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.

Background: Hemiarthroplasty is frequently used to treat displaced femoral neck fractures in elderly patients, but it has a higher risk of postoperative dislocation. We introduced the posterior approach and inferior capsulotomy (PAICO) to enhance joint stability after bipolar hemiarthroplasty for femoral neck fracture. We evaluated whether the PAICO would have a lower dislocation rate than the conventional posterior approach with superior capsulotomy. Methods: From January 2021 to December 2021, we prospectively recruited 25 patients (25 hips) aged 50 years or older who underwent bipolar hemiarthroplasty for femoral neck fractures due to low-energy trauma as the PAICO group. We compared the PAICO group with a historical control group who had undergone hemiarthroplasty in 7 institutes between 2010 and 2020. The primary endpoint was dislocation within 1 year after the surgery. We compared data from the PAICO group with the data from the historical control group from the Korean Hip Fracture Registry which was carried out in South Korea. Results: A total of 25 patients (25 hips) were enrolled in the present study; 3,477 patients (3,571 hips) who underwent bipolar hemiarthroplasty were reviewed as the historical control group. In the PAICO group, we observed no dislocation, whereas the dislocation rate in the control group was 1.3%. Conclusions In patients with displaced femoral neck fractures, the PAICO approach demonstrated comparable results in operation time and complication rates when compared to bipolar hemiarthroplasty using superior capsulotomy. Notably, there were no observed cases of dislocation among patients who underwent the PAICO approach. We recommend this PAICO approach to surgeons using the posterior approach, hoping to prevent dislocation in bipolar hemiarthroplasty.

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: : Collateral circulation is associated with the differential treatment effect of endovascular thrombectomy (EVT) in acute ischemic stroke. We aimed to verify the ability of the collateral map to predict futile EVT in patients with acute anterior circulation ischemic stroke. Methods: : This secondary analysis of a prospective observational study included data from participants underwent EVT for acute ischemic stroke due to occlusion of the internal carotid artery and/or the middle cerebral artery within 8 hours of symptom onset. Multiple logistic regression analyses were conducted to identify independent predictors of futile recanalization (modified Rankin scale score at 90 days of 4–6 despite of successful reperfusion). Results: : In a total of 214 participants, older age (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.56 to 3.67; p<0.001), higher baseline National Institutes of Health Stroke Scale (NIHSS) scores (OR, 1.12; 95% CI, 1.04 to 1.21; p=0.004), very poor collateral perfusion grade (OR, 35.09; 95% CI, 3.50 to 351.33; p=0.002), longer door-to-puncture time (OR, 1.08; 95% CI, 1.02 to 1.14; p=0.009), and failed reperfusion (OR, 3.73; 95% CI, 1.30 to 10.76; p=0.015) were associated with unfavorable functional outcomes. In 184 participants who achieved successful reperfusion, older age (OR, 2.30; 95% CI, 1.44 to 3.67; p<0.001), higher baseline NIHSS scores (OR, 1.12; 95% CI, 1.03 to 1.22; p=0.006), very poor collateral perfusion grade (OR, 4.96; 95% CI, 1.42 to 17.37; p=0.012), and longer door-to-reperfusion time (OR, 1.09; 95% CI, 1.03 to 1.15; p=0.003) were associated with unfavorable functional outcomes. Conclusion : The assessment of collateral perfusion status using the collateral map can predict futile EVT, which may help select ineligible patients for EVT, thereby potentially reducing the rate of futile EVT.

Purpose: Acetaminophen overdose accounts for the largest proportion of pediatric poisoning reported in South Korea. We investigated the characteristics and prognosis of pediatric acetaminophen overdose. Methods: We retrospectively reviewed medical records of patients younger than 19 years with acetaminophen overdose who visited the emergency department (ED) of Pusan National University Children’s Hospital from January 2009 through December 2022. We investigated age, sex, dose, clinical findings, and treatment, and compared the differences in the variables according to the intentionality of ingestion and the presence of hepatotoxicity. Results: Among the 132,691 pediatric patients who visited the ED during the period, 555 did for drug intoxication, of whom 51 with acetaminophen overdose were included in this study. The overdose was intentional in 43 patients (the intentional group; median age, 15.4 years [interquartile range, 13.9-16.8]) and accidental in 8 patients (the accidental group; 7.7 years [2.3-15.4]). The mean ingested dose was higher in the intentional group than in the accidental group (170.3 ± 129.0 vs. 105.3 ± 37.5 mg/kg; P = 0.016). Hospitalization tended to be implemented more frequently in the intentional group (53.5% vs. 12.5%; P = 0.081). All patients with hepatotoxicity (n = 10) belonged to the same group, and showed a higher or longer median age (15.9 [14.6-17.1] vs. 13.8 years [13.7-16.4]; P = 0.030), mean ingested dose (13,230.0 ± 10,544.8 vs. 7,654.0 ± 6,752.3 mg; P = 0.043), mean time from ingestion to arrival at the ED (22.6 ± 23.4 vs. 5.5 ± 6.4 hours; P = 0.048), and frequency of hospitalization (80.0% vs. 39.0%; P = 0.048). Conclusion It is necessary to track the occurrence of hepatotoxicity in patients who intentionally ingest acetaminophen.

