1.Catalpa bignonioides extract improves exercise performance through regulation of growth and metabolism in skeletal muscles
Hoibin Jeong ; Dong-joo Lee ; Sung-Pil Kwon ; SeonJu Park ; Song-Rae Kim ; Seung Hyun Kim ; Jae-Il Park ; Deug-chan Lee ; Kyung-Min Choi ; WonWoo Lee ; Ji-Won Park ; Bohyun Yun ; Su-Hyeon Cho ; Kil-Nam Kim
Asian Pacific Journal of Tropical Biomedicine 2024;14(2):47-54
Objective: To evaluate the effects of Catalpa bignonioides fruit extract on the promotion of muscle growth and muscular capacity in vitro and in vivo. Methods: Cell viability was measured using the 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide assay. Cell proliferation was assessed using a 5-bromo-2’-deoxyuridine (BrdU) assay kit. Western blot analysis was performed to determine the protein expressions of related factors. The effects of Catalpa bignonioides extract were investigated in mice using the treadmill exhaustion test and whole-limb grip strength assay. Chemical composition analysis was performed using high-performance liquid chromatography (HPLC). Results: Catalpa bignonioides extract increased the proliferation of C2C12 mouse myoblasts by activating the Akt/mTOR signaling pathway. It also induced metabolic changes, increasing the number of mitochondria and glucose metabolism by phosphorylating adenosine monophosphate-activated protein kinase. In an in vivo study, the extract-treated mice showed improved motor abilities, such as muscular endurance and grip strength. Additionally, HPLC analysis showed that vanillic acid may be the main component of the Catalpa bignonioides extract that enhanced muscle strength. Conclusions: Catalpa bignonioides improves exercise performance through regulation of growth and metabolism in skeletal muscles, suggesting its potential as an effective natural agent for improving muscular strength.
2.Contributions of the Distal Femur and Proximal Tibia to Idiopathic Genu Varum and Genu Valgum in Adolescents
Jae Woo SHIM ; Sung-Sahn LEE ; Kyung Rae KO
Clinics in Orthopedic Surgery 2024;16(6):1010-1018
Background:
Different from adults, adolescents with genu varum or valgum can be treated with hemi-epiphysiodesis. We conducted a study to report our recent experience of treating idiopathic genu varum and valgum with clinical relevance to planning of hemi-epiphysiodesis. The aim of this study was to compare the varus and valgus groups focusing on the contribution of the distal femur and proximal tibia to the deformities.
Methods:
Among patients who visited the outpatient clinic during the recent 4 years, adolescents with genu varum (the varus group) or valgum (the valgus group) greater than 5° were included. The mechanical lateral distal femoral angle (mLDFA) and medial proximal tibial angle (MPTA) were measured. The contribution to deformity (%) in each of the distal femur and the proximal tibia was calculated.
Results:
One hundred twenty patients and their 120 legs (randomly selected in bilateral cases) were included. In the varus group (n = 51), the mean hip-knee-ankle alignment was varus 7.1° (range, 5.1°–12.1°). The contribution to deformity was 74.1% ± 27.6% at the proximal tibia (MPTA, 81.9° ± 2.0°) and 14.9% ± 25.1% at the distal femur (mLDFA, 88.1° ± 1.7°). In the valgus group (n = 69), the mean alignment was valgus 6.6° (range, 5.1°–11.9°). The contribution was 69.8% ± 30.8% at the distal femur (mLDFA, 82.4° ± 2.1°) and 33.1% ± 27.8% at the proximal tibia (MPTA = 89.2° ± 1.9°). In subgroup analyses, the MPTA was significantly lower in the varus ≥ 8.4° group than the varus < 8.4° group. The mLDFA was significantly lower and the frequency of MPTA > 91.5° was significantly higher in the valgus ≥ 7.7° group than the valgus < 7.7° group.
Conclusions
Genu varum was mainly associated with deformity of the proximal tibia, whereas genu valgum was related to deformities of the distal femur and proximal tibia. Considering the predominant deformity of the proximal tibia, performing hemiepiphysiodesis only at the proximal tibia is ideal in most adolescents with genu varum.
