1.Role of PTEN-Induced Protein Kinase 1 as a Mitochondrial Dysfunction Regulator in Cardiovascular Disease Pathogenesis
Vascular Specialist International 2024;40(1):9-
Cardiovascular disease (CVD) remains a global health challenge, primarily due to atherosclerosis, which leads to conditions such as coronary artery disease, cerebrovascular disease, and peripheral arterial disease. Mitochondrial dysfunction initiates endothelial dysfunction, a key contributor to CVD pathogenesis, as well as triggers the accumulation of reactive oxygen species (ROS), energy stress, and cell death in endothelial cells, which are crucial for atherosclerosis development. This review explores the role of PTEN-induced protein kinase 1 (PINK1) in mitochondrial quality control, focusing on its significance in cardiovascular health. PINK1 plays a pivotal role in mitophagy (selective removal of damaged mitochondria), contributing to the prevention of CVD progression. PINK1-mediated mitophagy also affects the maintenance of cardiomyocyte homeostasis in ischemic heart disease, thus mitigating mitochondrial dysfunction and oxidative stress, as well as regulates endothelial health in atherosclerosis through influencing ROS levels and inflammatory response.We also investigated the role of PINK1 in vascular smooth muscle cells, emphasizing on its role in apoptosis and atherosclerosis. Dysfunctional mitophagy in these cells accelerates cellular senescence and contributes to adverse effects including plaque rupture and inflammation. Mitophagy has also been explored as a potential therapeutic target for vascular calcification, a representative lesion in atherosclerosis, with a focus on lactate-induced mechanisms. Finally, we highlight the current research and clinical trials targeting mitophagy as a therapeutic avenue for CVD.
2.Endotension Following Endovascular Aneurysm Repair: Retrospective Review of Treatment and Clinical Outcome
Joon-Young KIM ; Sang Ah LEE ; Jun Gyo GWON ; Youngjin HAN ; Yong-Pil CHO ; Tae-Won KWON
Vascular Specialist International 2024;40(1):10-
Purpose:
Endotension is a rare late complication characterized by an increase in sac size without any type of endoleak following endovascular aortic aneurysm repair (EVAR). Due to its rarity, few studies have demonstrated the mechanism behind and the management of endotension. In this study, we aimed to better understand the treatment and the long-term outcome of endotension in a single-center cohort.
Materials and Methods:
This study was designed for a retrospective review of the patients diagnosed with endotension between January 2006 and December 2017.The study patients were categorized into two groups (primary versus secondary) based on the presence of any type of endoleak before the diagnosis of endotension. We collected data related to endotension treatment, intraoperative findings, and long-term outcomes.
Results:
In a cohort of 15 patients diagnosed with endotension following EVAR, eight were classified into the primary endotension (PE) group without prior endoleak, and seven exhibited secondary endotension (SE). Among the eight PE patients, endovascular intervention for a preemptive purpose was conducted in six patients; however, three (50%) showed continuous sac expansion and finally received open conversion. Overall, eight patients (five in PE and three in SE) underwent open conversion, and one (12.5%) presented with an undetected endoleak during the operative findings. Postoperative morbidity was observed in three patients with no operative mortality.
Conclusion
Endotension can be managed initially through simple observation for changes on serial images, along with preemptive endovascular intervention.However, surgical intervention should be considered for patients with specific indications including continuous aneurysm sac enlargement, presence of symptoms, suspicions of migration of stent-graft with endoleak, and infection.
3.Treatment of abdominal aortic aneurysms in Korea: a nationwide study
Hyangkyoung KIM ; Tae-Won KWON ; Yong-Pil CHO ; Jun Gyo GWON ; Youngjin HAN ; Sang Ah LEE ; Ye-Jee KIM ; Seonok KIM
Annals of Surgical Treatment and Research 2023;105(1):37-46
Purpose:
Although endovascular aneurysm repair (EVAR) has been shown to be superior to open surgical repair (OSR) for abdominal aortic aneurysm (AAA) treatment, no large-scale studies in the Korean population have compared outcomes and costs.
