In situ facile-forming PEG cross-linked albumin hydrogels loaded with an apoptotic TRAIL protein

Kim, I.,Choi, J.S.,Lee, S.,Byeon, H.J.,Lee, E.S.,Shin, B.S.,Choi, H.G.,Lee, K.C.,Youn, Y.S. Elsevier Science Publishers 2015 Journal of controlled release Vol.214 No.-

The key to making a practicable hydrogel for pharmaceutical or medical purposes is to endow it with relevant properties, i.e., facile fabrication, gelation time-controllability, and in situ injectability given a firm basis for safety/biocompatibility. Here, the authors describe an in situ gelling, injectable, albumin-cross-linked polyethylene glycol (PEG) hydrogel that was produced using a thiol-maleimide reaction. This hydrogel consists of two biocompatible components, namely, thiolated human serum albumin and 4-arm PEG<SUB>20k</SUB>-maleimide, and can be easily fabricated and gelled in situ within 60s by simply mixing its two components. In addition, the gelation time of this system is controllable in the range 15s to 5min. This hydrogel hardly interacted with an apoptotic TRAIL protein, ensuring suitable release profiles that maximize therapeutic efficacy. Specifically, tumors (volume: 278.8mm<SUP>3</SUP>) in Mia Paca-2 cell-xenografted BALB/c nu/nu mice treated with the TRAIL-loaded HSA-PEG hydrogel were markedly smaller than mice treated with the hydrogel prepared via an amine-N-hydroxysuccinimide reaction or non-treated mice (1275.5mm<SUP>3</SUP> and 1816.5mm<SUP>3</SUP>, respectively). We believe that this hydrogel would be a new prototype of locally injectable sustained-release type anti-cancer agents, and furthermore offers practical convenience for a doctor and universal applicability for a variety of therapeutic proteins.

뇌경색증의 급성기에 발생한 변비에 대한 연구

최윤이,김소이,김성은,정혜경,김태헌 이화여자대학교 의과학연구소 2015 EMJ (Ewha medical journal) Vol.38 No.1

Objectives: The prevalence of constipation is high after stroke. Multiple factors such as long-term bed-ridden status, comorbidity, medical illnesses are combined in this condition. However, the change of bowel movement during the early stage of stroke remainsuncertain. Methods: Patients with first stroke who admitted in a single institute from 2008 to 2009 were reviewed retrospectively and 36 patients were enrolled. As a control group, 47 consecutive orthopedic patients needing bed rest without surgery in the same period were enrolled. Data of stroke associated factors, frequency of BM (bowel movement) during 5 weeks, use of gastrointestinal medications, and outcomes were collected from the medical records. Results: The cumulative incidence of decreased (<3/week) and severely decreased BM (<1/week) were 80.6% and 69.4% in stroke patients and 53.2% and 14.9% in control group (P<0.05). The cumulative incidence of increased BM (>3/day) was 38.9% in stroke and 14.9% in control group. In acute stroke, 58% of patient showed severely decreased BM in first week, and the proportion was rapidly decreased below 15% from second week. However, laxative use increased with hospital days. The occurrence of severely decreased BM in stroke patients was associated with National Institutes of Health Stroke Scale (NIHSS; P=0.004). Severely decreased BM was not associated with poor outcomes including death, morbidity, and stroke recurrence. Conclusion: Decreased BM is common in acute stroke. The occurrence of severely decreased BM is associated with NIHSS. However, the severe manifestation occurred mainly in the first week, and considered to be well controlled by laxatives.

충청지역에서 발생한 쭈쭈가무시병의 임상상, 원인균의 혈청형 및 혈청역학적 연구

김선영,김윤성,박장규,윤태영,강재승,송인숙,최명식,최인학,차창룡,이우곤,박종우,이증훈,장우현,유영해,윤광혁,송계용 대한감염학회 1989 감염 Vol.21 No.2

From September to december 1987, eighty-six cases of tsutsugamushi disease were diagnosed by indirect immunofluorecent test or by isolating the causative agent in Chungcheung area. Their clinical features and patterns of antibody response to R. tsutsugamushi were analyzed. For the indenfication of prevalent antigenic types of R. tsutsugamushi in Chungcheung area, twenty-seven strains isolated were tested by indirect immunofluorescent test. To assess the extent of exposure to R.tsutsugamushi of a general population in Korea, the prevalence of antibody was investigated in 6,572 sera obtained from the residents of Chungcheung area by indirect immunofluorescent test. The female patients slightly outnumbered the male patients. More cases (68%) were older than 40 years of age. The epidemic peaked in October. The mean incubation period estimated was about 8 days. The major clinical features were fever and chill, headache, rash, eschar, and lymphadenopathy. Increased serm transaminase was the most singificant laboratory findings. Abnormalities in the chest roentgenography were often observed. The antibody titer rose rapidly 5 days after the onset, reached its peak at 20 days (1:640), and then declined agradually until 7 months(1:20). The seroype of 23 out of the 27 isolates wase found to be karp, one was Gilliam, and 3 isolates could not be classified by using polyclonal mouse hyperimmune sera. The prevalence of antibody to R.tsutsugamushi in the residents of Chungcheung area was 4.8%. The prevalence of antibody was higher in the female than in the male. The prevalence was higher in the residents of age above 40 years than below 40 years, and was the lowest in the children less than 10 years of age. Of the 318 positive sera from normal residents, only 2 sera showed the titers higher than 1:80.

