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.Prognostic Implications of Selective Dissection of Left Lower Paratracheal Lymph Nodes in Patients with Left-Sided NonSmall Cell Lung Cancer
Hyo Kyen PARK ; Yelee KWON ; Geun Dong LEE ; Sehoon CHOI ; Hyeong Ryul KIM ; Yong-Hee KIM ; Dong Kwan KIM ; Seung-Il PARK ; Jae Kwang YUN
Journal of Chest Surgery 2024;57(5):467-476
Background:
This study aimed to examine the clinical implications of selective station 4L lymph node dissection (S4L-LND) on survival in non-small cell lung cancer (NSCLC) and to evaluate its potential advantages.
Methods:
We enrolled patients with primary left-sided NSCLC who underwent upfront video-assisted thoracoscopic surgery with R0 resection including lobectomy and segmentectomy, with or without S4L-LND, at our institution between January 2007 and December 2021. Following 1:1 propensity score matching (PSM), we compared overall survival (OS) and recurrence-free survival (RFS) between patients with and without S4L-LND.
Results:
The study included 2,601 patients, of whom 1,126 underwent S4L-LND and 1,475 did not. PSM yielded 1,036 patient pairs. Among those who underwent S4L-LND, 87 (7.7%) exhibited S4L-LN involvement. Neither OS (p=0.12) nor RFS (p=0.24) differed significantly between matched patients with and without S4L-LND. In patients with S4L-LN involvement, metastases were more common in the left upper lobe (LUL) than in the left lower lobe (LLL) (3.6% vs. 2.0%, p=0.061). Metastasis became significantly more frequent with more advanced clinical N (cN) stage (cN0, 2.3%; cN1, 5.8%; cN2, 32.6%; p<0.001). Multivariate logistic regression analysis revealed that cN stage and tumor location were independently associated with S4L-LN involvement (p<0.001 for both).
Conclusion
OS and RFS did not differ significantly between matched patients with and without S4L-LND. Among participants with S4L-LN involvement, metastases occurred more frequently in the LUL than the LLL, and their incidence increased significantly with more advanced cN stage. Thus, patients with LUL or advanced cN lung cancers may benefit from S4L-LND.
3.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.
4.Profiling of endogenous metabolites and changes in intestinal microbiota distribution after GEN-001 (Lactococcus lactis) administration
Min-Gul KIM ; Suin KIM ; Ji-Young JEON ; Seol Ju MOON ; Yong-Geun KWAK ; Joo Young NA ; SeungHwan LEE ; Kyung-Mi PARK ; Hyo-Jin KIM ; Sang-Min LEE ; Seo-Yeon CHOI ; Kwang-Hee SHIN
The Korean Journal of Physiology and Pharmacology 2024;28(2):153-164
This study aimed to identify metabolic biomarkers and investigate changes in intestinal microbiota in the feces of healthy participants following administration of Lactococcus lactis GEN-001. GEN-001 is a single-strain L. lactis strain isolated from the gut of a healthy human volunteer. The study was conducted as a parallel, randomized, phase 1, open design trial. Twenty healthy Korean males were divided into five groups according to the GEN-001 dosage and dietary control.Groups A, B, C, and D1 received 1, 3, 6, and 9 GEN-001 capsules (1 × 1011 colony forming units), respectively, without dietary adjustment, whereas group D2 received 9 GEN-001 capsules with dietary adjustment. All groups received a single dose. Fecal samples were collected 2 days before GEN-001 administration to 7 days after for untargeted metabolomics and gut microbial metagenomic analyses; blood samples were collected simultaneously for immunogenicity analysis. Levels of phenylalanine, tyrosine, cholic acid, deoxycholic acid, and tryptophan were significantly increased at 5–6 days after GEN-001 administration when compared with predose levels. Compared with predose, the relative abundance (%) of Parabacteroides and Alistipes significantly decreased, whereas that of Lactobacillus and Lactococcus increased; Lactobacillus and tryptophan levels were negatively correlated. A single administration of GEN-001 shifted the gut microbiota in healthy volunteers to a more balanced state as evidenced by an increased abundance of beneficial bacteria, including Lactobacillus, and higher levels of the metabolites that have immunogenic properties.
