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.Surgical outcome and risk scoring to predict survival after hepatic resection for hepatocellular carcinoma with portal vein tumor thrombosis
Tae-Seok KIM ; Kwangho YANG ; Gi Hong CHOI ; Hye Yeon YANG ; Dong-Sik KIM ; Hye-Sung JO ; Gyu-Seong CHOI ; Kwan Woo KIM ; Young Chul YOON ; Jaryung HAN ; Doo Jin KIM ; Shin HWANG ; Koo Jeong KANG
Annals of Hepato-Biliary-Pancreatic Surgery 2024;28(2):134-143
Background:
s/Aims: The hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is classified as the advanced stage (BCLC stage C) with extremely poor prognosis, and in current guidelines is recommended for systemic therapy. This study aimed to evaluate the surgical outcomes and long-term prognosis after hepatic resection (HR) for patients who have HCC combined with PVTT.
Methods:
We retrospectively analyzed 332 patients who underwent HR for HCC with PVTT at ten tertiary referral hospitals in South Korea.
Results:
The median overall and recurrence-free survival after HR were 32.4 and 8.6 months, while the 1-, 3-, and 5-year overall survival rates were 75%, 48%, and 39%, respectively. In multivariate analysis, tumor number, tumor size, AFP, PIVKA−II, neutrophil-to-lymphocyte ratio, and albumin–bilirubin (ALBI) grade were significant prognostic factors. The risk scoring was developed using these seven factors–tumor, inflammation and hepatic function (TIF), to predict patient prognosis. The prognosis of the patients was well stratified according to the scores (log-rank test, p < 0.001).
Conclusions
HR for patients who have HCC combined with PVTT provided favorable survival outcomes. The risk scoring was useful in predicting prognosis, and determining the appropriate treatment strategy for those patients who have HCC with PVTT.
5.Epidemiology and Characteristics of Ankle and Foot Injuries in Electric Scooter-Related Accidents
Tae Gyun KIM ; Jae Gyu CHOI ; Youn Moo HEO ; Jin Woong YI ; In Uk YEO ; Hyun Sik RYU ; Hyun Soo CHOI ; Jae Hwang SONG
Clinics in Orthopedic Surgery 2024;16(2):326-334
Background:
The use of electric scooters (e-scooters) continues to increase as a simple, inexpensive means of transport, resulting in a sharp increase in the incidence of scooter-related accidents. No study to date has closely examined the injury extent to the lower leg, joints, and extremities from e-scooter-related accidents. Here, we investigated the epidemiology and injury patterns of such accidents, focusing on injuries to the ankle and foot.
Methods:
Based on data from a single tertiary hospital’s database, the demographics of 563 patients with scooter-associated injuries were analyzed retrospectively. Among the patients, 229 patients who were injured by e-scooter riding were further investigated. Based on the data, the general demographics of whole scooter-associated injuries and the injury characteristics and fracture cases of the lower leg, ankle, and foot were analyzed.
Results:
During the 4-year study period, the number of patients injured by e-scooters increased every year. Lower extremities were the most common injury site (67.2%) among riders, whereas injuries to the head and neck (64.3%) were more common in riders of non-electric scooters. Among the lower leg, ankle, and foot injuries of riders (52 cases), the ankle joint (53.8%) was the most commonly injured site, followed by the foot (40.4%) and lower leg (21.2%). The fracture group scored significantly higher on the Abbreviated Injury Scale than the non-fracture group (p < 0.001). Among the fracture group (20 cases), ankle fractures (9 cases) were most common, including pronation external rotation type 4 injuries (4 cases) and pilon fractures (2 cases). Five patients (25%) had open fractures, and 12 patients (60%) underwent surgical treatment.
Conclusions
The ankle and foot are the most common injury sites in e-scooter-related accidents. Given the high frequency and severity of e-scooter-related ankle and foot injuries, we suggest that more attention be paid to preventing these types of injuries with greater public awareness of the dangers of using e-scooters.
