A building block of Antibiotic Ramoplanin A2

학위논문(석사) -- 서울대학교대학원 : 공과대학 화학생물공학부, 2021.8. 김영규.This paper covers the contents of the synthesis of building block of ramoplanin A2 based on the stereoselectivity of the L-threo-β-hydroxy aspartate. Ramoplanin A2, synthesized by Actinoplanes, is a type of glycolipodepsipeptide and exhibits clinical effects. In particular, ramoplanin A2 plays an effective role in the treatment of vancomycin-resistant E. faecium (VREF) in the gastrointestinal tract by inhibiting the biosynthesis of bacterial cell wall in Gram-positive bacteria. According to the currently published papers, ramoplanin A2 is composed of three key subunits and can be synthesized through coupling reactions and cyclization reactions. Among them, the structure of L-threo-β-hydroxy asparagine is considered to be important in terms of stereochemistry as the backbone of the second key subunit, pentadepsipeptide. In our group, we have studied the stereoselective synthesis of trans-oxazolidine. N-hydroxymethyl-α-amino aldehyde has a stable structure by shifting its equilibrium to hemiacetal and participates in the reaction. Trans-oxazolidine is synthesized through the reaction of N-hydroxymethyl-α-amino aldehyde with phenylsulfonyl-nitromethane, and H-eclipsed formation of transition state enhances the stereoselectivity of trans-oxazolidine structure in the ratio of 20:1. Through this procedure, L-threo-β-hydroxy aspartate was synthesized in a total of 11 steps, 11% from D-serine. This product was synthesized to contain different protection groups on each terminal, which allows selective conversions to other form such as L-threo-β-hydroxy asparagine. Moreover, the possibility of synthesizing ramoplanin A2 was confirmed through Yamaguchi coupling reaction with N-phenylalanine.본 논문은 L-트레오-β-하이드록시 아스파라진 구조의 입체선택적 특징을 기본으로 하는 라모플라닌 에이2의 전구체의 합성에 관한 내용을 다루고 있다. 악티노플라네스에 의해 합성되는 라모플라닌 에이2는 당지질 뎁시펩타이드의 한 종류로 임상효과를 나타낸다. 특히 라모플라닌 에이2는 그람 양성 박테리아에서 박테리아의 세포벽 생합성을 저해하여 소화기관에 존재하는 반코마이신 내성 장구균의 처리에 효과적인 역할을 한다. 현재 발표된 논문에 따르면 라모플라닌 에이2는 3개의 소단위체로 구성되어 커플링 반응과 고리화 반응을 통해 합성할 수 있다고 한다. 그 중 L-트레오-β-하이드록시 아스파라진 구조는 두 번째 주요 소단위인 펜타뎁시펩타이드의 뼈대로써 입체화학적 측면에서 중요하게 여겨진다. 우리 그룹은 트랜스-옥사졸리딘 구조를 형성할 때 일어날 수 있는 입체선택적 합성 방법에 대해 보고한 평형이 이동하여 안정한 구조를 가지고 반응에 참여한다. 트랜스-옥사졸리딘은 N-하이드록시메틸-α-아미노 알데하이드와 페닐설포닐나이트로메테인의 반응을 통해 합성되고, 전이상태에서의 H-가리움 형태로 인한 입체장애로 인해 트랜스-옥사졸리딘의 입체 선택성이 20:1의 비율로 높아진다. 이를 통하여 D-세린으로부터 L-트레오-β-하이드록시 아스팔테이트를 총 11단계, 11%로 합성하였다. 이 합성물은 각 말단이 서로 다른 종류의 보호기로 보호되어 L-트레오-β-하이드록시 아스파라진과 같은 형태로의 선택적 전환이 용이하게 합성되었다. 또한, N-페닐알라닌과의 야마구치 커플링 반응을 통한 뎁시펩타이드의 형성으로 라모플라닌 에이2의 합성 가능성을 확인하였다.1. Introduction 1 1.1 Introduction of Depsipeptide 1 1.2 Introduction of Ramoplanin A2 3 1.3 Introduction of building block of Ramoplanin A2 5 1.4 Introduction of N-protected-α-amino aldehyde 8 1.5 Introduction of trans-oxazolidine 10 2. Results and Discussion 13 2.1 Retrosynthesis of building block of Ramoplanin A2 13 2.2 Formation of D-serinal 14 2.3 Formation of stereoselective trans-oxazolidine 16 2.4 Formation of building block for Ramoplanin A2 18 3. Conclusion 21 4. Experimental Details 22 REFERENCES 30 APPENDICES 33 ABSTRACT IN KOREAN 50석

