1.Preliminary Investigation on Efficacy and Safety of Substance P-Coated Stent for Promoting Re-Endothelialization: A Porcine Coronary Artery Restenosis Model
Dae Sung PARK ; Seok OH ; Yu Jeong JIN ; Mi Hyang NA ; Munki KIM ; Jeong Ha KIM ; Dae Young HYUN ; Kyung Hoon CHO ; Young Joon HONG ; Ju Han KIM ; Youngkeun AHN ; Manuel HERMIDA-PRIETO ; José Manuel VÁZQUEZ-RODRIGUEZ ; Juan Luis GUTIÉRREZ- CHICO ; Luis MARINÃS-PARDO ; Kyung Seob LIM ; Jun-Kyu PARK ; Dae-Heung BYEON ; Young-Nan CHO ; Seung-Jung KEE ; Doo Sun SIM ; Myung Ho JEONG
Tissue Engineering and Regenerative Medicine 2024;21(1):53-64
BACKGROUND:
Current polymer-based drug-eluting stents (DESs) have fundamental issues about inflammation and delayed re-endothelializaton of the vessel wall. Substance-P (SP), which plays an important role in inflammation and endothelial cells, has not yet been applied to coronary stents. Therefore, this study compares poly lactic-co-glycolic acid (PLGA)-based everolimus-eluting stents (PLGA-EESs) versus 2-methacryloyloxyethyl phosphorylcholine (MPC)-based SP-eluting stents (MPC-SPs) in in-vitro and in-vivo models.
METHODS:
The morphology of the stent surface and peptide/drug release kinetics from stents were evaluated. The invitro proliferative effect of SP released from MPC-SP is evaluated using human umbilical vein endothelial cell. Finally, the safety and efficacy of the stent are evaluated after inserting it into a pig’s coronary artery.
RESULTS:
Similar to PLGA-EES, MPC-SP had a uniform surface morphology with very thin coating layer thickness (2.074 lm). MPC-SP showed sustained drug release of SP for over 2 weeks. Endothelial cell proliferation was significantly increased in groups treated with SP (n = 3) compared with the control (n = 3) and those with everolimus (n = 3) (SP:118.9 ± 7.61% vs. everolimus: 64.3 ± 12.37% vs. the control: 100 ± 6.64%, p < 0.05). In the animal study, the percent stenosis was higher in MPC-SP group (n = 7) compared to PLGA-EES group (n = 7) (MPC-SP: 28.6 ± 10.7% vs. PLGAEES: 16.7 ± 6.3%, p < 0.05). MPC-SP group showed, however, lower inflammation (MPC-SP: 0.3 ± 0.26 vs. PLGAEES: 1.2 ± 0.48, p < 0.05) and fibrin deposition (MPC-SP: 1.0 ± 0.73 vs. PLGA-EES: 1.5 ± 0.59, p < 0.05) around the stent strut. MPC-SP showed more increased expression of cluster of differentiation 31, suggesting enhanced reendothelialization.
CONCLUSION
Compared to PLGA-EES, MPC-SP demonstrated more decreased inflammation of the vascular wall and enhanced re-endothelialization and stent coverage. Hence, MPC-SP has the potential therapeutic benefits for the treatment of coronary artery disease by solving limitations of currently available DESs.
2.Efficacy and Safety Evaluation of Tacrolimus-Eluting Stent in a Porcine Coronary Artery Model
Dae Sung PARK ; Mi Hyang NA ; Myung Ho JEONG ; Doo Sun SIM ; Yu Jeong JIN ; Hae Jin KEE ; Mun Ki KIM ; Jeong Ha KIM ; Young Joon HONG ; Kyung Hoon CHO ; Dae Young HYUN ; Seok OH ; Kyung Seob LIM ; Dae-Heung BYEON ; Jeong Hun KIM
Tissue Engineering and Regenerative Medicine 2024;21(5):723-735
BACKGROUND:
A drug-eluting stent (DES) is a highly beneficial medical device used to widen or unblock narrowed blood vessels. However, the drugs released by the implantation of DES may hinder the re-endothelialization process, increasing the risk of late thrombosis. We have developed a tacrolimus-eluting stent (TES) that as acts as a potent antiproliferative and immunosuppressive agent, enhancing endothelial regeneration. In addition, we assessed the safety and efficacy of TES through both in vitro and in vivo tests.
