1.Observation of neutrophil extracellular traps in the development of diabetic nephropathy using diabetic murine models
You Hyun JEON ; Se-Hyun OH ; Soo-Jung JUNG ; Eun-Joo OH ; Jeong-Hoon LIM ; Hee-Yeon JUNG ; Ji-Young CHOI ; Sun-Hee PARK ; Chan-Duck KIM ; Yong-Lim KIM ; Chang-Won HONG ; Jang-Hee CHO
Laboratory Animal Research 2024;40(4):424-434
Background:
Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models.
Results:
Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis.
Conclusions
NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation.
2.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.Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part IV. Thyroid Cancer during Pregnancy 2024
Hwa Young AHN ; Ho-Cheol KANG ; Mijin KIM ; Bo Hyun KIM ; Sun Wook KIM ; Won Gu KIM ; Hee Kyung KIM ; Dong Gyu NA ; Young Joo PARK ; Young Shin SONG ; Dong Yeob SHIN ; Jee Hee YOON ; Dong-Jun LIM ; Yun Jae CHUNG ; Kwanhoon JO ; Yoon Young CHO ; A Ram HONG ; Eun Kyung LEE ;
International Journal of Thyroidology 2024;17(1):188-192
The prevalence of thyroid cancer in pregnant women is unknown; however, given that thyroid cancer commonly develops in women, especially young women of childbearing age, new cases are often diagnosed during pregnancy. This recommendation summarizes the follow-up and treatment when thyroid cancer is diagnosed during pregnancy and when a woman with thyroid cancer becomes pregnant. If diagnosed in the first trimester, surgery should be postponed until after delivery, and the patient should be monitored with ultrasound. If follow-up before 24–26 weeks of gestation shows that thyroid cancer has progressed, surgery should be considered. If it has not progressed at 24–26 weeks of gestation or if papillary thyroid cancer is diagnosed after 20 weeks of pregnancy, surgery should be considered after delivery.
4.Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Overview and Summary 2024
Young Joo PARK ; Eun Kyung LEE ; Young Shin SONG ; Bon Seok KOO ; Hyungju KWON ; Keunyoung KIM ; Mijin KIM ; Bo Hyun KIM ; Won Gu KIM ; Won Bae KIM ; Won Woong KIM ; Jung-Han KIM ; Hee Kyung KIM ; Hee Young NA ; Shin Je MOON ; Jung-Eun MOON ; Sohyun PARK ; Jun-Ook PARK ; Ji-In BANG ; Kyorim BACK ; Youngduk SEO ; Dong Yeob SHIN ; Su-Jin SHIN ; Hwa Young AHN ; So Won OH ; Seung Hoon WOO ; Ho-Ryun WON ; Chang Hwan RYU ; Jee Hee YOON ; Ka Hee YI ; Min Kyoung LEE ; Sang-Woo LEE ; Seung Eun LEE ; Sihoon LEE ; Young Ah LEE ; Joon-Hyop LEE ; Ji Ye LEE ; Jieun LEE ; Cho Rok LEE ; Dong-Jun LIM ; Jae-Yol LIM ; Yun Kyung JEON ; Kyong Yeun JUNG ; Ari CHONG ; Yun Jae CHUNG ; Chan Kwon JUNG ; Kwanhoon JO ; Yoon Young CHO ; A Ram HONG ; Chae Moon HONG ; Ho-Cheol KANG ; Sun Wook KIM ; Woong Youn CHUNG ; Do Joon PARK ; Dong Gyu NA ;
International Journal of Thyroidology 2024;17(1):1-20
Differentiated thyroid cancer demonstrates a wide range of clinical presentations, from very indolent cases to those with an aggressive prognosis. Therefore, diagnosing and treating each cancer appropriately based on its risk status is important. The Korean Thyroid Association (KTA) has provided and amended the clinical guidelines for thyroid cancer management since 2007. The main changes in this revised 2024 guideline include 1) individualization of surgical extent according to pathological tests and clinical findings, 2) application of active surveillance in low-risk papillary thyroid microcarcinoma, 3) indications for minimally invasive surgery, 4) adoption of World Health Organization pathological diagnostic criteria and definition of terminology in Korean, 5) update on literature evidence of recurrence risk for initial risk stratification, 6) addition of the role of molecular testing, 7) addition of definition of initial risk stratification and targeting thyroid stimulating hormone (TSH) concentrations according to ongoing risk stratification (ORS), 8) addition of treatment of perioperative hypoparathyroidism, 9) update on systemic chemotherapy, and 10) addition of treatment for pediatric patients with thyroid cancer.