5.The Role of Adjuvant Therapy Following Surgical Resection of Small Cell Lung Cancer: A Multi-Center Study
Seong Yong PARK ; Samina PARK ; Geun Dong LEE ; Hong Kwan KIM ; Sehoon CHOI ; Hyeong Ryul KIM ; Yong-Hee KIM ; Dong Kwan KIM ; Seung-Il PARK ; Tae Hee HONG ; Yong Soo CHOI ; Jhingook KIM ; Jong Ho CHO ; Young Mog SHIM ; Jae Ill ZO ; Kwon Joong NA ; In Kyu PARK ; Chang Hyun KANG ; Young-Tae KIM ; Byung Jo PARK ; Chang Young LEE ; Jin Gu LEE ; Dae Joon KIM ; Hyo Chae PAIK
Cancer Research and Treatment 2023;55(1):94-102
Purpose:
This multi-center, retrospective study was conducted to evaluate the long-term survival in patients who underwent surgical resection for small cell lung cancer (SCLC) and to identify the benefit of adjuvant therapy following surgery.
Materials and Methods:
The data of 213 patients who underwent surgical resection for SCLC at four institutions were retrospectively reviewed. Patients who received neoadjuvant therapy or an incomplete resection were excluded.
Results:
The mean patient age was 65.29±8.93 years, and 184 patients (86.4%) were male. Lobectomies and pneumonectomies were performed in 173 patients (81.2%), and 198 (93%) underwent systematic mediastinal lymph node dissections. Overall, 170 patients (79.8%) underwent adjuvant chemotherapy, 42 (19.7%) underwent radiotherapy to the mediastinum, and 23 (10.8%) underwent prophylactic cranial irradiation. The median follow-up period was 31.08 months (interquartile range, 13.79 to 64.52 months). The 5-year overall survival (OS) and disease-free survival were 53.4% and 46.9%, respectively. The 5-year OS significantly improved after adjuvant chemotherapy in all patients (57.4% vs. 40.3%, p=0.007), and the survival benefit of adjuvant chemotherapy was significant in patients with negative node pathology (70.8% vs. 39.7%, p=0.004). Adjuvant radiotherapy did not affect the 5-year OS (54.6% vs. 48.5%, p=0.458). Age (hazard ratio [HR], 1.032; p=0.017), node metastasis (HR, 2.190; p < 0.001), and adjuvant chemotherapy (HR, 0.558; p=0.019) were associated with OS.
Conclusion
Adjuvant chemotherapy after surgical resection in patients with SCLC improved the OS, though adjuvant radiotherapy to the mediastinum did not improve the survival or decrease the locoregional recurrence rate.
6.Guideline for the Surgical Management of Locally Invasive Differentiated Thyroid Cancer From the Korean Society of Head and Neck Surgery
Jun-Ook PARK ; Joo Hyun KIM ; Young Hoon JOO ; Sang-Yeon KIM ; Geun-Jeon KIM ; Hyun Bum KIM ; Dong-Hyun LEE ; Hyun Jun HONG ; Young Min PARK ; Eun-Jae CHUNG ; Yong Bae JI ; Kyoung Ho OH ; Hyoung Shin LEE ; Dong Kun LEE ; Ki Nam PARK ; Myung Jin BAN ; Bo Hae KIM ; Do Hun KIM ; Jae-Keun CHO ; Dong Bin AHN ; Min-Su KIM ; Jun Girl SEOK ; Jeon Yeob JANG ; Hyo Geun CHOI ; Hee Jin KIM ; Sung Joon PARK ; Eun Kyung JUNG ; Yeon Soo KIM ; Yong Tae HONG ; Young Chan LEE ; Ho-Ryun WON ; Sung-Chan SHIN ; Seung-Kuk BAEK ; Soon Young KWON
Clinical and Experimental Otorhinolaryngology 2023;16(1):1-19
The aim of this study was to develop evidence-based recommendations for determining the surgical extent in patients with locally invasive differentiated thyroid cancer (DTC). Locally invasive DTC with gross extrathyroidal extension invading surrounding anatomical structures may lead to several functional deficits and poor oncological outcomes. At present, the optimal extent of surgery in locally invasive DTC remains a matter of debate, and there are no adequate guidelines. On October 8, 2021, four experts searched the PubMed, Embase, and Cochrane Library databases; the identified papers were reviewed by 39 experts in thyroid and head and neck surgery. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence, and to develop and report recommendations. The strength of a recommendation reflects the confidence of a guideline panel that the desirable effects of an intervention outweigh any undesirable effects, across all patients for whom the recommendation is applicable. After completing the draft guidelines, Delphi questionnaires were completed by members of the Korean Society of Head and Neck Surgery. Twenty-seven evidence-based recommendations were made for several factors, including the preoperative workup; surgical extent of thyroidectomy; surgery for cancer invading the strap muscles, recurrent laryngeal nerve, laryngeal framework, trachea, or esophagus; and surgery for patients with central and lateral cervical lymph node involvement. Evidence-based guidelines were devised to help clinicians make safer and more efficient clinical decisions for the optimal surgical treatment of patients with locally invasive DTC.
