견종 경동맥을 이용한 자가 팽창성, 생분해성 폴리다이옥사논 스텐트의 생체적합성 연구

학위논문 (박사) -- 서울대학교 대학원 : 의과대학 의학과, 2021. 2. 오창완.Introduction: We report a preclinical study of polydioxanone (PDO) self-expanding, biodegradable, intracranial vascular stents for biocompatibility after experimental placement in canine carotid arteries and compare phosphorylcholine-coated and non-coated PDO stents. Materials and Methods: All experiments were approved by the committee of animal research. In vitro PDO filament degradation and platelet adhesion tests were performed. A total of 12 PDO stents and 12 phosphorylcholine-coated PDO stents were implanted in normal canine carotid arteries of 3.0- to 4.0-mm diameter in six dogs. The dogs were divided into three groups with 2 dogs per group. Each group was sacrificed at 4, 8, and 12 weeks after stent placement, respectively. Stent patency was assessed by angiography followed by a microscopic histological examination of the dissected carotid arteries. Results: Stent deployment was technically successful in all dogs without procedure-related complications. On angiographic analysis, in-stent stenosis (9.48 ± 7.13%) was documented in both stent groups at 4 weeks after implantation. Fifty percent of implanted carotid arteries were completely occluded with increased in-stent stenosis (15.80 ± 12.32%) in the other patent vessel at 8 weeks. Total occlusion at 12 weeks was observed in all implanted vessels. PDO filaments began to demonstrate a loss of 5% of their original mass by 4 weeks. PDO filaments started to degrade at 4 weeks and by 16 weeks reached about 50% of their original weight by using in vitro degradation examination. On histologic examination, the degradation of PDO stents started at 4-8 week and at 12 week periods, fragmentation of the braid was observed. According to the degradation of PDO polymer, PDO stents evoked extensive inflammatory responses at 8 and 12 week periods. Inflammatory scores (0-4) were 1.63 ± 0.71 at 4 weeks, 1.79 ± 0.83 at 8 weeks (p=0.360) and 2.33 ± 0.96 at 12 weeks (p=0.008). Although the phosphorylcholine-coated PDO stent showed statistical significance in platelet adhesion inhibition on in vitro platelet adhesions test compared with non-coated PDO stent, there was no different in vivo biocompatibility, such as luminal thrombosis formation and endothelialization between