1.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
2.Examining the Relationship Between Polystyrene Microplastics and Male Fertility: Insights From an In Vivo Study and In Vitro Sertoli Cell Culture
Byeong Jo JEON ; You Jin KO ; Jin Joo CHA ; Cherry KIM ; Min Young SEO ; Seung Hoon LEE ; Jae Young PARK ; Jae Hyun BAE ; Bum Sik TAE
Journal of Korean Medical Science 2024;39(38):e259-
Background:
While polystyrene microplastics (PS-MPs) are emerging as potentially significant health threats, linked to cancer and reproductive dysfunction, their precise effects on human health remain largely unknown. We aimed to investigate the underlying mechanisms promoting microplastic-induced damage in the reproductive system.
Methods:
Thirty C57BL/6 male mice were randomly allocated into six equal-sized groups.Mice were exposed to fluorescent PS-MPs (5 µm, < 18%, green) at a dose of 1 and 3 mg/dL via oral gavage for 28 and 56 days, respectively (control, 0 mg/dL). The presence of antibodies and inflammatory and oxidative stress markers were evaluated using western blotting. Sperm analysis was also performed. Mouse testis Sertoli TM4 cells were divided into two groups:control (medium only) and PS-MPs (medium containing, 1,000 μg/mL) groups and cultured in vitro for 1, 24, 48, or 72 hours. The cells were cultured in a Ham’s F12: Dulbecco's Modified Eagle Medium medium with 0.25% fetal bovine serum at 37°C with humidified atmosphere of 5% carbon dioxide in the air. Protein analyses for interleukin (IL)-6, IL-10, NADPH-oxidase (NOX)-2, NOX-4, hypoxia-inducible transcription factor (HIF)-2α, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β were performed using western blotting.
Results:
The testes were evaluated after 28 and 56 days of exposure. Varying sizes of PS-MPs were detected in the testes (ranging from 5.870 to 7.768 µm). Significant differences in sperm concentration, motility, and the proportion of normal sperm were observed between the two groups. An increase in TGF-β, HIF-2α, and NOX-4 levels was observed using western blot analysis. However, no dose-dependent correlations were observed between the two groups.In vitro evaluation of the PS-MPs group displayed PS-MP penetration of the lumen of Sertoli cells after 1 hour. Further PS-MP aggregation within Sertoli cells was observed at 24, 48, and 72 hours. A significant increase in inflammatory protein expressions (IL-10, TGF-β, MCP-1, IL-6, TNF-α, and HIF-2α) was observed through western blotting, although oxidative agents did not show a significant increase.
Conclusion
PS-MPs induced reproductive dysfunction in male mice provide new insights into PS-MPs-associated toxicity in mammals.
3.Association between Asymptomatic Cerebrovascular Stenosis and Early Neurological Deterioration in Single Subcortical Infarction Patients
Seong-Min HONG ; Hak-Loh LEE ; Hyunsoo KIM ; Kang-Ho CHOI ; Joon-Tae KIM ; Man-Seok PARK ; Byeong C. KIM
Journal of the Korean Neurological Association 2024;42(4):331-339
Background:
Patients with ischemic stroke may experience early neurological deterioration (END) during the acute phase. This study aimed to identify association between asymptomatic vascular stenosis and END in single subcortical infarction patients.
Methods:
The study included 562 patients admitted within 48 hours of symptom onset between January 2015 and August 2022. END was defined as a decrease of ≥1 point in the National Institutes of Health stroke scale (NIHSS) motor score or ≥2 points in the total NIHSS score within the first 48 hours after stroke onset. Clinical characteristics, including age, sex, smoking habits, underlying vascular risk factors, initial NIHSS score, trial of Org 10172 in acute stroke treatment classification, laboratory parameters, and presence of vascular stenosis or occlusion, were analyzed to identify predictors of END.
Results:
END occurred in 115 patients (20%) with single subcortical infarction. Age (odds ratio [OR], 1.0; p=0.011), female sex (OR, 1.7; p=0.042), location of cerebral infarction at corona radiata (OR, 3.0; p=0.023), systolic blood pressure (OR, 1.0; p=0.011) and presence of asymptomatic vascular stenosis (OR, 2.2; p=0.019) were independently associated with END in multivariable logistic regression.
Conclusions
This study suggests that age, sex, location of cerebral infarction, systolic blood pressure and the presence of asymptomatic vascular stenosis are independent predictors of END.
