Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Gastric cancer is one of the most common cancers in Korea and the world. Since 2004, this is the 4th gastric cancer guideline published in Korea which is the revised version of previous evidence-based approach in 2018. Current guideline is a collaborative work of the interdisciplinary working group including experts in the field of gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology and guideline development methodology. Total of 33 key questions were updated or proposed after a collaborative review by the working group and 40 statements were developed according to the systematic review using the MEDLINE, Embase, Cochrane Library and KoreaMed database. The level of evidence and the grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation proposition. Evidence level, benefit, harm, and clinical applicability was considered as the significant factors for recommendation. The working group reviewed recommendations and discussed for consensus. In the earlier part, general consideration discusses screening, diagnosis and staging of endoscopy, pathology, radiology, and nuclear medicine. Flowchart is depicted with statements which is supported by meta-analysis and references. Since clinical trial and systematic review was not suitable for postoperative oncologic and nutritional follow-up, working group agreed to conduct a nationwide survey investigating the clinical practice of all tertiary or general hospitals in Korea. The purpose of this survey was to provide baseline information on follow up. Herein we present a multidisciplinary-evidence based gastric cancer guideline.

Purpose: Deceased donor liver transplantation (DDLT) recipients in Korea are generally sicker due to an increasing organ shortage. In the present study, the risk factors for early 30-day liver graft failure after DDLT were identified. Methods: From August 2017 to February 2021, 265 adult DDLTs were performed. The characteristics of patients with and without 30-day graft failure were compared. Results: Liver graft failure occurred in 11 patients (17.7%) after DDLT. Baseline and perioperative characteristics of donors and recipients were not statistically significantly different between the 2 groups. The cumulative graft and overall survival rates at 6 months were 83.9% and 88.7%, respectively. Multivariate analysis showed ventilator support in the pretransplant period was a predisposing factor for 30-day graft failure after DDLT. Conclusion Present study indicates that cautious decision is required when allocating DDLT in critically ill patients on mechanical ventilatory support.

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.

Background/Aims: Efficient anti-fibrotic therapies are required for the treatment of liver cirrhosis. Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and cyclooxygenase-2 (COX-2) inhibitors have been reported to have anti-fibrotic effects. Here, we investigated whether combined treatment with a statin and a COX-2 inhibitor has synergistic anti-fibrotic effects. Methods: The effects of treatment strategies incorporating both simvastatin and a COX-2 inhibitor, NS-398, were investigated using an immortalized human hepatic stellate cell line (LX-2) and a hepatic fibrosis mouse model developed using thioacetamide (TAA) in drinking water. Cellular proliferation was investigated via 5-bromo-2-deoxyuridine uptake. Pro- and anti-apoptotic factors were investigated through Western blotting and real-time polymerase chain reaction analysis. Results: The evaluation of the anti-proliferative effects on LX-2 cells showed that the observed effects were more pronounced with combination therapy than with single-drug therapy. Moreover, hepatic fibrosis and collagen deposition decreased significantly in TAA-treated mice in response to the combined treatment strategy. The mechanisms underlying the anti-fibrotic effects of the combination therapy were investigated. The effects of the combination therapy were correlated with increased expression levels of extracellular signal-regulated kinase 1/2 signaling molecules, upregulation of the Bax/Bcl-2 signaling pathway, inhibition of the transforming growth factor-β signaling pathway, and inhibition of tissue inhibitor of matrix metalloproteinases 1 and 2. Conclusions The combination of simvastatin and NS-398 resulted in a synergistic anti-fibrotic effect through multiple pathways. These findings offer a theoretical insight into the possible clinical application of this strategy for the treatment of advanced liver diseases with hepatic fibrosis.

