소아청소년 수모세포종 환자에서 나노스트링 분석을 이용한 분자유전학적 분류와 면역화학염색 방법과의 비교

학위논문(석사) -- 서울대학교대학원 : 의과대학 의학과, 2022. 8. 김승기.Introduction: Molecular subgrouping of medulloblastoma has become important due to its impact on risk group stratification. Immunohistochemistry (IHC) has been widely used but it has innate limitations. The NanoString nCounter Elements assay has been proposed as an alternative method. This study aims to present the characteristics of medulloblastoma subgrouped by the NanoString assay and to compare the subgrouping results with the IHC method. Methods: Pediatric patients with histological diagnosis of medulloblastoma who underwent surgery from 2007 to 2021 were included. Clinical characteristics, pathological findings were reviewed. Molecular subgrouping was performed by IHC and by NanoString method. Test for concordance between two methods was made. Results: Among a total of 101 patients analyzed, subgrouping using the NanoString assay resulted in 14 (13.8%) WNT, 20 (19.8%) SHH, 18 (17.8%) Group 3, and 39 (38.6%) Group 4 subgroup cases. Survival analysis revealed the following from best to worse prognosis: WNT, Group 4, SHH, and Group 3. In SHH subgroup the large cell/anaplastic histology was present in 30% of cases. Seventy-one cases were analyzed for concordance between NanoString and IHC. Cohen’s kappa value indicated moderate agreement but identification of Groups 3 and 4 with IHC using NPR3 and KCNA1 markers exhibited poor results. Conclusion: The NanoString assay of Korean medulloblastoma patients revealed a more aggressive clinical course in the SHH subgroup which may be explained by a higher proportion of large cell/anaplastic histology being present in this subgroup. IHC did not distinguish Group 3 or 4 accurately. The NanoString assay may represent a good alternative method for practical use in the clinical field.서론 수모세포종에서 분자유전학적 아형의 분류는 위험 환자군의 결정에 큰 역할을 하기 때문에 중요성이 강조되고 있다. 면역화학염색법이 널리 사용되었으나 이 검사 방법은 한계를 지닌다. 나노스트링 분석이 대체할 수 있는 검사 방법으로 제시되었다. 본 연구를 통해 나노스트링 분석으로 분류된 수모세포종의 임상적 특성을 살펴보고 면역화학염색법으로 분류한 결과와 비교하고자 한다. 방법 2007년부터 2021년 까지 수술을 받고 병리학적으로 수모세포종 진단을 받은 소아청소년 환자를 대상으로 했다. 임상적 특징, 병리학적 소견을 분석하였다. 분자유전학적 분류는 면역화학염색 및 나노스트링 방법에 의해 이루어 졌고 두 방법의 일치도 검사를 시행하였다. 결과 나노스트링 분석으로 총 101명의 환자가 분류 되었고 14명(13.8%)의 WNT 아형, 20명(19.8%)의 SHH 아형, 18명(17,8%)의 Group 3 아형, 39명(38.6%)의 Group 4 아형이 확인 되었다. 생존분석 결과 WNT 아형이 가장 예후가 좋고 그 뒤를 따라 Group 4, SHH, Group 3 아형 순으로 점차 나쁜 예후를 보였다. SHH 아형의 30%에서는 거대세포/역형성 조직학적 특징을 보였다. 71개의 케이스에서 두 검사 방법의 일치도를 비교하였고 Cohen’s kappa 값은 중증도의 일치도를 보였지만 NPR3와 KCNA1 마커를 이용한 면역화학염색법으로 Group 3와 Group 4를 분류한 일치도는 낮았다. 결론 한국의 소아청소년 수모세포종 환자들을 대상으로 시행한 나노스트링 분석결과 SHH 아형에서 문헌보다 더 공격적인 임상경과를 보였으며 이는 높은 비율의 거대세포/역형성 조직학적으로 설명될 수 있다. 면역화학염색법으로는 Group 3와 Group 4의 구별이 잘 이루어지지 않았다. 나노스트링 분석이 임상에서 사용되기에 좋은 대체 검사방법이 될 수 있다.Chapter 1. Introduction 1 Chapter 2. Body 3 Chapter 3. Conclusion 24 References 25 Abstract in Korean 29석

Association Between Serum High-Density Lipoprotein Cholesterol Levels and Progression of Chronic Kidney Disease: Results From the KNOW-CKD