5.Observation of neutrophil extracellular traps in the development of diabetic nephropathy using diabetic murine models
You Hyun JEON ; Se-Hyun OH ; Soo-Jung JUNG ; Eun-Joo OH ; Jeong-Hoon LIM ; Hee-Yeon JUNG ; Ji-Young CHOI ; Sun-Hee PARK ; Chan-Duck KIM ; Yong-Lim KIM ; Chang-Won HONG ; Jang-Hee CHO
Laboratory Animal Research 2024;40(4):424-434
Background:
Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models.
Results:
Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis.
Conclusions
NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation.
6.The role of next‑generation sequencing in hematologic malignancies
Blood Research 2024;59():11-
Next-generation sequencing (NGS) allows high-throughput detection of molecular changes in tumors. Over the past 15 years, NGS has rapidly evolved from a promising research tool to a core component of the clinical labo‑ ratory. Sequencing of tumor cells provides an important step in detecting somatic driver mutations that not only characterize the disease but also influence treatment decisions. For patients with hematologic malignancies, NGS has been used for accurate classification and diagnosis based on genetic alterations. The recently revised World Health Organization classification and the European LeukemiaNet recommendations for acute myeloid leukemia con‑ sider genetic abnormalities as a top priority for diagnosis, prognostication, monitoring of measurable residual disease, and treatment choice. This review aims to present the role and utility of various NGS approaches for the diagnosis, treatment, and follow-up of hemato-oncology patients.
7.Clinical Significance of Human Papillomavirus DNA Test and p16 Overexpression in Oropharyngeal Cancer
Juhyun LEE ; Kwang Yoon JUNG ; Soon-Young KWON ; Jeong-Soo WOO ; Jae-Gu CHO ; Kyoung-Ho OH ; Jaehyeong KIM ; Seung-Kuk BAEK
Korean Journal of Otolaryngology - Head and Neck Surgery 2024;67(6):336-343
Background and Objectives:
Oropharyngeal squamous cell carcinoma (OPSCC) can be caused by human papilloma virus (HPV) infection or other factors like smoking. The 8th Edition of the AJCC Cancer Staging Manual recommends different staging and treatment approaches based on etiology. Despite criticisms of its low specificity, the current guidelines suggest using p16 immunohistochemistry (IHC) as a surrogate marker for the HPV-related OPSCC. This study assessed the reliability of p16 as a surrogate marker by correlating the survival rates of OPSCC patients with the results of p16 IHC and HPV-DNA testing.Subjects and Method A retrospective analysis was performed on patients treated for tonsil squamous cell carcinoma at a tertiary medical institution between 1994 and 2018. All patients underwent p16 immunostaining and HPV-DNA chip tests. Out of 88 patients, 17 were excluded due to insufficient data or secondary primary cancer, leaving 71 patients.
Results:
Among the 71 patients, 51 were p16 positive and 49 were HPV-DNA positive; both tests were associated with extended survival. However, discrepancies were noted in 18 patients: specifically, 11 patients were p16 positive but HPV-DNA negative, displaying a different survival pattern compared to HPV-associated and non-HPV-associated patients.
Conclusion
Both p16 immunostaining and HPV-DNA testing have their pros and cons. p16 immunostaining is cost-effective but has lower specificity. The study found discrepancies in 18 patients, suggesting that relying solely on p16 immunostaining may have limitations. It would be advisable to complement it with additional tests like the HPV-DNA chip test to predict the disease’s prognosis more accurately.
8.Effects of Short-term Repeated Sprint Exercise Training and Moderate Intensity Continuous Exercise Training on Vascular Function in Healthy Young Adults
Hye Rim HONG ; Ye Ji CHOI ; Tae Gu CHOI ; Jae Yeop KIM ; Yun Wook KIM ; Yong Joon JUNG ; Min Jeong CHO ; Hyun Jeong KIM ; Sae Young JAE
The Korean Journal of Sports Medicine 2024;42(2):136-144
Purpose:
Moderate-intensity continuous training (MICT) improves exercise capacity with vascular benefits, but time constraints hinder consistent adherence. High-intensity interval training (HIIT) has emerged as a time-efficient alternative, with repeated sprint training (RST) being the shortest format. We hypothesized that RST would be as effective as MICT in improving vascular function and exercise capacity in young adults.
Methods:
Twenty-three adults (mean age, 26.2±3.8 years) were randomly assigned to either RST or MICT. RST involved 20 sets of 4-second cycling sprints followed by 30-second active recovery, totaling 11 minutes. MICT consisted of 30-minute cycling at 50% to 60% of heart rate reserve. Vascular function evaluated via brachial artery flow-mediated dilation. Exercise capacity (maximum oxygen uptake, total exercise load test time) and anaerobic capacity (maximum power, anaerobic threshold) were measured using maximum exercise tests. These variables were measured befre and after a 6-week training.
