1.Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial
Jie-Eun LEE ; Seung Hee YU ; Sung Rae KIM ; Kyu Jeung AHN ; Kee-Ho SONG ; In-Kyu LEE ; Ho-Sang SHON ; In Joo KIM ; Soo LIM ; Doo-Man KIM ; Choon Hee CHUNG ; Won-Young LEE ; Soon Hee LEE ; Dong Joon KIM ; Sung-Rae CHO ; Chang Hee JUNG ; Hyun Jeong JEON ; Seung-Hwan LEE ; Keun-Young PARK ; Sang Youl RHEE ; Sin Gon KIM ; Seok O PARK ; Dae Jung KIM ; Byung Joon KIM ; Sang Ah LEE ; Yong-Hyun KIM ; Kyung-Soo KIM ; Ji A SEO ; Il Seong NAM-GOONG ; Chang Won LEE ; Duk Kyu KIM ; Sang Wook KIM ; Chung Gu CHO ; Jung Han KIM ; Yeo-Joo KIM ; Jae-Myung YOO ; Kyung Wan MIN ; Moon-Kyu LEE
Diabetes & Metabolism Journal 2024;48(4):730-739
Background:
It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia.
Methods:
This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment.
Results:
After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events.
Conclusion
The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.
3.Targeted Therapy Following Metastasectomy for Metastatic Renal Cell Carcinoma: A Systematic Review and Meta-analysis
Hui Mo GU ; Seung Il JUNG ; Dongdeuk KWON ; Myung Ha KIM ; Jae Hung JUNG ; Mi Ah HAN ; Seung Hwan LEE ; In Gab JEONG ; Sun Il KIM ; Eu Chang HWANG
Journal of Urologic Oncology 2024;22(1):34-41
Purpose:
The aim of this study was to assess the effects of tyrosine kinase inhibitors (TKIs) following metastasectomy in patients with metastatic renal cell carcinoma (mRCC).
Materials and Methods:
A systematic search of multiple electronic databases was conducted. The inclusion criteria encompassed randomized clinical trials evaluating the use of TKIs after metastasectomy in mRCC patients. Study outcomes were relapse-free survival (RFS)/disease-free survival (DFS), overall survival (OS), and adverse events of TKIs.
Results:
Two studies with 197 randomized participants that compared TKIs following metastasectomy versus metastasectomy alone were identified. According to these studies, TKIs following metastasectomy may result in little to no difference in RFS/DFS (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.65–1.57; I2=29%; low-certainty evidence). TKIs after metastasectomy may slightly increase OS, but the CI crossed the line of no effect (HR, 0.80; 95% CI, 0.06–9.87; I2=86%; low-certainty evidence). TKIs after metastasectomy likely resulted in a large increase in adverse events (risk ratio, 2.76; 95% CI: 1.65–4.62; I2=not applicable; moderatecertainty evidence).
Conclusions
TKIs following metastasectomy did not improve RFS/DFS, but slightly improved OS. It is likely that TKIs following metastasectomy increase adverse events compared to surgery only. The certainty of evidence ranged from moderate (signaling confidence that the reported effect size is likely close to the true effect) to low (indicating that the true effect may be substantially different from the effect estimate). The findings of this study should help to inform future guidelines and clinical decision-making at the point of care.
4.The Korean Society for Neuro-Oncology (KSNO) Guideline for the Management of Brain Tumor Patients During the Crisis Period: A Consensus Survey About Specific Clinical Scenarios (Version 2023.1)
Min-Sung KIM ; Se-Il GO ; Chan Woo WEE ; Min Ho LEE ; Seok-Gu KANG ; Kyeong-O GO ; Sae Min KWON ; Woohyun KIM ; Yun-Sik DHO ; Sung-Hye PARK ; Youngbeom SEO ; Sang Woo SONG ; Stephen AHN ; Hyuk-Jin OH ; Hong In YOON ; Sea-Won LEE ; Joo Ho LEE ; Kyung Rae CHO ; Jung Won CHOI ; Je Beom HONG ; Kihwan HWANG ; Chul-Kee PARK ; Do Hoon LIM ;
Brain Tumor Research and Treatment 2023;11(2):133-139
Background:
During the coronavirus disease 2019 (COVID-19) pandemic, there was a shortage of medical resources and the need for proper treatment guidelines for brain tumor patients became more pressing. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future. As part II of the guideline, this consensus survey is to suggest management options in specific clinical scenarios during the crisis period.
