Synthesis and biological activity of selenopsammaplin A and its analogues as antitumor agents with DOT1L inhibitory activity.

Disruptor of telomeric silencing-1 like (DOT1L) is a histone H3 methyltransferase which specifically catalyzes the methylation of histone H3 lysine-79 residue. Recent findings demonstrate that DOT1L is abnormally overexpressed and the upregulated DOT1L evokes the proliferation and metastasis in human breast cancer cells. Therefore, the DOT1L inhibitor is considered a promising strategy to treat breast cancers. Non-nucleoside DOT1L inhibitors, selenopsammaplin A and its analogues, were firstly reported in the present study. Selenopsammaplin A was newly designed and synthesized with 25% overall yield in 8 steps from 3-bromo-4-hydroxybenzaldahyde, and thirteen analogues of selenopsammaplin A were prepared for structure-activity relationship studies of their cytotoxicity against cancer cells and inhibitory activity toward DOT1L for antitumor potential. All synthetic selenopsammaplin A analogues exhibited the higher cytotoxicity compared to psammaplin A with up to 6 - 60 times depending on cancer cells, and most analogues showed significant inhibitory activities against DOT1L. Among the prepared analogues, the phenyl analogue (10) possessed the most potent activity with both cytotoxicity and inhibition of DOT1L. Compound 10 also exhibited the antitumor and antimetastatic activity in an orthotopic mouse metastasis model implanted with MDA-MB-231 human breast cancer cells. These biological findings suggest that analogue 10 is a promising candidate for development as a cancer chemotherapeutic agent in breast cancers.

Morphologic features of large choroidal vessel layer: age-related macular degeneration, polypoidal choroidal vasculopathy, and central serous chorioretinopathy.

PURPOSE: To compare choroidal vascular characteristics of age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PCV), and central serous chorioretinopathy (CSC) by qualitative and quantitative analyses using swept-source en face optical coherence tomographic (OCT) images. METHODS: Eyes with non-neovascular AMD (n = 32), neovascular AMD (n = 30), thick and thin choroid PCV (n = 33 and 27), and CSC (n = 34) were enrolled. Subfoveal choroidal thickness (SFCT) and the presence and patterns of pachyvessels were assessed. En face images of the large choroidal vessel layer were converted to binary images for the analysis of vascular density. RESULTS: Pachyvessels were identified in 8 (25%), 14 (46%), 28 (85%), 26 (96%), and 34 (100%) non-neovascular AMD, neovascular AMD, thin choroid PCV, thick choroid PCV, and CSC eyes, respectively (P < 0.001). The pattern of pachyvessels was focal in non-neovascular AMD (100%), neovascular AMD (79%), and thin choroid PCV (89%) while the pattern was mostly diffuse in CSC (88%) and thick choroid PCV (81%). The mean choroidal vascular density in a 6 × 6 mm2 macular area of each group was 45.3%, 46.9%, 47.0%, 52.5%, and 54.8%, respectively (P < 0.001). Post hoc analysis revealed significantly higher vascular density in CSC compared with other types (all P < 0.001) except PCV with thick choroid (P = 0.066). CONCLUSIONS: Similarities in vascular density of the large choroidal vessel layer and pachyvessel pattern were between CSC and thick choroid PCV and between AMD and thin choroid PCV, suggesting common pathophysiology involving choroidal changes in these eyes.

Suppression of inducible nitric oxide synthase expression by nyasol and broussonin A, two phenolic compounds from Anemarrhena asphodeloides, through NF-κB transcriptional regulation in vitro and in vivo.

Anemarrhena asphodeloides is widely used in traditional Chinese medicine, and is known to possess antidiabetic and anti-inflammatory properties. Because inducible nitric oxide synthase (iNOS) plays an important role in inflammation, we investigated the inhibitory effects of two known phenolic compounds, nyasol (1) and broussonin A (2), from A. asphodeloides, on iNOS and its plausible mechanism of action. Compounds 1 and 2 exhibited inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Compounds 1 and 2 also suppressed the expressions of iNOS protein and mRNA. Moreover, compounds 1 and 2 suppressed the expression of inflammatory cytokines such as interleukin-1ß (IL-1ß) and interferon-ß (IFN-ß). They also inhibited the transcriptional activity of NF-κB and degradation of IκB-α, as well as the activation of Akt and ERK in LPS-stimulated RAW 264.7 cells. In in vivo animal model, compounds 1 and 2 significantly inhibited TPA-induced mouse ear edema. These results suggest that 1 and 2 suppress LPS-stimulated iNOS expression at the transcriptional level through modulating NF-κB and down-regulation of the Akt and ERK signaling pathways. Taken together, these findings indicate that the suppressive effects of 1 and 2 on iNOS expression might provide one possible mechanism for their anti-inflammatory activities.

