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.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.
3.Efficacy and safety of sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir for hepatitis C in Korea: a Phase 3b study
Jeong HEO ; Yoon Jun KIM ; Sung Wook LEE ; Youn-Jae LEE ; Ki Tae YOON ; Kwan Soo BYUN ; Yong Jin JUNG ; Won Young TAK ; Sook-Hyang JEONG ; Kyung Min KWON ; Vithika SURI ; Peiwen WU ; Byoung Kuk JANG ; Byung Seok LEE ; Ju-Yeon CHO ; Jeong Won JANG ; Soo Hyun YANG ; Seung Woon PAIK ; Hyung Joon KIM ; Jung Hyun KWON ; Neung Hwa PARK ; Ju Hyun KIM ; In Hee KIM ; Sang Hoon AHN ; Young-Suk LIM
The Korean Journal of Internal Medicine 2023;38(4):504-513
Despite the availability of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection in Korea, need remains for pangenotypic regimens that can be used in the presence of hepatic impairment, comorbidities, or prior treatment failure. We investigated the efficacy and safety of sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir for 12 weeks in HCV-infected Korean adults. Methods: This Phase 3b, multicenter, open-label study included 2 cohorts. In Cohort 1, participants with HCV genotype 1 or 2 and who were treatment-naive or treatment-experienced with interferon-based treatments, received sofosbuvir–velpatasvir 400/100 mg/day. In Cohort 2, HCV genotype 1 infected individuals who previously received an NS5A inhibitor-containing regimen ≥ 4 weeks received sofosbuvir–velpatasvir–voxilaprevir 400/100/100 mg/day. Decompensated cirrhosis was an exclusion criterion. The primary endpoint was SVR12, defined as HCV RNA < 15 IU/mL 12 weeks following treatment. Results: Of 53 participants receiving sofosbuvir–velpatasvir, 52 (98.1%) achieved SVR12. The single participant who did not achieve SVR12 experienced an asymptomatic Grade 3 ASL/ALT elevation on day 15 and discontinued treatment. The event resolved without intervention. All 33 participants (100%) treated with sofosbuvir–velpatasvir–voxilaprevir achieved SVR 12. Overall, sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir were safe and well tolerated. Three participants (5.6%) in Cohort 1 and 1 participant (3.0%) in Cohort 2 had serious adverse events, but none were considered treatment-related. No deaths or grade 4 laboratory abnormalities were reported. Conclusions: Treatment with sofosbuvir–velpatasvir or sofosbuvir–velpatasvir–voxilaprevir was safe and resulted in high SVR12 rates in Korean HCV patients.
4.Hepatic hemangioma: proportion and predictor of surgical treatment with emphasis on its growth rate
Young Cheol SHIN ; Eun Ju CHO ; Hee Young NA ; Jai Young CHO ; Ho-Seong HAN ; Yoon Jin LEE ; Haeryoung KIM ; Sangmi JANG ; Gwang Hyeon CHOI ; Eun Sun JANG ; Jin-Wook KIM ; Sook-Hyang JEONG
The Korean Journal of Internal Medicine 2023;38(6):818-830
Background/Aims:
There are limited studies on the management of hepatic hemangiomas (HHs). We investigated the proportion and predictors of surgical resection and analyzed HH growth rates in addition to associated factors.
Methods:
A retrospective case-control study of patients treated in 2 centers was conducted. Thirty-six patients who underwent surgical resection were assigned to the case group. Patients who did not undergo surgical treatment were randomly sigselected at a 1:10 ratio and assigned to the control group (n = 360). Baseline characteristics, clinical course and surgical outcomes were analyzed.
Results:
The proportion of surgically treated HH patients was 0.3% (36 per 11,049). The longest diameter at diagnosis (mean ± standard deviation) was 7.7 ± 5.2 cm in the case group and 2.4 ± 1.8 cm in the control group (p < 0.001). In the multivariate analysis, the presence of more than 2 HHs (odds ratio [OR] 7.64, 95% confidence interval [CI] 1.40–41.72) and a growth rate of more than 4.8%/year (OR 30.73, 95% CI 4.86–194.51) were independently associated with surgical treatment. Symptom development during follow-up was related to HH size > 10 cm (OR 10.50, 95% CI 1.06–103.77, p = 0.04). The subgroup analysis showed substantial growth in 41.3% with an overall mean annual growth rate of 0.14 cm.
