1.Identification of signature gene set as highly accurate determination of metabolic dysfunction-associated steatotic liver disease progression
Sumin OH ; Yang-Hyun BAEK ; Sungju JUNG ; Sumin YOON ; Byeonggeun KANG ; Su-hyang HAN ; Gaeul PARK ; Je Yeong KO ; Sang-Young HAN ; Jin-Sook JEONG ; Jin-Han CHO ; Young-Hoon ROH ; Sung-Wook LEE ; Gi-Bok CHOI ; Yong Sun LEE ; Won KIM ; Rho Hyun SEONG ; Jong Hoon PARK ; Yeon-Su LEE ; Kyung Hyun YOO
Clinical and Molecular Hepatology 2024;30(2):247-262
Background/Aims:
Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression.
Methods:
Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD.
Results:
After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort.
Conclusions
We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.
2.The Association between Social Support, Metabolic Syndrome, and Incidence of Cardio-Cerebrovascular Diseases in Older Adults: The ARIRANG Study
Hae-Kweun NAM ; Sei-Jin CHANG ; Chun-Bae KIM ; Kyoung Sook JEONG ; Sung-Kyung KIM ; Dae Ryong KANG ; Yong Whi JEONG ; Hocheol LEE ; Bo ZHAO ; Sang-Baek KOH
Yonsei Medical Journal 2024;65(6):363-370
Purpose:
We investigated the association between social support, metabolic syndrome, and incident cardio-cerebrovascular disease (CCVD) in rural Koreans aged ≥50 years.
Materials and Methods:
We conducted a prospective study using the Korean Genome and Epidemiology Study on Atherosclerosis Risk of Rural Areas in the Korean General Population (KoGES-ARIRANG) dataset. From the baseline of 5169 adults, 1682 participants were finally included according to the exclusion criteria. For outcomes, myocardial infarction, angina, and stroke were included. For independent variables, the social support score and metabolic syndrome were used. Descriptive statistics and multivariate logistic regression were performed to investigate the association among the variables. Paired t-test was conducted to analyze the longitudinal variation of social support scores.
Results:
During the 6.37 years of median follow-up, 137 participants developed CCVD. The adjusted odds ratio (aOR) of metabolic syndrome with persistently high social support was 2.175 [95% confidence interval (CI): 1.479–3.119]. The aOR of metabolic syndrome with persistently low social support was 2.494 (95%CI: 1.141–5.452). The longitudinal variation of the social support score of persistently high social support group was increased significantly by 4.26±26.32. The score of the persistently low social support group was decreased by 1.34±16.87 with no statistical significance.
Conclusion
The presence of metabolic syndrome increases the likelihood of developing onset CCVD. Within the metabolic syndrome positive group, when social support was persistently low, the cohort developed more cardio-cerebrovascular disease compared to the persistently higher social support group. The social support score of the persistently low social support group could be improved through proper intervention. To prevent CCVD, metabolic syndrome components and low social support should be improved in the study participants.
3.Effects of Particulate Matter Exposure on the Eustachian Tube and Middle Ear Mucosa of Rats
Hyun Min LEE ; Youn-Suk SON ; Hyang-Sook KIM ; Joo-Young KIM ; Seok-Hyun KIM ; Jung Hee LEE ; Sung-Won CHOI ; Se-Joon OH ; Soo-Keun KONG ; Moo Jin BAEK ; Il-Woo LEE
Clinical and Experimental Otorhinolaryngology 2023;16(3):225-235
Objectives:
. Particulate matter (PM) is a risk factor for various diseases. Recent studies have established an association between otitis media (OM) and PM exposure. To confirm this relationship, we developed a novel exposure model designed to control the concentration of PM, and we observed the effects of PM exposure on the Eustachian tube (ET) and middle ear mucosa of rats.