Association Between Platelet-to-Lymphocyte Ratio and In-hospital Mortality in Elderly Patients with Severe Trauma.

Introduction: The platelet-to-lymphocyte ratio (PLR) is associated with the inflammatory response in various diseases. However, studies on the use of the PLR for the prognosis of elderly patients with severe trauma are lacking. In this study, we examined the relationship between the PLR and in-hospital mortality in elderly patients with severe trauma. Methods: This retrospective observational study included elderly (≥65 years) patients who were admitted for severe trauma (as defined by an Injury Severity Score [ISS] ≥ 16) between January-December 2022. We conducted multivariate analysis to assess the association between the PLR and in-hospital mortality using logistic regression of relevant covariates. We also performed receiver operating characteristic curve analysis to examine the prognostic performance of the PLR for in-hospital mortality. Results: Among the 222 patients included in the study, the in-hospital mortality rate was 19.4% (43). The PLR of non-survivors was lower than that of survivors (62.1 vs 124.5). The areas under the curve (AUC) of the Glasgow Coma Scale (GCS) score ≤12, ISS, hemoglobin level, and PLR for predicting in-hospital mortality were 0.730 (95% confidence interval [CI] 0.667-0.787), 0.771 (95% CI 0.710-0.824), 0.657 (95% CI 0.591-0.719), and 0.730 (95% CI 0.667-0.788), respectively. The AUC of the PLR was not significantly different from that of GCS score ≤12 and ISS for predicting in-hospital mortality. Multivariate analysis showed that the PLR was independently associated with in-hospital mortality (odds ratio: 0.993; 95% CI 0.987-0.999). Conclusion: Low platelet-to-lymphocyte ratio is independently associated with in-hospital mortality in elderly patients with severe trauma.

Effects of dexamethasone on the TGF-ß1-induced epithelial-to-mesenchymal transition in human peritoneal mesothelial cells.

The epithelial-to-mesenchymal transition (EMT) is known to have a role in appropriate embryonic development, the physiological response to injury and pathological events such as organ fibrosis and cancer progression. Glucocorticoid (GC), one of the most commonly used anti-inflammatory drugs, inhibits the deposition of extracellular matrix independent of its anti-inflammatory effect. The EMT of human peritoneal mesothelial cells (HPMCs) is a key mechanism of peritoneal fibrosis; however, it has not yet been investigated whether GC imposes any effect on the EMT of HPMCs. To investigate the therapeutic potential of GC on preserving peritoneal membrane function, we studied the effect of dexamethasone (DEXA), a synthetic GC, on the transforming growth factor-ß1 (TGF-ß1)-induced EMT in HPMCs. As assessed by changes in cell morphology, the expression of epithelial and mesenchymal cell markers (such as E-cadherin, ZO-1 and α-SMA, α-smooth muscle actin) and cell migration, DEXA inhibited the TGF-ß1-induced EMT. RU486, a glucocorticoid receptor (GR) antagonist, blocked the effect of DEXA on the TGF-ß1-induced EMT. Importantly, DEXA also induced the mesenchymal-to-epithelial transition of TGF-ß1-stimulated HPMCs. The beneficial effect of DEXA on the TGF-ß1-induced EMT was mediated through the amelioration of ERK and p38 mitogen-activated protein kinase (MAPK) phosphorylation; however, this effect was not related to the TGF-ß1-induced activation of Smad2/3 signaling. DEXA inhibited glycogen synthase kinase-3ß (GSK-3ß) phosphorylation and the Snail upregulation induced by TGF-ß1, which were also ameliorated by inhibitors of MAPK. In conclusion, this is the first study demonstrating the protective effect of DEXA on the EMT in TGF-ß1-stimulated HPMCs by inhibiting MAPK activation, GSK-3ß phosphorylation and Snail upregulation.