3.Contributions of the Distal Femur and Proximal Tibia to Idiopathic Genu Varum and Genu Valgum in Adolescents
Jae Woo SHIM ; Sung-Sahn LEE ; Kyung Rae KO
Clinics in Orthopedic Surgery 2024;16(6):1010-1018
Background:
Different from adults, adolescents with genu varum or valgum can be treated with hemi-epiphysiodesis. We conducted a study to report our recent experience of treating idiopathic genu varum and valgum with clinical relevance to planning of hemi-epiphysiodesis. The aim of this study was to compare the varus and valgus groups focusing on the contribution of the distal femur and proximal tibia to the deformities.
Methods:
Among patients who visited the outpatient clinic during the recent 4 years, adolescents with genu varum (the varus group) or valgum (the valgus group) greater than 5° were included. The mechanical lateral distal femoral angle (mLDFA) and medial proximal tibial angle (MPTA) were measured. The contribution to deformity (%) in each of the distal femur and the proximal tibia was calculated.
Results:
One hundred twenty patients and their 120 legs (randomly selected in bilateral cases) were included. In the varus group (n = 51), the mean hip-knee-ankle alignment was varus 7.1° (range, 5.1°–12.1°). The contribution to deformity was 74.1% ± 27.6% at the proximal tibia (MPTA, 81.9° ± 2.0°) and 14.9% ± 25.1% at the distal femur (mLDFA, 88.1° ± 1.7°). In the valgus group (n = 69), the mean alignment was valgus 6.6° (range, 5.1°–11.9°). The contribution was 69.8% ± 30.8% at the distal femur (mLDFA, 82.4° ± 2.1°) and 33.1% ± 27.8% at the proximal tibia (MPTA = 89.2° ± 1.9°). In subgroup analyses, the MPTA was significantly lower in the varus ≥ 8.4° group than the varus < 8.4° group. The mLDFA was significantly lower and the frequency of MPTA > 91.5° was significantly higher in the valgus ≥ 7.7° group than the valgus < 7.7° group.
Conclusions
Genu varum was mainly associated with deformity of the proximal tibia, whereas genu valgum was related to deformities of the distal femur and proximal tibia. Considering the predominant deformity of the proximal tibia, performing hemiepiphysiodesis only at the proximal tibia is ideal in most adolescents with genu varum.
4.Contributions of the Distal Femur and Proximal Tibia to Idiopathic Genu Varum and Genu Valgum in Adolescents
Jae Woo SHIM ; Sung-Sahn LEE ; Kyung Rae KO
Clinics in Orthopedic Surgery 2024;16(6):1010-1018
Background:
Different from adults, adolescents with genu varum or valgum can be treated with hemi-epiphysiodesis. We conducted a study to report our recent experience of treating idiopathic genu varum and valgum with clinical relevance to planning of hemi-epiphysiodesis. The aim of this study was to compare the varus and valgus groups focusing on the contribution of the distal femur and proximal tibia to the deformities.
Methods:
Among patients who visited the outpatient clinic during the recent 4 years, adolescents with genu varum (the varus group) or valgum (the valgus group) greater than 5° were included. The mechanical lateral distal femoral angle (mLDFA) and medial proximal tibial angle (MPTA) were measured. The contribution to deformity (%) in each of the distal femur and the proximal tibia was calculated.
Results:
One hundred twenty patients and their 120 legs (randomly selected in bilateral cases) were included. In the varus group (n = 51), the mean hip-knee-ankle alignment was varus 7.1° (range, 5.1°–12.1°). The contribution to deformity was 74.1% ± 27.6% at the proximal tibia (MPTA, 81.9° ± 2.0°) and 14.9% ± 25.1% at the distal femur (mLDFA, 88.1° ± 1.7°). In the valgus group (n = 69), the mean alignment was valgus 6.6° (range, 5.1°–11.9°). The contribution was 69.8% ± 30.8% at the distal femur (mLDFA, 82.4° ± 2.1°) and 33.1% ± 27.8% at the proximal tibia (MPTA = 89.2° ± 1.9°). In subgroup analyses, the MPTA was significantly lower in the varus ≥ 8.4° group than the varus < 8.4° group. The mLDFA was significantly lower and the frequency of MPTA > 91.5° was significantly higher in the valgus ≥ 7.7° group than the valgus < 7.7° group.
