Background/Aims: Cholangiocarcinoma frequently recurs even after curative resection. Expression levels of proteins such as epidermal growth factor receptor (EGFR), Snail, epithelial cadherin (E-cadherin), and interleukin-6 (IL-6) examined by immunohistochemistry have been studied as potential prognostic factors for cholangiocarcinoma. The aim of this study was to investigate significant factors affecting the prognosis of resectable cholangiocarcinoma. Methods: Ninety-one patients who underwent surgical resection at Samsung Medical Center for cholangiocarcinoma from 1995 to 2013 were included in this study. Expression levels of Ecadherin, Snail, IL-6, membranous EGFR, and cytoplasmic EGFR were analyzed by immunohistochemistry using tissue microarray blocks made from surgical specimens. Results: Patients with high levels of membranous EGFR in tissue microarrays had significantly shorter overall survival (OS) and disease-free survival (DFS): high membranous EGFR (score 0–2) 38.0 months versus low membranous EGFR (score 3) 14.4 months (p=0.008) and high membranous EGFR (score 0–2) 23.2 months versus low membranous EGFR (score 3) 6.1 months (p=0.004), respectively. On the other hand, E-cadherin, Snail, cytoplasmic EGFR, and IL-6 did not show significant association with OS or DFS. Patients with distant metastasis had significantly higher IL-6 levels than those with locoregional recurrence (p=0.01). Conclusions This study showed that overexpression of membranous EGFR was significantly associated with shorter OS and DFS in surgically resected bile duct cancer patients. In addition, higher IL-6 expression was a predictive marker for recurrence in cholangiocarcinoma patients with distant organ metastasis after surgical resection.

Objective: This study was carried out to establish a basis for understanding and correcting the problems of the emergency physicians (EP) in Korea by examining the current status through the 2020 emergency physician survey conducted by the Korean Society of Emergency Medicine (KSEM). Methods: An online survey was conducted from January 15 to February 26, 2021, through a website and mobile application. The final questionnaire was classified into three types based on the clinical work in the emergency department (ED), current position, and the year of board certification. The contents of the questionnaire were organized into eight themes, and a subcommittee was put in charge of each. Results: Of the 400 emergency medical institutions surveyed, 295 hospitals (74.2%) had board-certified EPs, and 1,453 EPs (72.5%) out of 2,000 were working in the ED. Of these, on average, 7.2 EPs worked together, and they worked 11.6 days/153.1 hours per month and did night shifts 5.9 days per month. 30.7% showed excessive sleepiness during the day, and only 9.6% said that they could adhere to mealtimes. 27.1% responded that they suffered from depression. The level of satisfaction was 3.2 points, and 43.0% responded that they would choose emergency medicine (EM) again as their major. The most important factor in choosing EM was the availability of adequate free time. Their responses indicated that the retirement age was 59.7 years, and the upper age limit for the night shift was 54.3 years. Conclusion Though there have been improvements since the first survey in 2010, there was no notable increase in EP satisfaction. Therefore, appropriate future policies should be formulated and implemented based on these survey results.