Choriocapillaris Flow Impairments in Association with Pachyvessel in Early Stages of Pachychoroid.

To analyze features of the choriocapillaris in eyes with earlier stages of pachychoroid spectrum, this study included 46 eyes with PPE, 32 age-matched eyes with pachychoroid without epitheliopathy, and 30 normal controls. Macular 3 × 3 mm2 angiographic images were obtained with swept-source optical coherence tomography. Vascular density and signal void area in the choriocapillaris were analyzed. Topographical correlation of signal voids with the dilated choroidal large vessel (pachyvessel) was assessed. Choriocapillaris vascular density was significantly lower in eyes with PPE compared with controls (p = 0.003). The number, the total area and the average size of signal voids was the highest in the PPE group followed by the pachychoroid without epitheliopathy and then controls (all p ≤ 0.001). 89.0% signal void area colocalized with pachyvessels. The average size of the signal void was higher if it was colocalized with pachyvessel (p < 0.001). In conclusion, the area of flow impairment in the choriocapillaris was increased in eyes with pachychoroid and even greater when epitheliopathy was present. Pachyvessel was associated with choriocapillaris flow impairment by location and size.

White Matter Microstructure Alterations in Schizophrenia With Auditory Verbal Hallucination: Diffusion Tensor Imaging Study / 신경정신의학

Objectives@#To compare the white matter microstructure alterations in schizophrenia with auditory verbal hallucinations (AVHs) with normal persons using diffusion tensor imaging. @*Methods@#Thirty-five schizophrenia patients with AVHs and 33 normal control persons were recruited from the National Forensic Hospital in Korea. The fractional anisotropy (FA) values of arcuate fasciculus (AF), Broca’s area, and Wernicke’s area were estimated from the diffusion tensor imaging data of each subject using the Johns Hopkins University-white matter tractography atlas to determine the difference in white matter integrity between schizophrenia patients with AVH and normal persons. @*Results@#Compared to the normal control group, the FA values of AF (t=4.349, p<0.001) were higher in the normal control group. On the other hand, there were no significant differences in Broca’s area and Wernicke’s area. @*Conclusion@#Microstructural changes of AF are certainly involved in schizophrenia patients with AVHs.

Tumor Microenvironment Modulation by Neoadjuvant Erlotinib Therapy and Its Clinical Impact on Operable EGFR-Mutant Non–Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have greatly improved survival in EGFR-mutant (EGFRm) non–small cell lung cancer (NSCLC); however, their effects on the tumor microenvironment (TME) are unknown. We assessed the changes induced by neoadjuvant erlotinib therapy (NE) in the TME of operable EGFRm NSCLC. @*Materials and Methods@#This was a single-arm phase II trial for neoadjuvant/adjuvant erlotinib therapy in patients with stage II/IIIA EGFRm NSCLC (EGFR exon 19 deletion or L858R mutations). Patients received up to 2 cycles of NE (150 mg/day) for 4 weeks, followed by surgery and adjuvant erlotinib or vinorelbine plus cisplatin therapy depending on observed NE response. TME changes were assessed based on gene expression analysis and mutation profiling. @*Results@#A total of 26 patients were enrolled; the median age was 61, 69% were female, 88% were stage IIIA, and 62% had L858R mutation. Among 25 patients who received NE, the objective response rate was 72% (95% confidence interval [CI], 52.4 to 85.7). The median disease-free and overall survival (OS) were 17.9 (95% CI, 10.5 to 25.4) and 84.7 months (95% CI, 49.7 to 119.8), respectively. Gene set enrichment analysis in resected tissues revealed upregulation of interleukin, complement, cytokine, transforming growth factor β, and hedgehog pathways. Patients with upregulated pathogen defense, interleukins, and T-cell function pathways at baseline exhibited partial response to NE and longer OS. Patients with upregulated cell cycle pathways at baseline exhibited stable/progressive disease after NE and shorter OS. @*Conclusion@#NE modulated the TME in EGFRm NSCLC. Upregulation of immune-related pathways was associated with better outcomes.