Background High-density lipoprotein cholesterol ( HDL -C) levels are generally decreased in patients with chronic kidney disease ( CKD ). However, studies on the relationship between HDL -C and CKD progression are scarce. Methods and Results We studied the association between serum HDL -C levels and the risk of CKD progression in 2168 participants of the KNOW - CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease). The primary outcome was the composite of a 50% decline in estimated glomerular filtration rate from baseline or end-stage renal disease. The secondary outcome was the onset of end-stage renal disease. During a median follow-up of 3.1 (interquartile range, 1.6-4.5) years, the primary outcome occurred in 335 patients (15.5%). In a fully adjusted Cox model, the lowest category with HDL -C of <30 mg/dL (hazard ratio, 2.21; 95% CI, 1.30-3.77) and the highest category with HDL -C of ≥60 mg/dL (hazard ratio, 2.05; 95% CI , 1.35-3.10) were associated with a significantly higher risk of the composite renal outcome, compared with the reference category with HDL -C of 50 to 59 mg/dL. This association remained unaltered in a time-varying Cox analysis. In addition, a fully adjusted cubic spline model with HDL -C being treated as a continuous variable yielded similar results. Furthermore, consistent findings were obtained in a secondary outcome analysis for the development of end-stage renal disease. Conclusions A U-shaped association was observed between serum HDL -C levels and adverse renal outcomes in this large cohort of patients with CKD . Our findings suggest that both low and high serum HDL -C levels may be detrimental to patients with nondialysis CKD .ope

Framingham risk score and risk of incident chronic kidney disease: A community-based prospective cohort study

Background: Cardiovascular disease and chronic kidney disease share several common risk factors. The Framingham risk score is hypothesized to predict chronic kidney disease development. We determined if the Framingham risk scoring system can correctly predict incident chronic kidney disease in the general population. Methods: This study included 9,080 subjects who participated in the Korean Genome and Epidemiology Study between 2001 and 2014 and had normal renal function. The subjects were classified into low- ( 20%) risk groups based on baseline Framingham risk scores. The primary endpoint was de novo chronic kidney disease development (estimated glomerular filtration rate [eGFR], < 60 mL/min/1.73 m2). Results: During a mean follow-up duration of 8.9 ± 4.3 years, 312 (5.3%), 217 (10.8%), and 205 (16.9%) subjects developed chronic kidney disease in the low, intermediate, and high risk groups, respectively (P < 0.001). Multivariable analysis after adjustment for confounding factors showed the hazard ratios for the high- and intermediate risk groups were 2.674 (95% confidence interval [CI], 2.197-3.255) and 1.734 (95% CI, 1.447-2.078), respectively. This association was consistently observed irrespective of proteinuria, age, sex, obesity, or hypertension. The predictive power of this scoring system was lower than that of renal parameters, such as eGFR and proteinuria, but increased when both were included in the prediction model. Conclusion: The Framingham risk score predicted incident chronic kidney disease and enhanced risk stratification in conjunction with traditional renal parameters in the general population with normal renal function.ope

Body mass index is inversely associated with mortality in patients with acute kidney injury undergoing continuous renal replacement therapy

BACKGROUND: Many epidemiologic studies have reported on the controversial concept of the obesity paradox. The presence of acute kidney injury (AKI) can accelerate energy-consuming processes, particularly in patients requiring continuous renal replacement therapy (CRRT). Thus, we aimed to investigate whether obesity can provide a survival benefit in this highly catabolic condition. METHODS: We conducted an observational study in 212 patients who had undergone CRRT owing to various causes of AKI between 2010 and 2014. The study end point was defined as death that occurred within 30 days after the initiation of CRRT. RESULTS: Patients were categorized into three groups according to tertiles of body mass index (BMI). During ≥30 days after the initiation of CRRT, 39 patients (57.4%) in the highest tertile died, as compared with 58 patients (78.4%) in the lowest tertile (P = 0.02). In a multivariable analysis adjusted for cofounding factors, the highest tertile of BMI was significantly associated with a decreased risk of death (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.37-0.87; P = 0.01). This significant association remained unaltered for 60-day (HR, 0.64; 95% CI, 0.43-0.94; P = 0.03) and 90-day mortality (HR, 0.66; 95% CI, 0.44-0.97; P = 0.03). CONCLUSION: This study showed that a higher BMI confer a survival benefit over a lower BMI in AKI patients undergoing CRRT.ope

Snoring and incident chronic kidney disease: a community-based prospective cohort study

