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.

The circadian rhythm for mood (CRM) is a digital therapeutic, which aims to prevent mood episode and improve clinical course in patients with major mood disorders. Developed on the circadian rhythm hypothesis of mood disorder, CRM predicts the impending risk of mood episode with its built-in algorithm, utilizing wearable devices data and daily self-reports, and provides personalized feedback. In a pilot study of the CRM, the users experienced less frequent and shorter duration of mood episodes than the non-users. To investigate the efficacy of the upgraded CRM, a double-blind, randomized, sham-controlled, parallel-group trial is designed. Patients aged between 19 and 70, diagnosed with bipolar I disorder, bipolar II disorder, or major depressive disorder, in a euthymic state for more than two months, can participate. During this 12-month trial, participants are assessed for episode recurrence every three months, and the efficacy of the CRM as a potential digital therapeutic is evaluated. Trial registration: ClinicalTrials.gov Identifier: NCT05400785.

Purpose: Few studies have investigated the association between smoking and microvascular complications in the Asian population with type 2 diabetes mellitus (T2DM). We aimed to investigate the relationship between smoking status and microvascular complications in Korean patients with T2DM. Materials and Methods: From the Korean National Diabetes Program cohort, we included 2316 Korean male with T2DM who had baseline clinical information available, including their smoking status, and underwent diabetic complication studies. Results: Compared to non-smokers, current smokers had higher odds of any-microvascular complications [adjusted odds ratio (aOR) 1.45, 95% confidence interval (CI) 1.07–1.97, p=0.016]. The odds of neuropathy were significantly higher; however, the odds of retinopathy were significantly lower in current smokers than in nonsmokers (all p<0.05). Among those who underwent repeated complication tests after 3 years, the risk of newly developed retinopathy was significantly increased in ex-smokers [aOR 3.77 (95% CI 1.61–8.87), p=0.002]. Within ex-smokers, long smoking duration and smoking cessation within the recent 5 years were associated with an increased risk of newly developed retinopathy (all p<0.05). Conclusion Male smokers had higher odds of having overall diabetic microvascular complications, including neuropathy. However, the odds of having retinopathy were significantly lower among current smokers. More attention and research are needed regarding the increased risk of retinopathy development in ex-smokers who have recently stopped smoking after a long history of smoking.

Purpose: This study proposed the optimal definition of biochemical recurrence (BCR) after salvage radiotherapy (SRT) following radical prostatectomy for prostate cancer. Materials and Methods: Among 1,117 patients who had received SRT, data from 205 hormone-naïve patients who experienced post-SRT prostate-specific antigen (PSA) elevation were included in a multi-institutional database. The primary endpoint was to determine the PSA parameters predictive of distant metastasis (DM). Absolute serum PSA levels and the prostate-specific antigen doubling time (PSA-DT) were adopted as PSA parameters. Results: When BCR was defined based on serum PSA levels ranging from 0.4 ng/mL to nadir+2.0 ng/mL, the 5-year probability of DM was 27.6%-33.7%. The difference in the 5-year probability of DM became significant when BCR was defined as a serum PSA level of 0.8 ng/ml or higher (1.0-2.0 ng/mL). Application of a serum PSA level of ≥ 0.8 ng/mL yielded a c-index value of 0.589. When BCR was defined based on the PSA-DT, the 5-year probability was 22.7%-39.4%. The difference was significant when BCR was defined as a PSA-DT ≤ 3 months and ≤ 6 months. Application of a PSA-DT ≤ 6 months yielded the highest c-index (0.660). These two parameters complemented each other; for patients meeting both PSA parameters, the probability of DM was 39.5%-44.5%; for those not meeting either parameter, the probability was 0.0%-3.1%. Conclusion A serum PSA level > 0.8 ng/mL was a reasonable threshold for the definition of BCR after SRT. In addition, a PSA-DT ≤ 6 months was significantly predictive of subsequent DM, and combined application of both parameters enhanced predictability.

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.

