1.KCTD17-mediated Ras stabilization promotes hepatocellular carcinoma progression
Young Hoon JUNG ; Yun Ji LEE ; Tam DAO ; Kyung Hee JUNG ; Junjie YU ; Ah-Reum OH ; Yelin JEONG ; HyunJoon GI ; Young Un KIM ; Dongryeol RYU ; Michele CARRER ; Utpal B. PAJVANI ; Sang Bae LEE ; Soon-Sun HONG ; KyeongJin KIM
Clinical and Molecular Hepatology 2024;30(4):895-913
Background/Aims:
Potassium channel tetramerization domain containing 17 (KCTD17) protein, an adaptor for the cullin3 (Cul3) ubiquitin ligase complex, has been implicated in various human diseases; however, its role in hepatocellular carcinoma (HCC) remains elusive. Here, we aimed to elucidate the clinical features of KCTD17, and investigate the mechanisms by which KCTD17 affects HCC progression.
Methods:
We analyzed transcriptomic data from patients with HCC. Hepatocyte-specific KCTD17 deficient mice were treated with diethylnitrosamine (DEN) to assess its effect on HCC progression. Additionally, we tested KCTD17-directed antisense oligonucleotides for their therapeutic potential in vivo.
Results:
Our investigation revealed the upregulation of KCTD17 expression in both tumors from patients with HCC and mouse models of HCC, in comparison to non-tumor controls. We identified the leucine zipper-like transcriptional regulator 1 (Lztr1) protein, a previously identified Ras destabilizer, as a substrate for KCTD17-Cul3 complex. KCTD17-mediated Lztr1 degradation led to Ras stabilization, resulting in increased proliferation, migration, and wound healing in liver cancer cells. Hepatocyte-specific KCTD17 deficient mice or liver cancer xenograft models were less susceptible to carcinogenesis or tumor growth. Similarly, treatment with KCTD17-directed antisense oligonucleotides (ASO) in a mouse model of HCC markedly lowered tumor volume as well as Ras protein levels, compared to those in control ASO-treated mice.
Conclusions
KCTD17 induces the stabilization of Ras and downstream signaling pathways and HCC progression and may represent a novel therapeutic target for HCC.
2.Prevalence and Associated Factors of Depression and Anxiety Among Healthcare Workers During the Coronavirus Disease 2019 Pandemic:A Nationwide Study in Korea
Shinwon LEE ; Soyoon HWANG ; Ki Tae KWON ; EunKyung NAM ; Un Sun CHUNG ; Shin-Woo KIM ; Hyun-Ha CHANG ; Yoonjung KIM ; Sohyun BAE ; Ji-Yeon SHIN ; Sang-geun BAE ; Hyun Wook RYOO ; Juhwan JEONG ; NamHee OH ; So Hee LEE ; Yeonjae KIM ; Chang Kyung KANG ; Hye Yoon PARK ; Jiho PARK ; Se Yoon PARK ; Bongyoung KIM ; Hae Suk CHEONG ; Ji Woong SON ; Su Jin LIM ; Seongcheol YUN ; Won Sup OH ; Kyung-Hwa PARK ; Ju-Yeon LEE ; Sang Taek HEO ; Ji-yeon LEE
Journal of Korean Medical Science 2024;39(13):e120-
Background:
A healthcare system’s collapse due to a pandemic, such as the coronavirus disease 2019 (COVID-19), can expose healthcare workers (HCWs) to various mental health problems. This study aimed to investigate the impact of the COVID-19 pandemic on the depression and anxiety of HCWs.
Methods:
A nationwide questionnaire-based survey was conducted on HCWs who worked in healthcare facilities and public health centers in Korea in December 2020. Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to measure depression and anxiety. To investigate factors associated with depression and anxiety, stepwise multiple logistic regression analysis was performed.
Results:
A total of 1,425 participating HCWs were included. The mean depression score (PHQ-9) of HCWs before and after COVID-19 increased from 2.37 to 5.39, and the mean anxiety score (GAD-7) increased from 1.41 to 3.41. The proportion of HCWs with moderate to severe depression (PHQ-9 ≥ 10) increased from 3.8% before COVID-19 to 19.5% after COVID-19, whereas that of HCWs with moderate to severe anxiety (GAD-7 ≥ 10) increased from 2.0% to 10.1%. In our study, insomnia, chronic fatigue symptoms and physical symptoms after COVID-19, anxiety score (GAD-7) after COVID-19, living alone, and exhaustion were positively correlated with depression. Furthermore, post-traumatic stress symptoms, stress score (Global Assessment of Recent Stress), depression score (PHQ-9) after COVID-19, and exhaustion were positively correlated with anxiety.