Background: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

Daidzein isolated from soybean (Glycine max) has been widely studied for its antioxidant and anti-inflammatory activities. However, the protective effects of 7,8,4′-trihydroxyisoflavone (THIF), a major metabolite of daidzein, on 6-hydroxydopamine (OHDA)-induced neurotoxicity are not well understood. In the current study, 7,8,4′-THIF significantly inhibited neuronal cell death and lactate dehydrogenase (LDH) release induced by 6-OHDA in SH-SY5Y cells, which were used as an in vitro model of Parkinson's disease (PD). Moreover, pretreatment with 7,8,4′-THIF significantly increased the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) and decreased malondialdehyde (MDA) activity in 6-OHDA-induced SH-SY5Y cells. In addition, 7,8,4′-THIF significantly recovered 6-OHDA-induced cleaved caspase-3, cleaved caspase-9, cleaved poly-ADP-ribose polymerase (PARP), increased Bax, and decreased Bcl-2 levels. Additionally, 7,8,4′-THIF significantly restored the expression levels of phosphorylated c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase 1/2 (ERK 1/2), phosphatidylinositol 3-kinases (PI3K)/Akt, and glycogen synthase kinase-3 beta (GSK-3β) in 6-OHDA-induced SH-SY5Y cells. Further, 7,8,4′-THIF significantly increased the reduced tyrosine hydroxylase (TH) level induced by 6-OHDA in SH-SY5Y cells. Collectively, these results suggest that 7,8,4′-THIF protects against 6-OHDA-induced neuronal cell death in cellular PD models. Also, these effects are mediated partly by inhibiting activation of the MAPK and PI3K/Akt/GSK-3β pathways.
Apoptosis ; Caspase 3 ; Caspase 9 ; Catalase ; Cell Death ; Glutathione ; Glycogen Synthase ; In Vitro Techniques ; JNK Mitogen-Activated Protein Kinases ; L-Lactate Dehydrogenase ; Malondialdehyde ; Neurons ; Oxidopamine ; Parkinson Disease ; Phosphatidylinositol 3-Kinases ; Phosphotransferases ; Protein Kinases ; Soybeans ; Superoxide Dismutase ; Tyrosine 3-Monooxygenase

BACKGROUND: When performing dental treatment under general anesthesia in adult patients who have difficulty cooperating due to intellectual disabilities, anesthesia induction may be difficult as well. In particular, patients who refuse to come into the dental office or sit in the dental chair may have to be forced to do so. However, for adult patients with a large physique, physical restraint may be difficult, while oral sedatives as premedication may be helpful. Here, a retrospective analysis was performed to investigate the effect of oral sedatives. METHODS: A hospital-based medical information database was searched for patients who were prescribed oral midazolam or triazolam between January 2009 and December 2017. Pre-anesthesia evaluation, anesthesia, and anesthesia recovery records of all patients were analyzed, and information on disability type, reason for prescribing oral sedatives, prescribed medication and dose, cooperation level during anesthesia induction, anesthesia duration, length of recovery room stay, and complications was retrieved. RESULTS: A total of 97 patients were identified, of whom 50 and 47 received midazolam and triazolam, respectively. The major types of disability were intellectual disabilities, autism, Down syndrome, blindness, cerebral palsy, and epilepsy. Analyses of changes in cooperation levels after drug administration showed that anesthesia induction without physical restraint was possible in 56.0% of patients in the midazolam group and in 46.8% of patients in the triazolam group (P = 0.312). CONCLUSIONS: With administration of oral midazolam or triazolam, general anesthesia induction without any physical restraint was possible in approximately 50% of patients, with no difference between the drugs.
Adult ; Anesthesia ; Anesthesia, General ; Autistic Disorder ; Blindness ; Cerebral Palsy ; Dental Offices ; Down Syndrome ; Epilepsy ; Humans ; Hypnotics and Sedatives ; Intellectual Disability ; Midazolam ; Premedication ; Recovery Room ; Restraint, Physical ; Retrospective Studies ; Triazolam

Melanin is a pigment produced from tyrosine in melanocytes. Although melanin has a protective role against UVB radiation-induced damage, it is also associated with the development of melanoma and darker skin tone. Tyrosinase is a key enzyme in melanin synthesis, which regulates the rate-limiting step during conversion of tyrosine into DOPA and dopaquinone. To develop effective RNA interference therapeutics, we designed a melanin siRNA pool by applying multiple prediction programs to reduce human tyrosinase levels. First, 272 siRNAs passed the target accessibility evaluation using the RNAxs program. Then we selected 34 siRNA sequences with ΔG ≥−34.6 kcal/mol, i-Score value ≥65, and siRNA scales score ≤30. siRNAs were designed as 19-bp RNA duplexes with an asymmetric 3′ overhang at the 3′ end of the antisense strand. We tested if these siRNAs effectively reduced tyrosinase gene expression using qRT-PCR and found that 17 siRNA sequences were more effective than commercially available siRNA. Three siRNAs further tested showed an effective visual color change in MNT-1 human cells without cytotoxic effects, indicating these sequences are anti-melanogenic. Our study revealed that human tyrosinase siRNAs could be efficiently designed using multiple prediction algorithms.
Dihydroxyphenylalanine ; Gene Expression ; Humans ; Melanins ; Melanocytes ; Melanoma ; Monophenol Monooxygenase* ; RNA ; RNA Interference ; RNA, Small Interfering* ; Skin Pigmentation ; Tyrosine ; Weights and Measures

