Lipid-coated microbubbles are widely used as an ultrasound contrast agent, as well as drug delivery carriers. However, the two main limitations in ultrasound diagnosis and drug delivery using microbubbles are the short half-life in the blood system, and the difficulty of surface modification of microbubbles for active targeting. The exosome, a type of extracellular vesicle, has a preferentially targeting ability for its original cell. In this study, exosome-fused microbubbles (Exo-MBs) were developed by embedding the exosome membrane proteins into microbubbles. As a result, the stability of Exo-MBs is improved over the conventional microbubbles. On the same principle that under the exposure of ultrasound, microbubbles are cavitated and self-assembled into nano-sized particles, and Exo-MBs are self-assembled into exosome membrane proteins-embedded nanoparticles (Exo-NPs). The Exo-NPs showed favorable targeting properties to their original cells. A photosensitizer, chlorin e6, was loaded into Exo-MBs to evaluate therapeutic efficacy as a drug carrier. Much higher therapeutic efficacy of photodynamic therapy was confirmed, followed by cancer immunotherapy from immunogenic cell death. We have therefore developed a novel ultrasound image-guided drug delivery platform that overcomes the shortcomings of the conventional ultrasound contrast agent and is capable of simultaneous photodynamic therapy and cancer immunotherapy.

Purpose: K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods. Materials and Methods: Colorectal, breast, non–small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non–small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers). Results: In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively. Conclusion The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.

Background: There has been controversy regarding the association between primary aldosteronism (PA) and dyslipidemia and few studies considered the effects of diabetes and renal function on lipid metabolism. We analyzed lipid profiles of PA patients and compared them to propensity-score (PS)-matched essential hypertension (EH) patients adjusting for glycemic status and renal function. Methods: Patients who were diagnosed with PA using a saline-infusion test at Seoul National University Hospital from 2000 to 2018 were retrospectively analyzed. EH patients who had aldosterone-renin ratio (ARR) results were selected as controls. Covariates, including diabetes, were PS-matched for patients with PA, lateralized PA, non-lateralized PA, and high ARR to EH patients, respectively. Results: Among a total of 80 PA and 80 EH patients, total cholesterol (TC) and triglyceride (TG) levels were significantly lower in the PA patients than in the EH patients (least-squares mean±standard error: 185.5±4.4 mg/dL vs. 196.2±4.4 mg/dL, P=0.047, for TC; and 132.3±11.5 mg/dL vs. 157.4±11.4 mg/dL, P=0.035, for TG) in fully adjusted model (adjusting for multiple covariates, including diabetes status, glycosylated hemoglobin level, and estimated glomerular filtration rate). There were no significant differences in high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol levels between the two groups. According to increments in aldosterone levels, an increasing tendency of HDL-C and decreasing tendencies of TG and non-HDL-C were observed. Conclusion PA patients had lower TC and TG levels than EH patients, independent of glycemic status and renal function.

Background: There has been controversy regarding the association between primary aldosteronism (PA) and dyslipidemia and few studies considered the effects of diabetes and renal function on lipid metabolism. We analyzed lipid profiles of PA patients and compared them to propensity-score (PS)-matched essential hypertension (EH) patients adjusting for glycemic status and renal function. Methods: Patients who were diagnosed with PA using a saline-infusion test at Seoul National University Hospital from 2000 to 2018 were retrospectively analyzed. EH patients who had aldosterone-renin ratio (ARR) results were selected as controls. Covariates, including diabetes, were PS-matched for patients with PA, lateralized PA, non-lateralized PA, and high ARR to EH patients, respectively. Results: Among a total of 80 PA and 80 EH patients, total cholesterol (TC) and triglyceride (TG) levels were significantly lower in the PA patients than in the EH patients (least-squares mean±standard error: 185.5±4.4 mg/dL vs. 196.2±4.4 mg/dL, P=0.047, for TC; and 132.3±11.5 mg/dL vs. 157.4±11.4 mg/dL, P=0.035, for TG) in fully adjusted model (adjusting for multiple covariates, including diabetes status, glycosylated hemoglobin level, and estimated glomerular filtration rate). There were no significant differences in high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol levels between the two groups. According to increments in aldosterone levels, an increasing tendency of HDL-C and decreasing tendencies of TG and non-HDL-C were observed. Conclusion PA patients had lower TC and TG levels than EH patients, independent of glycemic status and renal function.

