Background: s/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

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.

Objective: The 2020 Cardiopulmonary Resuscitation (CPR) guidelines recommend the use of feedback devices during CPR training and do not limit their use in actual CPR. Although there have been various studies on metronome-assisted CPR that use a metronome as a feedback device, there are no research results to determine a specific metronome setting rate. We analyzed the quality of CPR and the effectiveness of the metronome feedback according to the metronome setting rate within the recommended chest compression rate range. Methods: Fifty healthcare providers who had received CPR training or had performed CPR in the previous 2 years participated, and all of them performed CPR at three rates (100/min, 110/min, and 120/min). The CPR was performed for 2 minutes with only chest compressions. The smartphone metronome (Metronome version 13.0 Android, KHTSXR, Seoul, Korea) application was used for the rate setting, and Resusci Anne QCPR Mk II (Laerdal Medical, Stavanger, Norway) was used to measure the CPR quality. The difference in the CPR quality according to the setting rate was analyzed. Results: There was no significant difference in the “average compression depth (mm),” “adequate compression depth ratio (%),” and “adequate release ratio (%)” at the three set rates. The “adequate compression rate ratio (%)” was 98.48±5.27% at 110/min, which was higher than that at 120/min or 100/min, and this was a statistically significant difference (P=0.000). There was no significant difference in the “adequate compression site ratio (%).” Conclusion When performing metronome-assisted CPR, setting the rate to 110/min can more appropriately maintain the recommended chest compression rate range and can result in high-quality CPR.

Background: The risk of device thrombosis and device-oriented clinical outcomes with bioresorbable vascular scaffold (BVS) was reported to be significantly higher than with contemporary drug-eluting stents (DESs). However, optimal device implantation may improve clinical outcomes in patients receiving BVS. The current study evaluated mid-term safety and efficacy of Absorb BVS with meticulous device optimization under intravascular imaging guidance. Methods: The SMART-REWARD and PERSPECTIVE-PCI registries in Korea prospectively enrolled 390 patients with BVS and 675 patients with DES, respectively. The primary endpoint was target vessel failure (TVF) at 2 years and the secondary major endpoint was patientoriented composite outcome (POCO) at 2 years. Results: Patient-level pooled analysis evaluated 1,003 patients (377 patients with BVS and 626 patients with DES). Mean scaffold diameter per lesion was 3.24 ± 0.30 mm in BVS group.Most BVSs were implanted with pre-dilatation (90.9%), intravascular imaging guidance (74.9%), and post-dilatation (73.1%) at proximal to mid segment (81.9%) in target vessel.Patients treated with BVS showed comparable risks of 2-year TVF (2.9% vs. 3.7%, adjusted hazard ratio [HR], 1.283, 95% confidence interval [CI], 0.487–3.378, P = 0.615) and 2-year POCO (4.5% vs. 5.9%, adjusted HR, 1.413, 95% CI, 0.663–3.012,P = 0.370) than those with DES. The rate of 2-year definite or probable device thrombosis (0.3% vs. 0.5%, P = 0.424) was also similar. The sensitivity analyses consistently showed comparable risk of TVF and POCO between the 2 groups. Conclusion With meticulous device optimization under imaging guidance and avoidance of implantation in small vessels, BVS showed comparable risks of 2-year TVF and device thrombosis with DES.

Background: Brain metastases of peri-Rolandic area is crucial as it directly impacts the quality of life for cancer patients. Surgery or stereotactic radiosurgery (SRS) is considered for peri-Rolandic brain metastases as for other brain metastases. However, the benefit of each treatment modality on functional outcome has not been clearly defined for this tumor. The purpose of this study is to compare the functional course of each treatment and to suggest an effective treatment for patients’ quality of life. Methods: Fifty-two patients who had undergone SRS or surgery for brain metastasis confirmedby enhanced MRI were enrolled retrospectively. Overall survival (OS), progression free survival (PFS), and functional outcomes were estimated using the Kaplan-Meier method, univariate, multivariate analysis, and Cox proportional hazards regression. Results: Median OS and PFS were 13.3 months and 8.9 months in our study population.Treatment modalities were not significant factors for OS and PFS. Extracranial systemic cancer progression was significant factor for both parameters (p=0.030 for OS and p=0.040 for PFS). Median symptom improvement (improvement of at least 1 grade after surgery compared to preoperative state) time was significantly shorter in surgery group than in the SRS group (10.5 days vs. 37.5 days, p=0.034). Conclusion Surgery for brain metastases can contribute to a positive quality of life for the remain-ing duration of the patient’s life.