Dynamic changes in adipose tissue blood flow (ATBF) with nutritional status play a role in the regulation of metabolic and endocrine functions. Activation of the sympathetic nervous system via β-adrenergic receptors (β-AR) contributes to the control of postprandial enhancement of ATBF. Herein, we sought to identify the role of each β-AR subtype in the regulation of ATBF in mice. We monitored the changes in visceral epididymal ATBF (VAT BF), induced by local infusion of dobutamine, salbutamol, and CL316,243 (a selective β1-, β2-, and β3-AR agonist, respectively) into VAT of lean CD-1 mice and global adipose triglyceride lipase (ATGL) knockout (KO) mice, using laser Doppler flowmetry. Administration of CL316,243, known to promote lipolysis in adipocytes, significantly increased VAT BF of CD-1 mice to a greater extent compared to that of the vehicle, whereas administration of dobutamine or salbutamol did not produce significant differences in VAT BF. The increase in VAT BF induced by β3-AR stimulation disappeared in ATGL KO mice as opposed to their wild-type (WT) littermates, implying a role of ATGL-mediated lipolysis in the regulation of VAT BF. Different vascular reactivities occurred despite no significant differences in vessel density and adiposity between the groups. Additionally, the expression levels of the angiogenesis-related genes were significantly higher in VAT of ATGL KO mice than in that of WT, implicating an association of ATBF responsiveness with angiogenic activity in VAT. Our findings suggest a potential role of β3-AR signaling in the regulation of VAT BF via ATGL-mediated lipolysis in mice.

Dynamic changes in adipose tissue blood flow (ATBF) with nutritional status play a role in the regulation of metabolic and endocrine functions. Activation of the sympathetic nervous system via β-adrenergic receptors (β-AR) contributes to the control of postprandial enhancement of ATBF. Herein, we sought to identify the role of each β-AR subtype in the regulation of ATBF in mice. We monitored the changes in visceral epididymal ATBF (VAT BF), induced by local infusion of dobutamine, salbutamol, and CL316,243 (a selective β1-, β2-, and β3-AR agonist, respectively) into VAT of lean CD-1 mice and global adipose triglyceride lipase (ATGL) knockout (KO) mice, using laser Doppler flowmetry. Administration of CL316,243, known to promote lipolysis in adipocytes, significantly increased VAT BF of CD-1 mice to a greater extent compared to that of the vehicle, whereas administration of dobutamine or salbutamol did not produce significant differences in VAT BF. The increase in VAT BF induced by β3-AR stimulation disappeared in ATGL KO mice as opposed to their wild-type (WT) littermates, implying a role of ATGL-mediated lipolysis in the regulation of VAT BF. Different vascular reactivities occurred despite no significant differences in vessel density and adiposity between the groups. Additionally, the expression levels of the angiogenesis-related genes were significantly higher in VAT of ATGL KO mice than in that of WT, implicating an association of ATBF responsiveness with angiogenic activity in VAT. Our findings suggest a potential role of β3-AR signaling in the regulation of VAT BF via ATGL-mediated lipolysis in mice.

Purpose: To profile various clinical characteristics of sleep bruxism (SB) patients with idiopathic facial pain (IFP) in the orofacial region. Materials and Methods: We analyzed 28 SB patients among 210 patients with IFP complaints. The profiles were evaluated using patient charts including gender, age, pain duration, pain location, pain intensity and affected areas by pain. Results: SB with IFP occurred more often in females (85.7%) than males (14.3%). The mean age at presentation was 48.9 years. The most common IFP sites of SB patients were the right maxilla (28.6%) and the right mandible (25.0%). The pain complaints occurred mostly in 2 teeth or areas (50.0%), followed by 1 area (28.6%) and then in ≥ 3 teeth or areas (21.4%). The mean pain intensity was 5.9 on a visual analogue scale from 0 to 10. The pain was spontaneous in 20 patients (71.4%), and the mean pain duration was 24.4 months. Conclusion Identification of clinical characteristics of SB patients with IFP could be useful in the diagnosis of various IFP patients and beneficial in decreasing unnecessary care to reduce IFP. Further studies with larger number of subjects and extended duration are required for more systemized diagnostic methods and development of future treatment guidelines.