The area of endoscopic application has been continuously expanded since its introduction in the last century and the frequency of its use also increased stiffly in the last decades. Because gastrointestinal endoscopy is naturally exposed to diseased internal organs and contact with pathogenic materials, endoscopy mediated infection or disease transmission becomes a major concern in this field. Gastrointestinal endoscopy is not for single use and the proper reprocessing process is a critical factor for safe and reliable endoscopy procedures. What needed in these circumstances is a practical guideline for reprocessing the endoscope and its accessories which is feasible in the real clinical field to guarantee acceptable prevention of pathogen transmission. This guideline contains principles and instructions of the reprocessing procedure according to the step by step. And it newly includes general information and updated knowledge about endoscopy-mediated infection and disinfection. Multiple societies and working groups participated to revise; Korean Association for the Study of the Liver, the Korean Society of Infectious Diseases, Korean College of Helicobacter and Upper Gastrointestinal Research, the Korean Society of Gastroenterology, Korean Society of Gastrointestinal Cancer, Korean Association for the Study of Intestinal Diseases, Korean Pancreatobiliary Association, the Korean Society of Gastrointestinal Endoscopy Nurses and Associates and Korean Society of Gastrointestinal Endoscopy. Through this cooperation, we enhanced communication and established a better concordance. We still need more researches in this field and fill up the unproven area. And our guidelines will be renewed accordingly.

BACKGROUND: The aim of this study was to investigate the status of BRCA1/2 genetic testing practices in Korea in 2014. METHODS: A structured questionnaire was provided to the specialist in charge of BRCA1/2 genetic testing via e-mail between 28 July and 10 August 2015. A total of 11 genetic testing professionals from 14 organizations responded to the survey that asked about the status of BRCA1/2 genetic testing in the year 2014. RESULTS: The average number of BRCA1/2 genetic tests executed was 192; 6 organizations had executed less than 100 tests, and 5 organizations had conducted more than 100 tests. The primary testing method used was Sanger sequencing (100%), and 2 institutes performed multiplex ligation-dependent probe amplification (MLPA). The analysis software differed across the various organizations, with Sequencher (81.81%), Seqscape (27.27%), and Codoncode Aligner (9.09%) reported as utilized. We found that the guidelines for the interpretation of the genetic tests were different at each institution. CONCLUSIONS: Although this study only examined the status of the 2014 BRCA1/2 genetic testing practices of 11 institutions, it illustrates the necessity for standardized genetic testing or interpretation guidelines in Korea.
Academies and Institutes ; Electronic Mail ; Genetic Testing* ; Korea* ; Methods ; Multiplex Polymerase Chain Reaction ; Specialization ; Surveys and Questionnaires

Episodic ataxia type 2 (EA-2) is a rare disorder presenting with paroxysmal vertigo and cerebellar dysfunction. EA-2 is known to be caused by mutations of the CACNA1A gene on chromosome 19q13. We examined a family of EA-2 with a novel mutation of the CACNA1A gene showing characteristic ocular symptoms. A-36-year woman visited our hospital with paroxysmal vertigo. When she experienced vertigo attack, she also suffered from gait disturbance, dysarthria, and ataxia. She complained that she could not ride in a car or a train that moved fast, because she could not visually follow the moving objects. Her mother, grandmother, and uncle also complained of similar symptoms. Video nystagmographic findings showed loss of optokinetic nystagmus. We found a novel missense mutation, R279C (c.835C>T), on exon 6 in the CACNAIA gene. This is the first report of a family with new mutation of EA-2 in Korea.

PURPOSE: This study was performed in order to determine the changes over time in preventable and potentially preventable traumatic death rates, and to assess the factors that affected the deaths of trauma patients which occurred in Korean pre-hospital and hospital settings. METHODS: All trauma deaths occurring either in the emergency department (ED) or after admission at twenty Korean hospitals between August 2009 and July 2010 were retrospectively analyzed. The deaths were initially reviewed by a team of multidisciplinary specialists and classified into non-preventable, potentially preventable, and preventable deaths. Only preventable and potentially preventable deaths were the subject of our analysis. Structured data extraction included patient demographics, vital signs, injury severity, probability of survival, preventability of mortality, reported errors in the evaluation and management of the patient, and classification of error types (system, judgment, knowledge). RESULTS: During the study period, 446 trauma victims died in the ED or within 7 days after admission. The mean age was 52 years, 74.1% were men and the mean time from injury to death was 35.6 hours. The most common cause of death was head injury (44.7%) followed by hemorrhage (30.8%) and multi-organ failure (8.0%). The rates of preventable/potentially preventable deaths were 35.2% overall and 29.8% when limited to patients surviving to admission. Of all death classifications, 31.2% were potentially preventable and 4.0% were preventable. Errors leading to preventable death occurred in the emergency department (51.2%), pre-hospital setting (30.3%) and during inter-hospital transfer (60.8%). Most errors were related to clinical management (48.4%) and structural problems in the emergency medical system (36.5%). CONCLUSION: The preventable death rates for Korean trauma victims were higher than those found in other developed countries, possibly due to poorly established emergency medical systems for trauma victims in pre-hospital and hospital settings. A system wide approach based on the emergency medical system and well-developed in-hospital trauma teams should be adopted in order to improve the quality of care of trauma victims in Korea.
Cause of Death ; Craniocerebral Trauma ; Demography ; Developed Countries ; Emergencies ; Emergency Medical Services ; Hemorrhage ; Humans ; Judgment ; Korea ; Male ; Retrospective Studies ; Specialization ; Vital Signs