골시멘트 특성 및 스템 형상에 따른 시멘트 타입 인공관절의 생체역학적 평가

박흥석,전흥재,윤인찬,이문규,최귀원,Park, H.S.,Chun, H.J.,Youn, I.C.,Lee, M.K.,Choi, K.W. 대한의용생체공학회 2008 의공학회지 Vol.29 No.3

The total hip replacement (THR) has been used as the most effective way to restore the function of damaged hip joint. However, various factors have caused some side effects after the THR. Unfortunately, the success of the THR have been decided only by the proficiency of surgeons so far. Hence, It is necessary to find the way to minimize the side effect caused by those factors. The purpose of this study was to suggest the definite data, which can be used to design and choose the optimal hip implant. Using finite element analysis (FEA), the biomechanical condition of bone cement was evaluated. Stress patterns were analyzed in three conditions: cement mantle, procimal femur and stem-cement contact surface. Additionally, micro-motion was analyzed in the stem-cement contact surface. The 3-D femur model was reconstructed from 2-D computerized tomography (CT) images. Raw CT images were preprocessed by image processing technique (i.e. edge detection). In this study, automated edge detection system was created by MATLAB coding for effective and rapid image processing. The 3-D femur model was reconstructed based on anatomical parameters. The stem shape was designed using that parameters. The analysis of the finite element models was performed with the variation of parameters. The biomechanical influence of each parameter was analyzed and derived optimal parameters. Moreover, the results of FE A using commercial stem model (Zimmer's V erSys) were similar to the results of stem model that was used in this study. Through the study, the improved designs and optimal factors for clinical application were suggested. We expect that the results can suggest solutions to minimize various side effects.

Prospective Validation of LSM Using ARFI Elastography to Predict Advanced Fibrosis and Cirrhosis Based on Metavir and Laennec Staging in Patients with Alcoholic Liver Disease

( Youn-i Choi ),( Won Kim ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: Accurate assessment of advanced fibrosis and cirrhosis is important to predict long-term clinical outcomes in patients with alcoholic liver disease. Acoustic radiation force impulse (ARFI) elastography is one of the liver stiffness measurement (LSM) methods to assess liver fibrosis in patients with chronic liver disease. However, little is known about the correlation between LSM by means of ARFI and the severity of fibrosis in patients with alcoholic liver disease. Methods: We conducted a prospective cohort study including 170 alcoholic liver disease patients with ongoing or prior alcohol abuse history (male > 80g/day, female > 40g/day ) without any other cause of chronic liver disease. We used ARFI elastography for measuring liver stiffness and performed liver biopsy for staging fibrosis based on the Metavir stage and the Laennec sub-classification of cirrhosis. Diagnostic measurement of serum fibrosis indices and ARFI imaging were compared with predicted significant (≥F2)or advanced (≥F3) fibrosis or cirrhosis (F4) by analyzing the area under the receiver operating characteristic (AUROC) curve. Results: Aspartate aminotransferase to alanine aminotransferase ratio (AAR) (rs=0.35, p=0.00) aspartate aminotransferase to platelet ratio index (APRI)( rs=0.17, p=0.018), and Fib-4(rs=0.35, p=0.00) showed weak positive correlations with METAVIR stages. ROC curve analysis identified shear wave velocity (Vs) of liver ≥ 1.34m/s (AUROC of 0.917; SE, 0.0226; 95% CI, 0.865-0.954) as the optimal cut-off for predicting significant fibrosis (≥F2). For predicting advanced fibrosis (≥F3), the optimal cut-off of Vs of liver was ≥ 1.67m/s (AUROC of 0.929; SE, 0.0210; 95% CI, 0.879-0.962). For cirrhosis (F4), the optimal cut-off value was ≥ 2.09m/s of Vs of liver (AUROC of 0.929; SE, 0.0204; 95% CI, 0.877-0.961). A tendency toward increasing liver stiffness existed in a graded manner across METAVIR stages (P<0.001). Conclusions: In this prospective evaluation of patients with alcoholic liver disease, we suggest that ARFI elastography might be an excellent, non-invasive, diagnostic tool for predicting advanced fibrosis and cirrhosis in comparison with other noninvasive serum fibrosis indices.