ELM 플라즈마 모사를 위한 레일건 플라즈마의 특성에 대한 연구

학위논문 (석사)-- 서울대학교 대학원 : 에너지시스템공학부, 2013. 2. 황용석.토카막에서는 H-mode를 유지하면서 장시간 운전하는 것이 중요하지만, 일반적으로 고온 플라즈마 경계 면에서의 큰 압력 변화 때문에 불안정한 현상인 ELM (Edge Localized mode)이 발생하게 된다. 이렇게 불안정한 ELM에 의한 다이버터 (Divertor)의 손상에 대한 연구는 핵융합로의 수명과 관련하여 해결해야 할 중요한 과제 중 하나이다. 기존의 ELM 모사 장치들은 대면 재료에 대해 큰 열 부하를 주어 그 변화를 관찰하고 재료를 선정하는 것을 목적으로 하였기 때문에 실제로 ELM 플라즈마의 특성을 잘 재현해내기보다는 고출력 에너지를 만드는 복잡한 형태의 빔 발생 장치이었다. 또한 이러한 모사 장치를 대면 재료 시험에만 제한적으로 사용하였다. 이에 본 논문에서는, ELM과 유사한 플라즈마를 만들 수 있는 간단한 형태의 레일건 (rail gun)을 설계 및 제작하고, 실험과 전산모사를 통해 ITER 크기에서의 ELM 플라즈마의 밀도, 이온 유동 속도 측면에서 유사한 플라즈마 젯 (plasma jet)에 대한 연구를 수행하여 향후 다이버터에 ELM 플라즈마가 도달하기 전에 제어하는 연구에 기여하고자 하였다. 실험을 위해 일정한 방향으로 큰 로렌츠 힘을 발생시킬 수 있는 레일건 개념을 채택하였다. ELM 플라즈마의 특성을 바탕으로 전극 길이, 방전기체의 주입 시간, 충전 전압, 프로브 측정 위치와 같은 실험 조건들을 변화시키면서, ELM과 유사한 특성을 지닌 플라즈마를 발생시킬 수 있는 조건들을 고려하여 ELM 모사에 적합한 레일건을 제작하였다. 진공 환경에서 각각의 아르곤과 수소 기체를 전극 사이의 공간에 주입하면서 높은 펄스 전압을 전극에 인가하여 레일 사이에서 방전을 일으켜 고속의 플라즈마 젯을 만들 수 있었다. 레일건에서 플라즈마 젯이 방출되기 전에 레일을 따라 이동하는 아크 플라즈마 채널에 대한 동적 특성을 확인하기 위하여 레일 전극 사이를 초고속 카메라로 진단하였다. 방전으로 발생한 플라즈마가 덩어리의 형태로 전극 사이를 가속하여 이동하는 것을 관찰할 수 있었고, 이것으로 대략적인 플라즈마 채널의 운동 속도를 추정할 수 있었다. 전류가 흐르는 레일과 전력 시스템을 하나의 간단한 회로 형태로 모델링하여 모사한 결과 플라즈마 채널의 이동 거리와 속도를 예측할 수 있었고, 이는 초고속 카메라의 진단 결과와 유의미한 수준으로 유사함을 검증할 수 있었다. 또한 전극 안 쪽 뿐만 아니라 전극에서 분출되는 순간의 플라즈마 젯의 형태를 초고속 카메라를 통해 확인할 수 있었다. 이것은 입자 거동을 전산 모사할 수 있는 OOPIC을 통해 플라즈마 젯의 이동을 모사하여 비교하였다. 이러한 방식으로 플라즈마 젯의 형태와 초기 발생과정을 확인하였고, 레일건에서의 고속 플라즈마를 측정하기 적합한 4중 랑뮤어 탐침을 제작하여 방전기체, 충전전압에 따라 플라즈마 젯을 거리별로 측정하였다. 각각의 탐침으로 수집되는 신호를 처리하기 위해 회로를 제작하여 탐침 간 전위차와 전류에 대한 데이터를 받았고, 데이터를 바탕으로 비선형 방정식을 풀어 플라즈마 젯의 전자 온도, 전자 밀도, 이온 속도를 계산하였다. ELM 플라즈마의 입자를 제어하는 측면에서는 ELM과 유사한 플라즈마 젯의 밀도, 속도, 크기가 중요한 요소이다. 진단된 아르곤 플라즈마 젯의 파라미터들은 실제 ELM 필라멘트 플라즈마 특성과 비교했을 때 온도를 제외하고는 큰 차이가 없었다. 특히 플라즈마 젯의 밀도와 드리프트 속도는 각각 m-3와 10 km/s 이상 정도로 유사한 결과를 얻었고, 차후 플라즈마 입자를 전자기장으로 제어한다는 측면에서 봤을 때 실험실 환경에서 이 플라즈마 젯을 사용할 수 있을 것이다. 또한 진단된 수소 플라즈마 젯의 파라미터들 역시 실제 ELM 필라멘트의 플라즈마 특성과 비교했을 때 전자 밀도는 유사하지만 전자 온도가 상대적으로 매우 낮았다. 그러나 레일건의 로렌츠 힘을 이용하여 플라즈마 젯의 속도를 100 km/s 이상으로 만들어낼 수 있고, 충전 전압을 조절하여 원하는 속도로 올릴 수 있는 것이 가능함을 확인하였다. 실험에서의 플라즈마 속도에 대한 운동에너지로 실제 ELM 플라즈마의 대면 물질에 대한 충격 에너지와 유사하게 만드는 것이 가능할 것이다. 이와 같이 본 논문에서는 드리프트 속도와 에너지 측면에서 ELM 플라즈마에 근접한 특성을 지닌 플라즈마를 레일건을 이용하여 만들 수 있음을 확인할 수 있었다. 