Objective: This study aimed to investigate the perception of emergency medical service (EMS) providers and medical directors toward the field skill proficiency of EMS providers. We further examined differences in perception according to the certification and hospital career of individuals. Methods: This survey was conducted enrolling all active EMS providers in Busan, Ulsan, and Gyeongnam, as well as emergency physicians who participated in direct medical direction. Pre-developed questionnaires were sent as text messages to individual EMS providers and emergency physicians using an internet-based survey tool (Google Forms).Questionnaires were composed of 25 items in 7 categories: “airway management”, “ventilatory support”, “circulatory support”, “field assessment and management of trauma patients”, “field assessment and management of patients with chest pain”, “field assessment and management of patients with neurologic symptoms”, and “other items”. The response was based on a five-point Likert scale, where 0 score indicated no experience at all. Results: The questionnaire was distributed to 1,781 EMS providers and 52 medical directors; of these, 1,314 (73.7%) EMS providers and 34 (65.3%) medical directors completed the survey. EMS providers rated themselves as above average (3 points) for most of the questions. However, the majority responded that they had no experience or low proficiency in endotracheal intubation and prehospital delivery (median 2; interquartile range [IQR], 0-3). Conversely, medical directors assessed the EMS provider’s proficiency as above average in use of I-gel, recognition of hypoglycemia, field management of trauma patients, use of oropharyngeal and nasopharyngeal airway, use of laryngeal mask airway, and optimal oxygen supply (median, 4; IQR, 3-4), but responded with low scores for most other questions. Based on the EMS provider certification, nurses scored themselves more proficient than level-1 emergency medical technicians (EMTs) for intravenous access (P<0.001), whereas level-1 EMTs recognized themselves more proficient than nurses for endotracheal intubation (P<0.001), use of Magill forceps (P=0.004), and pediatric cardiopulmonary resuscitation (P<0.001). Conclusion This study recognized the discrepancies in the perception of EMS provider’s field skill proficiency, as perceived by EMS providers and medical directors, and between level-1 EMTs and nurses. We propose that regional EMS authorities need to make persistent efforts to narrow these perception gaps through effective educational programs for EMS providers and medical directors.

Since 2013, the Hospital-based Influenza Morbidity and Mortality (HIMM) surveillance system began a H7N9 influenza surveillance scheme for returning travelers in addition to pre-existing emergency room (ER)-based influenza-like illness (ILI) surveillance and severe acute respiratory infection (SARI) surveillance. Although limited to eastern China, avian A/H7N9 influenza virus is considered to have the highest pandemic potential among currently circulating influenza viruses. During the study period between October 1st, 2013 and April 30th, 2016, 11 cases presented with ILI within seven days of travel return. These patients visited China, Hong Kong, or neighboring Southeast Asian countries, but none of them visited a livestock market. Seasonal influenza virus (54.5%, 6 among 11) was the most common cause of ILI among returning travelers, and avian A/H7N9 influenza virus was not detected during the study period.
Asian Continental Ancestry Group ; China ; Emergency Service, Hospital ; Hong Kong ; Humans ; Influenza A Virus, H7N9 Subtype ; Influenza, Human ; Livestock ; Mortality ; Orthomyxoviridae ; Pandemics ; Seasons

Since sorafenib was introduced in 2007 for treating advanced hepatocellular carcinoma (HCC), 15 patients have achieved a complete response (CR) in advanced HCC. However, only four of these reports can be regarded as real CRs involving adequate assessments including imaging, serum tumor markers, and histologic examinations of completely resected specimens. A 54-year-old man with hepatitis C virus (HCV)-related liver cirrhosis (LC) presented to our unit. A CT scan demonstrated a 3.8-cm arterial hypervascular/portal-washout mass in the right lobe and invasion in the right portal vein. Twelve weeks after beginning sorafenib therapy, the AFP level was normalized and a CT scan showed a prominent decrease in the hepatic mass and a significant decrease in the volume of portal vein thrombosis (PVT). The patient received a right liver hemihepatectomy after 12 months. No viable tumor cells were found in the resected specimen, and there was no thrombotic obstruction of the portal vein. Twelve months later the patient showed no clinical evidence of HCC recurrence. This is the first case of CR in HCC treatment following sorafenib with histologically confirmed HCV-related HCC without LC evidence, HCC with PVT, and a follow-up of longer than 12 months. This case seems to be an extremely unusual clinical outcome in advanced HCC.
Biomarkers, Tumor ; Carcinoma, Hepatocellular* ; Follow-Up Studies ; Hepacivirus ; Hepatitis C ; Humans ; Liver ; Liver Cirrhosis ; Middle Aged ; Portal Vein ; Recurrence ; Response Evaluation Criteria in Solid Tumors ; Tomography, X-Ray Computed ; Venous Thrombosis

No abstract available.
Humans ; Noninvasive Ventilation* ; Weaning*