Conclusions
Genu varum was mainly associated with deformity of the proximal tibia, whereas genu valgum was related to deformities of the distal femur and proximal tibia. Considering the predominant deformity of the proximal tibia, performing hemiepiphysiodesis only at the proximal tibia is ideal in most adolescents with genu varum.
5.Contributions of the Distal Femur and Proximal Tibia to Idiopathic Genu Varum and Genu Valgum in Adolescents
Jae Woo SHIM ; Sung-Sahn LEE ; Kyung Rae KO
Clinics in Orthopedic Surgery 2024;16(6):1010-1018
Background:
Different from adults, adolescents with genu varum or valgum can be treated with hemi-epiphysiodesis. We conducted a study to report our recent experience of treating idiopathic genu varum and valgum with clinical relevance to planning of hemi-epiphysiodesis. The aim of this study was to compare the varus and valgus groups focusing on the contribution of the distal femur and proximal tibia to the deformities.
Methods:
Among patients who visited the outpatient clinic during the recent 4 years, adolescents with genu varum (the varus group) or valgum (the valgus group) greater than 5° were included. The mechanical lateral distal femoral angle (mLDFA) and medial proximal tibial angle (MPTA) were measured. The contribution to deformity (%) in each of the distal femur and the proximal tibia was calculated.
Results:
One hundred twenty patients and their 120 legs (randomly selected in bilateral cases) were included. In the varus group (n = 51), the mean hip-knee-ankle alignment was varus 7.1° (range, 5.1°–12.1°). The contribution to deformity was 74.1% ± 27.6% at the proximal tibia (MPTA, 81.9° ± 2.0°) and 14.9% ± 25.1% at the distal femur (mLDFA, 88.1° ± 1.7°). In the valgus group (n = 69), the mean alignment was valgus 6.6° (range, 5.1°–11.9°). The contribution was 69.8% ± 30.8% at the distal femur (mLDFA, 82.4° ± 2.1°) and 33.1% ± 27.8% at the proximal tibia (MPTA = 89.2° ± 1.9°). In subgroup analyses, the MPTA was significantly lower in the varus ≥ 8.4° group than the varus < 8.4° group. The mLDFA was significantly lower and the frequency of MPTA > 91.5° was significantly higher in the valgus ≥ 7.7° group than the valgus < 7.7° group.
Conclusions
Genu varum was mainly associated with deformity of the proximal tibia, whereas genu valgum was related to deformities of the distal femur and proximal tibia. Considering the predominant deformity of the proximal tibia, performing hemiepiphysiodesis only at the proximal tibia is ideal in most adolescents with genu varum.