그러므로 향후 본 연구의 실험 환경에서 ELM 플라즈마와 유사한 특성을 가진 플라즈마 젯을 외부 전자기장을 이용하여 표적에 대한 부하를 감소시키는 연구를 진행하는데 기초가 될 것이고, 추가적으로 간단한 장치로 대면 재료 시험을 하는데도 활용될 수 있을 것이다.Damages of divertor targets by plasma loads during edge localized modes (ELMs) are critical issue in fusion engineering because they reduce the lifetime of the divertor target. In the case of ITER, the plasma load on divertor target during ELM is up to tens of GW/m2 and its duration is approximately a few hundred microseconds. To evaluate the damages of divertor target during ELMs experimentally, various irradiation systems using a pulsed laser or particle beams have been proposed and tested. Among them, a pulsed plasma gun is thought to be suitable to simulate the ELM situation because it can give the particle load as well as the thermal heat load on the divertor target. Therefore, in this thesis, a small-sized rail gun is adopted to simulate the heat loads during ELMs and explore how to relieve the heat loads. The rail gun is designed and fabricated in configuration of two parallel electrodes: the separation between the electrodes is 1 cm wide and the length of the rail is 30 cm long. The rail gun is installed at the top of cylindrical chamber so that the plasma jet is ejected vertically downward from the muzzle of the rail gun. The electrical current is fed to the electrodes by fast discharge of electrical energy stored in low-inductance capacitor. Initiation of discharge is accomplished by fast injection of gas at the breech of the rail using a piezoelectric valve. Argon and hydrogen are used as working gases. Diagnostics of the plasma jet ejected from the muzzle of the rail gun is carried out with a quadruple Langmuir probe and a fast camera. The fast camera is also used to diagnose the formation and motion of the plasma channel between the electrodes, revealing almost linear increase in velocity with time. Dynamic motion of the plasma channel inside the rail is confirmed by a simple equivalent circuit model for parallel-plate rail gun, showing good agreements between the numerical calculation and the experimental observation. The quadruple Langmuir probe is used to measure the spatio-temporal changes for the properties of the plasma jet during the propagation in open space by moving the probe position vertically. With appropriate data processing, it provides the information on the time-dependent plasma properties, i.e. electron density, electron temperature and ion drift velocity, which are critical in studying the ELM-like plasmas. From a lot of experiments conducted using gases with large difference in mass, i.e. hydrogen and argon, it is suggested