Methods:
The KSNO Guideline Working Group consisted of 22 multidisciplinary experts on neuro-oncology in Korea. In order to confirm a consensus reached by the experts, opinions on 5 specific clinical scenarios about the management of brain tumor patients during the crisis period were devised and asked. To build-up the consensus process, Delphi method was employed.
Results:
The summary of the final consensus from each scenario are as follows. For patients with newly diagnosed astrocytoma with isocitrate dehydrogenase (IDH)-mutant and oligodendroglioma with IDH-mutant/1p19q codeleted, observation was preferred for patients with low-risk, World Health Organization (WHO) grade 2, and Karnofsky Performance Scale (KPS) ≥60, while adjuvant radiotherapy alone was preferred for patients with high-risk, WHO grade 2, and KPS ≥60. For newly diagnosed patients with glioblastoma, the most preferred adjuvant treatment strategy after surgery was radiotherapy plus temozolomide except for patients aged ≥70 years with KPS of 60 and unmethylated MGMT promoters. In patients with symptomatic brain metastasis, the preferred treatment differed according to the number of brain metastasis and performance status. For patients with newly diagnosed atypical meningioma, adjuvant radiation was deferred in patients with older age, poor performance status, complete resection, or low mitotic count.
Conclusion
It is imperative that proper medical care for brain tumor patients be sustained and provided, even during the crisis period. The findings of this consensus survey will be a useful reference in determining appropriate treatment options for brain tumor patients in the specific clinical scenarios covered by the survey during the future crisis.
5.The Korean Society for Neuro-Oncology (KSNO) Guideline for the Management of Brain Tumor Patients During the Crisis Period: A Consensus Recommendation Using the Delphi Method (Version 2023.1)
Min-Sung KIM ; Se-Il GO ; Chan Woo WEE ; Min Ho LEE ; Seok-Gu KANG ; Kyeong-O GO ; Sae Min KWON ; Woohyun KIM ; Yun-Sik DHO ; Sung-Hye PARK ; Youngbeom SEO ; Sang Woo SONG ; Stephen AHN ; Hyuk-Jin OH ; Hong In YOON ; Sea-Won LEE ; Joo Ho LEE ; Kyung Rae CHO ; Jung Won CHOI ; Je Beom HONG ; Kihwan HWANG ; Chul-Kee PARK ; Do Hoon LIM ;
Brain Tumor Research and Treatment 2023;11(2):123-132
Background:
During the coronavirus disease 2019 (COVID-19) pandemic, the need for appropriate treatment guidelines for patients with brain tumors was indispensable due to the lack and limitations of medical resources. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future.
Methods:
The KSNO Guideline Working Group was composed of 22 multidisciplinary experts on neuro-oncology in Korea. In order to reach consensus among the experts, the Delphi method was used to build up the final recommendations.
Results:
All participating experts completed the series of surveys, and the results of final survey were used to draft the current consensus recommendations. Priority levels of surgery and radiotherapy during crises were proposed using appropriate time window-based criteria for management outcome. The highest priority for surgery is assigned to patients who are life-threatening or have a risk of significant impact on a patient’s prognosis unless immediate intervention is given within 24–48 hours. As for the radiotherapy, patients who are at risk of compromising their overall survival or neurological status within 4–6 weeks are assigned to the highest priority. Curative-intent chemotherapy has the highest priority, followed by neoadjuvant/adjuvant and palliative chemotherapy during a crisis period. Telemedicine should be actively considered as a management tool for brain tumor patients during the mass infection crises such as the COVID-19 pandemic.
Conclusion
It is crucial that adequate medical care for patients with brain tumors is maintained and provided, even during times of crisis. This guideline will serve as a valuable resource, assisting in the delivery of treatment to brain tumor patients in the event of any future crisis.
6.Association between alcohol consumption and subclinical atrial fibrillation
Ga‑In YU ; Daehoon KIM ; Hee Tae YU ; Tae‑Hoon KIM ; Il‑Young OH ; Jong Sung PARK ; Hyung‑Seob PARK ; Junbeom PARK ; Young Soo LEE ; Ki‑Woon KANG ; Jaemin SHIM ; Jung‑Hoon SUNG ; Eue‑Keun CHOI ; Boyoung JOUNG ;
International Journal of Arrhythmia 2023;24(3):20-
Background:
It has become important to identify and manage risk factors for subclinical atrial fibrillation (AF) with an increase in its detection rate. Thus, this research aimed to investigate whether alcohol consumption contrib‑ utes to the development of subclinical AF.
Methods:
This prospective study enrolled 467 patients without AF from a multicenter pacemaker registry. The incidence of subclinical AF (episodes of atrial rate > 220 beats per minute without symptoms) was compared between alcohol-drinking and non-drinking groups.
