1.Robinetin Alleviates Metabolic Failure in Liver through Suppression of p300–CD38 Axis
Ji-Hye SONG ; Hyo-Jin KIM ; Jangho LEE ; Seung-Pyo HONG ; Min-Yu CHUNG ; Yu-Geun LEE ; Jae Ho PARK ; Hyo-Kyoung CHOI ; Jin-Taek HWANG
Biomolecules & Therapeutics 2024;32(2):214-223
Metabolic abnormalities in the liver are closely associated with diverse metabolic diseases such as non-alcoholic fatty liver disease, type 2 diabetes, and obesity. The aim of this study was to evaluate the ameliorating effect of robinetin (RBN) on the significant pathogenic features of metabolic failure in the liver and to identify the underlying molecular mechanism. RBN significantly decreased triglyceride (TG) accumulation by downregulating lipogenesis-related transcription factors in AML-12 murine hepatocyte cell line. In addition, mice fed with Western diet (WD) containing 0.025% or 0.05% RBN showed reduced liver mass and lipid droplet size, as well as improved plasma insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values.CD38 was identified as a target of RBN using the BioAssay database, and its expression was increased in OPA-treated AML-12 cells and liver tissues of WD-fed mice. Furthermore, RBN elicited these effects through its anti-histone acetyltransferase (HAT) activity. Computational simulation revealed that RBN can dock into the HAT domain pocket of p300, a histone acetyltransferase, which leads to the abrogation of its catalytic activity. Additionally, knock-down of p300 using siRNA reduced CD38 expression.The chromatin immunoprecipitation (ChIP) assay showed that p300 occupancy on the promoter region of CD38 was significantly decreased, and H3K9 acetylation levels were diminished in lipid-accumulated AML-12 cells treated with RBN. RBN improves the pathogenic features of metabolic failure by suppressing the p300–CD38 axis through its anti-HAT activity, which suggests that RBN can be used as a new phytoceutical candidate for preventing or improving this condition.
2.International Digestive Endoscopy Network consensus on the management of antithrombotic agents in patients undergoing gastrointestinal endoscopy
Seung Joo KANG ; Chung Hyun TAE ; Chang Seok BANG ; Cheol Min SHIN ; Young-Hoon JEONG ; Miyoung CHOI ; Joo Ha HWANG ; Yutaka SAITO ; Philip Wai Yan CHIU ; Rungsun RERKNIMITR ; Christopher KHOR ; Vu Van KHIEN ; Kee Don CHOI ; Ki-Nam SHIM ; Geun Am SONG ; Oh Young LEE ;
Clinical Endoscopy 2024;57(2):141-157
Antithrombotic agents, including antiplatelet agents and anticoagulants, are widely used in Korea because of the increasing incidence of cardiocerebrovascular disease and the aging population. The management of patients using antithrombotic agents during endoscopic procedures is an important clinical challenge. The clinical practice guidelines for this issue, developed by the Korean Society of Gastrointestinal Endoscopy, were published in 2020. However, new evidence on the use of dual antiplatelet therapy and direct anticoagulant management has emerged, and revised guidelines have been issued in the United States and Europe. Accordingly, the previous guidelines were revised. Cardiologists were part of the group that developed the guideline, and the recommendations went through a consensus-reaching process among international experts. This guideline presents 14 recommendations made based on the Grading of Recommendations, Assessment, Development, and Evaluation methodology and was reviewed by multidisciplinary experts. These guidelines provide useful information that can assist endoscopists in the management of patients receiving antithrombotic agents who require diagnostic and elective therapeutic endoscopy. It will be revised as necessary to cover changes in technology, evidence, or other aspects of clinical practice.