METHODS:
Tacrolimus and Poly(lactic-co-glycolic acid) (PLGA) were applied to the metal stent using electrospinning equipment. The surface morphology of the stent was examined before and after coating using a scanning electron microscope (SEM) and energy dispersive X-rays (EDX). The drug release test was conducted through high-performance liquid chromatography (HPLC). Cell proliferation and migration assays were performed using smooth muscle cells (SMC).The stent was then inserted into the porcine coronary artery and monitored for a duration of 4 weeks.
RESULTS:
SEM analysis confirmed that the coating surface was uniform. Furthermore, EDX analysis showed that the surface was coated with both polymer and drug components. The HPCL analysis of TCL at a wavelength of 215 nm revealed that the drug was continuously released over a period of 4 weeks. Smooth muscle cell migration was significantly decreased in the tacrolimus group (54.1% ± 11.90%) compared to the non-treated group (90.1% ± 4.86%). In animal experiments, the stenosis rate was significantly reduced in the TES group (29.6% ± 7.93%) compared to the bare metal stent group (41.3% ± 10.18%). Additionally, the fibrin score was found to be lower in the TES group compared to the group treated with a sirolimus-eluting stent (SES).
CONCLUSION
Similar to SES, TES reduces neointimal proliferation in a porcine coronary artery model, specifically decreasing the fibrins score. Therefore, tacrolimus could be considered a promising drug for reducing restenosis and thrombosis.
3.Microbiologic pattern and clinical outcome of non-ICU-acquired pneumonia: Korean HAP registry analysis
Jin Ho JANG ; Hye Ju YEO ; Taehwa KIM ; Woo Hyun CHO ; Kyung Hoon MIN ; Sang-Bum HONG ; Ae-Rin BAEK ; Hyun-Kyung LEE ; Changhwan KIM ; Youjin CHANG ; Hye Kyeong PARK ; Jee Youn OH ; Heung Bum LEE ; Soohyun BAE ; Jae Young MOON ; Kwang Ha YOO ; Hyun-Il GIL ; Kyeongman JEON ;
The Korean Journal of Internal Medicine 2023;38(3):450-450
4.Effect of oral health-related self efficacy and social support on oral health-related quality of life among adolescents
Boo Young CHOI ; Heung-Soo LEE ; Hyo-Won OH
Journal of Korean Academy of Oral Health 2023;47(1):32-39
Objectives:
This study aimed to examine the effects of oral health-related self efficacy and social support on oral health-related quality of life, and analyze the related factors.
Methods:
A cross-sectional study was carried out on 979 high school students living in Iksan. Data were collected from January 15 to 30, 2014. Individual self-administered surveys were conducted through the sampling method. The contents of the survey were the characteristics of the subjects, oral health-related self efficacy (OHSE), social support related to oral health (OHSS), and quality of life related to oral health (QHRQoL). A survey tool designed by the author was used to measure OHSE and OHSS. QHRQoL used Child Oral Health Impact Profile-Short Form 19 (COHIP-SF 19) for examination. The statistical analysis methods used were mean difference, correlation, and multiple regression analyses.
Results:
QHRQol was correlated with OHSE, but not OHSS. Per the multivariate analysis, factors that affected QHRQoL were gender, mother’s education level, academic stress, and OHSE; OHSS did not have any effect.
Conclusions
It was found that OHSE influenced QHRQoL. Therefore, it is necessary to develop education programs that can enhance OHSE.
5.The application of the health belief model in oral health-related dietary behavior
Ja-Young NA ; Hyo-Won OH ; Heung-Soo LEE
Journal of Korean Academy of Oral Health 2023;47(1):15-20
Objectives:
This study aimed to investigate the relationship between oral health beliefs and oral health-related dietary behavior.