Results:
During followup (median 18 months), the incidence and risk of long-duration atrial high-rate episodes (AHRE) ≥ 24 h were increased in the alcohol group compared to the non-alcohol group [5.47 vs. 2.10 per 100 personyears, adjusted hazard ratio (HR), 2.83; 95% confidence interval (CI), 1.14–7.04; P = 0.03]. After propensity score match‑ ing, the incidence and risk of long-duration AHRE were higher in the alcohol group (6.97 vs. 1.27 per 100 personyears, adjusted HR, 7.84; 95% CI, 1.21–50.93; P = 0.03). The mean burden of long-duration subclinical AF was higher in the alcohol group than in the non-alcohol group (0.18 vs. 1.61% during follow-up, P = 0.08).
Conclusion
Alcohol consumption was associated with an increased risk of subclinical AF. Long-duration AHRE inci‑ dence and AHRE burden were higher in alcohol drinkers than in non-drinkers.
7.Five-year Progress of Gastric MALT Lymphoma Presenting as Gastric Outlet Obstruction
Hyundam GU ; Dae Young CHEUNG ; Yeon Joo SEO ; Eunjung LEE ; Han Hee LEE ; Jin Il KIM ; Soo-Heon PARK ; Tae Jung KIM
The Korean Journal of Gastroenterology 2023;81(6):265-269
This paper reports a 70-year-old female with gastric extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (gastric MALT lymphoma) as a rare case of gastric outlet obstruction. Five years earlier, she initially presented with weight loss and anemia. Esophagogastroduodenoscopy (EGD) revealed multiple gastric and duodenal ulcers with a pyloric deformity, while histology revealed chronic active inflammation and a Helicobacter pylori (H. pylori) infection. Three years earlier, she underwent EGD per the National Cancer Screening Program and was diagnosed with antral and duodenal ulcers. A forceps biopsy specimen from one of the ulcers showed the findings of gastric MALT lymphoma, but she did not visit the hospital for proper management. She visited complaining of a loss of appetite. EGD revealed a gastric outlet obstruction (GOO) caused by antral deformity and pyloric narrowing. A staged workup with CT and PET revealed full-layered, encircling antral wall thickening and several enlarged mesenteric lymph nodes. She was finally diagnosed with a gastric MALT lymphoma at Ann Arbor stage I1E with translocation t(11;18). She was treated with palliative surgery for GOO and systemic chemotherapy with a CHOP regimen. This paper reports a gastric MALT lymphoma that progressed from superficial mucosal lesions to an overt mass with regional lymph node metastasis for five years. (Korean J Gastroenterol 2023;81:265 -269)
8.A Case With Herpes Zoster Ophthalmicus Mimicking Delayed Complication of Rhinoplasty
Il Gu JUNG ; Hahn Jin JUNG ; Woo Sub SHIM
Journal of Rhinology 2022;29(2):118-121
Herpes zoster ophthalmicus (HZO) occurs due to reactivation of dormant varicella zoster virus infection in the ophthalmic division of the trigeminal nerve. Hutchinson’s sign, a herpetic skin lesion in the nasal tip, is a predictor of ocular complications, as the nasal tip area and ocular structure are innervated by the same nasociliary nerve. Patients who present with Hutchinson’s sign should be referred to an ophthalmologist due to possibility of ocular complications. Here, we present a case of a 44-year-old man with HZO that was confused with delayed rhinoplasty complication. The patient presented with nasal tip skin lesions 17 years after undergoing augmentation rhinoplasty. A graft-related infection was suspected due to operation history and skin lesions. However, surgical exploration disclosed no infection or inflammation, and serological tests revealed positive varicella zoster virus immunoglobulin M, and immunoglobulin G, antibodies. Based on these findings, the patient was diagnosed with HZO. Further, the patient received antiviral treatment with famciclovir. The lesions gradually improved with conservative treatment and became almost unrecognizable. Therefore, HZO should be considered when there is an unexplained skin lesion at the nasal tip in patients with history of rhinoplasty.