Methods:
. Forty healthy, 10-week-old, male Sprague-Dawley rats were divided into 3-day, 7-day, 14-day exposure, and control groups (each, n=10). The rats were exposed to incense smoke as the PM source for 3 hours per day. After exposure, bilateral ETs and mastoid bullae were harvested, and histopathological findings were compared using microscopy and transmission electron microscopy (TEM). The expression levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and vascular endothelial growth factor (VEGF) in the middle ear mucosa of each group were compared using real-time reverse transcription polymerase chain reaction (RT-PCR).
Results:
. In the ET mucosa of the exposure group, the goblet cell count significantly increased after PM exposure (P=0.032). In the middle ear mucosa, subepithelial space thickening, increased angio-capillary tissue, and inflammatory cell infiltration were observed. Moreover, the thickness of the middle ear mucosa in the exposure groups increased compared to the control group (P<0.01). The TEM findings showed PM particles on the surface of the ET and middle ear mucosa, and RT-PCR revealed that messenger RNA (mRNA) expression of IL-1β significantly increased in the 3-day and 7-day exposure groups compared to the control group (P=0.035). VEGF expression significantly increased in the 7-day exposure group compared to the control and 3-day exposure groups (P<0.01).
Conclusion
. The ET and middle ear mucosa of rats showed histopathologic changes after acute exposure to PM that directly reached the ET and middle ear mucosa. Therefore, acute exposure to PM may play a role in the development of OM.
4.Impacts of Subtype on Clinical Feature and Outcome of Male Breast Cancer: Multicenter Study in Korea (KCSG BR16-09)
Jieun LEE ; Keun Seok LEE ; Sung Hoon SIM ; Heejung CHAE ; Joohyuk SOHN ; Gun Min KIM ; Kyung-Hee LEE ; Su Hwan KANG ; Kyung Hae JUNG ; Jae-ho JEONG ; Jae Ho BYUN ; Su-Jin KOH ; Kyoung Eun LEE ; Seungtaek LIM ; Hee Jun KIM ; Hye Sung WON ; Hyung Soon PARK ; Guk Jin LEE ; Soojung HONG ; Sun Kyung BAEK ; Soon Il LEE ; Moon Young CHOI ; In Sook WOO
Cancer Research and Treatment 2023;55(1):123-135
Purpose:
The treatment of male breast cancer (MBC) has been extrapolated from female breast cancer (FBC) because of its rarity despite their different clinicopathologic characteristics. We aimed to investigate the distribution of intrinsic subtypes based on immunohistochemistry, their clinical impact, and treatment pattern in clinical practice through a multicenter study in Korea.
Materials and Methods:
We retrospectively analyzed clinical data of 248 MBC patients from 18 institutions across the country from January 1995 to July 2016.
Results:
The median age of MBC patients was 63 years (range, 25 to 102 years). Among 148 intrinsic subtype classified patients, 61 (41.2%), 44 (29.7%), 29 (19.5%), and 14 (9.5%) were luminal A, luminal B, human epidermal growth factor receptor 2, and triple-negative breast cancer, respectively. Luminal A subtype showed trends for superior survival compared to other subtypes. Most hormone receptor-positive patients (166 patients, 82.6%) received adjuvant endocrine treatment. Five-year completion of adjuvant endocrine treatment was associated with superior disease-free survival (DFS) in patients classified with an intrinsic subtype (hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.04 to 0.49; p=0.002) and in all patients (HR, 0.16; 95% CI, 0.05 to 0.54; p=0.003).
Conclusion
Distribution of subtypes of MBC was similar to FBC and luminal type A was most common. Overall survival tended to be improved for luminal A subtype, although there was no statistical significance. Completion of adjuvant endocrine treatment was associated with prolonged DFS in intrinsic subtype classified patients. MBC patients tended to receive less treatment. MBC patients should receive standard treatment according to guidelines as FBC patients.