both stent groups. And, lower yet still severe inflammatory responses were observed for the phosphorylcholine-coated PDO stent group. Luminal thrombosis formation and histomorphometric stenosis also increased with increasing time intervals. Conclusion: The PDO stent induced an inflammatory reaction within the carotid artery with subsequent neo-intimal thickening. In 4-week follow-up period before polymer degradation, the vessel patency was preserved with mild in-stent stenosis. However, the degree of stenosis progressed according to the time interval and finally vessel occlusion was occurred. The observed tissue response may be attributable to the degradation of the polymer, which induced an inflammatory response, resulting in the occlusion of the arteries. The phosphorylcholine-coating did not show any difference compared with the non-coated PDO stent.서론: 저자는 자가 팽창성, 생분해성 폴리다이옥사논 스텐트의 생체적합성을 확인하기 위하여, 견종 경동맥에 스텐트 삽입 후 영상의학적, 조직학적 검사를 시행하였다. 또한, 추가적으로 포스폴린콜린 코팅한 스텐트와 비교하고자 하였다. 대상 및 방법: 모든 동물 실험은 동물 실험 위원회의 승인 하에 진행하였다. 총 여섯 마리의 개(비글)의 3mm에서 4mm 크기의 양측 경동맥에 총 12개의 폴리다이옥사논 스텐트와 12개의 포스폴린콜린 코팅한 폴리다이옥사논 스텐트를 삽입하였다. 개는 각각 두 마리씩 스텐트 삽입 후 4주, 8주, 12주에 혈관조영검사 및 조직검사를 시행하였다. 결과: 24개의 스텐트는 모두 합병증 없이 삽입하였다. 혈관 조영 검사 상에서 스텐트 삽입 후 4주 경과 후, 스텐트 내 협착은 9.48 ± 7.13% 보였으며, 8주 경과 시에는 15.80 ± 12.32%의 협착 소견이 보였다. 하지만, 8주 경과한 경동맥의 50%와 12주 경과한 경동맥은 완전 폐색된 상태였다. 체외에서 시행한 폴리다이옥사논 섬유 분해 실험에서, 4주에 분해되기 시작하여 16주에는 초기 질량의 50%의 감소를 보였다. 조직학적 검사 상에서 폴리다이옥사논 스텐트는 4에서 8주 사이에 분해하기 시작하였으며, 12주에는 작은 분절로 분열된 소견이 관찰되었다. 또한, 폴리다이옥사논 고분자의 분열에 따라, 8주에서 12주 추적 검사에서 스텐트 주변의 심한 염증성 반응을 동반하였다. 염증 수치 (0-4)는 4주에 1.63 ± 0.71, 8주에 1.79 ± 0.83, 12주에 2.33 ± 0.96으로 점차 증가하였으며, 12주에는 4주에 비해 통계적으로 유의하게 증가하였다. 체외 혈소판 응집 실험에서는 포스폴린콜린 코팅한 스텐트에서 혈소판 응집이 통계적으로 유의하게 감소하였으나, 생체 실험에서는 혈관내 혈전 생성이나 혈관 내피 생성 등에서 코팅하지 않은 스텐트와 차이점을 보이지 않았다. 또한, 포스폴린콜린 코팅한 스텐트에서는 염증 수치가 낮게 관찰되기는 하였으나, 통계적 의의는 보이지 않았다. 혈관내 혈전 생성 및 조직학적 협착도 염증 수치와 비슷하게 시간 경과에 따라 증가하는 소견을 보였다. 결론: 이 동물 실험에서 폴리다이옥사논 스텐트는 분해됨에 따라 혈관 내에서 심한 염증 반응과 혈관 내막의 과증식을 유발하였다. 생분해가 활발하게 일어나기 전의 4주 경과에서는 경도의 스텐트내 협착은 관찰되나 혈관 개방성은 유지되었다. 하지만, 시간 경과에 따라 혈관 협착이 증가하였으며, 이러한 염증 반응 및 혈관 내막의 증식으로 최종적으로 혈관의 완전 폐색이 유발되었다. 포스폴린콜린 코팅한 스텐트도 같은 반응을 보였다.Abstract i Contents iv List of tables v List of figures vi Introduction 1 Material and Methods 4 Results 12 Discussion 30 Conclusion 36 References 37 Abstract in Korean 46Docto