Conclusion
In Korea, during the COVID-19 pandemic, HCWs commonly suffered from mental health problems, including depression and anxiety. Regularly checking the physical and mental health problems of HCWs during the COVID-19 pandemic is crucial, and social support and strategy are needed to reduce the heavy workload and psychological distress of HCWs.
3.Clinical Outcomes of Clipping and Coil Embolization for Ruptured Intracranial Aneurysms Categorized by Region and Hospital Size: A Nationwide Cohort Study in Korea
Yu Deok WON ; Hyoung Soo BYOUN ; Tae Won CHOI ; Sang Hyo LEE ; Young Deok KIM ; Seung Pil BAN ; Jae Seung BANG ; O-Ki KWON ; Chang Wan OH ; Si Un LEE
Journal of Korean Medical Science 2024;39(23):e188-
Background:
To analyze the outcomes of clipping and coiling for ruptured intracranial aneurysms (RIAs) based on data from the National Health Insurance Service in South Korea, with a focus on variations according to region and hospital size.
Methods:
This study analyzed the one-year mortality rates for patients with RIAs who underwent clipping or coiling in 2018. Coiling was further categorized into non-stent assisted coiling (NSAC) and stent assisted coiling (SAC). Hospitals were classified as tertiary referral general hospitals (TRGHs), general hospitals (GHs), or semi-general hospitals (sGHs) based on size. South Korea’s administrative districts were divided into 15 regions for analysis.
Results:
In 2018, there were 2,194 (33.1%) clipping procedures (TRGH, 985; GH, 827; sGH, 382) and 4,431 (66.9%) coiling procedures (TRGH, 1,642; GH, 2076; sGH, 713) performed for RIAs treatment. Among hospitals performing more than 20 treatments, the one-year mortality rates following clipping or coiling were 11.2% and 16.0%, respectively, with no significant difference observed. However, there was a significant difference in one-year mortality between NSAC and SAC (14.3% vs. 19.5%, P = 0.034), with clipping also showing significantly lower mortality compared to SAC (P = 0.019). No significant differences in other treatment modalities were observed according to hospital size, but clipping at TRGHs had significantly lower mortality than at GHs (P = 0.042). While no significant correlation was found between the number of treatments and outcomes at GHs, at TRGHs, a higher volume of clipping procedures was significantly associated with lower total mortality (P = 0.023) and mortality after clipping (P = 0.022).
Conclusion
Using Korea NHIS data, mortality rates for RIAs showed no significant variation by hospital size due to coiling’s prevalence. However, differences in clipping outcomes by hospital size and volume in TRGH highlight the need for national efforts to improve clipping skills and standardization. Additionally, the higher mortality rate with SAC emphasizes the importance of precise indications for its application.
4.Efficacy and Safety of Lurasidone vs. Quetiapine XR in Acutely Psychotic Patients With Schizophrenia in Korea: A Randomized, Double-Blind, Active-Controlled Trial
Se Hyun KIM ; Do-Un JUNG ; Do Hoon KIM ; Jung Sik LEE ; Kyoung-Uk LEE ; Seunghee WON ; Bong Ju LEE ; Sung-Gon KIM ; Sungwon ROH ; Jong-Ik PARK ; Minah KIM ; Sung Won JUNG ; Hong Seok OH ; Han-yong JUNG ; Sang Hoon KIM ; Hyun Seung CHEE ; Jong-Woo PAIK ; Kyu Young LEE ; Soo In KIM ; Seung-Hwan LEE ; Eun-Jin CHEON ; Hye-Geum KIM ; Heon-Jeong LEE ; In Won CHUNG ; Joonho CHOI ; Min-Hyuk KIM ; Seong-Jin CHO ; HyunChul YOUN ; Jhin-Goo CHANG ; Hoo Rim SONG ; Euitae KIM ; Won-Hyoung KIM ; Chul Eung KIM ; Doo-Heum PARK ; Byung-Ook LEE ; Jungsun LEE ; Seung-Yup LEE ; Nuree KANG ; Hee Yeon JUNG
Psychiatry Investigation 2024;21(7):762-771
Objective:
This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia.
