1.Genomic and Transcriptomic Characterization of Gastric Cancer with Bone Metastasis
Sujin OH ; Soo Kyung NAM ; Keun-Wook LEE ; Hye Seung LEE ; Yujun PARK ; Yoonjin KWAK ; Kyu Sang LEE ; Ji-Won KIM ; Jin Won KIM ; Minsu KANG ; Young Suk PARK ; Sang-Hoon AHN ; Yun-Suhk SUH ; Do Joong PARK ; Hyung Ho KIM
Cancer Research and Treatment 2024;56(1):219-237
Purpose:
Bone metastasis (BM) adversely affects the prognosis of gastric cancer (GC). We investigated molecular features and immune microenvironment that characterize GC with BM compared to GC without BM.
Materials and Methods:
Targeted DNA and whole transcriptome sequencing were performed using formalin-fixed paraffin-embedded primary tumor tissues (gastrectomy specimens) of 50 GC cases with distant metastases (14 with BM and 36 without BM). In addition, immunohistochemistry (IHC) for mucin-12 and multiplex IHC for immune cell markers were performed.
Results:
Most GC cases with BM had a histologic type of poorly cohesive carcinoma and showed worse overall survival (OS) than GC without BM (p < 0.05). GC with BM tended to have higher mutation rates in TP53, KDR, APC, KDM5A, and RHOA than GC without BM. Chief cell-enriched genes (PGA3, PGC, and LIPF), MUC12, MFSD4A, TSPAN7, and TRIM50 were upregulated in GC with BM compared to GC without BM, which was correlated with poor OS (p < 0.05). However, the expression of SERPINA6, SLC30A2, PMAIP1, and ITIH2 were downregulated in GC with BM. GC with BM was associated with PIK3/AKT/mTOR pathway activation, whereas GC without BM showed the opposite effect. The densities of helper, cytotoxic, and regulatory T cells did not differ between the two groups, whereas the densities of macrophages were lower in GC with BM (p < 0.05).
Conclusion
GC with BM had different gene mutation and expression profiles than GC without BM, and had more genetic alterations associated with a poor prognosis.
2.Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE)
Nam Hoon KIM ; Juneyoung LEE ; Suk CHON ; Jae Myung YU ; In-Kyung JEONG ; Soo LIM ; Won Jun KIM ; Keeho SONG ; Ho Chan CHO ; Hea Min YU ; Kyoung-Ah KIM ; Sang Soo KIM ; Soon Hee LEE ; Chong Hwa KIM ; Soo Heon KWAK ; Yong‐ho LEE ; Choon Hee CHUNG ; Sihoon LEE ; Heung Yong JIN ; Jae Hyuk LEE ; Gwanpyo KOH ; Sang-Yong KIM ; Jaetaek KIM ; Ju Hee LEE ; Tae Nyun KIM ; Hyun Jeong JEON ; Ji Hyun LEE ; Jae-Han JEON ; Hye Jin YOO ; Hee Kyung KIM ; Hyeong-Kyu PARK ; Il Seong NAM-GOONG ; Seongbin HONG ; Chul Woo AHN ; Ji Hee YU ; Jong Heon PARK ; Keun-Gyu PARK ; Chan Ho PARK ; Kyong Hye JOUNG ; Ohk-Hyun RYU ; Keun Yong PARK ; Eun-Gyoung HONG ; Bong-Soo CHA ; Kyu Chang WON ; Yoon-Sok CHUNG ; Sin Gon KIM
Endocrinology and Metabolism 2024;39(5):722-731
Background:
Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined.
Methods:
This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months.
Conclusion
This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.
3.Association between soy products, fruits, vegetables, and dairy products and gastric cancer risk in Helicobacter pylori-infected subjects: a case-control study in Korea
Jung Hyun KWAK ; Chang Soo EUN ; Dong Soo HAN ; Yong Sung KIM ; Kyu Sang SONG ; Bo Youl CHOI ; Hyun Ja KIM
Nutrition Research and Practice 2023;17(1):122-134
BACKGROUND/OBJECTIVES:
Consumption of certain protective foods may help inhibit Helicobacter pylori (H. pylori) associated gastric pathologies. However, studies conducted to assess the efficacy of protective foods in H. pylori-infected subjects are either limited or inconsistent. This study evaluated the association of individual or a combination of protective foods on the incidence of gastric cancer (GC) in H. pylori-positive subjects through a casecontrol study.MATERIALS/METHODS: Subjects aged 20–79 years were selected from 2 hospitals between December 2002 and September 2006. In total, 134 patients and 212 controls tested positive for H. pylori infection. Among these, we included 82 pairs of cases and controls matched by sex, age (± 5 years), enrollment period (± 1 years), and hospital.