4.Serial Vascular Responses of BalloonExpandable Stent With Biodegradable Film-Type Graft in a Rabbit Iliac Artery Dissection Model (BioGard Study)
Sang Min PARK ; Kyung-Chan CHOI ; Byeong Han LEE ; Sang Yol YOO ; Christopher Y. KIM
Korean Circulation Journal 2024;54(8):499-512
Background and Objectives:
Arterial dissection during endovascular therapy rarely occurs but can be lethal. A fabric-based covered graft stents yield poor clinical outcomes. A novel balloon-expandable stent with biodegradable film graft for overcoming these issues was evaluated in a rabbit iliac artery model.Method: Eighteen rabbits with iliac artery dissections were induced by balloon over-inflation on angiography (Ellis type 2 or 3) and treated using the test device (3.0×24 mm). Subsequently, survived twelve animals underwent histologic examinations and micro-computed tomography (CT) at 0, 2, 4, and 8 weeks and 3, 6, 9, and 12 months and angiography at one-year.
Results:
There were no adverse cardiovascular events during the one-year. Early-stage histologic examination revealed complete sealing of disrupted vessels by the device, exhibiting mural hematoma, peri-stent red thrombi, and dense infiltration of inflammatory cells. Mid- and long-term histologic examination showed patent stents with neointimal hyperplasia over the stents (% area stenosis: 11.8 at 2 weeks, 26.1 at 1 month, 29.7 at 3months, 49.2 at 9 months, and 51.0 at 1 year), along with mild peri-strut inflammatory response (Grade: 1–2 at mid-term and 0–1 at long-term). The graft film became scarcely visible after six months. Both CT and angiography revealed no instances of thrombotic occlusion or in-stent restenosis (% diameter stenosis: 5.7 at 2 weeks, 12.3 at 1 month, 14.2 at 3 months, 25.1 at 9 months, and 26.6 at 1 year).
Conclusions
The novel balloon-expandable stent with a biodegradable film graft demonstrates feasibility in managing severe artery dissection and preventing lethal vascular events in animal model.
5.Clinical Outcomes After Drug-Coated Balloon Treatment in Popliteal Artery Disease: K-POP Registry 12-Month Results
Jong-Il PARK ; Young-Guk KO ; Seung-Jun LEE ; Chul-Min AHN ; Seung-Woon RHA ; Cheol-Woong YU ; Jong Kwan PARK ; Sang-Ho PARK ; Jae-Hwan LEE ; Su-Hong KIM ; Yong-Joon LEE ; Sung-Jin HONG ; Jung-Sun KIM ; Byeong-Keuk KIM ; Myeong-Ki HONG ; Donghoon CHOI
Korean Circulation Journal 2024;54(8):454-465
Background and Objectives:
The popliteal artery is generally regarded as a “no-stent zone.”Limited data are available on the outcomes of drug-coated balloons (DCBs) for popliteal artery disease. This study aimed to evaluate the 12-month clinical outcomes among patients who received DCB treatment for atherosclerotic popliteal artery disease.
Methods:
This prospective, multicenter registry study enrolled 100 patients from 7 Korean endovascular centers who underwent endovascular therapy using IN.PACT DCB (Medtronic) for symptomatic atherosclerotic popliteal artery disease. The primary endpoint was 12-month clinical primary patency and the secondary endpoint was clinically driven target lesion revascularization (TLR)–free rate.
Results:
The mean age of the study cohort was 65.7±10.8 years, and 77% of enrolled patients were men. The mean lesion length was 93.7±53.7 mm, and total occlusions were present in 45% of patients. Technical success was achieved in all patients. Combined atherectomy was performed in 17% and provisional stenting was required in 11%. Out of the enrolled patients, 91 patients completed the 12-month follow-up. Clinical primary patency and TLR-free survival rates at 12 months were 76.0% and 87.2%, respectively. A multivariate Cox regression analysis identified female and longer lesion length as the significant independent predictors of loss of patency.
Conclusions
DCB treatment yielded favorable 12-month clinical primary patency and TLRfree survival outcomes in patients with popliteal artery disease.
6.Serial Vascular Responses of BalloonExpandable Stent With Biodegradable Film-Type Graft in a Rabbit Iliac Artery Dissection Model (BioGard Study)
Sang Min PARK ; Kyung-Chan CHOI ; Byeong Han LEE ; Sang Yol YOO ; Christopher Y. KIM
Korean Circulation Journal 2024;54(8):499-512
Background and Objectives:
Arterial dissection during endovascular therapy rarely occurs but can be lethal. A fabric-based covered graft stents yield poor clinical outcomes. A novel balloon-expandable stent with biodegradable film graft for overcoming these issues was evaluated in a rabbit iliac artery model.Method: Eighteen rabbits with iliac artery dissections were induced by balloon over-inflation on angiography (Ellis type 2 or 3) and treated using the test device (3.0×24 mm). Subsequently, survived twelve animals underwent histologic examinations and micro-computed tomography (CT) at 0, 2, 4, and 8 weeks and 3, 6, 9, and 12 months and angiography at one-year.
