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.

In this study, the anti-inflammatory activity and ER stress modulation of the hexane fraction from Peucedanum insolens Kitag. root was investigated. The anti-inflammatory activity was evaluated by measuring nitric oxide inhibition and analyzing iNOS and COX-2 expression in LPS-treated RAW 264.7 macrophages using Western blot. The hexane fraction’s effect on ER stress was assessed by monitoring ATF6α transcriptional activity in the stable recombinant HLR-GV-hATF6α (333) cell line. Additionally, the expression levels of ER stress-related proteins, including eIF2α, p-eIF2α, GRP78, and CHOP, were analyzed by western blot in HeLa cells. Our results demonstrated that the hexane fraction strongly inhibited nitric oxide production and the expression of iNOS and COX-2 in LPS-treated RAW 264.7 cells. It also significantly reduced ATF6α transcriptional activation induced by thapsigargin or tunicamycin. In HeLa cells, the hexane fraction inhibited the expression of ER stress-related proteins GRP78 and CHOP induced by thapsigargin. Although the hexane fraction alone did not affect GRP78, CHOP and eIF2α levels, it enhanced eIF2α phosphorylation in a concentrationdependent manner. Co-treatment with the hexane extract and thapsigargin prevented both CHOP and GRP78 expressions and eIF2α phosphorylation. Taken together, our results suggest that the anti-inflammatory potency of the hexane-fraction of P. insolens might be related to its potential to modulate ER stress. To find out more detailed integrated actions of the hexanefraction of P. insolens against ER stress-induced inflammation signalling and to identify bioactive compound(s) associated with ERSR-related inflammation, further studies are required using a single cell type, such as RAW 264.7 or HeLa cells.

Objective: This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. Methods: Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. Results: Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35–4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. Conclusion Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.

Background: In this study, we prepared and evaluated an injectable poloxamer (P407) hydrogel formulation for intratympanic (IT) delivery of dexamethasone (DEX). Methods: DEX-loaded P407 hydrogels were characterized in terms of thermogelation, drug loading capacities, particle size, and drug release. The in vivo toxicity and drug absorption of the DEX-loaded P407 formulation after IT injection were evaluated using an animal model by performing histopathological analysis and drug concentration measurements. Results: The P407 hydrogel effectively solubilized hydrophobic DEX and demonstrated a sustained release compared to the hydrophilic DEX formulation. The in vivo study showed that the hydrogel formulation delivered considerable drug concentrations to the inner ear and displayed a favorable safety profile without apparent cytotoxicity or inflammation. Conclusion P407 hydrogel can be useful as an injectable inner ear delivery formulation for hydrophobic drugs due to their biocompatibility, drug-solubilizing capacity, thermogelation, and controlled release.

Purpose: To investigate the long-term outcomes of anterior chamber angle parameters in patients with primary angle closure glaucoma (PACG) after peripheral laser iridotomy (LI) combined with iridoplasty (PI) using a dual Scheimpflug analyzer. Methods: This retrospective study included 32 eyes in 32 patients diagnosed with PACG who underwent LI plus PI. Patients with an acute angle closure crisis were excluded. Dual Scheimpflug analyzer images were acquired before and 1 week after LI plus PI, and yearly afterwards. Anterior chamber depth (ACD) and volume (ACV), mean anterior chamber angle (ACA), and intraocular pressure (IOP) were also measured. Results: The mean follow-up was 32.28 ± 13.34 months. Baseline demographics were age 63 ± 7.9 years, 62.5% female, IOP 15.48 ± 4.79 mmHg, ACD 2.09 ± 0.19 mm, and visual field mean deviation -7.97 ± 8.49 dB. ACD increased from baseline to 2.15 ± 0.32 mm, but it was not significant (p = 0.136). ACV increased significantly from 78.32 ± 11.49 mm at baseline to 83.04 ± 11.16 mm at the last visit after LI (p = 0.011). The mean ACA increased significantly from 26.86 ± 2.53° at baseline to 28.82 ± 4.64° at the last visit (p = 0.022). IOP decreased significantly from baseline to 13.06 ± 2.21 mmHg at the last visit (p = 0.001). Conclusions The ACA parameters improved after LI combined with PI in patients with PACG and remained so on long-term follow-up. IOP was also significantly reduced for more than 2.5 years after LI plus PI.

Background/Aims: This study evaluated the long-term cardiovascular complications among Korean patients with hypertension and compared them with that of controls without hypertension. Methods: The Korean Hypertension Cohort (KHC) enrolled 11,043 patients with hypertension and followed them for more than 10 years. Age- and sex-matched controls without hypertension were enrolled at a 1:10 ratio. We compared the incidence of cardiovascular events and death among patients and controls without hypertension. Results: The mean age was 59 years, and 34.8% and 16.5% of the patients belonged to the high and moderate cardiovascular risk groups, respectively. During the 10-year follow-up, 1,591 cardiovascular events (14.4%) with 588 deaths (5.3%) occurred among patients with hypertension and 7,635 cardiovascular events (6.9%) with 4,826 deaths (4.4%) occurred among controls. Even the low-risk population with hypertension showed a higher cardiovascular event rate than the population without hypertension. Although blood pressure measurements in the clinic showed remarkable inaccuracy compared with those measured in the national health examinations, systolic blood pressure (SBP) ≥ 150 mmHg was significantly associated with a higher risk of cardiovascular events. Conclusions This long-term follow-up study confirmed the cardiovascular event rates among Korean hypertensive patients were substantial, reaching 15% in 10 years. SBP levels ≥ 150 mmHg were highly associated with occurrence of cardiovascular event rates.