RESULTS:
A higher intake of soy products was associated with a significantly lower risk of GC than a lower intake of soy products (odds ratio [OR] = 0.37, 95% confidence interval [CI] = 0.14–0.96). Additionally, a higher fruit intake resulted in a significantly lower risk of GC than a lower fruit intake (OR = 0.35, 95% CI = 0.13–0.94). A combination of food groups was evaluated, and a lower risk of GC was observed with a high intake of both soy products and fruits (OR = 0.20, 95% CI = 0.06–0.67), high intake of soy and dairy products (OR = 0.28, 95% CI = 0.10–0.78) and high intake of fruits and dairy products (OR = 0.28, 95% CI = 0.09–0.83).
CONCLUSIONS
A high intake of soy products or fruits was associated with a lower risk of GC.A combination of soy products or fruits with dairy products was associated with a lower risk of GC. A balanced intake of soy products, fruits, and dairy products may help reduce GC risk.
4.Survival Benefit of Adjuvant Chemotherapy in Patients with Pancreatic Ductal Adenocarcinoma Who Underwent Surgery Following Neoadjuvant FOLFIRINOX
So Heun LEE ; Dae Wook HWANG ; Changhoon YOO ; Kyu-pyo KIM ; Sora KANG ; Jae Ho JEONG ; Dongwook OH ; Tae Jun SONG ; Sang Soo LEE ; Do Hyun PARK ; Dong Wan SEO ; Jin-hong PARK ; Ki Byung SONG ; Jae Hoon LEE ; Woohyung LEE ; Yejong PARK ; Bong Jun KWAK ; Heung-Moon CHANG ; Baek-Yeol RYOO ; Song Cheol KIM
Cancer Research and Treatment 2023;55(3):956-968
Purpose:
The benefit of adjuvant chemotherapy following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant FOLFIRINOX is unclear. This study aimed to assess the survival benefit of adjuvant chemotherapy in this patient population.
Materials and Methods:
This retrospective study included 218 patients with localized non-metastatic PDAC who received neoadjuvant FOLFIRINOX and underwent curative-intent surgery (R0 or R1) between January 2017 and December 2020. The association of adjuvant chemotherapy with disease-free survival (DFS) and overall survival (OS) was evaluated in overall patients and in the propensity score matched (PSM) cohort. Subgroup analysis was conducted according to the pathology-proven lymph node status.
Results:
Adjuvant chemotherapy was administered to 149 patients (68.3%). In the overall cohort, the adjuvant chemotherapy group had significantly improved DFS and OS compared to the observation group (DFS: median, 13.8 months [95% confidence interval (CI), 11.0 to 19.1] vs. 8.2 months [95% CI, 6.5 to 12.0]; p < 0.001; and OS: median, 38.0 months [95% CI, 32.2 to not assessable] vs. 25.7 months [95% CI, 18.3 to not assessable]; p=0.005). In the PSM cohort of 57 matched pairs of patients, DFS and OS were better in the adjuvant chemotherapy group than in the observation group (p < 0.001 and p=0.038, respectively). In the multivariate analysis, adjuvant chemotherapy was a significant favorable prognostic factor (vs. observation; DFS: hazard ratio [HR], 0.51 [95% CI, 0.36 to 0.71; p < 0.001]; OS: HR, 0.45 [95% CI, 0.29 to 0.71; p < 0.001]).
Conclusion
Among PDAC patients who underwent surgery following neoadjuvant FOLFIRINOX, adjuvant chemotherapy may be associated with improved survival. Randomized studies should be conducted to validate this finding.