that the plasma gun developed in this study can be separately applicable for the different topics on researches of ELM plasma: ELM control experiments for argon and heat load tests for hydrogen. The argon plasma jet with ion velocity of 10 km/s is suitable for investigation of the control of ELM-like plasma because the ion drift velocity is similar to the ELM filament velocity approaching to the divertor target. While, the ion drift velocity for the hydrogen plasma jet is much higher up to 120 km/s, so that it is possible to use for simulating the heat load impacting on the divertor surface. The ion drift velocity, or equivalently ion kinetic energy, is easily increased by increasing the length of the rail as well as the discharge current. Therefore, the plasma gun developed and characterized in the present study is expected to be well utilized for the versatile researches on the future experiments on the ELM control and mitigation.Abstract ⅰ Contents ⅳ List of Tables ⅵ List of Figures ⅶ Chapter 1 Introduction 1 1.1 Research motivation and objectives 1 1.2 Thesis outline 4 Chapter 2 Background theory 5 2.1 ELM (Edge Localized Mode) 5 2.2 Rail gun dynamics 8 Chapter 3 Experimental setup 10 3.1 Design requirements 10 3.2 Construction of rail gun system 12 3.2.1 Power supply and gas puffing system 14 3.2.2 Rail gun design 14 3.2.3 Installation of diagnostic tools 18 3.3 Diagnostics 19 3.3.1 Fast camera 19 3.3.2 Quadruple Langmuir probe (QLP) 20 Chapter 4 Characterization of plasma jet 23 4.1 Visualization of the rail gun plasma using fast camera 23 4.1.1 Arc plasma channel inside rail electrodes 23 4.1.2 Plasma jet ejected from rail electrodes 25 4.2 Signal data acquisition using QLP 27 4.3 Plasma jet parameters 30 4.3.1 Calculation of plasma parameters 30 4.3.2 Time varying plasma jet 32 4.3.3 Variation of moving plasma jet characteristics 37 4.4 Correlation of the ELM plasma and experimental results 41 4.4.1 Analysis as the particle 41 4.4.2 Analysis as the energy 43 Chapter 5 Theoretical models for rail gun plasma 45 5.1 Theoretical slug model for the plasma gun 45 5.1.1 Simple system circuit model 45 5.1.2 Motion of an arc plasma channel in modeling 47 5.2 Particle-In-Cell simulation of rail gun plasma jet 49 5.2.1 Simulation setup for PIC simulation 49 5.2.2 Results of the plasma jet motion using PIC simulation 52 Chapter 6 Conclusions and future work 55 Bibliography 57 Abstract in Korean 60Maste