Methods:
The National Health Insurance Service database in Korea was screened to identify AAA patients treated with EVAR or OSR from 2008 to 2019. Perioperative, early postoperative, and long-term survival were compared, as were reinterventions and complications. Patients were followed-up through 2020.
Results:
Of the 13,631 patients identified, 2,935 underwent OSR and 10,696 underwent EVAR. Perioperative mortality rate was lower in the EVAR group (4.2% vs. 8.0%, P < 0.001) even after excluding patients with ruptured AAA (2.7% vs.3.3%, P = 0.003). However, long-term mortality rate per 100 person-years was significantly higher in the EVAR than in the OSR group (9.0 vs. 6.4, P < 0.001), and all-cause mortality was lower in the OSR group (hazard ratio, 0.9; 95% confidence interval, 0.87–0.97, P = 0.008). EVAR had a higher AAA-related reintervention rate per 100 person-years (1.75 vs. 0.52), and AAA-related reintervention costs were almost 10-fold higher with EVAR (US dollar [USD] 6,153,463) than with OSR (USD 624,216).
Conclusion
While EVAR may have short-term advantages, OSR may provide better long-term outcomes and costeffectiveness for AAA treatment in the Korean population, under the medical expense system in Korea.
4.Clinical outcomes of in situ graft reconstruction in treating infected abdominal aortic stent grafts following endovascular aortic aneurysm repair: a single-center experience
Sang Ah LEE ; Seon Jeong JEONG ; Jun Gyo GWON ; Youngjin HAN ; Yong-Pil CHO ; Tae-Won KWON
Annals of Surgical Treatment and Research 2023;104(6):339-347
Purpose:
This study aimed to review our experience with the explantation of infected endovascular aneurysm repair (EVAR) grafts.
Methods:
This single-center, retrospective, observational study analyzed the data of 12 consecutive patients who underwent infected aortic stent graft explantation following EVAR between January 1, 2010 and December 31, 2019, of which 11 underwent in situ graft reconstruction following graft removal. The presentation symptoms, infection route, original pathology of abdominal aortic aneurysms (AAA), graft materials, and clinical outcomes were analyzed.
Results:
Six patients underwent total explantation, whereas 5 underwent removal of only the fabric portions. For in situ reconstructions, prosthetic grafts and banked allografts were used in 8 and 3 patients, respectively. Four mechanisms of graft infection were noted in 11 patients: 4 had bacteremia from systemic infections, 3 had persistent infections following EVAR of primary infected AAA, 3 had ascending infections from adjacent abscesses, and 1 had an aneurysm sac erosion resulting in an aortoenteric fistula. No infection-related postoperative complications or reinfections occurred during the mean 65.27-month (standard deviation, ±52.51) follow-up period. One patient died postoperatively because of the rupture of the proximal aortic wall pseudoaneurysm that had occurred during forceful bare stent removal.
Conclusion
Regardless of graft material, in situ graft reconstruction is safe for interposition in treating an infected aortic stent graft following EVAR. In our experience, the residual bare stent is no longer a risk factor for reinfection. Therefore, it is important not to injure the proximal aortic wall when removing the bare stent by force.