Methods:
Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed.
Results:
Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35–4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea.
Conclusion
Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.
5.Comprehensive Study of Microsatellite Instability Testing and Its Comparison With Immunohistochemistry in Gastric Cancers
Yujun PARK ; Soo Kyung NAM ; Soo Hyun SEO ; Kyoung Un PARK ; Hyeon Jeong OH ; Young Suk PARK ; Yun-Suhk SUH ; Sang-Hoon AHN ; Do Joong PARK ; Hyung-Ho KIM ; Hye Seung LEE
Journal of Gastric Cancer 2023;23(2):264-274
Purpose:
In this study, polymerase chain reaction (PCR)-based microsatellite instability (MSI) testing was comprehensively analyzed and compared with immunohistochemistry (IHC) for mismatch repair (MMR) protein expression in patients with gastric cancer (GC).
Materials and Methods:
In 5,676 GC cases, PCR-based MSI testing using five microsatellites (BAT-26, BAT-25, D5S346, D2S123, and D17S250) and IHC for MLH1 were performed. Reevaluation of MSI testing/MLH1 IHC and additional IHC for MSH2, MSH6, and PMS2 were performed in discordant/indeterminate cases.
Results:
Of the 5,676 cases, microsatellite stable (MSS)/MSI-low and intact MLH1 were observed in 5,082 cases (89.5%), whereas MSI-high (MSI-H) and loss of MLH1 expression were observed in 502 cases (8.8%). We re-evaluated the remaining 92 cases (1.6%) with a discordant/ indeterminate status. Re-evaluation showed 1) 37 concordant cases (0.7%) (18 and 19 cases of MSI-H/MMR-deficient (dMMR) and MSS/MMR-proficient (pMMR), respectively), 2) 6 discordant cases (0.1%) (3 cases each of MSI-H/pMMR and MSS/dMMR), 3) 14 MSI indeterminate cases (0.2%) (1 case of dMMR and 13 cases of pMMR), and 4) 35 IHC indeterminate cases (0.6%) (22 and 13 cases of MSI-H and MSS, respectively). Finally, MSI-H or dMMR was observed in 549 cases (9.7%), of which 47 (0.8%) were additionally confirmed as MSI-H or dMMR by reevaluation. Sensitivity was 99.3% for MSI testing and 95.4% for MMR IHC.
Conclusions
Considering the low incidence of MSI-H or dMMR, discordant/indeterminate results were occasionally identified in GCs, in which case complementary testing is required.These findings could help improve the accuracy of MSI/MMR testing in daily practice.
6.Left Ventricular Remodeling After Catheter Ablation of Atrial Fibrillation:Changes of Myocardial Extracellular Volume Fraction by Cardiac MRI
Sang-Un KIM ; Soojung PARK ; Hyungjoon CHO ; Yongwon CHO ; Yu-Whan OH ; Yun Gi KIM ; Jaemin SHIM ; Jong-il CHOI ; Young-Hoon KIM ; Mun Young PAEK ; Sung Ho HWANG
Investigative Magnetic Resonance Imaging 2022;26(3):151-160
Purpose:
The aim of this study is to demonstrate the association between recurrent atrial fibrillation (AF) and left ventricular (LV) adverse remodeling after catheter ablation and to evaluate the change of myocardial extracellular volume fraction (ECV) by catheter ablation outcomes.
Materials and Methods:
We retrospectively recruited 60 patients (44 men and 16 women) with a median age of 57 years (range, 32–78 years) who underwent cardiac MRI before and at 6–12 months after catheter ablation of AF. Cardiac MRI quantified myocardial ECV (%) in the left ventricle. Depending on myocardial ECV after catheter ablation, patients were divided into two groups: 1) LV adverse remodeling with ECV ≥ 28%; and 2) no adverse LV remodeling with ECV < 28%. Multivariable analysis was performed to assess the association between recurrent AF and LV remodeling.
