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: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Background: The pathophysiological mechanisms underlying the post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) are not well understood.Our study aimed to investigate various aspects of theses mechanisms, including viral persistence, immunological responses, and laboratory parameters in patients with and without PASC. Methods: We prospectively enrolled adults aged ≥ 18 years diagnosed with coronavirus disease 2019 (COVID-19) between August 2022 and July 2023. Blood samples were collected at three time-points: within one month of diagnosis (acute phase) and at 1 month, and 3 months post-diagnosis. Following a recent well-designed definition of PASC, PASC patients were defined as those with a questionnaire-based PASC score ≥ 12 persisting for at least 4 weeks after the initial COVID-19 diagnosis. Results: Of 57 eligible COVID-19 patients, 29 (51%) had PASC, and 28 (49%) did not. The PASC group had significantly higher nucleocapsid protein (NP) antigenemia 3 months after COVID-19 diagnosis (P = 0.022). Furthermore, several cytokines, including IL-2, IL-17A, VEGF, RANTES, sCD40L, IP-10, I-TAC, and granzyme A, were markedly elevated in the PASC group 1 and/or 3 month(s) after COVID-19 diagnosis. In contrast, the median values of several serological markers, including thyroid markers, autoimmune indicators, and stress-related hormones, were within the normal range. Conclusion Levels of NP antigen and of various cytokines involved in immune responses become significantly elevated over time after COVID-19 diagnosis in PASC patients compared to non-PASC patients. This suggests that PASC is associated with prolonged immune dysregulation resulting from heightened antigenic stimulation.

Background: Patient age has been associated with the development of proximal junctional failure (PJF). The characteristics of adult spinal deformity (ASD) are considered different between younger and older age groups. We hypothesized that the radiographic risk factors of PJF would be different according to age groups. This study aimed to evaluate different radiographic risk factors of PJF between two age groups undergoing thoracolumbar fusion for ASD. Methods: ASD patients aged ≥ 60 years who underwent thoracolumbar fusion from the low thoracic level (T9–T12) to the sacrum were included. The minimum follow-up duration was 2 years. PJF was defined as proximal junctional angle (PJA) ≥ 20°, fixation failure, fracture, myelopathy, or necessity of revision surgery. Using various radiographic risk factors including age-adjusted ideal pelvic incidence (PI)-lumbar lordosis (LL), univariate and multivariate analyses were performed separately in two age groups: < 70 years and ≥ 70 years. Results: A total of 186 patients (90.3% women) with a mean age of 69 years were enrolled. The mean follow-up duration was 67.4 months. PJF developed in 97 patients (52.2%). There were fractures in 53 patients, PJA ≥ 20° in 26, fixation failure in 12, and myelopathy in 6. PJF developed more frequently in patients 70 years or older than in those younger than 70 years. In patients aged less than 70 years, preoperative LL, PI-LL, and a change in LL were significant risk factors in univariate analysis. Multivariate analysis showed only a change in LL was significant for PJF development (odds ratio [OR], 1.025; p = 0.021). On the other hand, in patients 70 years or older, postoperative LL, postoperative PI-LL, and overcorrection relative to the conventional PI-LL target (within ± 10°) and age-adjusted ideal PI-LL target were significant risk factors. On multivariate analysis, only overcorrection of PI-LL relative to the age-adjusted ideal target was a single significant risk factor of PJF (OR, 5.250; p = 0.024). Conclusions In patients younger than 70 years, a greater change in LL was associated with PJF development regardless of PIrelated values. However, in older patients, overcorrection of PI-LL relative to the age-adjusted PI-LL target was a significant risk factor of PJF.

Background: Previous reports with proximal junctional failure (PJF) included relatively young patients or deformity without sagittal imbalance. The present study focused on the two well-known risk factors for PJF, old age and severe sagittal imbalance. With these high-risk patients, the present study aimed to identify a strategy that could prevent PJF and to investigate whether the degree of correction would really affect the PJF occurrence. Methods: Patients who were ≥ 60 years of age and underwent long fusion (≥ 4) to the sacrum for severe sagittal imbalance (defined as pelvic incidence minus lumbar lordosis [PI–LL] ≥ 30°) were included. PJF was defined as a vertebral fracture at the uppermost instrumented vertebra (UIV) or UIV+1, failure of UIV fixation, myelopathy, or any need for proximal extension of fusion. Presumed risk factors were compared between the patients with and without PJF. Results: Total 146 patients (mean age, 68.4 years) with preoperative mean PI–LL of 46.8° were included. PJF developed in 39 patients (26.7%) at a mean of 18.1 months after surgery. Multivariate analysis showed that osteoporosis (odds ratio [OR], 2.812; p = 0.019) and UIV located below T10 (OR, 3.773; p = 0.010) were significant risk factors for developing PJF. However, the degree of correction did not affect PJF occurrence. Conclusions The present study indicates that osteoporosis should be well corrected preoperatively and extending the fusion above T10 should be considered for severe imbalance in old patients. However, the amount of correction was not associated with PJF development.