3.International Digestive Endoscopy Network Consensus on the Management of Antithrombotic Agents in Patients Undergoing Gastrointestinal Endoscopy
Seung Joo KANG ; Chung Hyun TAE ; Chang Seok BANG ; Cheol Min SHIN ; Young-Hoon JEONG ; Miyoung CHOI ; Joo Ha HWANG ; Yutaka SAITO ; Philip Wai Yan CHIU ; Rungsun RERKNIMITR ; Christopher KHOR ; Vu Van KHIEN ; Kee Don CHOI ; Ki-Nam SHIM ; Geun Am SONG ; Oh Young LEE ; The Korean Society of Gastrointestinal Endoscopy Task Force on Clinical Practice Guidelines
Gut and Liver 2024;18(5):764-780
Antithrombotic agents, including antiplatelet agents and anticoagulants, are widely used in Korea because of the increasing incidence of cardiocerebrovascular disease and the aging population. The management of patients using antithrombotic agents during endoscopic procedures is an important clinical challenge. The clinical practice guidelines for this issue, developed by the Korean Society of Gastrointestinal Endoscopy, were published in 2020. However, new evidence on the use of dual antiplatelet therapy and direct anticoagulant management has emerged, and revised guidelines have been issued in the United States and Europe. Accordingly, the previous guidelines were revised. Cardiologists were part of the group that developed the guideline, and the recommendations went through a consensus-reaching process among international experts. This guideline presents 14 recommendations made based on the Grading of Recommendations, Assessment, Development, and Evaluation methodology and was reviewed by multidisciplinary experts. These guidelines provide useful information that can assist endoscopists in the management of patients receiving antithrombotic agents who require diagnostic and elective therapeutic endoscopy. It will be revised as necessary to cover changes in technology, evidence, or other aspects of clinical practice.
4.Mortality associated with the neutrophil-lymphocyte ratio in septic acute kidney injury requiring continuous renal replacement therapy
Jinwoo LEE ; Jeongin SONG ; Seong Geun KIM ; Donghwan YUN ; Min Woo KANG ; Dong Ki KIM ; Kook-Hwan OH ; Kwon Wook JOO ; Yon Su KIM ; Seung Seok HAN ; Yong Chul KIM
Kidney Research and Clinical Practice 2024;43(3):337-347
Sepsis is an important cause of acute kidney injury in intensive care unit patients, accounting for 15% to 20% of renal replacement therapy prescriptions. The neutrophil-lymphocyte ratio (NLR), a marker of systemic inflammation and immune response, was previously associated with the mortality rate in multiple conditions. Herein, we aimed to examine how the NLR relates to the mortality rate in septic acute kidney injury patients requiring continuous renal replacement therapy (CRRT). Methods: The NLRs of 6 and 18 were used for dividing NLRs into three groups and, thus, were set higher than those in previous studies accounting for steroid use in sepsis. Cox proportional hazard models were used to calculate hazard ratios of mortality outcomes before and after matching their propensity scores. Results: A total of 798 septic acute kidney injury patients requiring CRRT were classified into three NLR groups (low, <6 [n = 277]; medium, ≥6 and <18 [n = 115], and high, ≥18 [n = 406], respectively). The in-hospital mortality rates per group were 83.4%, 74.8%, and 70.4%, respectively (p < 0.001). Per the univariable Cox survival analysis after propensity score matching, a high NLR was related to approximately 24% reduced mortality. The survival benefit of the high NLR group compared with the other two groups remained consistent across all subgroups, showing any p for interactions of >0.05. Conclusion: A high NLR is associated with better clinical outcomes, such as low mortality, in septic acute kidney injury patients undergoing CRRT.
5.IDEN Consensus on Management of Antithrombotic Agents in Patients Undergoing Gastrointestinal Endoscopy
Seung Joo KANG ; Chung Hyun TAE ; Chang Seok BANG ; Cheol Min SHIN ; Young-Hoon JEONG ; Miyoung CHOI ; Joo Ha HWANG ; Yutaka SAITO ; Philip Wai Yan CHIU ; Rungsun RERKNIMITR ; Christopher KHOR ; Vu Van KHIEN ; Kee Don CHOI ; Ki-Nam SHIM ; Geun Am SONG ; Oh Young LEE ;
The Korean Journal of Gastroenterology 2024;83(6):217-232
Antithrombotic agents, including antiplatelet agent and anticoagulants are widely used in Korea due to increasing incidence of cardio-cerebrovascular disease and aging population. The management of patients using antithrombotic agents during endoscopic procedures is an important clinical challenge. Clinical practice guideline regarding this issue which was developed by the Korean Society of Gastrointestinal Endoscopy was published in 2020. However, since then, new evidence has emerged for the use of dual antiplatelet therapy and direct anticoagulant management, and revised guidelines were issued in the US and Europe. Accordingly, the previous guidelines were revised, cardiologists also participated in the development group, and the recommendations went through a consensus process among international experts. This guideline presents 14 recommendations made according to the Grading of Recommendations, Assessment, Development, and Evaluation methodology, and was reviewed by multidisciplinary experts. This guideline provides useful information that can assist endoscopists in the management of patients on antithrombotic agents who require diagnostic and elective therapeutic endoscopy. It will be revised as necessary to cover changes in technology, evidence, or other aspects of clinical practice.