Primary epiploic appendagitis: compared with diverticulitis and focused on obesity and recurrence

Youn I Choi,Hyun Sun Woo,Jun-Won Chung,Young Sup Shim,Kwang An Kwon,Kyoung Oh Kim,Yoon Jae Kim,Dong Kyun Park 대한장연구학회 2019 Intestinal Research Vol.17 No.4

Background/Aims: There is limited data to compare the clinical characteristics and recurrence rates between left-sided primary epiploic appendagitis (PEA) versus left-sided acute colonic diverticulitis (ACD), and right-sided PEA versus right-sided ACD, respectively. Methods: We retrospectively reviewed the medical records and radiologic images of the patients who presented with left-sided or right-sided acute abdominal pain and had computer tomography performed at the time of presentation showing radiological signs of PEA or ACD between January 2004 and December 2014. We compared the clinical characteristics of left PEA versus left ACD and right PEA versus right ACD, respectively. Results: Fifty-six patients (left:right=27:29) and 308 patients (left:right=24:284) were diagnosed with symptomatic PEA and ACD, respectively. Left-sided PEA were statistically significantly younger (50.2±15.4 years vs. 62.1±15.8 years, P=0.009), more obese (body mass index [BMI]: 26.3±2.9 kg/m2 vs. 22.3±3.1 kg/m2, P<0.001), and had more tendencies with normal or mildly elevated high-sensitivity C-reactive protein (hsCRP) (1.2±1.3 mg/dL vs. 8.4±7.9 mg/dL, P<0.001) than patients with left-sided ACD. The discriminative function of age, BMI and CRP between left-sided PEA versus left-sided ACD was 0.71 (cutoff: age ≤59 years, sensitivity of 66.7%, specificity of 77.8%), 0.83 (cutoff: BMI >24.5 kg/m2, sensitivity of 80.0%, specificity of 80.0%) and 0.80 (cutoff: CRP <1.8 mg/dL, sensitivity of 72.2%, specificity of 85.7%). Conclusions: If patients with left lower quadrant abdominal pain are less than 60 years, obese (BMI >24.5 kg/m2) with or without normal to mild elevated CRP levels (CRP <1.8 mg/dL), it might be necessary for clinicians to suspect the diagnosis of PEA rather than ACD.

Light Dose of Alcohol Drinking and Risk of Fatty Liver: A Nationwide Population-Based Study

( Youn I Choi ),( Yun Soo Kim ),( Seung Kak Shin ),( Jung Woo Shim ),( Kibum Cho ),( Ju Hyun Kim ),( Oh Sang Kwon ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Many studies defined the dose of alcohol in non-alcoholic fatty liver disease (NAFLD) as less than moderate drinking. Some literatures reported that light alcohol drinking (LAD) prevent the development of NAFLD. In this study, we investigated effect of LAD on the risk of fatty liver (FL). Methods: The Korean health examinee study (2004-2017) was used. After exclusion of participants above moderate alcohol drinking and without data of fatty liver index (FLI), 132,523 participants were enrolled. Participants were grouped as life time abstainer (LTA) and LAD group (current and ex-drinker). Current drinkers were further divided into <10 and ≥10 years of alcohol drinking. Ex-drinkers were divided into <10 and ≥10 years of alcohol withdrawal. FL was defined by FLI above 60. The risk of FL between LTA and LAD group was compared. Results: The mean age and proportion of female were 52.9 ± 8.3 and 74.3%, respectively. The prevalence of FL in LTA (n=78829) and LAD group (n=53694) were 5.86% and 10.06%, respectively (P<0.001). Compared with LTA, LAD group had more proportion of male, younger age, obesity, diabetes mellitus, hypertension, and dyslipidemia. In evaluating FL risk, the odd ratio (OR) in LAD group was 1.32(95% CI: 1.25-1.40, P<0.001) after adjusting compounding factors (age, sex, body mass index, diabetes mellitus, hypertension, and dyslipidemia). The ≥10 years drinking group [1.69(95% CI: 1.35-2.10), P<0.001] had higher OR than that of the <10 years drinking group [1.16(95% CI: 1.00-1.35), P=0.06] after adjusting compounding factors. The <10 years withdrawal group [1.49(95% CI: 1.02-2.24), P=0.04] had higher OR than that of the ≥10 years of withdrawal group [1.27(95% CI: 0.89-1.81), P=0.19] after adjusting compounding factors. Model1: adjusted for age, sex, body mass index, waist circumference, total Calorie intake, total carbohydrate intake, total protein intake, total lipid intake Model2: adjusted for age, sex, body mass index, waist circumference, total Calorie intake, total carbohydrate intake, total protein intake, total lipid intake, regular exercise, alcohol ingestion duration, smoking status, diabetes mellitus type 2 history, hypertension history, and dyslipidemia Abbreviation: NAFLD, non alcoholic fatty liver disease; HR, hazard ratio; 95%CI, 95% confidence interval Conclusions: Compared to LTA, LAD was the independent risk factor for FL. Especially, LDAD ≥10 years and LDAD withdrawal <10 years were significant risk factor for FL.