Results:
There were no adverse cardiovascular events during the one-year. Early-stage histologic examination revealed complete sealing of disrupted vessels by the device, exhibiting mural hematoma, peri-stent red thrombi, and dense infiltration of inflammatory cells. Mid- and long-term histologic examination showed patent stents with neointimal hyperplasia over the stents (% area stenosis: 11.8 at 2 weeks, 26.1 at 1 month, 29.7 at 3months, 49.2 at 9 months, and 51.0 at 1 year), along with mild peri-strut inflammatory response (Grade: 1–2 at mid-term and 0–1 at long-term). The graft film became scarcely visible after six months. Both CT and angiography revealed no instances of thrombotic occlusion or in-stent restenosis (% diameter stenosis: 5.7 at 2 weeks, 12.3 at 1 month, 14.2 at 3 months, 25.1 at 9 months, and 26.6 at 1 year).
Conclusions
The novel balloon-expandable stent with a biodegradable film graft demonstrates feasibility in managing severe artery dissection and preventing lethal vascular events in animal model.
7.Clinical Outcomes After Drug-Coated Balloon Treatment in Popliteal Artery Disease: K-POP Registry 12-Month Results
Jong-Il PARK ; Young-Guk KO ; Seung-Jun LEE ; Chul-Min AHN ; Seung-Woon RHA ; Cheol-Woong YU ; Jong Kwan PARK ; Sang-Ho PARK ; Jae-Hwan LEE ; Su-Hong KIM ; Yong-Joon LEE ; Sung-Jin HONG ; Jung-Sun KIM ; Byeong-Keuk KIM ; Myeong-Ki HONG ; Donghoon CHOI
Korean Circulation Journal 2024;54(8):454-465
Background and Objectives:
The popliteal artery is generally regarded as a “no-stent zone.”Limited data are available on the outcomes of drug-coated balloons (DCBs) for popliteal artery disease. This study aimed to evaluate the 12-month clinical outcomes among patients who received DCB treatment for atherosclerotic popliteal artery disease.
Methods:
This prospective, multicenter registry study enrolled 100 patients from 7 Korean endovascular centers who underwent endovascular therapy using IN.PACT DCB (Medtronic) for symptomatic atherosclerotic popliteal artery disease. The primary endpoint was 12-month clinical primary patency and the secondary endpoint was clinically driven target lesion revascularization (TLR)–free rate.
Results:
The mean age of the study cohort was 65.7±10.8 years, and 77% of enrolled patients were men. The mean lesion length was 93.7±53.7 mm, and total occlusions were present in 45% of patients. Technical success was achieved in all patients. Combined atherectomy was performed in 17% and provisional stenting was required in 11%. Out of the enrolled patients, 91 patients completed the 12-month follow-up. Clinical primary patency and TLR-free survival rates at 12 months were 76.0% and 87.2%, respectively. A multivariate Cox regression analysis identified female and longer lesion length as the significant independent predictors of loss of patency.
Conclusions
DCB treatment yielded favorable 12-month clinical primary patency and TLRfree survival outcomes in patients with popliteal artery disease.
8.Association between Asymptomatic Cerebrovascular Stenosis and Early Neurological Deterioration in Single Subcortical Infarction Patients
Seong-Min HONG ; Hak-Loh LEE ; Hyunsoo KIM ; Kang-Ho CHOI ; Joon-Tae KIM ; Man-Seok PARK ; Byeong C. KIM
Journal of the Korean Neurological Association 2024;42(4):331-339
Background:
Patients with ischemic stroke may experience early neurological deterioration (END) during the acute phase. This study aimed to identify association between asymptomatic vascular stenosis and END in single subcortical infarction patients.
Methods:
The study included 562 patients admitted within 48 hours of symptom onset between January 2015 and August 2022. END was defined as a decrease of ≥1 point in the National Institutes of Health stroke scale (NIHSS) motor score or ≥2 points in the total NIHSS score within the first 48 hours after stroke onset. Clinical characteristics, including age, sex, smoking habits, underlying vascular risk factors, initial NIHSS score, trial of Org 10172 in acute stroke treatment classification, laboratory parameters, and presence of vascular stenosis or occlusion, were analyzed to identify predictors of END.