On the Optimum Cathodic Protection Design of Harbor Steel Piles in Terms of Sea Water Environment Factors and Steel Pile Surface Condition

With the rapid development of industry corrosion of steel structures exposed to the severe environment has generated numerous social and economical problems in the economical point of view. Furthermore, it has been revealed that the economical loss by corrosion of steel structures was approximately 2~4% of GNP in the U.S. in 1998. Although in Korea, the percentage of the economical loss by the corrosion was not clearly verified, it was assumed that the loss would be much greater than the U.S’. Therefore a corrosion control is being generally accepted as important issue not only in economical point of view but also in safety reason and those steel structures should be protected by an optimum protection method. And there are many protection methods for steel structureone of them is a cathodic protection including both impressed current method and sacrificial anode method, which are being mainly used for steel structures in marine environment. Recently, the corrosion property of sea water was being changed the increase of environmental contamination, so the optimum protection design should be changed corresponding to some parameters such as degree of contamination, temperature, velocity (flow rate) of sea water and surface condition of steel structure. In this study, the optimum protection design for steel structures in marine environment was investigated with some parameters such as variation of supplied cathodic current density, surface condition of cleaned or rusted and solution state of stirring or no stirring through the simulation technology, followed by both laboratory and field experiment. Chapter. 3.1 is to investigate the optimum protection potential and protection current density with some parameters such as variation of supplied cathodic current density, surface condition of cleaned or rusted and solution state of stirring or no stirring. The corrosion current density of the rusted surface was considerably amall compared to the cleaned one and the cathodic polarization potential of cleaned specimen was more negative than that of the rusted one at the same applied cathodic current density. However the protection potential of cleaned specimen was below -770 mV (SCE), on the other hand its potential of the rusted one was lower than -700 mV (SCE) irrespective of solution stirring condition and in the case of no stirring condition, the protection current density was 100 mA/m2 at both cleaned and rusted specimens, however, it was revealed that the protection current density in stirring condition was about 200 mA/m2 due to increasing of oxygen diffusion on the cathode surface. It is suggested that the optimum protection potential and current density should be controlled by the surface condition of structures as well as solution stirring condition. Chapter 3.2 is to reconfirm the experimental results of chapter 3.1 by field experiment. As the results of chapter 3.2, the consumption rate and producing current of anode in the case of rusted steel pile was much greater than the cleaned steel pile and the applied current density for protection potential (-770 mV (SCE)) was also much larger compared to the cleaned steel pile. Chapter 3.3 is to investigate the variation of anode producing current and cathodic polarization potential of some steel piles in case of their steel piles was protected by sacrificial anode in field experiment. When some steel piles electrically connected with the other adjacent piles which was protected or not by sacrificial anode was being also cathodically protected by sacrificial anode, anode producing current between sacrificial anode and their steel piles was varied with corresponding to whether the other adjacent piles were cathodically protected because anode producing current was consumed to the other adjacent piles for protection or saved due to their steel piles were protected slightly by other anode producing current between sacrifical anode and the other adjacent piles for protection. Therefore it is suggested that life time of sacrificial anode for some steel piles protection can be also varied with increasing or decreasing of anode producing current according to the other adjacent piles’ protection or not. Consequently it is concluded that for the optimum protection design, the surface condition as well as the contamination degree of sea water should be considered to determine some factors such as life time, current efficiency and protection current density.1. 서 론 1 2. 이론적 배경 4 2.1 부식의 기본이론 4 2.2 해수중 강 구조물의 부식특성과 방식법 19 2.2.1 해수의 성질 19 2.2.2 강구조물의 해양 부식특성 23 2.2.3 해수중 철강구조물의 부식에 미치는 영향 인자 26 2.2.4 해수중 강 파일의 방식법 31 2.3 강구조물 희생양극 방식설계상의 문제점 41 2.3.1 양극 전류효율의 문제점 41 2.3.2 양극발생전류 계산의 문제점 43 2.3.3 방식전류밀도 값의 문제점 44 2.3.4 설계 양극개수 산출의 문제점 47 2.3.5 등가직경(D) 계산의 문제점 47 2.3.6 방식설계에서 수질의 문제점 49 2.3.7 해양 강구조물 효율적인 방식설계 적용을 위한 시뮬레이션 연구 54 3. 연구결과 및 고찰 74 3.1 음극방식의 설계에 미치는 해수 환경인자 및 피 방식체 표면 상태의 영향 74 3.1.1 연구 배경 및 목적 74 3.1.2 시험편 제작 및 실험방법 74 3.1.3 실험결과 및 고찰 79 3.1.4 결과 요약 124 3.2 강 파일의 표면상태에 따른 희생양극소모량과 방식 전류밀도변화 125 3.2.1 연구배경 및 목적 125 3.2.2 대형 실험조 제작 및 해상 실험장 제작 125 3.2.3 실험방법 127 3.2.4 실험결과 및 고찰 133 3.2.5 결과 요약 141 3.3 음극방식에 의해 강 파일에 유입한 방식전류가 인접한 강 파일에 미치는 영향 142 3.3.1 연구배경 및 목적 142 3.3.2 실험 방법 142 3.3.3 실험 결과 및 고찰 148 3.3.4 결과 요약 159 4. 총괄 결론 160 참 고 문 헌 16