Methods:
The participants of this cross-sectional study were 728 middle school students living in Jeonju who were selected through convenience sampling. For the survey, self-administered questionnaires were completed in individual settings. The analysis model was the oral health belief model, and the analysis method was path analysis.
Results:
Among oral health beliefs, perceived susceptibility, perceived severity, perceived barriers, and self-efficacy were found to be correlated with the oral health-related dietary behavior index. Multiple regression analysis showed that factors affecting the oral health-related dietary behavior index were gender (female), perceived susceptibility, perceived severity, perceived barriers, and self-efficacy. Path analysis showed that variables that significantly impact the oral health-related dietary behavior index are perceived susceptibility, perceived benefits, perceived barriers, and likelihood of action. The factor with the greatest impact was perceived barrier; the lower the barrier, the higher the level of dietary behavior undertaken to prevent dental caries.
Conclusions
Oral health beliefs are related to oral health-related dietary behavior. Since perceived barriers had the greatest correlation with oral health-related dietary behavior, measures must be taken to help remove the barriers.
6.Empiric Anti-Pseudomonal β-Lactam Monotherapy Versus Fluoroquinolone Combination Therapy in Patients With Hospital-Acquired Pneumonia: A Multicenter Cohort Study With Propensity Score Matching
Moon Seong BAEK ; Ae-Rin BAEK ; Sang-Bum HONG ; Soohyun BAE ; Hye Kyeong PARK ; Changhwan KIM ; Hyun-Kyung LEE ; Woo Hyun CHO ; Jin Hyoung KIM ; Youjin CHANG ; Heung Bum LEE ; Hyun-Il GIL ; Beomsu SHIN ; Kwang Ha YOO ; Jae Young MOON ; Jee Youn OH ; Kyung Hoon MIN ; Kyeongman JEON ;
Journal of Korean Medical Science 2023;38(41):e353-
Background:
There is insufficient data on the benefits of empiric antibiotic combinations for hospital-acquired pneumonia (HAP). We aimed to investigate whether empiric antipseudomonal combination therapy with fluoroquinolones decreases mortality in patients with HAP.
Methods:
This multicenter, retrospective cohort study included adult patients admitted to 16 tertiary and general hospitals in Korea between January 1 and December 31, 2019.Patients with risk factors for combination therapy were divided into anti-pseudomonal non-carbapenem β-lactam monotherapy and fluoroquinolone combination therapy groups.Primary outcome was 30-day mortality. Propensity score matching (PSM) was used to reduce selection bias.
Results:
In total, 631 patients with HAP were enrolled. Monotherapy was prescribed in 54.7% (n = 345) of the patients, and combination therapy was prescribed in 45.3% (n = 286).There was no significant difference in 30-day mortality between the two groups (16.8% vs.18.2%, P = 0.729) or even after the PSM (17.5% vs. 18.2%, P = 0.913). After the PSM, adjusted hazard ratio for 30-day mortality from the combination therapy was 1.646 (95% confidence interval, 0.782–3.461; P = 0.189) in the Cox proportional hazards model. Moreover, there was no significant difference in the appropriateness of initial empiric antibiotics between the two groups (55.0% vs. 56.8%, P = 0.898). The proportion of multidrug-resistant (MDR) pathogens was high in both groups.
Conclusion
Empiric anti-pseudomonal fluoroquinolone combination therapy showed no survival benefit compared to β-lactam monotherapy in patients with HAP. Caution is needed regarding the routine combination of fluoroquinolones in the empiric treatment of HAP patients with a high risk of MDR.