Conclusions
Approximately one in 300 patients with an HH underwent surgical treatment. Multiple HHs and a growth rate of more than 4.8%/year were indications for surgical treatment. Nearly half of the HHs showed growing pattern in our study.
5.The first reported hepatitis E outbreak in a food manufacturing factory: Korea, 2022
Hansol YEOM ; Soonryu SEO ; Youngsil YOON ; Jaeeun LEE ; Myung-Guk HAN ; Deog-Yong LEE ; Sun-Whan PARK ; Song A PARK ; Sook-Hyang JEONG ; Jin GWACK
Osong Public Health and Research Perspectives 2023;14(1):15-22
Objectives:
On February 16, 2022, 12 cases of hepatitis E virus (HEV) infection were reported in a food manufacturing factory in Korea. The aim of this study was to identify additional cases and to determine the source of this HEV outbreak.
Methods:
This study was an in-depth investigation of 12 HEV immunoglobulin M (IgM)-positive cases and their demographic, clinical, and epidemiological characteristics. On-site specimens were collected from the environment and from humans, and a follow-up investigation was conducted 2 to 3 months after the outbreak.
Results:
Among 80 production workers in the factory, 12 (15.0%) had acute HEV infection, all of whom were asymptomatic. The follow-up investigation showed that 3 cases were HEV IgM-positive, while 6 were HEV IgG-positive. HEV genes were not detected in the HEV IgM-positive specimens. HEV genes were not detected in the food products or environmental specimens collected on-site. HEV was presumed to be the causative pathogen. However, it could not be confirmed that the source of infection was common consumption inside the factory.
Conclusion
This was the first domestic case of an HEV infection outbreak in a food manufacturing factory in Korea. Our results provide information for the future control of outbreaks and for the preparation of measures to prevent domestic outbreaks of HEV infection.
6.Hepatocellular carcinoma with Budd-Chiari syndrome due to membranous obstruction of the inferior vena cava with long-term follow-up: a case report
Choong Hee KIM ; Gwang Hyeon CHOI ; Hee Young NA ; Chang Jin YOON ; Jai Young CHO ; Sangmi JANG ; Ji Hye KIM ; Eun Sun JANG ; Jin-Wook KIM ; Sook-Hyang JEONG
Journal of Liver Cancer 2022;22(2):194-201
Membranous obstruction of the inferior vena cava (MOVC) is a rare subset of Budd-Chiari syndrome (BCS) with a subacute onset that is often complicated by cirrhosis and hepatocellular carcinoma (HCC). Here we report a case of recurrent HCC in a patient with cirrhosis and BCS that was treated with several episodes of transarterial chemoembolization followed by surgical tumorectomy, whereas the MOVC was successfully treated with balloon angioplasty followed by endovascular stenting. The patient was followed up for 9.9 years without anticoagulation and experienced no stent thrombosis. After the tumorectomy, the patient was HCC-free for 4.4 years of follow-up.
7.Efficacy and Safety of Glecaprevir/Pibrentasvir in Korean Patients with Chronic Hepatitis C: A Pooled Analysis of Five Phase II/III Trials
Jeong HEO ; Yoon Jun KIM ; Jin-Woo LEE ; Ji Hoon KIM ; Young-Suk LIM ; Kwang-Hyub HAN ; Sook-Hyang JEONG ; Mong CHO ; Ki Tae YOON ; Si Hyun BAE ; Eric D. CROWN ; Linda M. FREDRICK ; Negar Niki ALAMI ; Armen ASATRYAN ; Do Hyun KIM ; Seung Woon PAIK ; Youn-Jae LEE
Gut and Liver 2021;15(6):895-903
Background/Aims:
Glecaprevir/pibrentasvir (G/P) is the first pan-genotypic direct-acting antiviral combination therapy approved in Korea. An integrated analysis of five phase II and III trials was conducted to evaluate the efficacy and safety of G/P in Korean patients with chronic hepatitis C virus (HCV) infection.