7.Antibiotics use patterns in end-of-life cancer patients and medical staff’s perception of antimicrobial stewardship programs
Min Kwan KWON ; Kyung Hwa JUNG ; Sungim CHOI ; Hyeonjeong KIM ; Chang-Yun WOO ; Mingee LEE ; Jeong Geun JI ; Hyo-Ju SON
The Korean Journal of Internal Medicine 2023;38(5):758-768
Background/Aims:
While most cancer patients with end-of-life (EOL) care receive antibiotic treatments, antibiotic use should be decided appropriately considering the benefits, side effects, resistance, and cost effects. Antimicrobial stewardship programs (ASP) are important for patients with EOL care, but there is limited study analyzing actual antibiotic use in EOL care and the perceptions of Korean medical staff.
Methods:
Electronic medical records of 149 deceased cancer patients hospitalized in the medical hospitalist units at Asan Medical Center in Seoul from May 2019 to September 2021 were reviewed. Basic information, antibiotic use, duration, and changes were investigated. We surveyed medical staff’s perceptions of antibiotics in cancer patients with EOL.
Results:
Of the 149 cancer patients with EOL care, 146 (98.0%) agreed with physician orders for life-sustaining treatment (POLST). In total, 143 (95.9%) received antibiotics, 110 (76.9%) received combination antibiotic treatment, and 116 (81.1%) were given antibiotics until the day of death. In a survey of 60 medical staff, 42 (70.0%) did not know about ASP, and 24 (40.0%) thought ASP was important in EOL care. Nineteen doctors (31.7%) discussed the use or discontinuation of antibiotics with patients or caregivers when writing POLST, but only 8 patients (5.6%) stopped antibiotics after POLST.
Conclusions
Most cancer patients with EOL care continue to receive antibiotics until just before their death. A careful approach is needed, considering the benefits and side effects of antibiotic use, and the patient’s right to self-decision. It is necessary to actively improve awareness of ASP and its importance for medical staff.
8.Impact of a Psychiatric Consultation Program on COVID-19 Patients: An Experimental Study
Geun Hui WON ; Hye Jeong LEE ; Jong Hun LEE ; Tae Young CHOI ; Hyo-Lim HONG ; Chi Young JUNG
Psychiatry Investigation 2023;20(5):471-480
Objective:
Following the coronavirus disease-2019 (COVID-19) outbreak, the importance of addressing acute stress induced by psychological burdens of diseases became apparent. This study attempted to evaluate the effectiveness of a new mode of psychiatric intervention designed to target similar psychological crises.
Methods:
Participants included 32 out of 114 COVID inpatients at a hospital in Daegu, Korea, who were assessed between March 30 and April 7, 2020. Multiple scales for screening psychological difficulties such as depressed mood, anxiety, insomnia, acute stress, and suicidality were done. Psychological problem evaluations and interventions were conducted in the form of consultations to alleviate participants’ psychological challenges via telepsychiatry. The interventions’ effects, as well as clinical improvements before and after the intervention, were analyzed.
Results:
As a result of screening, 21 patients were experiencing psychological difficulties beyond clinical thresholds after COVID-19 infection (screening positive group). The remaining 11 were screening negative groups. The two groups differed significantly in past psychiatric histories (p=0.034), with the former having a higher number of diagnoses. The effect of the intervention was analyzed, and clinical improvement before and after the intervention was observed. Our intervention was found to be effective in reducing the overall emotional difficulties.
Conclusion
This study highlighted the usefulness of new interventions required in the context of healthcare following the COVID-19 pandemic.