Machine Learning Based Pattern Recognition Software to Predict 5-Year Recurrence Risk after Surgical Resection in Hepatocellular Carcinoma Patients: A Multicenter Study

( Youn I Choi ),( Seung Kak Shin ),( Young Jae Kim ),( Kwang Gi Kim ),( Young Kul Jung ),( Tae Hyung Kim ),( Bo Hyun Kim ),( Oh Sang Kwon ),( Yun Soo Kim ),( Ju Hyun Kim ) 대한간학회 2021 춘·추계 학술대회 (KASL) Vol.2021 No.1

위 절제술 환자에서 헬리코박터 파일로리 감염의 진단 및 치료

Youn I Choi,정준원 대한상부위장관ㆍ헬리코박터학회 2020 Korean Journal of Helicobacter Upper Gastrointesti Vol.20 No.3

The role of Helicobacter pylori (H. pylori) eradication in patients undergoing gastrectomy for gastric cancer is unclear. Although European and Asian guidelines strongly recommend H. pylori eradication in patients who undergo endoscopic resection for early gastric cancer, these guidelines do not specify the tests useful for diagnosing H. pylori infection, the optimal timing and appropriate eradication regimens, and follow-up strategies in patients undergoing gastrectomy for gastric cancer. This review aims to update the guidelines for the diagnosis and management of H. pylori infection in patients undergoing gastrectomy for gastric cancer. We have focused on the following issues: 1) diagnostic tests for H. pylori infection in the remnant stomach, 2) optimal timing and regimen for H. pylori eradication, and 3) role of H. pylori eradication in reducing the risk of metachronous gastric cancer in the remnant stomach.

Machine Learning Model to Predict Risk of Cardiovascular Disease among Non-Alcoholic Fatty Liver Disease Patients: Results from Two Nationwide Long- Term Follow Up Studies

( Youn I Choi ),( Seung Kak Shin ),( Ju Hyun Kim ),( Oh Sang Kwon ),( Yun Soo Kim ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: There have been emerging evidences on increased cardiovascular disease (CVD) risk among non-alcoholic fatty liver (NAFLD) patients. Improved method to risk-stratify and predict CVD risk among NAFLD patients is a significant unmet need in clinical field. The aim of this study was to develop and externally validate a machine learning (ML) model to predict 7 year- risk of CVD among NAFLD patients using nationally representative long-term follow up studies in Korea. Methods: We used data from the Korean health examinee (HEXA) study (baseline: 2004-2013, follow up: 2012-2017, n= 173290), and CAVAS study ((baseline: 2005-2011, follow up: 2007-2016, n=28337) to develop, and externally validate ML prediction model, respectively. After exclusion of participants with excessive alcohol ingestion, baseline CVD history, and no data on CVD in follow up study, total of 24539 NAFLD patients from HEXA study, and 9563 NAFLD patients from CAVAS study who were free of CVD at baseline were finally enrolled. NAFLD was defined by Hepatic Steatosis Index over 36, and CVD included myocardial infarction and cerebrovascular attack history. For training and test sets for ML algorithm, 5- fold cross validation was done using HEXA study data. ML algorithms included support vector machine, random forest, artificial neural network, XGBoost, and ensemble methods. Area under receive operating curves (AUROC) of each methods were compared using 5- fold cross validated HEXA data and externally validated CAVAS data. Results: During follow up period, incidental 491 cases of CVD cases from HEXA study (306918 person-years of follow up), and 199 cases of CVD cases from CAVAS study (72678 person- year of follow up) occurred. Among ML models, Ensemble methods showed best function with statistical significance (P<0.001). ML model of Ensemble method for prediction of 7-year risk of CVD risk among NAFLD patients from 5- fold cross validation of HEXA study data yielded AUC of 0.86 (95% confidence interval (CI):0.80-0.90) using lifestyle factors (diet, physical activity, smoking and alcohol), anthropometric indices, laboratory data, presence of liver fibrosis, and medical history. Externally validated using CAVAS study, ML model of Ensemble method for prediction of CVD risk among NAFLD patients yielded AUCs of 0.81 (95% CI:0.79-0.85). Conclusions: ML based prediction model for CVD risk among NAFLD patients could be used to identify at risk CVD among NAFLD patients and enable physicians to close follow up based on patient level estimation through ML algorithm.