6.Oxidized LDL Accelerates CartilageDestruction and Inflammatory Chondrocyte Death in Osteoarthritis by Disrupting the TFEB-Regulated Autophagy-Lysosome Pathway
Jeong Su LEE ; Yun Hwan KIM ; JooYeon JHUN ; Hyun Sik NA ; In Gyu UM ; Jeong Won CHOI ; Jin Seok WOO ; Seung Hyo KIM ; Asode Ananthram SHETTY ; Seok Jung KIM ; Mi-La CHO
Immune Network 2024;24(3):e15-
Osteoarthritis (OA) involves cartilage degeneration, thereby causing inflammation and pain. Cardiovascular diseases, such as dyslipidemia, are risk factors for OA; however, the mechanism is unclear. We investigated the effect of dyslipidemia on the development of OA. Treatment of cartilage cells with low-density lipoprotein (LDL) enhanced abnormal autophagy but suppressed normal autophagy and reduced the activity of transcription factor EB (TFEB), which is important for the function of lysosomes. Treatment of LDL-exposed chondrocytes with rapamycin, which activates TFEB, restored normal autophagy. Also, LDL enhanced the inflammatory death of chondrocytes, an effect reversed by rapamycin. In an animal model of hyperlipidemia-associated OA, dyslipidemia accelerated the development of OA, an effect reversed by treatment with a statin, an anti-dyslipidemia drug, or rapamycin, which activates TFEB. Dyslipidemia reduced the autophagic flux and induced necroptosis in the cartilage tissue of patients with OA. The levels of triglycerides, LDL, and total cholesterol were increased in patients with OA compared to those without OA. The C-reactive protein level of patients with dyslipidemia was higher than that of those without dyslipidemia after total knee replacement arthroplasty. In conclusion, oxidized LDL, an important risk factor of dyslipidemia, inhibited the activity of TFEB and reduced the autophagic flux, thereby inducing necroptosis in chondrocytes.
7.A Randomized, Double-Blind, Active-Control, Noninferiority, Multicenter, Phase 4 Study to Evaluate the Efficacy and Safety of Esomeprazole/Sodium Bicarbonate 20/800 mg in Patients with Nonerosive Gastroesophageal Reflux Disease
Su Hyun PARK ; Kang Nyeong LEE ; Oh Young LEE ; Myung Gyu CHOI ; Jie-Hyun KIM ; In-Kyung SUNG ; Jae Young JANG ; Kyung Sik PARK ; Hoon Jai CHUN ; Eun Young KIM ; Jun Kyu LEE ; Jin Seok JANG ; Gwang Ha KIM ; Su Jin HONG ; Yong Chan LEE ; Suck-Chei CHOI ; Hyun Soo KIM ; Tae Oh KIM ; Gwang Ho BAIK ; Yong Cheol JEON
Gut and Liver 2023;17(2):226-233
Background/Aims:
Efficacy of proton pump inhibitors is limited in patients with nonerosive reflux disease (NERD). The aim of this study was to comparatively evaluate the efficacy and safety of esomeprazole with sodium bicarbonate and esomeprazole alone.
Methods:
This was a multicenter, randomized, double-blind, active-controlled, noninferiority comparative study. A total of 379 patients with NERD were randomly allocated to receive either EsoduoⓇ/sup> (esomeprazole 20 mg with sodium bicarbonate 800 mg) or NexiumⓇ/sup> (esomeprazole 20 mg) once daily for 4 weeks from January 2019 to December 2019. The patients had a history of heartburn for at least 2 days in the week before randomization as well as in the last 3 months and no esophageal mucosal breaks on endoscopy. The primary endpoint was a complete cure of heartburn at week 4. The secondary and exploratory endpoints as well as the safety profiles were compared in the groups at weeks 2 and 4.
Results:
A total of 355 patients completed the study (180 in the EsoduoⓇ/sup> group and 175 in the NexiumⓇ/sup> group). The proportions of patients without heartburn in the entire 4th week of treatment were not different between the two groups (33.33% in the EsoduoⓇ/sup> group and 35% in the NexiumⓇ/sup> group, p=0.737). There were no significant differences in most of the secondary and exploratory endpoints as well as the safety profiles.
Conclusions
EsoduoⓇ/sup> is as effective and safe as NexiumⓇ/sup> for managing typical symptoms in patients with NERD (ClinicalTrial.gov identifier: NCT03928470).
8.Prevalence and impact of airway diseases on clinical outcomes in idiopathic pulmonary fibrosis
Heemoon PARK ; Jaeyoung CHO ; Jinwoo LEE ; Young Sik PARK ; Chang-Hoon LEE ; Sang-Min LEE ; Chul-Gyu YOO ; Young Whan KIM ; Sung Koo HAN ; Sun Mi CHOI
The Korean Journal of Internal Medicine 2022;37(2):387-397
Background/Aims:
The prevalence and effects of airway diseases, including asthma, eosinophilic bronchitis (EB), chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO) have not been thoroughly studied in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to evaluate the prevalence of airway diseases in patients with IPF and to identify the differences in symptoms based on the presence of airway diseases.