Analysis of results and problematic cases in interventional therapy for cerebral aneurysms

Thesis (master`s)--서울대학교 대학원 :의학과 신경외과학 전공,2003.Maste

Case study analysis of Korea's disaster emergency relief and investigation of humanitarian values

국제보건학과/석사냉전시대가 종식된 이후 국제적으로 급속히 분쟁과 자연재해 등 재난사태가 증가하였다. 인도주의적 지원을 통한 재난 상황에 빠진 이들을 돕는 국제사회의 노력 속에서, 일부 국가들은 재난을 이용한 정치적, 안보적, 경제적 영향력의 확대를 꾀하고 있다. 우리나라는 1994년 첫 해외재난 긴급구호 활동에 참여한 이후, 민간차원의 긴급구호 참여가 본격화된 초동기를 거쳐, 2004년 서남아시아 쓰나미와 2005년 파키스탄 지진의 과도기 속에서 전문성은 결여된 채 모금과 홍보에만 치우치는 우리의 문제점을 명확하게 인식하게 되었다. 그리고 2010년 아이티 지진 당시 우리나라 대부분 구호팀들은 재난 발생 1주일이 지난 아급성기 현장에서 독자적인 1차진료를 실행하였으며, 평균 5.8일의 단기 의료지원활동만 펼치고 귀국하였다. 이후 문제의식은 보다 확장되었고, 긴급구호의 효율성과 전문성의 개선을 통해 새로운 도약을 기대하고 있다. 2010년 아이티 지진 이후 정부는 ‘해외 긴급구호 선진화 방안’을 발표하였고, 민관 사이의 원활한 의사소통과 역할 분담을 통해 긴급구호의 효율성을 높이고자 노력중이다. 구체적으로 급성기 인명구조는 국가가 전담하며, 이후 의료지원과 구호사업은 민간단체들이 맡아서 추진하는 형태를 마련하고 있다. 의료계에서 강하게 제기하였던 긴급구호 장비개선에 대해서는 예산증액을 통한 이동식 현장 병원 등의 장비구입이 추진되고 있다. 그러나 한편으로는 형식과 외형에만 치중하여 국제적 활동 기준과 인도주의적 정신 및 그 윤리적 가치판단에 대한 성숙은 간과되고 있는 것 같다. 오늘날 인도주의 지원 현장이 보이지 않는 영토분쟁처럼 국력 과시의 장이 되어버렸더라도 국제 사회에서는 GHD(선진 인도적지원 공여국 협의회)나 HLF(세계개발원조총회)처럼 인도주의의 본디 정신을 유지하려는 노력은 계속 되고 있다. 국가의 품격이란 것은 겉으로 포장된 것이 아닌 정직한 약속과 그것을 이행하려는 노력으로 만들어진다는 것을 우리는 HRI(인도주의적 대응 지수)의 순위에서 미국, 독일, 프랑스, 일본 등의 소위 원조 강대국들이 낮은 순위에 머물고 있는 것을 통해 알 수 있다. 진정한 우리의 국격 외교에 대해 진정성을 담은 패러다임을 갖출 수 있는 사회적 담론이 필요하다. 그래서 본 논문은 인도주의적 정신에 충실한 성숙한 해외재난 긴급의료지원 활동의 선결과제로 다음의 세 가지를 제안한다. 첫째, 효율성 보다는 피해지역 주민들과 지역사회의 역량강화가 우선되는 효과성에 기반한 목표설정이 이루어져야 한다. 둘째, 모든 해외재난 긴급구호의 사전 계획과 모금 및 현장 활동 그리고 이후 성과까지 활동 전반의 내용들은 문서적 자료로 축적되어야 한다. 이를 통해 정부 및 구호단체의 내부적 역량 강화뿐 아니라, 투명성과 책무성을 향상시킬 수 있다. 셋째, 정부와 구호단체들, 그리고 의료계까지 포함한 인도주의 정신과 그 윤리성에 대한 지속적인 대화의 장이 마련되어야 한다. 이를 통한 인도주의적 패러다임의 형성은 급변하는 국제 정세 속에서도 흔들리지 않는 윤리적 가치 기제를 지켜줄 것이다. 끝으로 향후 우리나라의 해외재난 긴급의료지원의 대안적 모델로 그동안 우리가 해왔던 1차 진료를 현지민, 특히 취약계층의 필요와 현장의 1차 보건의료 체계의 회복에 기여할 수 있는 방식으로 개선하고 발전시켜 나가야 한다. 이를 위해 언론의 관심을 좇는 급성기 경쟁적 구호활동을 지양하고, 철저한 사전조사를 통한 성공지표, 현지민 역량강화를 위한 목표설정, 그리고 구호활동 전반에 대한 상시적인 평가와 보완 작업이 병행되어야 한다.restrictio

Clinical Outcomes of Large (> 10 mm) Unruptured Posterior Circulation Aneurysms and Their Predictors

Objective : The treatment of large aneurysms of the posterior circulation is complicated and remains challenging. We here analyzed our institutional clinical outcomes of large unruptured aneurysms of the posterior circulation. Methods : This study included 56 patients who presented with a large (>10 mm) unruptured aneurysm of the posterior circulation between 2002 and 2018. Results : There were 18 (32.1%) male and 38 (67.9%) female patients, with a mean age of 53.4 years. The most common location was the vertebral artery, followed by the basilar tip and posterior cerebral artery. The median follow-up duration was 29 months. Eighteen patients (32.1%) were treated by transcranial surgery and 38 (67.9%) were treated by endovascular treatment (EVT). Post-treatment complications occurred in 16 patients (28.6%), with there being no significant difference between the transcranial surgery and EVT groups. Complete obliteration was achieved in 30 patients (53.6%), with there being no statistically significant difference between the transcranial surgery and EVT groups. Recurrence occurred in 17 patients (30.4%), and the rate of recurrence was higher in the EVT group than in the transcranial surgery group (39.5% vs. 11.1%, p=0.03). Forty-four (84%) of 56 patients showed a favorable functional outcome. In saccular aneurysm, EVT was negative predictor of worsening of functional status. Conclusion : Treatment of these aneurysms harbors an inherent high risk of morbidity. No superiority was found between transcranial surgery and EVT in terms of complications and complete obliteration, but transcranial surgery showed a higher treatment durability than EVT