7.Predicting stage ypT0–1N0 for nonradical management in patients with middle or low rectal cancer who undergo neoadjuvant chemoradiotherapy: a retrospective cohort study
Jeehye LEE ; In Jun YANG ; Jung Wook SUH ; Hong-min AHN ; Heung-Kwon OH ; Duck-Woo KIM ; Young-Hoon KIM ; Kyoung Ho LEE ; Sung-Bum KANG
Annals of Surgical Treatment and Research 2022;103(1):32-39
Purpose:
It is important to discover predictive factors that can identify rectal cancer patients who will respond well to neoadjuvant concurrent chemoradiotherapy (CCRT) to develop management strategies, preserve sphincter and avoid overtreatment. This study explored clinical factors that would predict the adequacy of nonradical management after CCRT in patients with middle or low rectal cancer.
Methods:
We retrospectively evaluated 447 patients with middle or low rectal cancer who were treated with curative surgery after neoadjuvant CCRT between January 2010 and December 2019. The good response group comprised patients with stages ypT0–1N0 on resection after CCRT; the remaining patients were included in the poor response group.
Results:
Of 447 patients (mean age, 60.37 ± 11.85 years), 108 (24.2%) had ypT0–1N0 (71.3% with ypT0N0, 4.6% with ypTisN0, and 24.1% with ypT1N0). Overall, 19 patients with cT1–2 (50.0% vs. 21.8% with cT3–4, P < 0.001), 22 with well-differentiated tumors (51.2% vs. 21.3% with moderately/poorly differentiated tumors, P < 0.001), 16 with fungating tumors (47.1% vs.22.3% with other types, P = 0.001), and 66 with anterior/posterior circumference direction (28.9% vs. 19.2% with lateral/ encircling direction, P = 0.016) had stage ypT0–1N0. On multivariable analysis, cT1–2 (P = 0.021) and well-differentiated tumor (P = 0.001) were independent predictors of ypT0–1N0. Fungating tumors were not significantly associated with ypT0– 1N0 (P = 0.054).
Conclusion
Stage cT1–2 and well differentiation are predictors of ypT0–1N0, while fungating tumors could be considered clinically meaningful, possibly identifying candidates for nonradical treatment post-CCRT.
8.Long-term follow-up results of cytarabine-containing chemotherapy for acute promyelocytic leukemia
Young Hoon PARK ; Dae-Young KIM ; Yeung-Chul MUN ; Eun Kyung CHO ; Jae Hoon LEE ; Deog-Yeon JO ; Inho KIM ; Sung-Soo YOON ; Seon Yang PARK ; Byoungkook KIM ; Soo-Mee BANG ; Hawk KIM ; Young Joo MIN ; Jae Hoo PARK ; Jong Jin SEO ; Hyung Nam MOON ; Moon Hee LEE ; Chul Soo KIM ; Won Sik LEE ; So Young CHONG ; Doyeun OH ; Dae Young ZANG ; Kyung Hee LEE ; Myung Soo HYUN ; Heung Sik KIM ; Sung-Hyun KIM ; Hyukchan KWON ; Hyo Jin KIM ; Kyung Tae PARK ; Sung Hwa BAE ; Hun Mo RYOO ; Jung Hye CHOI ; Myung-Ju AHN ; Hwi-Joong YOON ; Sung-Hyun NAM ; Bong-Seog KIM ; Chu-Myong SEONG
The Korean Journal of Internal Medicine 2022;37(4):841-850
Background/Aims:
We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL).
Methods:
We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up.
Results:
The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis.
Conclusions
Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.
9.Microbiologic pattern and clinical outcome of non-ICU-acquired pneumonia: Korean HAP registry analysis
Jin Ho JANG ; Hye Ju YEO ; Taehwa KIM ; Woo Hyun CHO ; Kyung Hoon MIN ; Sang-Bum HONG ; Ae-Rin BAEK ; Hyun-Kyung LEE ; Changhwan KIM ; Youjin CHANG ; Hye Kyeong PARK ; Jee Youn OH ; Heung Bum LEE ; Soohyun BAE ; Jae Young MOON ; Kwang Ha YOO ; Hyun-Il GIL ; Kyeongman JEON ;
The Korean Journal of Internal Medicine 2022;37(4):800-810
Background/Aims:
Most studies on hospital-acquired pneumonia (HAP) have been conducted in intensive care unit (ICU) settings. This study aimed to investigate the microbiological and clinical characteristics of non-ICU-acquired pneumonia (NIAP) and to identify the factors affecting clinical outcomes in Korea.