Methods:
This single-institution prospective cohort study was conducted from June 2017 to September 2018, at the Seoul National University Hospital. Spirometry with bronchodilator, methacholine bronchial provocation test, induced sputum with eosinophil stain, and exhaled nitric oxide were performed to confirm the presence of airway disease. The modified Medical Research Council (mMRC) dyspnea scale, COPD assessment test (CAT), St. George’s Respiratory Questionnaire (SGRQ), EuroQol-5 dimension (EQ-5D) index, and cough-specific quality of life questionnaire (CQLQ) data were collected to assess symptom severity.
Results:
Total 147 patients with IPF were screened, and 70 patients were analyzed. The prevalence of airway diseases in the participants was as follows: 5.0% had COPD, 1.7% had asthma, 3.3% had ACO, and 1.7% had EB. The mMRC, CAT, SGRQ, EQ-5D, and CQLQ scores did not differ regardless of combined airway disease. After 3 months, the SGRQ (p = 0.028) and CQLQ (p = 0.030) scores were significantly higher in patients with airway disease than in those without.
Conclusions
The prevalence of airway diseases in patients with IPF is low, but when airway diseases are accompanied by IPF, symptom severity and quality of life may worsen rapidly.
9.Safety and efficacy of nilotinib in adult patients with chronic myeloid leukemia: a post-marketing surveillance study in Korea
Seo-Yeon AHN ; Sang Kyun SON ; Gyu Hyung LEE ; Inho KIM ; June-Won CHEONG ; Won Sik LEE ; Byung Soo KIM ; Deog-Yeon JO ; Chul Won JUNG ; Chu Myoung SEONG ; Jae Hoon LEE ; Young Jin YUH ; Min Kyoung KIM ; Hun-Mo RYOO ; Moo-Rim PARK ; Su-Hee CHO ; Hoon-Gu KIM ; Dae Young ZANG ; Jinny PARK ; Hawk KIM ; Seryeon LEE ; Sung-Hyun KIM ; Myung Hee CHANG ; Ho Sup LEE ; Chul Won CHOI ; Jihyun KWON ; Sung-Nam LIM ; Suk-Joong OH ; Inkyung JOO ; Dong-Wook KIM
Blood Research 2022;57(2):144-151
Background:
Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea.
Methods:
An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph + CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response.
Results:
During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients).
Conclusion
This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph + CML in routine clinical practice settings.
10.The importance of muscle mass in predicting intradialytic hypotension in patients undergoing maintenance hemodialysis
Hyung Eun SON ; Ji Young RYU ; Kyunghoon LEE ; Young Il CHOI ; Myeong Sung KIM ; Inwhee PARK ; Gyu Tae SHIN ; Heungsoo KIM ; Curie AHN ; Sejoong KIM ; Ho Jun CHIN ; Ki Young NA ; Dong-Wan CHAE ; Soyeon AHN ; Seung Sik HWANG ; Jong Cheol JEONG
Kidney Research and Clinical Practice 2022;41(5):611-622
Patients undergoing hemodialysis are susceptible to sarcopenia. As intracellular reservoirs of water, skeletal muscles are important contributors to intradialytic hypotension. This study was designed to determine the role of skeletal muscle mass in intradialytic hypotension. Methods: In a cross-sectional study, the body composition of 177 patients was measured immediately after hemodialysis using bioelectrical impedance analysis. The parameters measured were skeletal muscle mass, intracellular and extracellular water contents, total body water, and cell-membrane functionality (in phase angle at 50 kHz). Data from laboratory tests, chest radiography, measurements of handgrip strength and mid-arm circumference, and questionnaires were collected. The main outcome was intradialytic hypotension, defined as more than two episodes of hypotension (systolic blood pressure of <90 mmHg) with intervention over the 3 months following enrollment. Logistic regression models including each parameter related to sarcopenia were compared with a clinical model. Results: Patients with a low ratio of skeletal muscle mass to dry body weight (SMM/WT) had a higher rate of intradialytic hypotension (40.7%). Most low-SMM/WT patients were female, obese, diabetic, and had a lower handgrip strength compared with the other patients. In the high-SMM/WT group, the risk of intradialytic hypotension was lower, with an odds ratio of 0.08 (95% confidence interval [CI], 0.02–0.28) and adjusted odds ratio of 0.06 (95% CI, 0.01–0.29). Conclusion: Measurement and maintenance of skeletal muscle can help prevent intradialytic hypotension in frail patients undergoing hemodialysis.

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