Ho YI ; Yong PARK ; Youngil KOH ; Ho-Young YHIM ; Yunsuk CHOI ; Yeung-Chul MUN ; Won-Sik LEE ; Seok LEE ; Deok-Hwan YANG ;
Yonsei Medical Journal 2020;61(6):452-459
Purpose:
Allogeneic hematopoietic stem cell transplantation (HSCT) with optimal conditioning has helped better long-term survival in acute lymphoblastic leukemia (ALL). This study investigated the efficacy and safety of reduced-intensity conditioning (RIC) with busulfan and fludarabine in adult ALL patients unfit for myeloablation.
Materials and Methods:
Records of 78 patients who underwent HSCT with RIC consisting of 3.2 mg/kg/day of busulfan for 2 or 3 days and 30 mg/m2/day of fludarabine for 5 or 6 days were analyzed.
Results:
The median age at diagnosis was 49 years. Over a median follow-up of 22 months, 2-year estimates of relapse-free survival (RFS) and overall survival were 57.4% and 68.7%, respectively. Multivariate analysis showed a trend of improved RFS in patients with chronic graft-versus-host disease (GVHD) (hazard ratio, 0.53; 95% confidence interval, 0.26–1.08; p=0.080). The cumulative incidences of relapse and non-relapse mortality were 42.9% and 19.6%, respectively and one case of central nervous system relapse was noted. No hepatic veno-occlusive disease was reported. Grade II–IV acute GVHD and any grade chronic GVHD occurred in 21.1% and 41.7%, respectively.
Conclusion
RIC with busulfan and fludarabine is an effective and safe conditioning regimen for adult ALL patients unfit for myeloablation.

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