1.A Phase 3 Randomized Clinical Trial to Compare Efficacy and Safety between Combination Therapy and Monotherapy in Elderly Patients with Advanced Gastric Cancer (KCSG ST13-10)
Keun-Wook LEE ; Dae Young ZANG ; Min-Hee RYU ; Hye Sook HAN ; Ki Hyang KIM ; Mi-Jung KIM ; Sung Ae KOH ; Sung Sook LEE ; Dong-Hoe KOO ; Yoon Ho KO ; Byeong Seok SOHN ; Jin Won KIM ; Jin Hyun PARK ; Byung-Ho NAM ; In Sil CHOI
Cancer Research and Treatment 2023;55(4):1250-1260
Purpose:
This study evaluated whether combination therapy is more effective than monotherapy in elderly patients with metastatic or recurrent gastric cancer (MRGC) as first-line chemotherapy.
Materials and Methods:
Elderly (≥ 70 years) chemo-naïve patients with MRGC were allocated to receive either combination therapy (group A: 5-fluorouracil [5-FU]/oxaliplatin, capecitabine/oxaliplatin, capecitabine/cisplatin, or S-1/cisplatin) or monotherapy (group B: 5-FU, capecitabine, or S-1). In group A, starting doses were 80% of standard doses, and they could be escalated to 100% at the discretion of the investigator. Primary endpoint was to confirm superior overall survival (OS) of combination therapy vs. monotherapy.
Results:
After 111 of the planned 238 patients were randomized, enrollment was terminated due to poor accrual. In the full-analysis population (group A [n=53] and group B [n=51]), median OS of combination therapy vs. monotherapy was 11.5 vs. 7.5 months (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.56 to 1.30; p=0.231). Median progression-free survival (PFS) was 5.6 vs. 3.7 months (HR, 0.53; 95% CI, 0.34 to 0.83; p=0.005). In subgroup analyses, patients aged 70-74 years tended to have superior OS with combination therapy (15.9 vs. 7.2 months, p=0.056). Treatment-related adverse events (TRAEs) occurred more frequently in group A vs. group B. However, among severe TRAEs (≥ grade 3), there were no TRAEs with a frequency difference of > 5%.
Conclusion
Combination therapy was associated with numerically improved OS, although statistically insignificant, and a significant PFS benefit compared with monotherapy. Although combination therapy showed more frequent TRAEs, there was no difference in the frequency of severe TRAEs.
2.Modified Cardiovascular Sequential Organ Failure Assessment Score in Sepsis: External Validation in Intensive Care Unit Patients
Byuk Sung KO ; Seung Mok RYOO ; Eunah HAN ; Hyunglan CHANG ; Chang June YUNE ; Hui Jai LEE ; Gil Joon SUH ; Sung-Hyuk CHOI ; Sung Phil CHUNG ; Tae Ho LIM ; Won Young KIM ; Jang Won SOHN ; Mi Ae JEONG ; Sung Yeon HWANG ; Tae Gun SHIN ; Kyuseok KIM ; On behalf of Korean Shock Society
Journal of Korean Medical Science 2023;38(50):e418-
Background:
There is a need to update the cardiovascular (CV) Sequential Organ Failure Assessment (SOFA) score to reflect the current practice in sepsis. We previously proposed the modified CV SOFA score from data on blood pressure, norepinephrine equivalent dose, and lactate as gathered from emergency departments. In this study, we externally validated the modified CV SOFA score in multicenter intensive care unit (ICU) patients.
Methods:
A multicenter retrospective observational study was conducted on ICU patients at six hospitals in Korea. We included adult patients with sepsis who were admitted to ICUs. We compared the prognostic performance of the modified CV/total SOFA score and the original CV/total SOFA score in predicting 28-day mortality. Discrimination and calibration were evaluated using the area under the receiver operating characteristic curve (AUROC) and the calibration curve, respectively.
Results:
We analyzed 1,015 ICU patients with sepsis. In overall patients, the 28-day mortality rate was 31.2%. The predictive validity of the modified CV SOFA (AUROC, 0.712; 95% confidence interval [CI], 0.677–0.746; P < 0.001) was significantly higher than that of the original CV SOFA (AUROC, 0.644; 95% CI, 0.611–0.677). The predictive validity of modified total SOFA score for 28-day mortality was significantly higher than that of the original total SOFA (AUROC, 0.747 vs. 0.730; 95% CI, 0.715–0.779; P = 0.002). The calibration curve of the original CV SOFA for 28-day mortality showed poor calibration. In contrast, the calibration curve of the modified CV SOFA for 28-day mortality showed good calibration.