In this study, the Ti6Al4V specimens were fabricated using selective laser melting (SLM) method (Ti6Al4V-AS group). These specimens were performed to heat treatment at 950℃ and 550℃ using vacuum electric furnace (Ti6Al4V-HT group). The mechanical properties, metallographic shape, crystalline structure, and chemical compositions of the alloy specimens before and after heat treatment were analyzed. The Ti6Al4V-AS group showed ultimate tensile strength (UTS) and low elongation values. Acicular crystal grains were observed in metallographic image and the α'-Ti phase was dominant. After heat treatment (Ti6Al4V-HT group), the UTS was lowered and the elongation was increased. In addition, a lamellar structure in which columnar crystal grains are arranged was observed, α+β-Ti phase was formed, and crystallinity increased. As a result of analyzing the chemical composition, the Ti6Al4V-AS specimen contained a higher carbon content than the Ti6Al4V-HT specimen. This high carbon content could be related to the formation of α'-phase, high strength and low elongation of the Ti6Al4V-AS specimen. Ti6Al4V-HT specimen showed that the overall carbon content was low, but the carbon content was locally high in the α-Ti phase region. Therefore, it is necessary to control effectively the incorporation of carbon gas in the production of Ti6Al4V specimens using SLM.

Background: The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection. Results: K18-hACE2 mice were intranasally infected with 1 × 105 PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7 days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection. Conclusion Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model.

Objective: Easy-to-understand information on emergency patient transportation and emergency medical resources is required to operate emergency medical resources appropriately. This study evaluated emergency patient transport routes using a geographic information system (GIS) and converted them into visual information to understand the current status of emergency medical resource use in the region. Methods: The basic data used in this study were collected from the 119 safety centers in Gangwon-do, South Korea, under the fire-fighting headquarters in Gangwon-do from January 2017 to December 2020. The data were analyzed using the geographic information system and converted to visual information. Results: The number of patients with cardiovascular disease, cerebrovascular disease, and traffic accidents was 12,944. Of these, 9,393 patients (72.6%) were transported from Chuncheon city, and 3,551 patients (27.4%) were transported out of Chuncheon city. The number of patients with cardiovascular diseases during the study period was 1,219 (9.4%); 782 patients (64.2%) were transported to the K-EMC (emergency medical center), and 437 patients (35.8%) were transported to the H-EMC. For cerebrovascular disease, 913 patients (7.1%) were transported to the EMC of Chuncheon city, with 585 (64.1%) K-EMC and 328 (35.9%) H-EMC patients. The number of traffic accident patients was 1,266 (9.8%). Five hundred and forty (42.7%) and 726 (57.3%) patients were transported to the K-EMC and H-EMC, respectively. Conclusion The adequacy of facilities, equipment, and human resources required to treat cardiac and cerebrovascular diseases in K-EMC and severe trauma in H-EMC needs to be reviewed.

Purpose: To differentiate a non-cancer-related temporary increase in prostate-specific antigen (PSA) triggering unnecessary biopsy, we intentionally delayed biopsy with a serial follow-up, then investigated the efficacy of this strategy in identifying a significant prostate cancer (PCa). Materials and Methods: Retrospective data of patients who initially presented with a suspicious level of serum PSA (3–20 ng/mL), managed using the delayed strategy, and then eventually underwent biopsy were obtained from 4 tertiary centers between 2018–2020. Results: The collected 271 subjects had a median (interquartile range) PSA, age, and prostate volume of 5.03 ng/mL (4.46–7.79 ng/mL), 67 years (61–73 years), and 38 g (28–50 g), respectively. During the delay period of 8 weeks (4–19 weeks), most were managed with alpha-blockers (85.6%, n=232). Ninety-four (34.7%) experienced a PSA decrease of 20.53% (8.82–38.16). Eventual biopsy revealed 115 PCa cases (42.5%) including 82 significant ones and 46 high-risk diseases. Men with a PSA decrease had a lower probability of PCa (31.9% vs. 48%, p=0.014), a significant disease (21.3% vs. 35.0%, p=0.026), and high-risk PCa (7.4% vs. 22.0%, p=0.002) than the PSA-elevated counterparts. However, the degree of PSA decrease was not associated with the presence or the severity of PCa. In patients with PSA normalization (≤3 ng/mL), though 4 patients of them (66%) had PCa including a single significant disease, none had high-risk disease. Conclusions About one-third of individuals initially indicated for transrectal biopsy experienced a decrease in PSA, and their chance for significant PCa was diminished. This retrospective study suggests PSA normalization could be an acceptable notion, though requires further investigation.

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.