Results:
Both groups showed comparable improvements in flow-mediated dilation (p< 0.05). Maximum oxygen intake slightly improved, while total exercise time significantly increased for both (p< 0.05). Anaerobic threshold unchanged, while maximum power improved (p< 0.05).
Conclusion
These findings underscore that RST is a time-efficient exercise strategy, which improves vascular function and exercise capacity as effectively as MICT in young adults.
9.Effects of Isometric Handgrip Exercise on Carotid Arterial Function and Cardiovascular Vasoreactivity Response to Sympathetic Stress in Young Adults
Yun Wook KIM ; Joon Youp SEONG ; Ho Jeong MIN ; Tae Gu CHOI ; Yong Joon JUNG ; Min Jeong CHO ; Hyun Jeong KIM ; Sae Young JAE
The Korean Journal of Sports Medicine 2024;42(1):38-45
Purpose:
Isometric handgrip exercise (IHE) has a favorable cardiovascular effect and improves hemodynamic responses. Whether IHE attenuates stress-related hemodynamic reactivity assessed during a sympathetic challenge remains unexplored. We tested the hypothesis that an acute bout of IHE would improve carotid arterial function and attenuate cardiovascular vasoreactivity response to sympathetic stress in healthy adults.
Methods:
In a randomized cross-over design, sixteen healthy adults (aged 21.8±3.1 years) were enrolled. Participants completed two testing sessions, separated by 1 week. Trials were either a control trial or performed IHE for two sets of 2 minutes at 30% of maximal voluntary contraction for each hand. The participant’s hand was immersed in an ice water bath (4 ℃ ) up to the wrist for 2 minutes. Carotid artery diameter, β-stiffness index, and compliance using ultrasound machine and brachial blood pressure (BP), heart rate (HR) were measured as indices of vasoreactivity at baseline, during, and recovery from cold pressor testing (CPT).
Results:
The BP, HR, carotid artery diameter, and β-stiffness index increased similarly during CPT in both trials (p< 0.001), without any interaction effect. Compared with the IHE trial, arterial compliance decreased in the control groups at 120 seconds during recovery with a significant interaction effect (p=0.02).
Conclusion
These findings suggest that an acute IHE did not attenuate BP, HR, carotid artery diameter and β-stiffness index vasoreactivity, but improved carotid artery compliance to sympathetic activation in healthy young adults.
10.Eosinophilia Is a Favorable Marker for Pneumonia in Chronic Obstructive Pulmonary Disease
Kang-Mo GU ; Jae-Woo JUNG ; Min-Jong KANG ; Deog Kyeom KIM ; Hayoung CHOI ; Young-Jae CHO ; Seung Hun JANG ; Chang-Hoon LEE ; Yeon Mok OH ; Ji Sook PARK ; Jae Yeol KIM
Tuberculosis and Respiratory Diseases 2024;87(4):465-472
Background:
Patients with chronic obstructive pulmonary disease (COPD) expressing eosinophilia experience slightly fewer episodes of community-acquired pneumonia (CAP), than those without eosinophilia. However, the severity and burden of hospitalized pneumonia patients with COPD involving eosinophilia have not been assessed.
Methods:
We evaluated the differences in clinical characteristics between patients with CAP and COPD with or without eosinophilia by a post hoc analysis of a prospective, multi-center, cohort study data.
Results:
Of 349 CAP patients with COPD, 45 (12.9%) had eosinophilia (blood eosinophil ≥300 cells/μL). Patients with eosinophilia had a lower sputum culture percentile (8.1% vs. 23.4%, p<0.05), a lower percentile of neutrophils (70.3% vs. 80.2%, p<0.05), reduced C-reactive protein levels (30.6 mg/L vs. 86.6 mg/L, p<0.05), and a lower pneumonia severity index score (82.5 vs. 90.0, p<0.05), than those without eosinophilia. The duration of antibiotic treatment (8.0 days vs. 10.0 days, p<0.05) and hospitalization (7.0 days vs. 9.0 days, p<0.05) were shorter in eosinophilic patients. The cost of medical care per day (256.4 US$ vs. 291.0 US$, p<0.05), cost for the medication (276.4 US$ vs. 349.9 US$, p<0.05), and cost for examination (685.5 US$ vs. 958.1 US$, p<0.05) were lower in patients with eosinophilia than those without eosinophilia.
Conclusion
Eosinophilia serves as a favorable marker for the severity of pneumonia, health-care consumption, and cost of medical care in patients with CAP and COPD.

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