Conclusion
In patients with sepsis in the ICU, the modified SOFA score performed better than the original SOFA score in predicting 28-day mortality.
3.Reducing Microbial Contamination in Hematopoietic Stem Cell Products and Quality Improvement Strategy: Retrospective Analysis of 1996-2021 Data
You Keun KO ; Jong Kwon LEE ; Hye Kyung PARK ; Ae Kyung HAN ; Sun Kyoung MUN ; Hye Jeong PARK ; Hae Kyoung CHOUNG ; Se Mi KIM ; Kwang Mo CHOI ; Nam Yong LEE ; Duck CHO ; Dae Won KIM ; Eun-Suk KANG
Annals of Laboratory Medicine 2023;43(5):477-484
Background:
Sterility and safety assurance of hematopoietic stem cell (HSC) products is critical in transplantation. Microbial contamination can lead to product disposal and increases the risk of unsuccessful clinical outcomes. Therefore, it is important to implement and maintain good practice guidelines and regulations for the HSC collection and processing unit in each hospital. We aimed to share our experiences and suggest strategies to improve the quality assurance of HSC processing.
Methods:
We retrospectively analyzed microbial culture results of 11,743 HSC products processed over a 25-year period (January 1996 to May 2021). Because of reorganization of the HSC management system in 2008, the 25-year period was divided into periods 1 (January 1996 to December 2007) and 2 (January 2008 to May 2021). We reviewed all culture results of the HSC products and stored aliquot samples and collected culture results for peripheral blood and catheter samples.
Results:
Of the 11,743 products in total, 35 (0.3%) were contaminated by microorganisms, including 19 (0.5%) of 3,861 products during period 1 and 16 (0.2%) of 7,882 products during period 2. Penicillium was the most commonly identified microorganism (15.8%) during period 1 and coagulase-negative Staphylococcus was the most commonly identified (31.3%) during period 2. HSC product contamination occurred most often during HSC collection and processing.
Conclusions
The contamination rate decreased significantly during period 2, when the HSC management system was reorganized. Our results imply that handling HSC products by trained personnel and adopting established protocols, including quality assurance programs, aid in decreasing the contamination risk.
4.Effects of Iron Dietary Supplements to Prevent Iron Deficiency in Repeat Blood Donors
Ja Young LEE ; Jae Sook LEE ; Deuk Yeong KO ; Ji Yeong SEON ; Jin Hyuk YANG ; Jun Nyun KIM ; Mi Ae YOUN
Korean Journal of Blood Transfusion 2021;32(2):102-111
Background:
The purpose of this study was to prepare data for the prevention and management of iron deficiency by analyzing the effects of taking iron supplements provided by blood centers for repeat blood donors.
Methods:
The high-risk groups with a potential iron deficiency were defined as three or more whole blood donations within the previous year and were provided with iron supplements for three months. Their hemoglobin and ferritin levels were checked up once a month for six months. The effectiveness of the iron supplements was evaluated by analyzing the changes in the initial and monthly hemoglobin and ferritin results.
Results:
At the time of recruitments, an average 50.4% (40.8% of men and 65.3% of women, respectively) of participants had ferritin levels of less than 15 ng/mL, the World Health Organization iron deficiency standard, but after three months iron supplementation, the results decreased to 10.9% (9.0% of men and 13.8% of women). The ferritin levels increased significantly after taking iron supplements for three months and showed significant increases in both men and women, particularly after two months (P<0.05).
Conclusion
The dietary iron supplements containing low-dose iron were effective in preventing iron deficiency in repeat blood donors by increasing the ferritin levels.
5.Spontaneous Rupture of the Right Gastroepiploic Artery Immediately after Gastroscopy
Do Young JUNG ; Hye-kyung JUNG ; Yun Mi KO ; Ayoung LEE ; Ji Taek HONG ; Chang Mo MOON ; Seong Eun KIM ; Chung Hyun TAE ; Ki Nam SHIM ; Sung Ae JUNG ; Ran KIM ; Sun Young CHOI
The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2021;21(3):235-238
Idiopathic spontaneous intraperitoneal hemorrhage is both rare and potentially fatal. The incidence of gastroepiploic artery rupture, especially a non-aneurysmal rupture, is extremely low. We report the case of an elderly woman who was mistakenly diagnosed with procedure-related bleeding after gastroscopy. A 0.3 cm polyp was identified and removed during the procedure. The patient later developed shock due to which gastroscopy was repeated; however, no unusual findings were observed. Therefore, abdominopelvic computerized tomography was performed and gastroepiploic artery rupture was detected. Transcatheter arterial embolization was immediately performed without laparotomy, without any complications. The bleeding was controlled, and the patient was discharged after embolization. It is important to acknowledge the possibility of spontaneous rupture of the visceral arteries in elderly individuals with hypertension or atherosclerosis, especially in the event of sudden abdominal pain or shock immediately after an endoscopic procedure. This is the first case report of idiopathic spontaneous rupture of the right gastroepiploic artery successfully managed by transcatheter arterial embolization in South Korea.