Prevalence of cerebrovascular diseases that can cause hemorrhagic stroke in liver transplantation recipients: a 6-year comparative study with 24,681 healthy adults

Background and purpose Cerebrovascular diseases are a leading cause of mortality after liver transplantation (LT). The prevalence of potentially hemorrhagic cerebrovascular diseases (HCVDs) that could cause a hemorrhagic stroke in patients with severe liver diseases has not been reported. We aimed to analyze the underlying prevalence of HCVDs that could lead to hemorrhagic strokes in LT recipients compared with that in previously healthy controls. Methods A retrospective study with 1,920 consecutive LT recipients and 24,681 adults who underwent a health checkup during the same period was conducted (January 2011?December 2016). The prevalence of cerebral aneurysms (CA), cerebral arteriovenous malformation (AVM), and cavernous malformation (CM) was evaluated using brain imaging, including computed tomography angiography, magnetic resonance imaging, magnetic resonance angiography, and digital subtraction angiography. Results The prevalence of CA and CM were 3.1% and 0.5%, respectively, in the LT group and 3.8% and 0.4%, respectively, in the control group. According to the location of the cerebral artery, paraclinoid internal carotid artery aneurysms (odds ratio [OR] 0.440; P = 0.009) had a lower prevalence in LT recipients than in healthy controls. Anterior communicating artery (OR 3.080; P = 0.002) and superior cerebellar artery (OR 8.767; P = 0.017) aneurysms had a higher prevalence in the LT group than in the control. The prevalence of AVM was significantly higher in LT recipients (0.26%) than in healthy controls (0.06%). Conclusion LT recipients showed a different distribution of CA prevalence according to the locations of the cerebral artery and had a higher overall prevalence of AVM than previously healthy controls

A Prognostic Model of Pontine Hemorrhage Based on Hemorrhage Volume and Location

Objective Spontaneous pontine hemorrhages have the highest mortality rate. Posterior pontine hemorrhage has a poor prognosis, although more research is required in this area. Herein, we attempted to determine the prognosis of pontine hemorrhage by schematically illustrating the volume and location and developing a scoring model to predict the relationship between initial hemorrhage characteristics and clinical outcome. Methods This multicenter, retrospective study was conducted between January 2010 and December 2019. We developed a scoring model using computed tomography (5-mm sections) to plot the location and volume of pontine hemorrhages. All hemorrhage volumes were classified as mild (0.5?5 cm3), moderate (5?10 cm3), or severe (10?16 cm3). Results As the pontine hemorrhage volume increased, the Glasgow Coma Scale (GCS) and Eastern Cooperative Oncology Group scores (ECOG) were significantly lower, while the modified Rankin Scale (mRS) was higher (p<0.001). In the mild and moderate groups, the GCS recovered from 11.36 to 12.89 and 4.68 to 7.31 over 24 months, respectively. The mRS improved from 3.25 to 2.82 in the mild hemorrhage group but deteriorated in the moderate hemorrhage group from 4.93 to 5.24 over 24 months. More extensive pontine hemorrhages were associated with shorter life expectancy. The mild, moderate, and severe groups showed 32.79%, 89.29%, and 100% mortality, respectively (p<0.0001). The anterior and posterior hemorrhage groups had 69.44% and 42.86% mortality (p=0.0020), respectively. Conclusion According to our prognosis model, initial hemorrhage volume was the most significantly related neurological outcome. Hemorrhage location showed no relationship with neurological outcome. However, anterior upper pontine hemorrhage volume was correlated with shortened survival time

Reactive Oxygen Species Scavenger in Acute Intracerebral Hemorrhage Patients A Multicenter, Randomized Controlled Trial