6.Antiproliferative Activity of Piceamycin by Regulating Alpha-Actinin-4 in Gemcitabine-Resistant Pancreatic Cancer Cells
Jee-Hyung LEE ; Jin Ho CHOI ; Kyung-Min LEE ; Min Woo LEE ; Ja-Lok KU ; Dong-Chan OH ; Yern-Hyerk SHIN ; Dae Hyun KIM ; In Rae CHO ; Woo Hyun PAIK ; Ji Kon RYU ; Yong-Tae KIM ; Sang Hyub LEE ; Sang Kook LEE
Biomolecules & Therapeutics 2024;32(1):123-135
Although gemcitabine-based regimens are widely used as an effective treatment for pancreatic cancer, acquired resistance to gemcitabine has become an increasingly common problem. Therefore, a novel therapeutic strategy to treat gemcitabine-resistant pancreatic cancer is urgently required. Piceamycin has been reported to exhibit antiproliferative activity against various cancer cells; however, its underlying molecular mechanism for anticancer activity in pancreatic cancer cells remains unexplored. Therefore, the present study evaluated the antiproliferation activity of piceamycin in a gemcitabine-resistant pancreatic cancer cell line and patient-derived pancreatic cancer organoids. Piceamycin effectively inhibited the proliferation and suppressed the expression of alpha-actinin-4, a gene that plays a pivotal role in tumorigenesis and metastasis of various cancers, in gemcitabine-resistant cells. Long-term exposure to piceamycin induced cell cycle arrest at the G0/G1 phase and caused apoptosis. Piceamycin alsoinhibited the invasion and migration of gemcitabine-resistant cells by modulating focal adhesion and epithelial-mesenchymal transition biomarkers. Moreover, the combination of piceamycin and gemcitabine exhibited a synergistic antiproliferative activity in gemcitabine-resistant cells. Piceamycin also effectively inhibited patient-derived pancreatic cancer organoid growth and induced apoptosis in the organoids. Taken together, these findings demonstrate that piceamycin may be an effective agent for overcoming gemcitabine resistance in pancreatic cancer.
7.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.
8.Prognostic Implication of Platelet Reactivity According to Left Ventricular Systolic Dysfunction Status in Patients Treated With Drug-Eluting Stent Implantation:Analysis of the PTRG-DES Consortium
Donghoon HAN ; Sun-Hwa KIM ; Dong Geum SHIN ; Min-Kyung KANG ; Seonghoon CHOI ; Namho LEE ; Byeong-Keuk KIM ; Hyung Joon JOO ; Kiyuk CHANG ; Yongwhi PARK ; Young Bin SONG ; Sung Gyun AHN ; Jung-Won SUH ; Sang Yeub LEE ; Ae-Young HER ; Young-Hoon JEONG ; Hyo-Soo KIM ; Moo Hyun KIM ; Do-Sun LIM ; Eun-Seok SHIN ; Jung Rae CHO ; For the PTRG Investigator
Journal of Korean Medical Science 2024;39(3):e27-
Background:
Coronary artery disease patients undergoing percutaneous coronary intervention (PCI) often exhibit reduced left ventricular ejection fraction (LVEF). However, the impact of LV dysfunction status in conjunction with platelet reactivity on clinical outcomes has not been previously investigated.
Methods:
From the multicenter PTRG-DES (Platelet function and genoType-Related long-term prognosis in DES-treated patients) consortium, the patients were classified as preserved-EF (PEF: LVEF ≥ 50%) and reduced-EF (REF: LVEF< 5 0%) group by echocardiography. Platelet reactivity was measured using VerifyNow P2Y 12 assay and high platelet reactivity (HPR) was defined as PRU ≥ 252. The major adverse cardiac and cerebrovascular events (MACCEs) were a composite of death, myocardial infarction, stent thrombosis and stroke at 5 years after PCI. Major bleeding was defined as Bleeding Academic Research Consortium bleeding types 3–5.
Results:
A total of 13,160 patients from PTRG-DES, 9,319 (79.6%) patients with the results of both PRU and LVEF were analyzed. The incidence of MACCE and major bleeding was higher in REF group as compared with PEF group (MACCEs: hazard ratio [HR] 2.17, P < 0.001, 95% confidence interval [CI] 1.85–2.55; major bleeding: HR 1.78, P < 0.001, 95% CI 1.39–2.78).The highest rate of MACCEs was found in patients with REF and HPR, and the difference between the groups was statistically significant (HR 3.14 in REF(+)/HPR(+) vs. PEF(+)/HPR(-) group,P <0.01, 95% CI 2.51–3.91). The frequency of major bleeding was not associated with the HPR in either group.
Conclusion
LV dysfunction was associated with an increased incidence of MACCEs and major bleeding in patients who underwent PCI. The HPR status further exhibited significant increase of MACCEs in patients with LV dysfunction in a large, real-world registry.Trial Registration: ClinicalTrials.gov Identifier: NCT04734028
9.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.
10.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.

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