Background/Aims: Hypertension (HT) has a significant impact on public health and medical expenses. However, HT is a chronic disease that requires the long-term follow-up of a large number of patients. Methods: The Korean Hypertension Cohort (KHC) study aimed to develop a model for calculating cardiovascular risk in HT patients by linking and utilizing the detailed clinical and longitudinal data from hospitals and the national health insurance claim database, respectively. This cohort had a planned sample size of over 11,000 HT patients and 100,000 non-HT controls. Eligible patients were hypertensive patients, who were presenting for the first time and were diagnosed with HT as a main disease from 2006 to 2011. Long-term survival data over a period of approximately 9 years were obtained from the national health insurance claim and national health examination data. Results: This cohort enrolled 11,083 patients with HT. The mean age was 58.87 ± 11.5 years, 50.5% were male, and 31.4% were never-treated HT. Of the enrolled patients, 32.9% and 37.7% belonged to the high and moderate cardiovascular risk groups, respectively. Initial blood pressures were 149.4 ± 18.5/88.5 ± 12.5 mmHg. During the 2 years hospital data follow-up period, blood pressures lowered to 130.8 ± 14.1/78.0 ± 9.7 mmHg with 1.9 ± 1.0 tablet doses of antihypertensive medication. Cardiovascular events occurred in 7.5% of the overall patients; 8.5%, 8.8%, and 4.7% in the high, moderate, and low risk patients, respectively. Conclusions The KHC study has provided important information on the long-term outcomes of HT patients according to the blood pressure, comorbid diseases, medication, and adherence, as well as health behaviors and health resource use.

Background: and Purpose The aim of this study was to survey the expert opinions on treatments for convulsive status epilepticus (CSE) and nonconvulsive status epilepticus (NCSE) in adults. Methods: Forty-two South Korean epileptologists participated in this survey. They completed an online questionnaire regarding various patient scenarios and evaluated the appropriateness of medications used to treat CSE and NCSE. Results: Initial treatment with a benzodiazepine (BZD) followed by either a second BZD or an antiepileptic drug (AED) monotherapy was the preferred treatment strategy. More than two-thirds of the experts used a second BZD when the first one failed, and consensus was reached for 84.8% of the survey items. The preferred BZD was intravenous (IV) lorazepam for the initial treatment of status epilepticus. IV fosphenytoin and IV levetiracetam were chosen for AED monotherapy after the failure of BZD. The treatments for NCSE were similar to those for CSE. Continuous IV midazolam infusion was the treatment of choice for iatrogenic coma in refractory CSE, but other AEDs were preferred over iatrogenic coma in refractory NCSE. Conclusions The results of this survey are consistent with previous guidelines, and can be cautiously applied in clinical practice when treating patients with CSE or NCSE.

Status epilepticus (SE) is one of the most serious neurologic emergencies. SE is a condition that encompasses a broad range of semiologic subtypes and heterogeneous etiologies. The treatment of SE primarily involves the management of the underlying etiology and the use of antiepileptic drug therapy to rapidly terminate seizure activities. The Drug Committee of the Korean Epilepsy Society performed a review of existing guidelines and literature with the aim of providing practical recommendations for antiepileptic drug therapy. This article is one of a series of review articles by the Drug Committee and it summarizes staged antiepileptic drug therapy for SE. While evidence of good quality supports the use of benzodiazepines as the first-line treatment of SE, such evidence informing the administration of second- or third-line treatments is lacking; hence, the recommendations presented herein concerning the treatment of established and refractory SE are based on case series and expert opinions. The choice of antiepileptic drugs in each stage should consider the characteristics and circumstances of each patient, as well as their estimated benefit and risk to them. In tandem with the antiepileptic drug therapy, careful searching for and treatment of the underlying etiology are required.

Background/Aims: Hypertension (HT) has a significant impact on public health and medical expenses. However, HT is a chronic disease that requires the long-term follow-up of a large number of patients. Methods: The Korean Hypertension Cohort (KHC) study aimed to develop a model for calculating cardiovascular risk in HT patients by linking and utilizing the detailed clinical and longitudinal data from hospitals and the national health insurance claim database, respectively. This cohort had a planned sample size of over 11,000 HT patients and 100,000 non-HT controls. Eligible patients were hypertensive patients, who were presenting for the first time and were diagnosed with HT as a main disease from 2006 to 2011. Long-term survival data over a period of approximately 9 years were obtained from the national health insurance claim and national health examination data. Results: This cohort enrolled 11,083 patients with HT. The mean age was 58.87 ± 11.5 years, 50.5% were male, and 31.4% were never-treated HT. Of the enrolled patients, 32.9% and 37.7% belonged to the high and moderate cardiovascular risk groups, respectively. Initial blood pressures were 149.4 ± 18.5/88.5 ± 12.5 mmHg. During the 2 years hospital data follow-up period, blood pressures lowered to 130.8 ± 14.1/78.0 ± 9.7 mmHg with 1.9 ± 1.0 tablet doses of antihypertensive medication. Cardiovascular events occurred in 7.5% of the overall patients; 8.5%, 8.8%, and 4.7% in the high, moderate, and low risk patients, respectively. Conclusions The KHC study has provided important information on the long-term outcomes of HT patients according to the blood pressure, comorbid diseases, medication, and adherence, as well as health behaviors and health resource use.