5.Korean Practice Guidelines for Gastric Cancer 2022: An Evidence-based, Multidisciplinary Approach
Tae-Han KIM ; In-Ho KIM ; Seung Joo KANG ; Miyoung CHOI ; Baek-Hui KIM ; Bang Wool EOM ; Bum Jun KIM ; Byung-Hoon MIN ; Chang In CHOI ; Cheol Min SHIN ; Chung Hyun TAE ; Chung sik GONG ; Dong Jin KIM ; Arthur Eung-Hyuck CHO ; Eun Jeong GONG ; Geum Jong SONG ; Hyeon-Su IM ; Hye Seong AHN ; Hyun LIM ; Hyung-Don KIM ; Jae-Joon KIM ; Jeong Il YU ; Jeong Won LEE ; Ji Yeon PARK ; Jwa Hoon KIM ; Kyoung Doo SONG ; Minkyu JUNG ; Mi Ran JUNG ; Sang-Yong SON ; Shin-Hoo PARK ; Soo Jin KIM ; Sung Hak LEE ; Tae-Yong KIM ; Woo Kyun BAE ; Woong Sub KOOM ; Yeseob JEE ; Yoo Min KIM ; Yoonjin KWAK ; Young Suk PARK ; Hye Sook HAN ; Su Youn NAM ; Seong-Ho KONG ;
Journal of Gastric Cancer 2023;23(1):3-106
Gastric cancer is one of the most common cancers in Korea and the world. Since 2004, this is the 4th gastric cancer guideline published in Korea which is the revised version of previous evidence-based approach in 2018. Current guideline is a collaborative work of the interdisciplinary working group including experts in the field of gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology and guideline development methodology. Total of 33 key questions were updated or proposed after a collaborative review by the working group and 40 statements were developed according to the systematic review using the MEDLINE, Embase, Cochrane Library and KoreaMed database. The level of evidence and the grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation proposition. Evidence level, benefit, harm, and clinical applicability was considered as the significant factors for recommendation. The working group reviewed recommendations and discussed for consensus. In the earlier part, general consideration discusses screening, diagnosis and staging of endoscopy, pathology, radiology, and nuclear medicine. Flowchart is depicted with statements which is supported by meta-analysis and references. Since clinical trial and systematic review was not suitable for postoperative oncologic and nutritional follow-up, working group agreed to conduct a nationwide survey investigating the clinical practice of all tertiary or general hospitals in Korea. The purpose of this survey was to provide baseline information on follow up. Herein we present a multidisciplinary-evidence based gastric cancer guideline.
6.Erratum: Korean Practice Guidelines for Gastric Cancer 2022: An Evidencebased, Multidisciplinary Approach
Tae-Han KIM ; In-Ho KIM ; Seung Joo KANG ; Miyoung CHOI ; Baek-Hui KIM ; Bang Wool EOM ; Bum Jun KIM ; Byung-Hoon MIN ; Chang In CHOI ; Cheol Min SHIN ; Chung Hyun TAE ; Chung sik GONG ; Dong Jin KIM ; Arthur Eung-Hyuck CHO ; Eun Jeong GONG ; Geum Jong SONG ; Hyeon-Su IM ; Hye Seong AHN ; Hyun LIM ; Hyung-Don KIM ; Jae-Joon KIM ; Jeong Il YU ; Jeong Won LEE ; Ji Yeon PARK ; Jwa Hoon KIM ; Kyoung Doo SONG ; Minkyu JUNG ; Mi Ran JUNG ; Sang-Yong SON ; Shin-Hoo PARK ; Soo Jin KIM ; Sung Hak LEE ; Tae-Yong KIM ; Woo Kyun BAE ; Woong Sub KOOM ; Yeseob JEE ; Yoo Min KIM ; Yoonjin KWAK ; Young Suk PARK ; Hye Sook HAN ; Su Youn NAM ; Seong-Ho KONG
Journal of Gastric Cancer 2023;23(2):365-373
7.Rituximab plus multiagent chemotherapy for newly diagnosed CD20-positive acute lymphoblastic leukemia: a prospective phase II study
Dong Won BAEK ; Han-Seung PARK ; Sang Kyun SOHN ; Dae Young KIM ; Inho KIM ; Jae-Sook AHN ; Young Rok DO ; Se Ryeon LEE ; Hyeon-Seok EOM ; Won-Sik LEE ; Sung-Hyun KIM ; Ho Sup LEE ; Yoo Jin LEE ; Joon Ho MOON ; Je-Hwan LEE ;
The Korean Journal of Internal Medicine 2023;38(5):734-746
Background/Aims:
We performed a prospective study to determine the efficacy and safety of rituximab including chemotherapy in CD20-positive acute lymphoblastic leukemia (ALL).