Results:
END occurred in 115 patients (20%) with single subcortical infarction. Age (odds ratio [OR], 1.0; p=0.011), female sex (OR, 1.7; p=0.042), location of cerebral infarction at corona radiata (OR, 3.0; p=0.023), systolic blood pressure (OR, 1.0; p=0.011) and presence of asymptomatic vascular stenosis (OR, 2.2; p=0.019) were independently associated with END in multivariable logistic regression.
Conclusions
This study suggests that age, sex, location of cerebral infarction, systolic blood pressure and the presence of asymptomatic vascular stenosis are independent predictors of END.
9.Serial Vascular Responses of BalloonExpandable Stent With Biodegradable Film-Type Graft in a Rabbit Iliac Artery Dissection Model (BioGard Study)
Sang Min PARK ; Kyung-Chan CHOI ; Byeong Han LEE ; Sang Yol YOO ; Christopher Y. KIM
Korean Circulation Journal 2024;54(8):499-512
Background and Objectives:
Arterial dissection during endovascular therapy rarely occurs but can be lethal. A fabric-based covered graft stents yield poor clinical outcomes. A novel balloon-expandable stent with biodegradable film graft for overcoming these issues was evaluated in a rabbit iliac artery model.Method: Eighteen rabbits with iliac artery dissections were induced by balloon over-inflation on angiography (Ellis type 2 or 3) and treated using the test device (3.0×24 mm). Subsequently, survived twelve animals underwent histologic examinations and micro-computed tomography (CT) at 0, 2, 4, and 8 weeks and 3, 6, 9, and 12 months and angiography at one-year.
Results:
There were no adverse cardiovascular events during the one-year. Early-stage histologic examination revealed complete sealing of disrupted vessels by the device, exhibiting mural hematoma, peri-stent red thrombi, and dense infiltration of inflammatory cells. Mid- and long-term histologic examination showed patent stents with neointimal hyperplasia over the stents (% area stenosis: 11.8 at 2 weeks, 26.1 at 1 month, 29.7 at 3months, 49.2 at 9 months, and 51.0 at 1 year), along with mild peri-strut inflammatory response (Grade: 1–2 at mid-term and 0–1 at long-term). The graft film became scarcely visible after six months. Both CT and angiography revealed no instances of thrombotic occlusion or in-stent restenosis (% diameter stenosis: 5.7 at 2 weeks, 12.3 at 1 month, 14.2 at 3 months, 25.1 at 9 months, and 26.6 at 1 year).
Conclusions
The novel balloon-expandable stent with a biodegradable film graft demonstrates feasibility in managing severe artery dissection and preventing lethal vascular events in animal model.
10.Clinical Outcomes After Drug-Coated Balloon Treatment in Popliteal Artery Disease: K-POP Registry 12-Month Results
Jong-Il PARK ; Young-Guk KO ; Seung-Jun LEE ; Chul-Min AHN ; Seung-Woon RHA ; Cheol-Woong YU ; Jong Kwan PARK ; Sang-Ho PARK ; Jae-Hwan LEE ; Su-Hong KIM ; Yong-Joon LEE ; Sung-Jin HONG ; Jung-Sun KIM ; Byeong-Keuk KIM ; Myeong-Ki HONG ; Donghoon CHOI
Korean Circulation Journal 2024;54(8):454-465
Background and Objectives:
The popliteal artery is generally regarded as a “no-stent zone.”Limited data are available on the outcomes of drug-coated balloons (DCBs) for popliteal artery disease. This study aimed to evaluate the 12-month clinical outcomes among patients who received DCB treatment for atherosclerotic popliteal artery disease.
Methods:
This prospective, multicenter registry study enrolled 100 patients from 7 Korean endovascular centers who underwent endovascular therapy using IN.PACT DCB (Medtronic) for symptomatic atherosclerotic popliteal artery disease. The primary endpoint was 12-month clinical primary patency and the secondary endpoint was clinically driven target lesion revascularization (TLR)–free rate.
Results:
The mean age of the study cohort was 65.7±10.8 years, and 77% of enrolled patients were men. The mean lesion length was 93.7±53.7 mm, and total occlusions were present in 45% of patients. Technical success was achieved in all patients. Combined atherectomy was performed in 17% and provisional stenting was required in 11%. Out of the enrolled patients, 91 patients completed the 12-month follow-up. Clinical primary patency and TLR-free survival rates at 12 months were 76.0% and 87.2%, respectively. A multivariate Cox regression analysis identified female and longer lesion length as the significant independent predictors of loss of patency.
Conclusions
DCB treatment yielded favorable 12-month clinical primary patency and TLRfree survival outcomes in patients with popliteal artery disease.

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