Results:
Of 60 patients, 21 (35%) were in the LV adverse remodeling group (mean ECV ± standard deviation [SD]: 29.8% ± 1.4%) and 39 (65%) were in the no adverse LV remodeling group (mean ECV ± SD: 24.7% ± 1.5%). The incidence of recurrent AF was significantly greater in the LV adverse remodeling group than in the no adverse LV remodeling group (81% vs. 13%, p < 0.001). In patients with recurrent AF, mean myocardial ECV significantly increased from 27.7% ± 2.3% to 29.2% ± 2.3% (p = 0.004) after catheter ablation. In a multivariable analysis after adjusting sex, age, and myocardial ECV before catheter ablation, recurrent AF was independently associated with LV adverse remodeling after catheter ablation (odds ratio: 28.9, 95% confidence interval: 6.8–121.7, p < 0.001).
Conclusion
When monitoring with cardiac MRI, sustained AF was significantly associated with LV adverse remodeling through an increase in myocardial ECV after catheter ablation of AF.
7.Multidisciplinary treatment strategy for early colon cancer
Gyung Mo SON ; Su Bum PARK ; Tae Un KIM ; Byung-Soo PARK ; In Young LEE ; Joo-Young NA ; Dong Hoon SHIN ; Sang Bo OH ; Sung Hwan CHO ; Hyun Sung KIM ; Hyung Wook KIM
Journal of the Korean Medical Association 2022;65(9):558-567
Treatment for early colon cancer has progressed rapidly with endoscopic resection and minimally invasive surgery. Selection of patients without risk of lymph node metastasis is necessary before deciding on endoscopic resection for early colon cancer treatment. We aimed to review the optimal multidisciplinary treatment strategies for early colon cancer, including endoscopy and surgery.Current Concepts: Pathological risk factors include histologic grade of cancer cell differentiation, lymphovascular invasion, perineural invasion, tumor budding, and deep submucosal invasion. These risk factors for predicting lymph node metastasis are crucial for determining the treatment strategy of endoscopic excision and radical resection for early colon cancer. Prediction of the depth of invasion in early colon cancer using endoscopic optical assessments is vital to determine the appropriate treatment method for endoscopic or surgical resection. Furthermore, optical assessment of pit and vascular patterns is useful for estimating the depth of submucosal invasion using magnifying chromoendoscopy and narrow-band imaging endoscopy. Performing an endoscopic and pathologic evaluation of the risk factors for lymph node metastasis is imperative when selecting endoscopic or surgical resection. Endoscopic treatments include cold snare polypectomy, endoscopic mucosal resection, and endoscopic submucosal dissection. In addition, appropriate surgical treatment should be recommended for patients with early colon cancer with a high risk of lymph node metastasis.Discussion and Conclusion: A multidisciplinary approach should be recommended to establish an optimized treatment strategy, minimize the risk of complications, and obtain excellent oncologic outcomes via patienttailored treatment in patients with early colon cancer.
8.Dynamics of viral load and anti-SARS-CoV-2 antibodies in patients with positive RT-PCR results after recovery from COVID-19
Kyoung-Ho SONG ; Dong-Min KIM ; Hyunju LEE ; Sin Young HAM ; Sang-Min OH ; Hyeonju JEONG ; Jongtak JUNG ; Chang Kyung KANG ; Ji Young PARK ; Yu Min KANG ; Ji-Yeon KIM ; Jeong Su PARK ; Kyoung Un PARK ; Eu Suk KIM ; Hong Bin KIM
The Korean Journal of Internal Medicine 2021;36(1):11-14
Recently, the number of patients with coronavirus disease 2019 (COVID-19) who have tested positive for severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), via the reverse transcription polymerase chain reaction (RT-PCR) test, after recovery has increased; this has caused a dilemma regarding the medical measures and policies. We evaluated the dynamics of viral load and anti-SARSCoV-2 antibodies in four patients with positive RT-PCR results after recovery. In all patients, the highest levels of immunoglobulin G (IgG) and IgM antibodies were reached after about a month of the onset of the initial symptoms. Then, the IgG titers plateaued, and the IgM titers decreased, regardless of RT-PCR results.The IgG and IgM levels did not increase after the post-negative positive RT-PCR results in any of the patients. Our results reinforced that the post-negative positive RT-PCR results may be due to the detection of RNA particles rather than reinfection in individuals who have recovered from COVID-19.