9.A Multicenter Study to Identify the Respiratory Pathogens Associated with Exacerbation of Chronic Obstructive Pulmonary Disease in Korea
Hyun Woo LEE ; Yun Su SIM ; Ji Ye JUNG ; Hyewon SEO ; Jeong-Woong PARK ; Kyung Hoon MIN ; Jae Ha LEE ; Byung-Keun KIM ; Myung Goo LEE ; Yeon-Mok OH ; Seung Won RA ; Tae-Hyung KIM ; Yong il HWANG ; Chin Kook RHEE ; Hyonsoo JOO ; Eung Gu LEE ; Jin Hwa LEE ; Hye Yun PARK ; Woo Jin KIM ; Soo-Jung UM ; Joon Young CHOI ; Chang-Hoon LEE ; Tai Joon AN ; Yeonhee PARK ; Young-Soon YOON ; Joo Hun PARK ; Kwang Ha YOO ; Deog Kyeom KIM
Tuberculosis and Respiratory Diseases 2022;85(1):37-46
Background:
Although respiratory tract infection is one of the most important factors triggering acute exacerbation of chronic obstructive pulmonary disease (AE-COPD), limited data are available to suggest an epidemiologic pattern of microbiology in South Korea.
Methods:
A multicenter observational study was conducted between January 2015 and December 2018 across 28 hospitals in South Korea. Adult patients with moderate-to-severe acute exacerbations of COPD were eligible to participate in the present study. The participants underwent all conventional tests to identify etiology of microbial pathogenesis. The primary outcome was the percentage of different microbiological pathogens causing AE-COPD. A comparative microbiological analysis of the patients with overlapping asthma–COPD (ACO) and pure COPD was performed.
Results:
We included 1,186 patients with AE-COPD. Patients with pure COPD constituted 87.9% and those with ACO accounted for 12.1%. Nearly half of the patients used an inhaled corticosteroid-containing regimen and one-fifth used systemic corticosteroids. Respiratory pathogens were found in 55.3% of all such patients. Bacteria and viruses were detected in 33% and 33.2%, respectively. Bacterial and viral coinfections were found in 10.9%. The most frequently detected bacteria were Pseudomonas aeruginosa (9.8%), and the most frequently detected virus was influenza A (10.4%). Multiple bacterial infections were more likely to appear in ACO than in pure COPD (8.3% vs. 3.6%, p=0.016).
Conclusion
Distinct microbiological patterns were identified in patients with moderate-to-severe AE-COPD in South Korea. These findings may improve evidence-based management of patients with AE-COPD and represent the basis for further studies investigating infectious pathogens in patients with COPD.
10.Myristoleic Acid Promotes Anagen Signaling by Autophagy through Activating Wnt/β-Catenin and ERK Pathways in Dermal Papilla Cells
Youn Kyung CHOI ; Jung-Il KANG ; Jin Won HYUN ; Young Sang KOH ; Ji-Hoon KANG ; Chang-Gu HYUN ; Kyung-Sup YOON ; Kwang Sik LEE ; Chun Mong LEE ; Tae Yang KIM ; Eun-Sook YOO ; Hee-Kyoung KANG
Biomolecules & Therapeutics 2021;29(2):211-219
Alopecia is a distressing condition caused by the dysregulation of anagen, catagen, and telogen in the hair cycle. Dermal papilla cells (DPCs) regulate the hair cycle and play important roles in hair growth and regeneration. Myristoleic acid (MA) increases Wnt reporter activity in DPCs. However, the action mechanisms of MA on the stimulation of anagen signaling in DPCs is not known. In this study, we evaluated the effects of MA on anagen-activating signaling pathways in DPCs. MA significantly increased DPC proliferation and stimulated the G2/M phase, accompanied by increasing cyclin A, Cdc2, and cyclin B1. To elucidate the mechanism by which MA promotes DPC proliferation, we evaluated the effect of MA on autophagy and intracellular pathways. MA induced autophagosome formation by decreasing the levels of the phospho-mammalian target of rapamycin (phospho-mTOR) and increasing autophagy-related 7 (Atg7) and microtubule-associated protein 1A/1B-light chain 3II (LC3II). MA also increased the phosphorylation levels of Wnt/β-catenin proteins, such as GSK3β ( Ser9 ) and β-catenin (Ser 552 and Ser675 ). Treatment with XAV939, an inhibitor of the Wnt/β-catenin pathway, attenuated the MA-induced increase in β-catenin nuclear translocation. Moreover, XAV939 reduced MA-induced effects on cell cycle progression, autophagy, and DPC proliferation. On the other hand, MA increased the levels of phospho (Thr202 /Tyr204 )-extracellular signal regulated kinases (ERK). MA-induced ERK phosphorylation led to changes in the expression levels of Cdc2, Atg7 and LC3II, as well as DPC proliferation. Our results suggest that MA promotes anagen signaling via autophagy and cell cycle progression by activating the Wnt/β-catenin and ERK pathways in DPCs.

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