Methods:
This multicenter retrospective cohort study was conducted in patients admitted to 13 tertiary hospitals between July 1, 2019 and December 31, 2019. Patients diagnosed with NIAP were included in this study. To assess the prognostic factors of NIAP, the study population was classified into treatment success and failure groups.
Results:
Of 526 patients with HAP, 379 were diagnosed with NIAP. Overall, the identified causative pathogen rate was 34.6% in the study population. Among the isolated organisms (n = 113), gram-negative bacilli were common pathogens (n = 91), such as Pseudomonas aeruginosa (n = 25), Acinetobacter baumannii (n = 23), and Klebsiella pneumoniae (n = 21). The multidrug resistance rates of A. baumannii, P. aeruginosa, and K. pneumoniae were 91.3%, 76.0%, and 57.1%, respectively. Treatment failure was significantly associated with K. pneumoniae (odds ratio [OR], 3.50; 95% confidence interval [CI], 1.35 to 9.05; p = 0.010), respiratory viruses (OR, 3.81; 95% CI, 1.34 to 10.82; p = 0.012), hematological malignancies (OR, 3.54; 95% CI, 1.57 to 8.00; p = 0.002), and adjunctive corticosteroid treatment (OR, 2.40; 95% CI, 1.27 to 4.52; p = 0.007).
Conclusions
The causative pathogens of NIAP in Korea are predominantly gram-negative bacilli with a high rate of multidrug resistance. These were not different from the common pathogens of ICU-acquired pneumonia.
10.Fluvoxamine Treatment of Patients with Symptomatic COVID-19 in a Community Treatment Center:A Preliminary Result of Randomized Controlled Trial
Hyeonji SEO ; Haein KIM ; Seongman BAE ; Seonghee PARK ; Hyemin CHUNG ; Heung-sup SUNG ; Jiwon JUNG ; Min Jae KIM ; Sung-Han KIM ; Sang-Oh LEE ; Sang-Ho CHOI ; Yang Soo KIM ; Ki Young SON ; Yong Pil CHONG
Infection and Chemotherapy 2022;54(1):102-113
Background:
This study aimed to evaluate whether fluvoxamine reduces clinical deterioration in adult patients with mild to moderate coronavirus disease 2019 (COVID-19), and to identify risk factors for clinical deterioration in patients admitted to a community treatment center (CTC).
Materials and Methods:
A randomized, placebo-controlled trial was conducted in a CTC, in Seoul, Korea from January 15, 2021, to February 19, 2021. Symptomatic adult patients with positive results of severe acute respiratory syndrome coronavirus 2 real timepolymerase chain reaction within 3 days of randomization were assigned at random to receive 100 mg of fluvoxamine or placebo twice daily for 10 days. The primary outcome was clinical deterioration defined by any of the following criteria: oxygen requirement to keep oxygen saturation over 94.0%, aggravation of pneumonia with dyspnea, or World Health Organization clinical progression scale 4 or greater.
Results:
Of 52 randomized participants [median (interquartile range) age, 53.5 (43.3 - 60.0) years; 31 (60.0%) men], 44 (85.0%) completed the trial. Clinical deterioration occurred in 2 of 26 patients in each group (P >0.99). There were no serious adverse events in either group. Clinical deterioration occurred in 15 (6.0%) of 271 patients admitted to the CTC, and all of them were transferred to a hospital. In multivariate analysis, age between 55 and 64, fever and pneumonia at admission were independent risk factors for clinical deterioration.
Conclusion
In this study of adult patients with symptomatic COVID-19 who were admitted to the CTC, there was no significant differences in clinical deterioration between patients treated with fluvoxamine and placebo (ClinicalTrials.gov Identifier: NCT04711863).

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