Background: Increasing longevity has caused the very old population to become the fastest-growing segment. The number of centenarians (over 100 years old) is increasing rapidly. Fractures in the elderly lead to excessive medical costs and decreased quality of life with socioeconomic burdens. However, little research has thoroughly examined the functional outcomes and mortality of hip fractures in centenarians. Methods: This is a retrospective observational study. Sixty-eight centenarian hip fracture patients were admitted to the 10 institutions from February 2004 to December 2019. Fifty-six patients with 1-year follow-up were finally included. The following data were obtained: sex, age, body mass index, Charlson comorbidity index value on the operation day, Koval’s classification for ambulatory ability, type of fracture, the time interval from trauma to surgery, American Society of Anesthesiologists grade, surgery-related complications, and duration of hospital stay. Postoperative Koval’s classification (at 1 year after surgery) and information about death were also collected. Multivariate analysis was performed to analyze the risk factors affecting mortality 1 year after surgery. Results: Mortality rates were 26.8% at 6 months and 39.3% at 1 year. The 90-day mortality was 19.6%, and one of them (2.1%) died in the hospital. The 1-year mortality rates for the community ambulatory and non-community ambulatory groups were 29% and 52%, respectively. Only 9 (16.1%) were able to walk outdoors 1 year after surgery. The remaining 47 patients (83.9%) had to stay indoors after surgery. Multivariate analysis demonstrated that the pre-injury ambulatory level (adjusted hazard ratio, 2.884; p = 0.034) was associated with the risk of mortality. Conclusions We report a 1-year mortality rate of 39.3% in centenarian patients with hip fractures. The risk factor for mortality was the pre-injury ambulatory status. This could be an important consideration in the planning of treatment for centenarian hip fracture patients.

Background: The purpose of this study was to verify the accuracy and validity of using machine learning (ML) to select risk factors, to discriminate differences in feature selection by ML between men and women, and to develop predictive models for patients with osteoporosis in a big database. Methods: The data on 968 observed features from a total of 3,484 the Korea National Health and Nutrition Examination Survey participants were collected. To find preliminary features that were well-related to osteoporosis, logistic regression, random forest, gradient boosting, adaptive boosting, and support vector machine were used. Results: In osteoporosis feature selection by 5 ML models in this study, the most selected variables as risk factors in men and women were body mass index, monthly alcohol consumption, and dietary surveys. However, differences between men and women in osteoporosis feature selection by ML models were age, smoking, and blood glucose level. The receiver operating characteristic (ROC) analysis revealed that the area under the ROC curve for each ML model was not significantly different for either gender. Conclusions ML performed a feature selection of osteoporosis, considering hidden differences between men and women. The present study considers the preprocessing of input data and the feature selection process as well as the ML technique to be important factors for the accuracy of the osteoporosis prediction model.

Background: Dual energy X-ray absorptiometry (DXA) is a preferred modality for screening or diagnosis of osteoporosis and can predict the risk of hip fracture. However, the DXA test is difficult to implement easily in some developing countries, and fractures have been observed before patients underwent DXA. The purpose of this systematic review is to search for studies that predict the risk of hip fracture using artificial intelligence (AI) or machine learning, organize the results of each study, and analyze the usefulness of this technology. Methods: The PubMed, OVID Medline, Cochrane Collaboration Library, Web of Science, EMBASE, and AHRQ databases were searched including “hip fractures” AND “artificial intelligence”. Results: A total of 7 studies are included in this study. The total number of subjects included in the 7 studies was 330,099. There were 3 studies that included only women, and 4 studies included both men and women. One study conducted AI training after 1:1 matching between fractured and non-fractured patients. The area under the curve of AI prediction model for hip fracture risk was 0.39 to 0.96. The accuracy of AI prediction model for hip fracture risk was 70.26% to 90%. Conclusions We believe that predicting the risk of hip fracture by the AI model will help select patients with high fracture risk among osteoporosis patients. However, to apply the AI model to the prediction of hip fracture risk in clinical situations, it is necessary to identify the characteristics of the dataset and AI model and use it after performing appropriate validation.

Background: This study aimed to investigate real-world data of C-terminal telopeptide (CTX), propeptide of type I collagen (P1NP), and osteocalcin through present multicenter clinical study, and retrospectively analyze the usefulness of bone turnover markers (BTMs) in Koreans. Methods: The study focused on pre- and post-menopausal patients diagnosed with osteoporosis and excluded patients without certain test results or with test intervals of over 1 year. The demographic data and 3 BTMs (CTX, P1NP, and osteocalcin) were collected. The patients were classified by demographic characteristics and the BTM concentrations were analyzed by the group. Results: Among women with no history of fractures, the levels of P1NP (N=2,100) were 43.544±36.902, CTX (N=1,855) were 0.373 ±0.927, and osteocalcin (N=219) were 10.81 ±20.631. Among men with no history of fractures, the levels of P1NP (N=221) were 48.498±52.892, CTX (N=201) were 0.370±0.351, and osteocalcin (N=15) were 7.868 ±10.674. Treatment with teriparatide increased the P1NP levels after 3 months in both men and women, with a 50% increase observed in women. Similarly, treatment with denosumab decreased the CTX levels after 3 months in both men and women, with a reduction of 50% observed in women. Conclusions The results of this study can contribute to the accurate assessment of bone replacement status in Koreans. We also provide the P1NP level in the Korean population for future comparative studies with other populations.

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.