9.Comparison of the Suicide Attempt Characteristics Associated with Mixed and Non-Mixed Depression in Koreans
Hyeon-Seok CHOI ; Sung-Jin KIM ; Sang-Hun NAM ; Do-Un JUNG ; Jung-Joon MOON ; Yeon-Sue KIM ; Min-Kyung OH ; Dong-Wook JEON ; Yong Min AHN
Korean Journal of Psychosomatic Medicine 2021;29(2):199-206
Objectives:
:This study aimed to compare the characteristics of suicide attempts among Korean patients with mixed and non-mixed depression.
Methods:
:Patients who visited the emergency room due to a suicide attempt and participated in the Korean Cohort for the Model Predicting a Suicide and Suicide-related Behavior study were included. Using the Montgomery-Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS), 111 patients were classified into the mixed depression (n=46) and non-mixed depression groups (n=65). The Koukopoulos Mixed Depression Rating Scale (KMDRS) score was calculated using the MADRS and YMRS scores. Suicide attempt characteristics were evaluated using the Columbia Suicidal Severity Rating Scale (C-SSRS) and Suicide Intent Scale (SIS).
Results:
:In the mixed depression group, the reason item among the ideation intensity score of the C-SSRS was higher, and the deterrent item score was lower. Scores on the timing and suicide note items of the SIS were higher, and scores for overt communication items were lower in the mixed depression group. The KMDRS score was positively correlated with the C-SSRS ideation intensity and total SIS score. After adjusting for additional variables,the KMDRS scores had a significant effect on the C-SSRS ideation intensity and total SIS scores.
Conclusions
:The mixed depression group showed a difference in the intensity of suicidal ideation and suicidal intention compared to those in the non-mixed depression group. The overall suicidal ideation intensity and suicidal intention increased according to the degree of mixed depression.
10.Clinical Outcomes of Clipping and Coiling in Elderly Patients with Unruptured Cerebral Aneurysms: a National Cohort Study in Korea
Sang Hyo LEE ; Si Un LEE ; O-Ki KWON ; Jae Seung BANG ; Seung Pil BAN ; Tackeun KIM ; Young Deok KIM ; Hyoung Soo BYOUN ; Chang Wan OH
Journal of Korean Medical Science 2021;36(26):e178-
Background:
We aimed to analyze outcomes of clipping and coiling in treating unruptured intracranial aneurysms (UIAs) in elderly patients and to identify the age at which perioperative risk increases based on national cohort data in South Korea.
Methods:
The incidence of perioperative intracranial hemorrhage (ICRH), perioperative cerebral infarction (CI), mortality, and moderate to severe disability data of the patients who underwent coiling or clipping for UIAs were retrieved. Estimated breakpoint (EBP) was calculated to identify the age at which the risk of treatment increases.
Results:
A total of 38,207 patients were treated for UIAs. Among these, 22,093 (57.8%) patients underwent coiling and 16,114 (42.2%) patients underwent clipping. The incidence of ICRH, requiring a secondary operation, within 3 months in patients ≥ 65 years that underwent coiling and clipping was 1.13% and 4.81%, respectively, and that of both groups assessed were significantly higher in patients ≥ 75 years (coiling, P = 0.013, relative risk (RR) 1.81; clipping, P = 0.015) than younger patients. The incidence of CI within 3 months in patients aged ≥ 65 was 13.90% and 9.19% in the coiling and clipping groups, respectively. The incidence of CI after coiling in patients aged ≥ 75 years (P < 0.001, RR 1.96) and after clipping in patients aged ≥ 70 years (P < 0.001, RR 1.76) was significantly higher than that in younger patients. The mortality rates within 1 year in patients with perioperative ICRH or CI were 2.41% and 3.39% for coiling and clipping groups, respectively, in patients ≥ 65. These rates increased significantly at age 70 in the coiling group and at age 75 for the clipping group (P = 0.012 and P < 0.001, respectively).
Conclusion
The risk of treatment increases with age, and this risk increases dramatically in patients aged ≥ 70 years. Therefore, the treatment decisions in patients aged ≥ 70 years should be made with utmost care.

Result Analysis
Print
Save
E-mail