Methods:
Patients with newly diagnosed ALL, aged ≥ 15 years, were eligible for the study if their leukemic blast cells in bone marrow expressed CD20 ≥ 20% at the time of diagnosis. Patients received multiagent chemotherapy with rituximab. After achieving complete remission (CR), patients received five cycles of consolidation with concomitant rituximab. Rituximab was administered monthly from day 90 of transplantation for patients who received allogeneic hematopoietic cell transplantation.
Results:
In patients with Philadelphia (Ph)-negative ALL, 39 of 41 achieved CR (95.1%), the 2- and 4-year relapse-free survival (RFS) rates were 50.4% and 35.7%, and the 2- and 4-year overall survival (OS) rates were 51.5% and 43.2%, respectively. In the group with Ph-positive ALL, all 32 patients achieved CR, the 2- and 4-year RFS rates were 60.7% and 52.1%, and the 2- and 4-year OS rates were 73.3% and 52.3%, respectively. In the Ph-negative ALL group, patients with higher CD20 positivity experienced more favorable RFS (p < 0.001) and OS (p = 0.06) than those with lower CD20 positivity. Patients who received ≥ 2 cycles of rituximab after transplantation had significantly improved RFS (hazard ratio [HR], 0.31; p = 0.049) and OS (HR, 0.29; p = 0.021) compared with those who received < 2 cycles.
Conclusions
The addition of rituximab to conventional chemotherapy for CD20-positive ALL is effective and tolerable (Clinicaltrials. gov NCT01429610).
8.Impact of Wildfire Smoke Exposure on Health in Korea
Kihyun LEE ; Sung-Soo OH ; Kyoung Sook JEONG ; Yeon-Soon AHN ; Sei Jin CHANG ; Se Hwa HONG ; Dae Ryong KANG ; Sung-Kyung KIM ; Sang-Baek KOH
Yonsei Medical Journal 2022;63(8):774-782
Purpose:
The characteristic topography and climate often affect the occurrence of large-scale wildfires in the Eastern Gangwon-do region of Korea. However, there are no studies on the health effects of these wildfires in Korea. This study aimed to analyze the differences in medical use between a wildfire-affected area and an adjacent non-affected area before and after a wildfire in 2019 in Gangwon-do, Korea.
Materials and Methods:
We used medical usage data from the Korean National Health Insurance Corporation. Rates of medical use were determined for citizens of a wildfire-affected area in the Eastern Yeongdong region and a non-affected area in the Western Yeongseo region. Logistic regression analysis was performed considering an increase in medical use per individual as a dependent variable; age, sex, income, smoking, drinking, and exercise were included as confounding variables.
Results:
The odds ratio for medical use in Yeongdong region increased significantly after 3 days, 3 months, and 1 year after a fire occurred, compared with Yeongseo region.
Conclusion
The results of this study confirmed that the use of medical care increased for residents of a wildfire-affected area, compared with those of an adjacent non-affected area. This is the first study on the relationship between wildfires and inpatient medical use in Korea.