6.Downregulation of MicroRNA-495 Alleviates IL-1β Responses among Chondrocytes by Preventing SOX9 Reduction
Soyeong JOUNG ; Dong Suk YOON ; Sehee CHO ; Eun Ae KO ; Kyoung-Mi LEE ; Kwang Hwan PARK ; Jin Woo LEE ; Sung-Hwan KIM
Yonsei Medical Journal 2021;62(7):650-659
Purpose:
Our previous work demonstrated that miRNA-495 targets SOX9 to inhibit chondrogenesis of mesenchymal stem cells.In this study, we aimed to investigate whether miRNA-495-mediated SOX9 regulation could be a novel therapeutic target for osteoarthritis (OA) using an in vitro cell culture model.
Materials and Methods:
An in vitro model mimicking the OA environment was established using TC28a2 normal human chondrocyte cells. Interleukin-1β (IL-1β, 10 ng/mL) was utilized to induce inflammation-related changes in TC28a2 cells. Safranin O staining and glycosaminoglycan assay were used to detect changes in proteoglycans among TC28a2 cells. Expression levels of COX-2, ADAMTS5, MMP13, SOX9, CCL4, and COL2A1 were examined by qRT-PCR and/or Western blotting. Immunohistochemistry was performed to detect SOX9 and CCL4 proteins in human cartilage tissues obtained from patients with OA.
Results:
miRNA-495 was upregulated in IL-1β-treated TC28a2 cells and chondrocytes from damaged cartilage tissues of patients with OA. Anti-miR-495 abolished the effect of IL-1β in TC28a2 cells and rescued the protein levels of SOX9 and COL2A1, which were reduced by IL-1β. SOX9 was downregulated in the damaged cartilage tissues of patients with OA, and knockdown of SOX9 abolished the effect of anti-miR-495 on IL-1β-treated TC28a2 cells.
Conclusion
We demonstrated that inhibition of miRNA-495 alleviates IL-1β-induced inflammatory responses in chondrocytes by rescuing SOX9 expression. Accordingly, miRNA-495 could be a potential novel target for OA therapy, and the application of anti-miR-495 to chondrocytes could be a therapeutic strategy for treating OA.
7.Effects of Iron Dietary Supplements to Prevent Iron Deficiency in Repeat Blood Donors
Ja Young LEE ; Jae Sook LEE ; Deuk Yeong KO ; Ji Yeong SEON ; Jin Hyuk YANG ; Jun Nyun KIM ; Mi Ae YOUN
Korean Journal of Blood Transfusion 2021;32(2):102-111
Background:
The purpose of this study was to prepare data for the prevention and management of iron deficiency by analyzing the effects of taking iron supplements provided by blood centers for repeat blood donors.
Methods:
The high-risk groups with a potential iron deficiency were defined as three or more whole blood donations within the previous year and were provided with iron supplements for three months. Their hemoglobin and ferritin levels were checked up once a month for six months. The effectiveness of the iron supplements was evaluated by analyzing the changes in the initial and monthly hemoglobin and ferritin results.
Results:
At the time of recruitments, an average 50.4% (40.8% of men and 65.3% of women, respectively) of participants had ferritin levels of less than 15 ng/mL, the World Health Organization iron deficiency standard, but after three months iron supplementation, the results decreased to 10.9% (9.0% of men and 13.8% of women). The ferritin levels increased significantly after taking iron supplements for three months and showed significant increases in both men and women, particularly after two months (P<0.05).
Conclusion
The dietary iron supplements containing low-dose iron were effective in preventing iron deficiency in repeat blood donors by increasing the ferritin levels.