Clinical Practice Guideline of Acute Respiratory Distress Syndrome

There is no well-stated practical guideline for mechanically ventilated patients with or without acute respiratory distress syndrome (ARDS). We generate strong (1) and weak (2) grade of recommendations based on high (A), moderate (B) and low (C) grade in the quality of evidence. In patients with ARDS, we recommend low tidal volume ventilation (1A) and prone position if it is not contraindicated (1B) to reduce their mortality. However, we did not support high-frequency oscillatory ventilation (1B) and inhaled nitric oxide (1A) as a standard treatment. We also suggest high positive end-expiratory pressure (2B), extracorporeal membrane oxygenation as a rescue therapy (2C), and neuromuscular blockage for 48 hours after starting mechanical ventilation (2B). The application of recruitment maneuver may reduce mortality (2B), however, the use of systemic steroids cannot reduce mortality (2B). In mechanically ventilated patients, we recommend light sedation (1B) and low tidal volume even without ARDS (1B) and suggest lung protective ventilation strategy during the operation to lower the incidence of lung complications including ARDS (2B). Early tracheostomy in mechanically ventilated patients can be performed only in limited patients (2A). In conclusion, of 12 recommendations, nine were in the management of ARDS, and three for mechanically ventilated patients.ope

Comparison of self-reported and accelerometer-assessed measurements of physical activity according to socio-demographic characteristics in Korean adults

OBJECTIVES: Previous studies have shown relatively low correlations between self-reported and accelerometer-assessed physical activity (PA). However, this association differs by socio-demographic factors, and this relationship has not been fully investigated in the general population. Thus, we investigated the correlation between self-reported and accelerometer-assessed PA and whether it differed by demographic and socioeconomic factors among the Korean general population. METHODS: This cross-sectional study included 623 participants (203 men and 420 women) aged 30 to 64 years, who completed a PA questionnaire and wore a wrist-worn accelerometer on the non-dominant wrist for 7 days. We examined the agreement for metabolic equivalent task minutes per week (MET-min/wk) between the 2 measures and calculated Spearman correlation coefficients according to demographic and socioeconomic factors. RESULTS: The kappa coefficient between tertiles of self-reported and accelerometer-assessed total MET-min/wk was 0.16 in the total population, suggesting overall poor agreement. The correlation coefficient between the 2 measurements was 0.26 (p<0.001) in the total population, and the correlation tended to decrease with increasing age (p for trend <0.001) and depression scores (p for trend <0.001). CONCLUSIONS: We found a low correlation between self-reported and accelerometer-assessed PA among healthy Korean adults, and the correlation decreased with age and depression score. When studying PA using accelerometers and/or questionnaires, age and depression need to be considered, as should differences between self-reported and accelerometer-assessed PA.ope