9.Maternal and Neonatal Outcomes in Pregnant Women With Coronavirus Disease 2019 in Korea
Youseung CHUNG ; Eun Jin KIM ; Hee-Sung KIM ; Kyung-Hwa PARK ; Ji Hyeon BAEK ; Jungok KIM ; Ji Yeon LEE ; Chang-Seop LEE ; Seungjin LIM ; Shin-Woo KIM ; Eu Suk KIM ; Hye Jin SHI ; Shin Hee HONG ; Jae-Bum JUN ; Kyung-Wook HONG ; Jae-Phil CHOI ; Jinyeong KIM ; Kyung Sook YANG ; Young Kyung YOON
Journal of Korean Medical Science 2022;37(41):e297-
Background:
This study aimed to describe the maternal, obstetrical, and neonatal outcomes in pregnant women with coronavirus disease 2019 (COVID-19) and identify the predictors associated with the severity of COVID-19.
Methods:
This multicenter observational study included consecutive pregnant women admitted because of COVID-19 confirmed using reverse transcriptase-polymerase chain reaction (RT-PCR) test at 15 hospitals in the Republic of Korea between January 2020 and December 2021.
Results:
A total of 257 women with COVID-19 and 62 newborns were included in this study. Most of the patients developed this disease during the third trimester. Nine patients (7.4%) developed pregnancy-related complications. All pregnant women received inpatient treatment, of whom 9 (3.5%) required intensive care, but none of them died. The gestational age at COVID-19 diagnosis (odds ratio [OR], 1.096, 95% confidence interval [CI], 1.04–1.15) and parity (OR, 1.703, 95% CI, 1.13–2.57) were identified as significant risk factors of severe diseases. Among women who delivered, 78.5% underwent cesarean section. Preterm birth (38.5%), premature rupture of membranes (7.7%), and miscarriage (4.6%) occurred, but there was no stillbirth or neonatal death. The RT-PCR test of newborns’ amniotic fluid and umbilical cord blood samples was negative for severe acute respiratory syndrome coronavirus 2.
Conclusion
At the time of COVID-19 diagnosis, gestational age and parity of pregnant women were the risk factors of disease severity. Vertical transmission of COVID-19 was not observed, and maternal severity did not significantly affect the neonatal prognosis.
10.Capacitive coupling leading to electrical skin burn injury during laparoscopic surgery
Woo Jun KIM ; Gyung Mo SON ; In Young LEE ; Sung Uk YUN ; Gye Rok JEON ; Dong-Hoon SHIN ; Myung Sook KWON ; Jae Yeong KWAK ; Kwang-Ryul BAEK
Journal of Minimally Invasive Surgery 2022;25(3):106-111
Purpose:
Trocar-site burns occurring during laparoscopic surgery have been reported in various cases, and several efforts to reduce them are underway. This study aimed to analyze the effect of capacitive coupling on trocar site by observing electrical and histological changes for electrical skin burn injury.
Methods:
To measure the electrical changes relating to capacitive coupling, the temperature, current, voltage, and impedance around the trocar were measured when an open circuit and a closed circuit were formed using insulation intact instruments and repeated after insulation failure. After the experiment, the tissue around the trocar was collected, and microscopic examination was performed.
Results:
When open circuits were formed with the intact insulation, the impedance was significantly reduced compared to the cases of closed circuits (142.0 Ω vs. 109.3 Ω, p = 0.040). When the power was 30 W and there was insulation failure, no significant difference was measured between the open circuit and the closed circuit (147.7 Ω vs. 130.7 Ω, p = 0.103). Collagen hyalinization, nuclear fragmentation, and coagulation necrosis suggesting burns were observed in the skin biopsy at the trocar insertion site.
Conclusion
This study demonstrated that even with a plastic trocar and electrosurgical instruments that have intact insulation, if an open circuit is formed, capacitive coupling increases, and trocar-site burn can occur. When using electrocautery, careful manipulation must be taken to avoid creating an open circuit to prevent capacitive coupling related to electrical skin burn.

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