Public Perception Towards Drug Abuse in South Korea: The Effects of Overconfidence and Affirmation

Objective@#The abuse of prescription drugs and over-the-counter medicines has been a major issue addressed as a serious public health problem worldwide. This study explored factors contributing to substance abuse in Korea by examining the status of substance abuse among Korean adults and evaluating their knowledge, attitudes, and intentions toward substance abuse. @*Methods@#Data were collected online from a sample of participants 19 years old or older from May 20 to June 1, 2020 (n=1,020). The survey consisted of questions on demographics, perceptions of drug risk, motives for drug use, and attitudes toward drug addiction treatment. Principal component and multiple logistic regression analyses were used to explore the factors contributing to the perception of drug abuse. @*Results@#In the multivariate regression analysis, overconfidence in handling drug usage, acceptance of addictive substances, and affirmation of public support for drug abuse were associated with opioid abuse (Nagelkerke R2=0.486), and additionally affirmation of legal cannabis usage and motivation to use diet pills were associated with diet pill abuse (Nagelkerke R2=0.569). @*Conclusion@#The findings of this study suggest that the actual situation of substance abuse among Korean adults increases awareness of and attitudes toward drug use related to substance abuse.

Antiproliferative Activity of Gibbosic Acid H throughInduction of G0/G1 Cell Cycle Arrest and Apoptosis inHuman Lung Cancer Cells

Lung cancer is one of the most common causative cancers worldwide. Particularly, non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. NSCLC is a serious form of lung cancer that requires prompt diagnosis, and the 5-year survival rate for patients with this disease is only 24%. Gibbosic acid H (GaH), a natural lanostanoid obtained from the Ganoderma species (Ganodermataceae), has antiproliferative activities against colon and lung cancer cells. The aim of the present study was to evaluate the antiproliferative activity of GaH in NSCLC cells and to elucidate the underlying molecular mechanisms.GaH was found to induce G0/G1 cell cycle arrest and autophagy by activating adenosine monophosphate-activated protein kinase in A549 and H1299 cells. The induction of this cell cycle arrest was associated with the downregulation of cyclin E1 and CDK2.Additionally, the induction of autophagy by GaH was correlated with the upregulation of LC3B, beclin-1, and p53 expression. GaH also induced apoptosis by upregulating cleaved caspase-3 and Bax in the lung cancer cells. These findings suggest that GaH has a potential in the growth inhibition of human lung cancer cells.

Association between prehospital oxygen saturation and 30-day mortality in patients with isolated traumatic brain injury

Objective@#The present study analyzes the prognostic performance of prehospital oxygen saturation (SpO2) for 30-day mortality in patients with isolated traumatic brain injury (TBI). @*Methods@#This retrospective observational study included patients with severe isolated TBI admitted through the prehospital emergency medical services system between January 2019 and December 2020. Multivariate analysis was performed using logistic regression of relevant covariates, including prehospital SpO2, for predicting 30-day mortality. Receiver operating characteristics analysis examined the prognostic performance of prehospital SpO2. The primary outcome was 30-day mortality. @*Results@#A total of 189 patients were included in the study. The 30-day mortality rate was determined to be 16.9% (n=32). Prehospital SpO2 of survivors was higher than that of non-survivors—98% (95%-98%) vs. 89% (81%-97%). Results of multivariate analysis revealed that prehospital SpO2 (odds ratio, 0.868; 95% confidence interval [CI], 0.789-0.954) is independently associated with 30-day mortality. The area under the curve of prehospital SpO2 was 0.768 (95% CI, 0.701-0.826; P<0.001). @*Conclusion@#Results of the present study indicate that prehospital SpO2 is associated with 30-day mortality in patients with severe isolated TBI. Therefore, determining the prehospital SpO2 will help to rapidly classify and transport patients with TBI to the appropriate hospital.