OBJECTIVE: Chest pain is one of the most common complaints in the emergency department (ED). Cardiac computed tomography angiography (CCTA) is a frequently used tool for the early triage of patients with low- to intermediate-risk acute chest pain. We present a study protocol for a multicenter prospective randomized controlled clinical trial testing the hypothesis that a low-dose CCTA protocol using prospective electrocardiogram (ECG)-triggering and limited-scan range can provide sufficient diagnostic safety for early triage of patients with acute chest pain. METHODS: The trial will include 681 younger adult (aged 20 to 55) patients visiting EDs of three academic hospitals for acute chest pain or equivalent symptoms who require further evaluation to rule out acute coronary syndrome. Participants will be randomly allocated to either low-dose or conventional CCTA protocol at a 2:1 ratio. The low-dose group will undergo CCTA with prospective ECG-triggering and restricted scan range from sub-carina to heart base. The conventional protocol group will undergo CCTA with retrospective ECG-gating covering the entire chest. Patient disposition is determined based on computed tomography findings and clinical progression and all patients are followed for a month. The primary objective is to prove that the chance of experiencing any hard event within 30 days after a negative low-dose CCTA is less than 1%. The secondary objectives are comparisons of the amount of radiation exposure, ED length of stay and overall cost. RESULTS AND CONCLUSION: Our low-dose protocol is readily applicable to current multi-detector computed tomography devices. If this study proves its safety and efficacy, dose-reduction without purchasing of expensive newer devices would be possible.
Acute Coronary Syndrome ; Adult ; Angiography* ; Chest Pain ; Coronary Angiography ; Electrocardiography ; Emergencies* ; Emergency Service, Hospital ; Heart ; Humans ; Length of Stay ; Prospective Studies ; Radiation Exposure ; Retrospective Studies ; Thorax ; Triage

PURPOSE: Colorectal obstruction develops most frequently by carcinoma, and 7%–30% of these colorectal carcinomas are acute cases. The oncologic safety of self-expanding metal stent (SEMS) insertion as a bridge to surgery has not yet been established. Thus, we investigated the oncologic safety of SEMS insertion as a bridge to surgery in patients with obstructive colorectal cancer.METHODS: This retrospective had 56 patients enrolled requiring emergency management for obstructive colorectal cancer at stage II or III, who had undergone curative surgery between July 2008 and June 2011. These subjects were divided into two groups: patients who had undergone emergency surgery without SEMS insertion (non-stent group) and those who had undergone elective surgery after preoperative decompression with SEMS insertion (stent group). The two groups were compared for clinicopathologic characteristics, postoperative complications, and survival rate.RESULTS: Enterostomy was performed in 25 patients (100.0%) in the non-stent group and 1 patient (3.2%) in the stent group; laparoscopic surgery was carried out in 7 patients (28.0%) in the non-stent group and 19 patients (61.29%) in the stent group, each showing statistically significant differences. There was no statistically significant difference in postoperative complications and 5-year disease-free survival rate (72% vs. 74.19%, P=0.87, respectively).CONCLUSION: In treatment of malignant colorectal obstruction, elective operation after stent insertion had similar oncologic outcomes compared with emergency operation. Preoperative stent insertion not only lowers the incidence of enterostomy but also makes laparoscopic surgery possible, thereby enhancing patients' quality of life. Therefore, preoperative stent insertion is a useful method that may replace emergency surgery in treatment of malignant colorectal obstruction.
Colorectal Neoplasms ; Decompression ; Disease-Free Survival ; Emergencies ; Enterostomy ; Humans ; Incidence ; Intestinal Obstruction ; Laparoscopy ; Methods ; Postoperative Complications ; Quality of Life ; Retrospective Studies ; Stents ; Survival Rate

No abstract available.
Hematoma, Epidural, Spinal* ; Humans ; Polycythemia Vera* ; Spinal Puncture* ; Subarachnoid Hemorrhage*