Naphthalene-based fluorescent probes for glutathione and their applications in living cells and patients with sepsis

Rationale: Among the biothiols-related diseases, sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection and can result in severe oxidative stress and damage to multiple organs. In this study, we aimed to develop a fluorescence chemosensor that can both detect GSH and further predict sepsis. Methods: In this study, two new naphthalene dialdehyde compounds containing different functional groups were synthesized, and the sensing abilities of these compounds towards biothiols and its applications for prediction of sepsis were investigated. Results: Our study revealed that the newly developed probe 6-methoxynaphthalene-2, 3-dicarbaldehyde (MNDA) has two-photon is capable of detecting GSH in live cells with two-photon microscopy (TPM) under the excitation at a wavelength of 900 nm. Furthermore, two GSH detection probes naphthalene-2,3-dicarboxaldehyde (NDA) and 6-fluoronaphthalene-2,3-dicarbaldehyde (FNDA) not only can detect GSH in living cells, but also showed clinical significance for the diagnosis and prediction of mortality in patients with sepsis. Conclusions: These results open up a promising direction for further medical diagnostic techniques.ope

Patterns and determinants of COPD-related healthcare utilization by severity of airway obstruction in Korea

BACKGROUND: We investigated patients with chronic obstructive pulmonary disease (COPD) to analyze patterns and identify determinants of healthcare use, according to the severity of airflow obstruction. We used retrospective cohort data from a combination of the 4th Korea National Health and Nutritional Examination Survey (KNHANES) and Korean National Health Insurance (NHI) claims. METHODS: Demographic and medical claims data were retrospectively analyzed from the 4th KNHANES along with NHI claims. Eligible patients were aged ≥40 years, who underwent complete pulmonary function tests (PFTs), and had at least one inpatient or outpatient claim coded as COPD between January 1, 2007 and December 31, 2010. RESULTS: Among 6,663 eligible participants, 897 (13.5%) had airway obstruction. Self-reported physician-diagnosed COPD comprised only 3%, and there were 870 undiagnosed COPD patients (97%). Self-reported physician-diagnosed asthma made up 3.7%. Of the 897 respondents, 244 (27.2%) used COPD-related healthcare services. The frequency of healthcare visits increased with increasing severity of airway obstruction. After a 3-year follow-up period, 646 (74.2% of those initially undiagnosed) remained undiagnosed and only 224 (25.8%) were diagnosed and treated for COPD. Only 27.5% of the 244 participants with airway obstruction who used COPD-related healthcare underwent PFTs during the study period. The percentage of prescribed medications associated with COPD increased in accordance with the severity of the COPD. Inhaled long-acting anticholinergics were prescribed for 10.9% of patients with moderate airway obstruction and for 52.4% of patients with severe obstruction. Inhaled long-acting β-agonists combined with corticosteroids were prescribed for 50% of patients with severe airway obstruction. Conversely, 44.6% of healthcare users were prescribed oral theophylline for COPD treatment, and 21.7% were also prescribed an oral corticosteroid. The determinants of COPD-associated healthcare use in respondents with obstructive lung disease were advanced age, severe airflow limitation, presence of comorbidities, and self-reported physician diagnosis of COPD. CONCLUSIONS: This study ascertained marked underdiagnosed COPD. Although the percentage of prescribed medication used to treat COPD increased with the severity of the COPD, medications primarily prescribed such as oral theophylline or oral corticosteroids are inappropriate for first-line COPD treatment.ope

Advantage of Vital Sign Monitoring Using a Wireless Wearable Device for Predicting Septic Shock in Febrile Patients in the Emergency Department: A Machine Learning-Based Analysis