Impact of Nrf2 overexpression on cholangiocarcinoma treatment and clinical prognosis

Purpose@#Nrf2 regulates antioxidant protein expression and protects against drug toxicity and oxidative stress, whereas Keap1 controls Nrf2 activity. The Keap1-Nrf2 pathway affects the prognosis of various cancers, however, its effect on cholangiocarcinoma chemoresistance and prognosis remains unclear. This study aimed to determine whether the Keap1-Nrf2 pathway affects chemoresistance and prognosis of distal cholangiocarcinoma. @*Methods@#We investigated the correlation between Nrf2 and Keap1 expression and clinical characteristics and prognosis in 91 patients with distal cholangiocarcinoma who underwent curative surgery. Immunohistochemical staining was performed on paraffin blocks using primary antibodies against Nrf2 and Keap1. The relationship between Keap1 and Nrf2 protein expression levels, and clinical characteristics and prognosis was examined. @*Results@#Nrf2 expression was not associated with overall survival in patients who did not receive adjuvant chemotherapy (P=0.994). Among patients receiving adjuvant chemotherapy, the Nrf2 low expression group had a significantly longer median overall survival than the Nrf2 high expression group in Kaplan-Meier survival analysis (P=0.019). In multivariate analysis, high expression of Nrf2 was confirmed as an independent poor prognostic factor in the group receiving adjuvant chemotherapy (P=0.041). @*Conclusion@#This study suggests that Nrf2 overexpression reduces the efficacy of adjuvant chemotherapy in distal cholangiocarcinoma.

A Randomized Phase II Study of Irinotecan Plus Cisplatin with or without Simvastatin in Ever-Smokers with Extended Disease Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study evaluated whether an addition of simvastatin to chemotherapy improves survival in ever-smokers with extensive disease (ED)–small cell lung cancer (SCLC). @*Materials and Methods@#This is an open-label randomized phase II study conducted in National Cancer Center (Goyang, Korea). Chemonaive patients with ED-SCLC, smoking history (≥ 100 cigarettes lifetime), and Eastern Cooperative Oncology Group performance status of ≤ 2 were eligible. Patients were randomized to receive irinotecan plus cisplatin alone or with simvastatin (40 mg once daily orally) for a maximum of six cycles. Primary endpoint was the the 1-year survival rate. @*Results@#Between September 16, 2011, and September 9, 2021, 125 patients were randomly assigned to the simvastatin (n=62) or control (n=63) groups. The median smoking pack year was 40 years. There was no significant difference in the 1-year survival rate between the simvastatin and control groups (53.2% vs. 58.7%, p=0.535). The median progression-free survival and overall survival between the simvastatin arm vs. the control groups were 6.3 months vs. 6.4 months (p=0.686), and 14.4 months vs. 15.2 months, respectively (p=0.749). The incidence of grade 3-4 adverse events was 62.9% in the simvastatin group and 61.9% in the control group. In the exploratory analysis of lipid profiles, patients with hypertriglyceridemia had significantly higher 1-year survival rates than those with normal triglyceride levels (80.0% vs. 52.7%, p=0.046). @*Conclusion@#Addition of simvastatin to chemotherapy provided no survival benefit in ever-smokers with ED-SCLC. Hypertriglyceridemia may be associated with better prognosis in these patient population.

Effect of a Motivational InterviewingBased Brief Intervention on Alcohol Use Behavior in Korean Internal Medicine Settings

A motivational interviewing (MI)-based brief intervention was performed with high-risk drinking outpatients screened at internal medicine settings in Korea after the doctor advised them to reduce alcohol consumption. Participants were assigned to a MI group or a control group where they received a brochure with information on the harm of high-risk drinking and tips on managing drinking habits. Four-week follow-up results showed that Alcohol Use Disorders Identification Test-Concise (AUDIT-C) scores decreased in the MI group and the control group compared to baseline scores. The difference between groups was not significant; however, group by time interaction was significant between the two groups: the slope of decreasing AUDIT-C scores over time was greater in the intervention group than in the control group (P = 0.042). The findings suggest that short comments received from doctors might be a key component in performing brief interventions for high-risk drinking management in Korean clinical settings.