5.Molecular and Clinical Features of Fluconazole Non-susceptible Candida albicans Bloodstream Isolates Recovered in Korean Multicenter Surveillance Studies
Min Ji CHOI ; Yong Jun KWON ; Seung A BYUN ; Mi-Na KIM ; Wee Gyo LEE ; Jaehyeon LEE ; Dongeun YONG ; Chulhun L. CHANG ; Eun Jeong WON ; Soo Hyun KIM ; Seung Yeob LEE ; Jong Hee SHIN
Annals of Laboratory Medicine 2023;43(6):614-619
Acquired fluconazole resistance (FR) in bloodstream infection (BSI) isolates of Candida albicans is rare. We investigated the FR mechanisms and clinical features of 14 fluconazole non-susceptible (FNS; FR and fluconazole-susceptible dose-dependent) BSI isolates of C. albicans recovered from Korean multicenter surveillance studies during 2006–2021. Mutations causing amino acid substitutions (AASs) in the drug-target gene ERG11 and the FR-associated transcription factor genes TAC1 , MRR1, and UPC2 of the 14 FNS isolates were compared with those of 12 fluconazole-susceptible isolates. Of the 14 FNS isolates, eight and seven had Erg11p (K143R, F145L, or G464S) and Tac1p (T225A, R673L, A736T, or A736V) AASs, respectively, which were previously described in FR isolates. Novel Erg11p, Tac1p, and Mrr1p AASs were observed in two, four, and one FNS isolates, respectively. Combined Erg11p and Tac1p AASs were observed in seven FNS isolates. None of the FR-associated Upc2p AASs were detected. Of the 14 patients, only one had previous azole exposure, and the 30-day mortality rate was 57.1% (8/14). Our data show that Erg11p and Tac1p AASs are likely to contribute to FR in C. albicans BSI isolates in Korea and that most FNS C. albicans BSIs develop without azole exposure.
6.Treatment Outcomes of Patients With Ruptured Abdominal Aortic Aneurysms
Hyangkyoung KIM ; Tae-Won KWON ; Yong-Pil CHO ; Jun Gyo GWON ; Youngjin HAN ; Sang Ah LEE ; Ye-Jee KIM ; Seonok KIM
Journal of Korean Medical Science 2023;38(39):e321-
Background:
Ruptured abdominal aortic aneurysm (rAAA) is a serious complication of abdominal aortic aneurysm associated with high operative mortality and morbidity rates. The present study evaluated the perioperative and long-term outcomes of Korean patients with rAAA based on national health insurance claims data.
Methods:
The National Health Insurance Service (NHIS) database was searched retrospectively to identify patients with rAAA who underwent endovascular aneurysm repair (EVAR) and open surgical repair (OSR) from 2009 to 2018. Perioperative (≤ 30 days), early postoperative (≤ 3 month), and long-term (> 3 month) survival, reinterventions, and complications were assessed.
Results:
The search identified 1,034 patients with rAAA, including 594 who underwent EVAR and 440 who underwent OSR. When the study period was divided into two, the total numbers of patients with rAAA, patients who underwent EVAR, and octogenarians were higher during the second half. The perioperative mortality rate was 29.8% in the EVAR and 35.0% in the OSR group (P = 0.028). Hartmann’s procedure for bowel infarction was performed more frequently in the OSR than in the EVAR group (adjusted odds ratio, 6.28; 95% confidence interval [CI], 2.33–21.84; P = 0.001), but other complication rates did not differ significantly. All-cause mortality during the entire observation period did not differ significantly in the EVAR and OSR groups (adjusted hazard ratio, 1.17; 95% CI, 0.98–1.41; P = 0.087). Abdominal aortic aneurysm-related reintervention rate was significantly lower in the OSR group (adjusted hazard ratio, 0.31; 95% CI, 0.14–0.70; P = 0.005).
Conclusion
Although EVAR showed somewhat superior perioperative outcomes for rAAA, the long-term outcomes of EVAR after excluding initial 3 months were significantly worse than OSR. When anatomically feasible for both treatments, the perioperative mortality risk and reasonable prospects of long-term survival should be considered in rAAA.