5.The principles of presenting statistical results using figures
Jae Hong PARK ; Dong Kyu LEE ; Hyun KANG ; Jong Hae KIM ; Francis Sahngun NAHM ; EunJin AHN ; Junyong IN ; Sang Gyu KWAK ; Chi-Yeon LIM
Korean Journal of Anesthesiology 2022;75(2):139-150
Tables and figures are commonly adopted methods for presenting specific data or statistical analysis results. Figures can be used to display characteristics and distributions of data, allowing for intuitive understanding through visualization and thus making it easier to interpret the statistical results. To maximize the positive aspects of figure presentation and increase the accuracy of the content, in this article, the authors will describe how to choose an appropriate figure type and the necessary components to include. Additionally, this article includes examples of figures that are commonly used in research and their essential components using virtual data.
6.Baseline use of hydroxychloroquine or immunosuppressive drugs and the risk of coronavirus disease 2019
Ji-Won KIM ; Sang Gyu KWAK ; Hwajeong LEE ; Seong-Kyu KIM ; Jung-Yoon CHOE ; Sung-Hoon PARK
The Korean Journal of Internal Medicine 2022;37(3):673-680
Background/Aims:
The preventive role of hydroxychloroquine (HCQ) on coronavirus disease 2019 (COVID-19) remains unclear. The aim of this study was to examine the effects of HCQ and other immunosuppressive drugs on the incidence of COVID-19.
Methods:
The data were collected from the South Korea National Health Insurance Sharing-COVID-19 database. All individuals who underwent nasopharyngeal and oropharyngeal swab tests for COVID-19 from January 2020 to May 2020 are included. The association between COVID-19 risk and HCQ use was examined in a propensity score-matched population. Factors associated with COVID-19 were identified using multiple logistic regression analysis.
Results:
Total 8,070 patients with COVID-19 and 121,050 negative controls were included from the database. Among all participants, 381 were HCQ users. In a propensity score-matched population, the incidence of COVID-19 was 7.1% in HCQ users and 6.8% in non-users. The odds ratio (OR) for HCQ use was 1.05 with a 95% confidence interval (CI) of 0.58 to 1.89. Among the subpopulation of patients with rheumatoid arthritis (RA), 33 were diagnosed with COVID-19 and 478 were not. Use of HCQ, glucocorticoids, or other immunosuppressive drugs was not associated with COVID-19 risk, whereas abatacept use was. Chronic lung disease was an independent risk factor for COVID-19 diagnosis in patients with RA (adjusted OR, 6.07; 95% CI, 1.10 to 33.59).
Conclusions
The risk of COVID-19 did not differ between HCQ users and non-users. Glucocorticoids, conventional disease-modifying antirheumatic drugs (DMARDs), and biological DMARDs other than abatacept did not increase the risk of COVID-19.
7.Comparison between the coronal diameters of the cervical spinal canal and spinal cord measured using computed tomography and magnetic resonance imaging in Korean patients
So Young LEE ; In Young KIM ; Kyung Wook JEONG ; Taeha RYU ; Sang Kyu KWAK ; Jin Yong JUNG
Korean Journal of Anesthesiology 2022;75(4):323-330
Background:
If the proportion of the spinal cord in the epidural space can be determined under C-arm fluoroscopy during cervical epidural block, a safe entry point for the epidural needle can be established. The aim of this study was the measurement of the cord to canal transverse diameter ratio of each cervical spines.
Methods:
We retrospectively evaluated the imaging data of 100 patients who underwent both cervical computed tomography (CT) and cervical magnetic resonance imaging (MRI) at our hospital. We measured the diameters of the spinal canal and spinal cord from the 3rd cervical vertebra to the 1st thoracic vertebra (T1) at each level by using the patients’ cervical CT and MRI images. The spinal cord and spinal canal diameters were measured in the transverse plane of the cervical MRI and CT images, respectively.
Results:
The spinal cord to spinal canal diameter ratio was the highest at the 4th and 5th cervical vertebrae (0.64 ± 0.07) and the lowest at T1 (0.55 ± 0.06, 99% CI [0.535, 0.565].
Conclusions
Our findings suggest that the cord to canal transverse diameter ratio could be used as a reference to reduce direct spinal cord injuries during cervical epidural block under C-arm fluoroscopy. In the C-arm fluoroscopic image, if an imaginary line connecting the left and right innermost lines of the pedicles of T1 is drawn and if the needle is inserted into the outer one-fifth of the left and right sides, the risk of puncturing the spinal cord would be relatively reduced.