Background and Purpose: Patients with intracerebral hemorrhage (ICH) have oxidative stress. Oxidative stress contributes to the development and progression of perihematomal edema (PHE) in brain hemorrhage patients. We hypothesized that reactive oxygen species (ROS) scavengers might have a neuroprotective role in the acute period of patients with ICH. Methods: This prospective, multicenter, single-blind, randomized study was conducted between June 2017 and October 2019. Intracranial bleeding, including spontaneous ICH, secondary ICH due to vascular anomalies, venous thrombosis, neoplasms, or hemorrhagic infarction, were included in our study. These ROS scavengers were given for 14 days with a dose of N-acetylcysteine 2000 mg/d and selenium 1600 mu g/d intravenously. Other patients received a placebo. The primary outcome was hemorrhage and PHE volume changes in 2-week follow-up computed tomography between ROS scavenger versus placebo groups. Results: In total, 448 patients were enrolled with 123 patients remaining after applying the inclusion and exclusion criteria. There were no significant differences in baseline characteristics between the ROS scavenger (n=57) and placebo (n=66) groups. No significant differences in baseline hematoma and PHE volumes were observed but 2 weeks follow-up computed tomography showed significant differences in PHE volume (21.90 +/- 17.63 versus 30.66 +/- 32.35, P<0.01) and PHE ratio (1.19 +/- 0.73 versus 2.05 +/- 1.27, P<0.01). Among clinical factors, time to reach target Richmond Agitation Sedation Scale (5.98 hours [95% CI, 4.82-7.241 versus 8.42 hours], [95% CI, 6.57-10.77], P<0.01) and the length of intensive care unit stays (6.46 days [95% CI, 2.38-10.55 versus 12.66 days], [95% CI, 8.47-16.85], P<0.01) were significantly shortened among patients who received ROS scavengers than among patients who did not receive ROS scavenger. Conclusions: ROS scavenger showed a significantly reduced PHE volume, time to reach target Richmond Agitation Sedation Scale, and shortened length of intensive care unit stay in patients with acute ICH. Early and high doses of ROS scavengers in a combination regimen may have played a key role in obtaining a favorable outcome in our study. Registration: URL: ; Unique identifier: KCT0004628

Development and validation of a risk scoring model for postoperative adult moyamoya disease

OBJECTIVE The current grading system for moyamoya disease (MMD) is focused on angiographic studies with limited clinical application. The authors aimed to determine relevant factors that may impact postoperative outcome and establish a scoring system to predict the functional outcome. METHODS Adult patients with MMD who underwent treatment between 1998 and 2016 were included. Factors such as age, sex, comorbidity, smoking, MMD family history, initial presentation, multimodal imaging modalities, and types of surgical revascularization were thoroughly reviewed. These factors were analyzed to determine possible risk factors related to unfavorable 6-month postoperative outcomes using the modified Rankin Scale (mRS) (unfavorable: mRS score ≥ 3). A scoring system was developed using these independent risk factors to predict the outcome and validated using prospectively collected data from multiple centers between 2017 and 2018. RESULTS Of 302 patients for whom applications were submitted, 260 patients (321 hemispheres) met the diagnostic criteria. In multivariate analysis, hyperlipidemia, smoking, cerebral infarction on preoperative CT or MRI, and moderately to severely reduced regional cerebrovascular reserve results from Diamox SPECT were significantly related to unfavorable outcome. The authors developed a scoring system and stratified patients into risk groups according to their scores: low-risk (score 0?3), intermediate-risk (score 4?6), and high-risk (score 7?9) groups. This model demonstrated both good discrimination and calibration using C-statistics and the Hosmer-Lemeshow goodness-of-fit test showing 0.812 (95% CI 0.743?0.881) (p = 0.568) for the development and 0.954 (95% CI 0.896?1) (p = 0.097) for the temporal and external validation cohort. CONCLUSIONS The authors’ scoring system is readily adoptable to predict the postoperative outcome for MMD. Their data revealed the importance of smoking and hyperlipidemia, which were the only modifiable factors included in the scoring system. The authors validated their scoring system both internally and externally and maintained good performance, highlighting the system’s generalizability and reliability