7.Clinical and Genetic Features of Korean Inherited Arrhythmia Probands
Joo Hee JEONG ; Suk-Kyu OH ; Yun Gi KIM ; Yun Young CHOI ; Hyoung Seok LEE ; Jaemin SHIM ; Yae Min PARK ; Jun-Hyung KIM ; Yong-Seog OH ; Nam-Ho KIM ; Hui-Nam PAK ; Young Keun ON ; Hyung Wook PARK ; Gyo-Seung HWANG ; Dae-Kyeong KIM ; Young-Ah PARK ; Hyoung-Seob PARK ; Yongkeun CHO ; Seil OH ; Jong-Il CHOI ; Young-Hoon KIM
Korean Circulation Journal 2023;53(10):693-707
Background and Objectives:
Inherited arrhythmia (IA) is a more common cause of sudden cardiac death in Asian population, but little is known about the genetic background of Asian IA probands. We aimed to investigate the clinical characteristics and analyze the genetic underpinnings of IA in a Korean cohort.
Methods:
This study was conducted in a multicenter cohort of the Korean IA Registry from 2014 to 2017. Genetic testing was performed using a next-generation sequencing panel including 174 causative genes of cardiovascular disease.
Results:
Among the 265 IA probands, idiopathic ventricular fibrillation (IVF) and Brugada Syndrome (BrS) was the most prevalent diseases (96 and 95 cases respectively), followed by long QT syndrome (LQTS, n=54). Two-hundred-sixteen probands underwent genetic testing, and 69 probands (31.9%) were detected with genetic variant, with yield of pathogenic or likely pathogenic variant as 6.4%. Left ventricular ejection fraction was significantly lower in genotype positive probands (54.7±11.3 vs. 59.3±9.2%, p=0.005). IVF probands showed highest yield of positive genotype (54.0%), followed by LQTS (23.8%), and BrS (19.5%).
Conclusions
There were significant differences in clinical characteristics and genetic yields among BrS, LQTS, and IVF. Genetic testing did not provide better yield for BrS and LQTS. On the other hand, in IVF, genetic testing using multiple gene panel might enable the molecular diagnosis of concealed genotype, which may alter future clinical diagnosis and management strategies.
8.Elucidating the characteristics of Mx1 and resistance to influenza A virus subtype H1N1 in the newly developed KWM/Hym mice
Hajin NAM ; Boyoung KIM ; Avishekh GAUTAM ; Yoo Yeon KIM ; Eun Sun PARK ; Jong Sun LEE ; Hyung-Joo KWON ; Je Kyung SEONG ; Jun Gyo SUH
Laboratory Animal Research 2022;38(3):219-225
Background:
Inbred mice have several advantages, including genetic similarity to humans, a well-established gene manipulation system, and strong tolerance to inbreeding. However, inbred mice derived from a limited genetic pool have a small genetic diversity. Thus, the development of new inbred strains from wild mice is needed to overcome this limitation. Hence, in this study, we used a new strain of inbred mice called KWM/Hym. We sequenced the Mx1 gene to elucidate the genetic diversities of KWM/Hym mice and observed the biological alterations of the Mx1 protein upon influenza A infection.
Results:
The Mx1 gene in KWM/Hym mice had 2, 4, and 38 nucleotide substitutions compared to those in the Mx1 gene in A2G, CAST/EiJ, and Mus spretus mice, respectively. Moreover, the Mx1 protein in KWM/Hym mice had 2 and 25 amino acid substitutions compared to those in the Mx1 protein in CAST/EiJ and M. spretus mice, respectively. To elucidate the function of the Mx1 protein, we inoculated the influenza A virus (A/WSN/1933) in KWM/Hym mice. Nine days after infection, all infected KWM/Hym mice survived without any weight loss. Four days after infection, the lungs of the infected KWM/Hym mice showed mild alveolitis and loss of bronchiolar epithelium; however, the pulmonary viral titers of the infected KWM/Hym mice were significantly lower than that in the infected BALB/c mice (2.17 × plaqueforming units mL −1 ).
Conclusions
Our results demonstrate that the KWM/Hym mice are resistant to influenza A virus infection. Further, these mice can be used as a model organism to understand the mechanism of influenza A virus susceptibility.