9.Clinical Features and Long-term Prognosis of Crohn’s Disease in Korea: Results from the Prospective CONNECT Study
Seung Wook HONG ; Byong Duk YE ; Jae Hee CHEON ; Ji Hyun LEE ; Ja Seol KOO ; Byung Ik JANG ; Kang-Moon LEE ; You Sun KIM ; Tae Oh KIM ; Jong Pil IM ; Geun Am SONG ; Sung-Ae JUNG ; Hyun Soo KIM ; Dong Il PARK ; Hyun-Soo KIM ; Kyu Chan HUH ; Young-Ho KIM ; Jae Myung CHA ; Geom Seog SEO ; Chang Hwan CHOI ; Hyun Joo SONG ; Gwang Ho BAIK ; Ji Won KIM ; Sung Jae SHIN ; Young Sook PARK ; Chang Kyun LEE ; Jun LEE ; Sung Hee JUNG ; Yunho JUNG ; Sung Chul PARK ; Young-Eun JOO ; Yoon Tae JEEN ; Dong Soo HAN ; Suk-Kyun YANG ; Hyo Jong KIM ; Won Ho KIM ; Joo Sung KIM
Gut and Liver 2022;16(6):907-920
Background/Aims:
The prospective Crohn’s Disease Clinical Network and Cohort Study is a nationwide multicenter cohort study of patients with Crohn’s disease (CD) in Korea, aiming to prospectively investigate the clinical features and long-term prognosis associated with CD.
Methods:
Patients diagnosed with CD between January 2009 and September 2019 were prospectively enrolled. They were divided into two cohorts according to the year of diagnosis: cohort 1 (diagnosed between 2009 and 2011) versus cohort 2 (between 2012 and 2019).
Results:
A total of 1,175 patients were included, and the median follow-up duration was 68 months (interquartile range, 39.0 to 91.0 months). The treatment-free durations for thiopurines (p<0.001) and anti-tumor necrosis factor agents (p=0.018) of cohort 2 were shorter than those of cohort 1. Among 887 patients with B1 behavior at diagnosis, 149 patients (16.8%) progressed to either B2 or B3 behavior during follow-up. Early use of thiopurine was associated with a reduced risk of behavioral progression (adjusted hazard ratio [aHR], 0.69; 95% confidence interval [CI], 0.50 to 0.90), and family history of inflammatory bowel disease was associated with an increased risk of behavioral progression (aHR, 2.29; 95% CI, 1.16 to 4.50). One hundred forty-one patients (12.0%) underwent intestinal resection, and the intestinal resection-free survival time was significantly longer in cohort 2 than in cohort 1 (p=0.003). The early use of thiopurines (aHR, 0.35;95% CI, 0.23 to 0.51) was independently associated with a reduced risk of intestinal resection.
Conclusions
The prognosis of CD in Korea appears to have improved over time, as evidenced by the decreasing intestinal resection rate. Early use of thiopurines was associated with an improved prognosis represented by a reduced risk of intestinal resection.
10.Foreign Body Complications in Ears due to Mishandled Hearing Aid Fitting and Proposed Clinical Guidelines to Address the Complications
Eun-Hyun CHO ; Eun-Hyun CHO ; Leeseul SHIM ; Leeseul SHIM ; Hyo Geun CHOI ; Hyo Geun CHOI ; Sung Kwang HONG ; Sung Kwang HONG ; Hyung-Jong KIM ; Hyung-Jong KIM ; Hyo-Jeong LEE ; Hyo-Jeong LEE
Journal of Korean Medical Science 2022;37(2):e19-
Background:
South Korea has one of the world’s fastest aging populations and is witnessing increased age-related hearing impairment cases as well as an increase in the number of hearing aid users. The aim of this study was to analyze complications caused by hearing aid mold materials. In addition, we hope to raise awareness of the harm and danger that inexperienced hearing aid providers can cause to patients.
Methods:
We retrospectively reviewed the medical records of 11 patients who were diagnosed with hearing aid mold material as a foreign body in the ear at a tertiary center between 2016 and 2020. The following data were analyzed: symptoms, endoscopic findings, audiometry, temporal bone CT images, treatment methods, and complications after removal. The currently available literature was also reviewed to develop clinical guidelines, to identify the systematic weaknesses in the South Korean hearing aid market, and to identify policies that warrant better quality control.
Results:
Among the 11 cases, 9 were restricted to the external auditory canal, all of which were successfully removed under endoscopy with minor complications. Two cases with middle ear involvement resulted in infection and thus required surgical removal with mastoidectomy. The average age of these patients was 76.4, and all patients received their molding procedure at private hearing aid shops without an otolaryngologist’s examination.
Conclusion
Thorough patient history-taking and otologic examination must be performed to identify patients at higher risk of complications. Such patients should be referred to an otolaryngologist. If a patient exhibits alarming symptoms, early referral is critical since prompt surgery can minimize complications. A CT scan is highly recommended to determine an optimal approach for foreign body removal. Systematic and regulatory changes in hearing aid dispensers, such as requiring apprenticeship, raising the required level of education, and legally mandating referrals, can help reduce these complications.

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