BACKGROUND: Characterization of clinical features of bacteremic severe sepsis acquired from the community has been inadequate; therefore, our goal in this study was to identify prognostic factors associated with outcome in patients with community-acquired bacteremic severe sepsis. MATERIALS AND METHODS: Adult patients (> or =18 years) with community-acquired severe sepsis in whom pathogens were identified from blood cultures were included in the study. Data were collected prospectively from 12 teaching hospitals between May, 2005, and February, 2009. Data included demographic characteristics, co-morbid medical conditions, primary infection sites, sepsis severity, mortality, causative microorganisms, and the appropriateness of initial empirical antibiotic therapy. RESULTS: During the study period, 1,152 patients were diagnosed with community-acquired severe sepsis and 422 patients were found to harbor pathogens in their blood. Among the 422 patients analyzed, 253 (60.0%) patients went into shock and 121 patients (28.7%) died during hospitalization. Risk factors, including respiratory tract infection (odds ratio [OR], 2.60; 95% confidence interval [CI], 1.11-6.09), number of organ dysfunctions (OR, 1.39; 95% CI, 1.13-1.71), and higher APACHE II scores (OR, 1.08; 95% CI, 1.03-1.13) showed an association with poor survival, whereas Escherichia coli as a pathogen (OR, 0.31; 95% CI, 0.16-0.64) showed an association with lower mortality. CONCLUSIONS: In addition to severity of illness, the primary site of infection and causative microorganisms were also identified as important prognostic factors in patients with community-acquired bacteremic severe sepsis.
Adult ; APACHE ; Bacteremia ; Community-Acquired Infections ; Escherichia coli ; Hospitalization ; Hospitals, Teaching ; Humans ; Prospective Studies ; Respiratory Tract Infections ; Risk Factors ; Sepsis ; Shock ; Shock, Septic

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disease that involves a clonal proliferation of Langerhans cells. LCH has a predilection for hypothalamo-pituitary axis (HPA) dysfunction, and this leads to diabetes insipidus (DI) and/or anterior pituitary dysfunction. Here, we describe the endocrine dysfunction and clinical characteristics of adult patients with LCH and we analyzed the differences between an adult-onset type and a childhood-onset type. METHODS: The data was obtained from a retrospective chart review of the patients with LCH that involved the HPA and who attended Seoul National University Hospital. The patients were classified into the adult-onset type (age at the time of diagnosis > or = 16) and the childhood-onset type (age at the time of diagnosis < or = 15). RESULTS: Ten patients (9 males and 1 female) were diagnosed with LCH involving the HPA. Five patients were classified as an adultonset type and the other five patients were classified as a childhood-onset type. The median follow-up duration was 6 (3-12) years for the adult-onset type and 16 (15-22) years for the childhood-onset type. All the patients presented with DI as the initial manifestation of HPA involvement. Four adult-onset patients and three childhood-onset patients had a multi-system disease. Panhypopituitarism developed in three adult-onset patients and in one childhood-onset patient. The pituitary lesion of the three adult-onset patients had spread to the brain during the follow-up duration. In contrast, the pituitary lesion of the other two adult-onset patients without panhypopituitarism and all the childhood-onset patients had not changed. CONCLUSION: DI was the initial presentation symptom of HPA involvement. Anterior pituitary hormone deficiency followed in some patients. Compared with the childhood-onset patients, the adult-onset patients were more likely to have panhypopituitarism and a poor prognosis.
Adult ; Brain ; Diabetes Insipidus ; Follow-Up Studies ; Histiocytosis, Langerhans-Cell ; Humans ; Hypopituitarism ; Langerhans Cells ; Male ; Prognosis ; Rare Diseases ; Retrospective Studies ; Axis, Cervical Vertebra