Methods:
The study analyzed pooled data on Korean patients with HCV infection enrolled in the ENDURANCE 1 and 2, SURVEYOR II part 4 and VOYAGE I and II trials, which evaluated the efficacy and safety of 8 or 12 weeks of G/P treatment. The patients were either treatment-naïve or had received sofosbuvir or interferon-based treatment. Efficacy was evaluated by assessing the rate of sustained virologic response at 12 weeks posttreatment (SVR12). Safety was evaluated by monitoring adverse events (AEs) and laboratory assessments.
Results:
The analysis included 265 patients; 179 (67.5%) were HCV treatment-naïve, and most patients were either subgenotype 1B (48.7%) or 2A (44.5%). In the intention-to-treat population, 262 patients (98.9%) achieved SVR12. Three patients did not achieve SVR12: one had virologic failure and two had non-virologic failures. Most AEs were grade 1/2; eight patients (3.0%) expe-rienced at least one grade ≥3 AE. No serious AEs related to G/P treatment were reported, and grade ≥3 hepatic laboratory abnormalities were rare (0.8%).
Conclusions
G/P therapy was highly efficacious and well tolerated in Korean patients with HCV infection, with most patients achieving SVR12. The safety profile was comparable to that observed in a pooled analysis of a global pan-genotypic population of patients with HCV infection who received G/P.
8.Job Analysis of Nurse Care Coordinators for Chronic Illness Management in Primary Care Settings: Using Developing a Curriculum Process
Ju-Hee HWANG ; Yong-Jun CHOI ; Mi-Sook KIM ; Seng-Eun YI ; Yong-Soon PARK ; Ji-Hyang KIM ; Ju-Young YOON ; Dong-Soo SHIN
Journal of Korean Academy of Nursing 2021;51(6):758-768
Purpose:
This study aimed to conduct a job analysis of nurse carecoordinators and to identify the frequency, importance and difficulty of each task of their job.
Methods:
A committee for developing a curriculum (DACUM) was formed and members of the committee defined nurse care coordinators’ jobs and enumerated the duties, tasks and task elements by applying the DACUM technique. Then nurse care coordinators enrolled in the pilot project evaluated the frequency, importance and difficulty of each task.
Results:
From the job descriptions of nurse care coordinators, we identified 12 duties and 42 tasks. Each task comprised 1~5 task elements. Among tasks, ‘assess the patient’s general health status’ was carried out most frequently. Nurse care coordinators perceived that ‘check vital signs’ and ‘strengthen patient competence to promote health behaviors’ were more important than all other tasks. The most difficult task was ‘develop professionalism as a nurse care coordinator’.
Conclusion
The nurse care coordinators' roles developed in this study will serve as the key guidelines for human resource management of care coordinators. Further, job specifications for nurse care coordinators need to be developed, which is necessary for designing education and training programs. We also need to integrate primary health care as an essential component in nursing education.
9.Analysis of a COVID-19 Prescreening Process in an Outpatient Clinic at a University Hospital during the COVID-19 Pandemic
Ui Yoon CHOI ; Seung Eun JUNG ; Mi Sook KIM ; Hyang Sook OH ; Young Mi KWON ; Jehoon LEE ; Jung-Hyun CHOI
Journal of Korean Medical Science 2021;36(42):e295-
Background:
To minimize nosocomial infection against coronavirus disease 2019 (COVID-19), most hospitals conduct a prescreening process to evaluate the patient or guardian of any symptoms suggestive of COVID-19 or exposure to a COVID-19 patient at entrances of hospital buildings. In our hospital, we have implemented a two-level prescreening process in the outpatient clinic: an initial prescreening process at the entrance of the outpatient clinic (PPEO) and a second prescreening process is repeated in each department. If any symptoms or epidemiological history are identified at the second level, an emergency code is announced through the hospital's address system. The patient is then guided outside through a designated aisle. In this study, we analyze the cases missed in the PPEO that caused the emergency code to be applied.