BACKGROUND/AIMS: Although cardiovascular (CV) risk factors are well established, some patients experience acute myocardial infarction (AMI) even without any risk factors. METHODS: We analyzed total 11,390 patients (63.6 ± 12.6 years old, 8,401 males) with AMI enrolled in Korea Acute Myocardial Infarction Registry-National Institute of Health from November, 2011 to December, 2015. Patients were divided into two groups according to the presence of any CV risk factors (group I, without risk factors, n = 1,420 [12.5%]; group II, with risk factors, n = 9,970 [87.5%]). In-hospital outcomes were defined as in-hospital mortality and complications. One-year clinical outcomes were defined as the composite of major adverse cardiac events (MACE). RESULTS: Group I was older (67.3 ± 11.6 years old vs. 63.0 ± 12.7 years old, p < 0.001) and had higher prevalence of female gender (36.2% vs. 24.8%, p < 0.001) than the group II. Group I experienced less previous history of angina pectoris (7.0% vs. 9.4%, p = 0.003) and the previous history of cerebrovascular accidents (3.4% vs. 6.9%, p < 0.001). In-hospital mortality (2.6% vs. 3.0%, p = 0.450) and complications (20.6% vs. 20.0%, p = 0.647) were no differences between the groups. And 1 year clinical outcomes (5.7% vs. 5.1%, p = 0.337) were no differences between the groups. In multivariate logistic regression analysis, serum creatinine level (hazard ratio, 1.35; 95% confidence interval, 1.05 to 1.75; p = 0.021) were independent predictors of 1 year MACE in patients without any CV risk factors. CONCLUSIONS Elderly female patients were prone to develop AMI even without any modifiable CV risk factors. We suggest that more intensive care is needed in AMI patients without any CV risk factors who have high serum creatinine levels.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) involves dysregulation of the complement system, but whether this also occurs in thrombotic thrombocytopenic purpura (TTP) remains unclear. Although these conditions are difficult to differentiate clinically, TTP can be distinguished by low (<10%) ADAMTS13 activity. The aim was to identify the differences in complement activation products between TTP and aHUS and investigate ADAMTS13 activity as a prognostic factor in aHUS. METHODS: We analyzed patients with thrombotic microangiopathy diagnosed as TTP (N=48) or aHUS (N=50), selected from a Korean registry (N=551). Complement activation products in the plasma samples collected from the patients prior to treatment and in 40 healthy controls were measured by ELISA. RESULTS: The levels of generalized (C3a), alternate (factor Bb), and terminal (C5a and C5b-9) markers were significantly higher (all P<0.01) in the patients than in the healthy controls. Only the factor Bb levels significantly differed (P=0.008) between the two disease groups. In aHUS patients, high normal ADAMTS13 activity (≥77%) was associated with improved treatment response (OR, 6.769; 95% CI, 1.605–28.542; P=0.005), remission (OR, 6.000; 95% CI, 1.693–21.262; P=0.004), exacerbation (OR, 0.242; 95% CI, 0.064–0.916; P=0.031), and disease-associated mortality rates (OR, 0.155; 95% CI, 0.029–0.813; P=0.017). CONCLUSION: These data suggest that complement biomarkers, except factor Bb, are similarly activated in TTP and aHUS patients, and ADAMTS13 activity can predict the treatment response and outcome in aHUS patients.
Atypical Hemolytic Uremic Syndrome ; Biomarkers ; Complement Activation ; Complement System Proteins ; Enzyme-Linked Immunosorbent Assay ; Humans ; Mortality ; Plasma ; Purpura, Thrombotic Thrombocytopenic ; Thrombotic Microangiopathies

This study investigated the effects of ombuoside, a flavonol glycoside, on dopamine biosynthesis in PC12 cells. Ombuoside at concentrations of 1, 5, and 10 µM increased intracellular dopamine levels at 1 – 24 h. Ombuoside (1, 5, and 10 µM) also significantly increased the phosphorylation of tyrosine hydroxylase (TH) (Ser40) and cyclic AMP-response element binding protein (CREB) (Ser133) at 0.5 – 6 h. In addition, ombuoside (1, 5, and 10 µM) combined with L-DOPA (20, 100, and 200 µM) further increased intracellular dopamine levels for 24 h compared to L-DOPA alone. These results suggest that ombuoside regulates dopamine biosynthesis by modulating TH and CREB activation in PC12 cells.
Animals ; Carrier Proteins ; Dopamine ; Levodopa ; PC12 Cells ; Phosphorylation ; Tyrosine 3-Monooxygenase

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder that is associated with repetitive head injury and has distinctive neuropathological features that differentiate this disease from other neurodegenerative diseases. Intraneuronal tau aggregates, although they occur in different patterns, are diagnostic neuropathological features of CTE, but the precise mechanism of tauopathy is not known in CTE. We performed whole RNA sequencing analysis of post-mortem brain tissue from patients with CTE and compared the results to normal controls to determine the transcriptome signature changes associated with CTE. The results showed that the genes related to the MAP kinase and calcium-signaling pathways were significantly downregulated in CTE. The altered expression of protein phosphatases (PPs) in these networks further suggested that the tauopathy observed in CTE involves common pathological mechanisms similar to Alzheimer's disease (AD). Using cell lines and animal models, we also showed that reduced PPP3CA/PP2B phosphatase activity is directly associated with increases in phosphorylated (p)-tau proteins. These findings provide important insights into PP-dependent neurodegeneration and may lead to novel therapeutic approaches to reduce the tauopathy associated with CTE.
Alzheimer Disease ; Brain ; Brain Injury, Chronic* ; Cell Line ; Craniocerebral Trauma ; Gene Expression Profiling* ; Humans ; Models, Animal ; Neurodegenerative Diseases ; Phosphoprotein Phosphatases ; Phosphotransferases ; Sequence Analysis, RNA ; Tauopathies* ; Transcriptome*