Intermittent manual measurement of vital signs may not rapidly predict sepsis development in febrile patients admitted to the emergency department (ED). We aimed to evaluate the predictive performance of a wireless monitoring device that continuously measures heart rate (HR) and respiratory rate (RR) and a machine learning analysis in febrile but stable patients in the ED. We analysed 468 patients (age, ≥18 years; training set, n = 277; validation set, n = 93; test set, n = 98) having fever (temperature &gt;38 °C) and admitted to the isolation care unit of the ED. The AUROC of the fragmented model with device data was 0.858 (95% confidence interval [CI], 0.809-0.908), and that with manual data was 0.841 (95% CI, 0.789-0.893). The AUROC of the accumulated model with device data was 0.861 (95% CI, 0.811-0.910), and that with manual data was 0.853 (95% CI, 0.803-0.903). Fragmented and accumulated models with device data detected clinical deterioration in febrile patients at risk of septic shock 9 h and 5 h 30 min earlier, respectively, than those with manual data. Continuous vital sign monitoring using a wearable device could accurately predict clinical deterioration and reduce the time to recognise potential clinical deterioration in stable ED patients with fever.ope

Soluble IL-2R Levels Predict in-Hospital Mortality in COVID-19 Patients with Respiratory Failure

Acute respiratory distress syndrome is the primary cause of death in patients with coronavirus disease 2019 (COVID-19) pneumonia. Our study aims to determine the association between serum markers and mortality in COVID-19 patients with respiratory failure. This retrospective study was conducted in a tertiary care hospital in South Korea. Forty-nine patients with COVID-19, who required high flow nasal cannulation or mechanical ventilation from February 2020 to April 2021, were included. Demographic and laboratory data were analyzed at baseline and on Day 7 of admission. We found that serum creatinine, troponin, procalcitonin, and soluble interleukin-2 receptor (sIL-2R) at baseline were more elevated in the non-survivor group, but were not associated with mechanical ventilator use on Day 7. Older age, PaO2/FiO2 ratio, lymphocyte and platelet counts, lactate dehydrogenase, IL-6, C-reactive protein, and sIL-2R on Day 7 were significantly associated with mortality. Delta sIL-2R (Day 7-Day 0) per standard deviation was significantly higher in the non-survivor group (adjusted hazard ratio 3.225, 95% confidence interval (CI) 1.151-9.037, p = 0.026). Therefore, sIL-2R could predict mortality in COVID-19 patients with respiratory failure. Its sustained elevation suggests a hyper-inflammatory state, and mirrors the severity of COVID-19 in patients with respiratory failure, thereby warranting further attention.ope

Optimal timing of initiating continuous renal replacement therapy in septic shock patients with acute kidney injury

Acute kidney injury (AKI) in patients with septic shock is associated with high mortality, but the appropriate timing for initiating continuous renal replacement therapy (CRRT) is controversial. We retrospectively enrolled 158 septic shock patients with AKI in the medical intensive care unit (ICU) from July 2016 to April 2018. The time from AKI onset to CRRT initiation was compared according to ICU mortality using Cox proportional hazard, receiver operating characteristic, and Kaplan-Meier survival analyses. At the time of ICU discharge, the mortality rate was 50.6% (n = 80). It took longer to initiate CRRT in non-survivors than in survivors (hazard ratio 1.009; 95% confidence interval [CI] 1.003-1.014; P = 0.002). The cut-off time from AKI onset to CRRT initiation for ICU mortality was 16.5 hours (area under the curve 0.786; 95% CI 0.716-0.856; P < 0.001). The cumulative mortality rate was significantly higher in patients in whom CRRT was initiated beyond 16.5 hours after AKI onset than in those in whom CCRT was initiated within 16.5 hours (log-rank test, P < 0.001). Several clinical situations must be considered to determine the optimal timing of CRRT initiation in these patients. Close observation and CRRT initiation within 16.5 hours after AKI onset may help improve survival.ope