8.Distribution of Gastrointestinal Parasitic Infection in Domestic Pigs in the Republic of Korea: Nationwide Survey from 2020-2021
Subin LEE ; Badriah ALKATHIRI ; Dongmi KWAK ; Sang-Myeong LEE ; Wan-Kyu LEE ; Jae-Won BYUN ; Seung-Hun LEE
The Korean Journal of Parasitology 2022;60(3):207-211
This study aimed to examine the distribution of gastrointestinal parasitic infections in domestic pigs in the Republic of Korea. From May 2020 to October 2021, 364 pig fecal samples were collected from 75 farms in 7 Provinces and microscopically examined. A total of 170 (46.7%) pigs were infected with at least one of the following parasites: Balantioides coli, strongyles, Ascaris suum, Trichuris suis, and coccidia. By parasite species, B. coli, strongyles, A. suum, T. suis, and coccidia oocysts or eggs were detected in 144 (39.6%), 24 (6.6%), 14 (3.8%), 4 (1.1%), and 1 (0.3%) samples, respectively. One hundred fifty-four, 15, and 1 cases showed single, double, and triple infections, respectively. Of the swine fecal samples from 75 farms, 69 specimens (92.0%) were infected with 1 or more parasites. All surveyed farms across the country exhibited a positive rate of over 30%, among which the highest positive rate was 65.0% in Chungcheongnam-do, and Jeollabuk-do was followed by 61.9%. Winter showed a statistically lower prevalence than other seasons. This study showed that gastrointestinal parasites are prevalent in pigs in Korea, although the diversity of parasites is low.
9.Three-Dimensional Distribution of Cochlear Macrophages in the Lateral Wall of Cleared Cochlea
Seong Hoon BAE ; Sang Hyun KWAK ; Jee Eun YOO ; Kyu Min KIM ; Young Min HYUN ; Jae Young CHOI ; Jinsei JUNG
Clinical and Experimental Otorhinolaryngology 2021;14(2):179-184
Objectives:
. Resident macrophages are well known to be present in the cochlea, but the exact patterns thereof in spiral ligaments have not been discussed in previous studies. We sought to document the distribution of macrophages in intact cochleae using three-dimensional imaging.
Methods:
. Cochleae were obtained from C-X3-C motif chemokine receptor 1+/GFP mice, and organ clearing was performed. Three-dimensional images of cleared intact cochleae were reconstructed using two-photon microscopy. The locations of individual macrophages were investigated using 100-μm stacked images to reduce bias. Cochlear inflammation was then induced by lipopolysaccharide (LPS) inoculation into the middle ear through the tympanic membrane. Four days after inoculation, three-dimensional images were obtained.
Results:
. Macrophages were scarce in areas adjacent to the stria vascularis, particularly the area just beneath it even though many have suspected macrophages to be abundant in this area. This finding remained consistent upon LPS-induced cochlear inflammation, despite a significant increase in the number of macrophages, compared to non-treated cochlea.
Conclusion
. Resident macrophages in spiral ligaments are scarce in areas adjacent to the stria vascularis.
10.Fatal Necrotizing Fasciitis Following Uncomplicated Colonoscopic Polypectomy: A Case Report
Min Kyu CHAE ; Sang Youn SHIN ; Min Seob KWAK ; Jin Young YOON ; Ha Il KIM ; Jae Myung CHA
Clinical Endoscopy 2021;54(2):280-284
Necrotizing fasciitis (NF) is a life-threatening infection that can be caused by various procedures or surgery and may develop in healthy elderly patients. Here, we report a case of a 66-year-old man with diabetes mellitus who underwent colonoscopic polypectomy, without complications. However, he visited the emergency department 24 hours after the procedure complaining of abdominal pain. Abdominopelvic computed tomography revealed multiple air bubbles in the right lateral abdominal muscles. After a diagnosis of NF was made, immediate surgical debridement was performed. However, despite three sessions of extensive surgical debridement and best supportive care at the intensive care unit, the patient died because of sepsis and NF-associated multiple-organ failure. In conclusion, physicians should pay special attention to the possibility of NF if a patient with risk factors for NF develops sepsis after colonoscopic polypectomy.

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