6.Effective Endoscopic Submucosal Dissection of a Huge Esophageal Liposarcoma: A Case Report
Myeong Jin LEE ; Moon Won LEE ; Dong Chan JOO ; Seung Min HONG ; Dong Hoon BAEK ; Bong Eun LEE ; Gwang Ha KIM ; Geun Am SONG
The Korean Journal of Gastroenterology 2024;83(6):243-246
This case report presents the successful endoscopic submucosal dissection (ESD) of a well-differentiated esophageal liposarcoma in a 51-year-old male with persistent dysphagia. The cause was initially diagnosed as a 10 cm pedunculated lesion extending from the upper esophageal sphincter to the mid-esophagus. An ESD was chosen over traditional surgery because it is less invasive. The procedure involved a precise submucosal injection and excision with special techniques to manage bleeding from a central vessel.Despite the extraction challenges owing to the size of the lesion, it was successfully removed orally. A histopathological examination of the 8.3×4.2×2.3 cm specimen revealed the characteristic features of a well-differentiated liposarcoma, including MDM2 and CDK4 positivity. The follow-up revealed no recurrence, and active surveillance has been performed since. This report highlights the versatility of ESD in treating significant esophageal tumors and provides evidence for its efficacy as a minimally invasive alternative.
8.High vegetable consumption and regular exercise are associated with better quality of life in patients with gout
Hyunsue DO ; Hyo Jin CHOI ; Byoongyong CHOI ; Chang-Nam SON ; Sang-Hyon KIM ; You-Jung HA ; Ji Hyoun KIM ; Min Jung KIM ; Kichul SHIN ; Hyun-Ok KIM ; Ran SONG ; Sung Won LEE ; Joong Kyong AHN ; Seung-Geun LEE ; Chang Hoon LEE ; Kyeong Min SON ; Ki Won MOON
The Korean Journal of Internal Medicine 2024;39(5):845-854
Background/Aims:
The Gout Impact Scale (GIS), a part of the Gout Assessment Questionnaire 2.0, is used to measure gout-specific health-related quality of life (HRQOL). Although several studies have been conducted on the factors affecting the HRQOL of patients with gout, few have focused on lifestyle factors. This study aimed to investigate the correlation between lifestyle habits and HRQOL using the GIS in patients with gout.
Methods:
We used data from the Urate-Lowering TheRApy in Gout (ULTRA) registry, a prospective cohort of Korean patients with gout treated at multiple centers nationwide. The patients were aged ≥18 years and met the 2015 American College of Rheumatology/European League Against Rheumatism gout classification criteria. They were asked to complete a GIS and questions regarding their lifestyle habits at enrollment.
Results:
The study included 232 patients. ‘Gout concern overall’ scores in the GIS were significantly lower in patients who exercised more frequently and consumed soft drinks and meat less, and ‘well-being during attack’ scores were significantly lower in patients who consumed vegetables and exercised more frequently. The frequency of vegetable consumption had a negative linear relationship with the ‘well-being during attack’ and ‘gout concern during attack’ scores (p = 0.01, p = 0.001, respectively). The frequency of exercise had a negative linear relationship with the ‘gout concern overall’ and ‘gout concern during attack’ scores (p = 0.04 and p = 0.002, respectively).