9.Surveillance of Chigger Mite Vectors for Tsutsugamushi Disease in the Hwaseong Area, Gyeonggi-do, Republic of Korea, 2015
Young Yil BAHK ; Hojong JUN ; Seo Hye PARK ; Haneul JUNG ; Seung JEGAL ; Myung-Deok KIM-JEON ; Jong Yul ROH ; Wook-Gyo LEE ; Seong Kyu AHN ; Jinyoung LEE ; Kwangsig JOO ; Young Woo GONG ; Mun Ju KWON ; Tong-Soo KIM
The Korean Journal of Parasitology 2020;58(3):301-308
Owing to global climate change, the global resurgence of vector-borne infectious diseases and their potential to inflict widespread casualties among human populations has emerged as a pivotal burden on public health systems. Tsutsugamushi disease (scrub typhus) in the Republic of Korea is steadily increasing and was designated as a legal communicable disease in 1994. The disease is a mite-borne acute febrile disease most commonly contracted from October to December. In this study, we tried to determine the prevalence of tsutsugamushi disease transmitted by chigger mites living on rodents and investigated their target vector diversity, abundance, and distribution to enable the mapping of hotspots for this disease in 2015. A total of 5 species belonging to 4 genera (109 mites): Leptotrombidium scutellare 60.6%, L. pallidum 28.4% Neotrombicula tamiyai 9.2%, Euschoengastia koreaensis/0.9%), and Neoschoengastia asakawa 0.9% were collected using chigger mite collecting traps mimicking human skin odor and sticky chigger traps from April to November 2015. Chigger mites causing tsutsugamushi disease in wild rodents were also collected in Hwaseong for the zoonotic surveillance of the vector. A total of 77 rodents belonging to 3 genera: Apodemus agrarius (93.5%), Crocidura lasiura (5.2%), and Micromys minutus (1.3%) were collected in April, October, and November 2015. The most common mite was L. pallidum (46.9%), followed by L. scutellare (18.6%), and L. orientale (18.0%). However, any of the chigger mite pools collected from rodent hosts was tested positive for Orientia tsutsugamushi, the pathogen of tsutsugamushi disease, in this survey.
10.Validation of Electronic Foot Function Index in Patients with Foot and Ankle Disease: A Randomized, Prospective Multicenter Study
Dong Yeon LEE ; Yu Mi KIM ; Jun Hyung LEE ; Jin KIM ; Ji Beom KIM ; Bom Soo KIM ; Gi Won CHOI ; Sang Gyo SEO ; Jun Beom KIM ; Se Jin PARK ; Yoon Chung KIM ; Young Rak CHOI ; Dong Oh LEE ; Jae Ho CHO ; Dong Il CHUN ; Hyong Nyun KIM ; Jae Yong PARK
Journal of Korean Foot and Ankle Society 2019;23(1):24-30
PURPOSE: To evaluate the efficiency of the electronic foot function index (eFFI) through a prospective, random based, multi-institutional study. MATERIALS AND METHODS: The study included 227 patients ranging in age from 20 to 79 years, visited for surgery in different 15 institutes, and agreed to volunteer. The patients were assigned randomly into a paper-based evaluated group (n=113) and tablet-based evaluated group (n=114). The evaluation was done on the day of hospital admission and the method was changed on the second day of surgery and re-evaluated. PADAS 2.0 (https://www.proscore.kr) was used as an electronic evaluation program. RESULTS: There were no differences in age and sex in both groups. The intraclass correlation coefficient (ICC) evaluation revealed an eFFI ICC of 0.924, showing that both results were similar. The evaluation time was shorter in the tablet-based group than the paper-based group (paper vs tablet, 3.7±3.8 vs 2.3±1.3 minutes). Thirty-nine patients (17.2%) preferred to use paper and 131 patients (57.7%) preferred the tablet. Fifty-seven patients (25.1%) found both ways to be acceptable. CONCLUSION: eFFI through tablet devices appears to be more constant than the paper-based program. In addition, it required a shorter amount of time and the patients tended to prefer the tablet-based program. Overall, tablet and cloud system can be beneficial to a clinical study.
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