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.

Leucine-rich repeat kinase 2 (LRRK2), a large GTP-regulated serine/threonine kinase, is well-known for its mutations causing late-onset Parkinson’s disease. However, the role of LRRK2 in glioblastoma (GBM) carcinogenesis has not yet been fully elucidated. Here, we discovered that LRRK2 was overexpressed in 40% of GBM patients, according to tissue microarray analysis, and high LRRK2 expression correlated with poor prognosis in GBM patients. LRRK2 and stemness factors were highly expressed in various patient-derived GBM stem cells, which are responsible for GBM initiation. Canonical serum-induced differentiation decreased the expression of both LRRK2 and stemness factors.Given that LRRK2 is a key regulator of glioma stem cell (GSC) stemness, we developed DNK72, a novel LRRK2 kinase inhibitor that penetrates the blood-brain barrier. DNK72 binds to the phosphorylation sites of active LRRK2 and dramatically reduced cell proliferation and stemness factors expression in in vitro studies. Orthotopic patient-derived xenograft mouse models demonstrated that LRRK2 inhibition with DNK72 effectively reduced tumor growth and increased survival time. We propose that LRRK2 plays a significant role in regulating the stemness of GSCs and that suppression of LRRK2 kinase activity leads to reduced GBM malignancy and proliferation. In the near future, targeting LRRK2 in patients with high LRRK2-expressing GBM could offer a superior therapeutic strategy and potentially replace current clinical treatment methods.

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 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.

Background: The epidemiology of pathogenic bacteria varies according to the socioeconomic status and antimicrobial resistance status. However, longitudinal epidemiological studies to evaluate the changes in species distribution and antimicrobial susceptibility of pathogenic bacteria nationwide are lacking. We retrospectively investigated the nationwide trends in species distribution and antimicrobial susceptibility of pathogenic bacteria over the last 20 years in Korea. Methods: From 1997 to 2016, annual cumulative antimicrobial susceptibility and species distribution data were collected from 12 university hospitals in five provinces and four metropolitan cities in South Korea. Results: The prevalence of Staphylococcus aureus was the highest (13.1%) until 2012 but decreased to 10.3% in 2016, consistent with the decrease in oxacillin resistance from 76.1% in 2008 to 62.5% in 2016. While the cefotaxime resistance of Escherichia coli increased from 9.0% in 1997 to 34.2% in 2016, E. coli became the most common species since 2013, accounting for 14.5% of all isolates in 2016. Pseudomonas aeruginosa and Acinetobacter baumannii rose to third and fifth places in 2008 and 2010, respectively, while imipenem resistance increased from 13.9% to 30.8% and 0.7% to 73.5% during the study period, respectively.Streptococcus agalactiae became the most common pathogenic streptococcal species in 2016, as the prevalence of Streptococcus pneumoniae decreased since 2010. During the same period, pneumococcal penicillin susceptibility decreased to 79.0%, and levofloxacin susceptibility of S. agalactiae decreased to 77.1% in 2016. Conclusion The epidemiology of pathogenic bacteria has changed significantly over the past 20 years according to trends in antimicrobial resistance in Korea. Efforts to confine antimicrobial resistance would change the epidemiology of pathogenic bacteria and, consequently, the diagnosis and treatment of infectious diseases.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces excessive pro-inflammatory cytokine release and cell death, leading to organ damage and mortality.High-mobility group box 1 (HMGB1) is one of the damage-associated molecular patterns that can be secreted by pro-inflammatory stimuli, including viral infections, and its excessive secretion levels are related to a variety of inflammatory diseases. Here, the aim of the study was to show that SARS-CoV-2 infection induced HMGB1 secretion via active and passive release. Active HMGB1 secretion was mediated by post-translational modifications, such as acetylation, phosphorylation, and oxidation in HEK293E/ACE2-C-GFP and Calu-3 cells during SARS-CoV-2 infection. Passive release of HMGB1 has been linked to various types of cell death; however, we demonstrated for the first time that PANoptosis, which integrates other cell death pathways, including pyroptosis, apoptosis, and necroptosis, is related to passive HMGB1 release during SARS-CoV-2 infection. In addition, cytoplasmic translocation and extracellular secretion or release of HMGB1 were confirmed via immunohistochemistry and immunofluorescence in the lung tissues of humans and angiotensin-converting enzyme 2-overexpressing mice infected with SARS-CoV-2.

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.

Background/Aims: The study investigated the incidence of thromboembolic events (TEE) in head and neck (H&N) cancer patients who received concurrent chemoradiotherapy (CCRT) with cisplatin, and analyzed the factors affecting TEE occurrence Methods: Two hundred and fifty-seven patients who started CCRT with cisplatin for H&N cancer from January 2005 to December 2019 were analyzed. Results: TEE occurred in five patients, an incidence rate of 1.9%. The 2-, 4-, and 6-month cumulative incidences of TEE were 0.8%, 1.6%, and 1.9%, respectively. Khorana score was the only factor associated with TEE occurrence (p = 0.010). Conclusions The incidence of TEE in H&N cancer patients who underwent CCRT with cisplatin was relatively low when compared to other types of cancer. However, patients with a high Khorana score require more careful surveillance for possible TEE occurrence.

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.