Conclusions
Patients with gout who frequently consumed vegetables and exercised regularly experienced less impact of gout, exhibiting a better GIS that represented HRQOL.
9.Effects of Tegoprazan Versus Esomeprazole on Nighttime Heartburn and Sleep Quality in Gastroesophageal Reflux Disease: A Multicenter Double-blind Randomized Controlled Trial
Joon Sung KIM ; Seung In SEO ; Sun Hyung KANG ; Sang Kil LEE ; Ah Rong KIM ; Hyun Wook PARK ; Bong Tae KIM ; Geun Seog SONG
Journal of Neurogastroenterology and Motility 2023;29(1):58-64
Background/Aims:
Patients with gastroesophageal reflux disease (GERD) frequently experience nighttime heartburn and sleep disturbance. Tegoprazan is a new potassium-competitive acid blocker that can rapidly block acid secretion. This study aims to evaluate the efficacy of tegoprazan compared with esomeprazole in relieving nighttime heartburn and sleep disturbances.
Methods:
Patients with erosive esophagitis, nighttime heartburn, and sleep disturbances were randomized to receive tegoprazan 50 mg or esomeprazole 40 mg for 2 weeks. The primary endpoint was time to first nighttime heartburn-free interval. The percentage of nighttime heartburn-free days was also compared between the 2 groups.
Results:
A total of 46 patients were enrolled in this study. Time to the first nighttime heartburn-free interval was shorter with tegoprazan than with esomeprazole but the difference was not statistically significant (1.5 days vs 3 days, P = 0.151). The percentage of nighttime heartburn-free days was higher in the tegoprazan group but the difference was insignificant (57.8% vs 43.1%, P = 0.107). Adverse events occurred in 2 patients. They were mild in severity.
Conclusions
Tegoprazan may induce faster relief of nighttime heartburn symptoms and may improve sleep disorders associated with nighttime heartburn. Further large-scale studies are required to validate our findings.
10.The prognostic impact of reduced variant burden in elderly patients with acute myeloid leukemia treated with decitabine
Mihee KIM ; TaeHyung KIM ; Seo-Yeon AHN ; Jun Hyung LEE ; Ju Heon PARK ; Myung-Geun SHIN ; Sung-Hoon JUNG ; Ga-Young SONG ; Deok-Hwan YANG ; Je-Jung LEE ; Seung Hyun CHOI ; Mi Yeon KIM ; Jae-Sook AHN ; Hyeoung-Joon KIM ; Dennis Dong Hwan KIM
The Korean Journal of Internal Medicine 2023;38(4):534-545
Background/Aims:
We evaluated the role of next-generation sequencing (NGS)-based disease monitoring for elderly patients diagnosed with acute myeloid leukemia (AML) who received decitabine therapy.
Methods:
A total of 123 patients aged > 65 years with AML who received decitabine were eligible. We analyzed the dynamics of variant allele frequency (VAF) in 49 available follow-up samples after the fourth cycle of decitabine. The 58.6% VAF clearance (Δ, [VAF at diagnosis − VAF at follow-up] × 100 / VAF at diagnosis) was the optimal cut-off for predicting overall survival (OS).
Results:
The overall response rate was 34.1% (eight patients with complete remission [CR], six of CR with incomplete hematologic recovery, 22 with partial responses, and six with morphologic leukemia-free status). Responders (n = 42) had significantly better OS compared with non-responders (n = 42) (median, 15.3 months vs. 6.5 months; p < 0.001). Of the 49 patients available for follow-up targeted NGS analysis, 44 had trackable gene mutations. The median OS of patients with ΔVAF ≥ 58.6% (n=24) was significantly better than that of patients with ΔVAF < 58.6% (n = 19) (20.5 months vs. 9.8 months, p = 0.010). Moreover, responders with ΔVAF ≥ 58.6% (n = 20) had a significantly longer median OS compared with responders with VAF < 58.6% (n = 11) (22.5 months vs. 9.8 months, p = 0.004).
Conclusions
This study suggested that combining ΔVAF ≥ 58.6%, a molecular response, with morphologic and hematologic responses can more accurately predict OS in elderly AML patients after decitabine therapy.

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