OBJECTIVES: Previous studies have shown that symptoms of sleep-disordered breathing are associated with metabolic derangements and vascular disease development. However, the relationship between snoring and renal function is not well investigated. The association between snoring and the development of incident chronic kidney disease (CKD) in subjects with normal renal function was evaluated. DESIGN: Prospective cohort study. SETTING: Ansung (rural community) and Ansan (urban community) cities. PARTICIPANTS: Community-based cohort participants aged 40-69 years. METHODS: A total of 9062 participants in the Ansung-Ansan cohort study were prospectively followed up from 2001 to 2014. The participants were classified into three groups: non-snorer, <1 day/week and ≥1 day/week. The main outcome was incident CKD, which was defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m2 during the follow-up period. PRIMARY OUTCOME: Incident CKD. RESULTS: The mean subject age was 52.0±8.9 years, and 4372 (48.2%) subjects were male. The non-snorer,<1 day/week and ≥1 day/week groups included 3493 (38.5%), 3749 (41.4%), and 1820 (20.1%) subjects, respectively. Metabolic syndrome was more prevalent in the snoring groups than in the non-snoring group. Snoring frequency showed a significant positive relationship with age, waist:hip ratio, fasting glucose, total cholesterol (Tchol) and low-density lipoprotein cholesterol. During a mean follow-up of 8.9 years, 764 (8.4%) subjects developed CKD. Cox proportional hazards model analysis revealed that the risk of CKD development was significantly higher in subjects who snored ≥1 day/week than in non-snorers, even after adjustments for confounding factors (HR 1.23, 95% CI 1.09 to 1.38, p<0.01). CONCLUSION: Snoring may increase the risk of CKD development in subjects with normal renal function.ope

Policy network & policy output in the policy separating the prescribing from the dispensing of drugs : on the focus of policy paradigm shift

본 연구는 의약분업정책사례를 중심으로 정책의 지속성과 변화에 대한 정책네트워크적 분석을 시도하였다. 일련의 정책적 논의에도 불구하고 의약혼재정책이 40여 년 동안 지속될 수 있던 원인과 의약분업으로 정책변화가 이루어진 원인을 정책네트워크적 접근을 통해 분석하고자 하였다. 나아가 이를 통해 정책네트워크라는 제도적 특성이 정책반응에 어떤 영향을 미치는지를 분석하고자 하였다. 분석결과, 먼저 의약혼재에서 의약분업으로 정책이 변경된 원인은 다음과 같다. 첫째, 의약혼재정책이 유지될 수 있던 원인은 정부와 이익집단으로 구성된 정책공동체적 성격에 의한 경로의존성에 기인한다. 둘째, 의약분업정책으로 전환은 이들 정책공동체에 시민단체가 참여함으로써 그 성격이 이슈네트워크화 하였다는 데서 원인을 찾을 수 있다. 다음으로 정책네트워크와 정책반응과의 관계에서 확인 할 수 있던 것은, 첫째 소수의 강한 응집성을 가진 정책네트워크는 정책 변화의 요구를 무의사결정화 한다. 둘째, 소수의 정책행위자들 간의 응집성 약화는 정책수정, 즉 정책의 제한된 변화를 수반한다. 셋째, 새로운 정책행위자들의 등장과 이들의 정책네트워크의 진입시도는 정책네트워크의 문제해결능력을 제약함으로써 새로운 정책기제의 모색을 낳게 하는 원천이다. 넷째, 정책네트워크의 성격변화는 정책의 근본적인 변화를 낳게 한다. This study is trying to analyze, focused on the Policy Separating the Prescribing from the Dispensing of Drugs (PSPDD), policy continuations and changes by networks. To figure out how the Policy of Mixed Prescribing and Drugs (PMPD) could be kept for more than 40 years in spite of a series of arguments, this research uses policy network approaches. Moreover, the relations between policy networks and policy responses can be estimated by these approaches. The results of these analyses are like follows. First of all, it is the first reason that policy community, consisted of governments and interest groups, was sustained with supporting PMPD. NGOs' participation gave influence to change the characteristics of policy networks and this made possible to achieve PSPDD. The degree of policy networks intensity is the second reason. The more intensive policy networks, the easier for non-decision making. On the contrary, weak stability among policy actors results in limited policies. Besides, appearances of new policy entrepreneurs and their trials to enter policy networks restrict the problem solving capability of policy networks. Furthermore, the changes of policy networks bring policy shifts and changes. As a result, policy networks impact on policy responses

쪽(polygonum tinctorium)의 현탁배양중 엘리시테이션이 인디 루빈 색소 생산에 미치는 영향

Thesis (master`s)--서울대학교 대학원 :식품공학과,1995.Maste

Mark-On: Encouraging Student Questions in Class

2

State-business relations in developmental state : a critical study of industrialization in the Korean ship-building industry and the thesis of "support-discipline"

학위논문(박사)--서울대학교 대학원 :정치학과,1999.Docto

日別(day-to-day)通行行態分析 硏究 : Markov chain 技法을 利用

학위논문(석사)--서울대학교 환경대학원 :환경계획학과 교통전공,1998.Maste