Methods:
All cases reported from March 2020 to April 2021 were analyzed retrospectively. We calculated the incidence of cases missed by the PPEO per 1,000 outpatients and compared the incidence between first-time hospital visitors and those visiting for the second time or more; morning and afternoon office hours; and days of the week.
Results:
During the study period, the emergency code was applied to 449 cases missed by the PPEO. Among those cases, 20.7% were reported in otorhinolaryngology, followed by 11.6% in gastroenterology, 5.8% in urology, and 5.8% in dermatology. Fever was the most common symptom (59.9%), followed by cough (19.8%). The incidence of cases per 1,000 outpatients was significantly higher among first-time visitors than among those visiting for the second time or more (1.77 [confidence interval (CI), 1.44–2.10] vs. 0.59 [CI, 0.52–0.65], respectively) (P < 0.001).
Conclusion
Fever was the most common symptom missed by the PPEO, and otorhinolaryngology and gastroenterology most frequently reported missed cases. Cases missed by the PPEO were more likely to occur among first-time visitors than returning visitors. The results obtained from this study can provide insights or recommendations to other healthcare facilities in operating prescreening processes during the COVID-19 pandemic.
10.Risk Factors and Comorbidities Associated With the Allergic Rhinitis Phenotype in Children According to the ARIA Classification
Sungsu JUNG ; So Yeon LEE ; Jisun YOON ; Hyun Ju CHO ; Young Ho KIM ; Dong In SUH ; Song I YANG ; Ji won KWON ; Gwang Cheon JANG ; Yong Han SUN ; Sung Il WOO ; You Sook YOUN ; Kang Seo PARK ; Eun LEE ; Hwa Jin CHO ; Myung Hee KOOK ; Hye Ryoung YI ; Hai Lee CHUNG ; Ja Hyeong KIM ; Hyung Young KIM ; Jin A JUNG ; Hyang Ok WOO ; Jeom Kyu LEE ; Woo Sung CHANG ; Nam Hee DO ; Hyejoo CHO ; Soo Jong HONG
Allergy, Asthma & Immunology Research 2020;12(1):72-85
PURPOSE: Data are lacking on the association between the allergic rhinitis (AR) phenotype and sensitization to specific allergens or bronchial hyperresponsiveness (BHR) in children. We here investigated risk factors and comorbidities, including sensitization to specific allergens and BHR, for the AR phenotype by AR and its Impact on Asthma (ARIA) classification in a general population-based birth cohort study. METHODS: We enrolled 606 children aged 7 years from the Panel Study of Korean Children. The AR phenotype was assigned in accordance with the ARIA classification in children. Skin prick tests and Provocholine provocation test were performed. Risk factors and comorbidities for AR phenotypes were then analyzed. RESULTS: The prevalence of mild and moderate to severe AR in our study cohort was 37.2% and 8.8%, respectively. Recent use of analgesics or antipyretics and current cat ownership were associated with the risk of mild persistent AR. Sensitizations to Dermatophagoides Pteronyssinus (Der p), Japanese hop and cat were associated with moderate to severe persistent AR. Children with moderate to severe AR had a higher risk of current asthma and BHR compared to mild AR cases (adjusted odds ratio [aOR], 5.26; 95% confidence interval [CI], 1.77–15.62). Moderate to severe AR with allergic sensitization was associated with the highest risk of BHR (aOR, 11.77; 95% CI, 3.40–40.74). CONCLUSIONS: Moderate to severe-persistent AR is more closely related to respiratory comorbidities and sensitizations than mild AR. Stratifying the AR phenotype by ARIA classification may assist in disease management.
Allergens
;
Analgesics
;
Animals
;
Antipyretics
;
Asian Continental Ancestry Group
;
Asthma
;
Bronchial Hyperreactivity
;
Cats
;
Child
;
Classification
;
Cohort Studies
;
Comorbidity
;
Dermatophagoides pteronyssinus
;
Disease Management
;
Humans
;
Methacholine Chloride
;
Odds Ratio
;
Ownership
;
Parturition
;
Phenotype
;
Prevalence
;
Rhinitis, Allergic
;
Risk Factors
;
Skin

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