8.Spontaneous Rupture of the Right Gastroepiploic Artery Immediately after Gastroscopy
Do Young JUNG ; Hye-kyung JUNG ; Yun Mi KO ; Ayoung LEE ; Ji Taek HONG ; Chang Mo MOON ; Seong Eun KIM ; Chung Hyun TAE ; Ki Nam SHIM ; Sung Ae JUNG ; Ran KIM ; Sun Young CHOI
The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2021;21(3):235-238
Idiopathic spontaneous intraperitoneal hemorrhage is both rare and potentially fatal. The incidence of gastroepiploic artery rupture, especially a non-aneurysmal rupture, is extremely low. We report the case of an elderly woman who was mistakenly diagnosed with procedure-related bleeding after gastroscopy. A 0.3 cm polyp was identified and removed during the procedure. The patient later developed shock due to which gastroscopy was repeated; however, no unusual findings were observed. Therefore, abdominopelvic computerized tomography was performed and gastroepiploic artery rupture was detected. Transcatheter arterial embolization was immediately performed without laparotomy, without any complications. The bleeding was controlled, and the patient was discharged after embolization. It is important to acknowledge the possibility of spontaneous rupture of the visceral arteries in elderly individuals with hypertension or atherosclerosis, especially in the event of sudden abdominal pain or shock immediately after an endoscopic procedure. This is the first case report of idiopathic spontaneous rupture of the right gastroepiploic artery successfully managed by transcatheter arterial embolization in South Korea.
9.Downregulation of MicroRNA-495 Alleviates IL-1β Responses among Chondrocytes by Preventing SOX9 Reduction
Soyeong JOUNG ; Dong Suk YOON ; Sehee CHO ; Eun Ae KO ; Kyoung-Mi LEE ; Kwang Hwan PARK ; Jin Woo LEE ; Sung-Hwan KIM
Yonsei Medical Journal 2021;62(7):650-659
Purpose:
Our previous work demonstrated that miRNA-495 targets SOX9 to inhibit chondrogenesis of mesenchymal stem cells.In this study, we aimed to investigate whether miRNA-495-mediated SOX9 regulation could be a novel therapeutic target for osteoarthritis (OA) using an in vitro cell culture model.
Materials and Methods:
An in vitro model mimicking the OA environment was established using TC28a2 normal human chondrocyte cells. Interleukin-1β (IL-1β, 10 ng/mL) was utilized to induce inflammation-related changes in TC28a2 cells. Safranin O staining and glycosaminoglycan assay were used to detect changes in proteoglycans among TC28a2 cells. Expression levels of COX-2, ADAMTS5, MMP13, SOX9, CCL4, and COL2A1 were examined by qRT-PCR and/or Western blotting. Immunohistochemistry was performed to detect SOX9 and CCL4 proteins in human cartilage tissues obtained from patients with OA.
Results:
miRNA-495 was upregulated in IL-1β-treated TC28a2 cells and chondrocytes from damaged cartilage tissues of patients with OA. Anti-miR-495 abolished the effect of IL-1β in TC28a2 cells and rescued the protein levels of SOX9 and COL2A1, which were reduced by IL-1β. SOX9 was downregulated in the damaged cartilage tissues of patients with OA, and knockdown of SOX9 abolished the effect of anti-miR-495 on IL-1β-treated TC28a2 cells.
Conclusion
We demonstrated that inhibition of miRNA-495 alleviates IL-1β-induced inflammatory responses in chondrocytes by rescuing SOX9 expression. Accordingly, miRNA-495 could be a potential novel target for OA therapy, and the application of anti-miR-495 to chondrocytes could be a therapeutic strategy for treating OA.
10.Validation of Adult Fall Assessment Scale Korean Version for Adult Patients in General Hospitals in Korea
Eun Hee CHOI ; Mi Suk KO ; Shin Ae LEE ; Jung Ha PARK
Journal of Korean Clinical Nursing Research 2020;26(2):265-273
Purpose:
The purpose of this study was to test the predictive validity of the Fall Assessment Scale-Korean version (FAS-K) and to find the most appropriate cutoff score to screen high-risk fall groups in adult patients in general hospitals in Korea.
Methods:
We performed a prospective evaluation study in medical and surgical ward patients at two major general hospitals in Seoul. Data were collected from Nov. 1, 2018 to Feb. 28, 2019, nurses performed 651 observation series. The researcher measured the fall risk assessment score by applying FAS-K, MFS (Morse Fall Scale), and JHFRAT (Johns Hopkins Hospital Fall Risk Assessment tool) to the patients twice a week between 10 am and 12 noon. Data were analyzed using Pearson's corelation coefficients, and the sensitivity, specificity, predictive value, and the area under the curve (AUC) of the three tools. Results: The FAS-K was positively correlated with the MFS (r=.70, p<.001) and the JHFRAT (r=.82, p<.001). According to the receiver operating characteristics (ROC) curve analysis of the FAS-K, sensitivity, specificity, and positive and negative prediction values were 85.3%, 49.4%, 8.5%, and 98.4%, respectively, when the FAS-K score was 4. Therefore, the cut-off score of the FAS-K to identify groups with high fall risk was 4.
Conclusion
The FAS-K is a valid tool for measuring fall risk in adult inpatients.In addition, the FAS-K score, 4, can be used to identify high-risk fall groups and know specific points in time to provide active interventions to prevent falls.

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