Association between pralidoxime administration during cardiopulmonary resuscitation and brain tissue oxygen tension in a swine model of cardiac arrest

Objective@#Previous studies have suggested that epinephrine reduces brain tissue O2 tension (PbtO2) after the return of spontaneous circulation (ROSC) via α1-adrenoceptor stimulation and that pralidoxime had α1-adrenoceptor inhibitory action together with non-adrenergic vasopressor action. We sought to investigate the effects of pralidoxime administered during cardiopulmonary resuscitation (CPR) as a sole vasopressor on PbtO2 after ROSC. We hypothesized that pralidoxime administration would lead to a comparable ROSC rate and a higher PbtO2 after ROSC when compared to epinephrine administration. @*Methods@#After 7 minutes of ventricular fibrillation, 24 pigs randomly received either pralidoxime or epinephrine during CPR. Cerebral measurements, including PbtO2, were measured from the parietal cortices during the 60-minute postROSC period. @*Results@#Coronary perfusion pressure (CPP) during CPR was significantly higher in the epinephrine group than in the pralidoxime group (P=0.012). All the animals in the epinephrine group achieved ROSC, while seven (58.3%) did so in the pralidoxime group (P=0.037). The area under the curves for PbtO2 during the post-ROSC period did not differ between the two groups. @*Conclusion@#Pralidoxime alone was significantly inferior to epinephrine in increasing CPP and achieving ROSC. In addition, pralidoxime administration did not improve PbtO2 during the post-resuscitation period as compared with epinephrine.

Social Stigma and Discrimination Toward People With Drug Addiction: A National Survey in Korea

Objective@#This study aims to understand the attitudes, stigma, and discrimination of the general adult population toward drug addiction. @*Methods@#We conducted a cross-sectional nationwide survey with 1,020 Korean adults using an Internet web-based panel. Self-reported data were collected on demographics, experience with substance abuse, perceptions of narcotic analgesic use, beliefs about the legalization of cannabis use, coping with substance abuse and addiction, and perceptions of drug risks. All statistical analysis in this study utilized the IBM SPSS Statistics 26 program. @*Results@#In this study, 1.6% of the participants reported abuse of opioid analgesics, 88.0% reported negative perceptions of drug addiction, and 76.9% reported agreeing to unfair treatment of drug addicts. Logistic regression analysis found that perceived stigma was more prevalent among women (odd ratio [OR]=2.087, p<0.01), old adults (OR=1.939, p<0.01), those with no personal experience of opioid misuse (OR=8.172, p<0.05), and those who were non-smoking (OR=2.011, p<0.01). In addition, the discriminatory attitude was more prevalent among participants with higher income (OR=1.989, p<0.001) and those who are non-smoking (OR=1.608, p<0.05). @*Conclusion@#This study provides information and guidelines for public intervention in drug addiction by identifying factors influencing social stigma and discriminatory behaviors toward drug addiction. The findings suggest that education on drug addiction prevention for the general adult population is necessary, and this education should include knowledge on coping with drug addiction and reducing stigma and discrimination toward drug addicts.

Expert opinion on evidence after 2020 Korean Cardiopulmonary Resuscitation Guidelines

Considerable evidence has been published since the 2020 Korean Cardiopulmonary Resuscitation Guidelines were reported. The International Liaison Committee on Resuscitation (ILCOR) also publishes the Consensus on CPR and Emergency Cardiovascular Care Science with Treatment Recommendations (CoSTR) summary annually. This review provides expert opinions by reviewing the recent evidence on CPR and ILCOR treatment recommendations. The authors reviewed the CoSTR summary published by ILCOR in 2021 and 2022. PICO (population, intervention, comparator, outcome) questions for each topic were reviewed using a systemic or scoping review methodology. Two experts were appointed for each question and reviewed the topic independently. Topics suggested by the reviewers for revision or additional description of the guidelines were discussed at a consensus conference. Forty-three questions were reviewed, including 15 on basic life support, seven on advanced life support, two on pediatric life support, 11 on neonatal life support, six on education and teams, one on first aid, and one related to coronavirus disease 2019 (COVID-19). Finally, the current Korean CPR Guideline was maintained for 28 questions, and expert opinions were suggested for 15 questions.

Effects of Cannabidiol on Adaptive Behavior and Quality of Life in Pediatric Patients With Treatment-Resistant Epilepsy

Background@#and Purpose Data regarding the effects of cannabidiol (CBD) on the quality of life (QOL) are currently inadequate. We assessed the QOL of pediatric patients with epilepsy who were treated with CBD. @*Methods@#This prospective, open-label study included pediatric and adolescent patients (aged 2–18 years) with Dravet syndrome or Lennox-Gastaut syndrome. Oral CBD was administered at 10 mg/kg/day. The Korean version of the Quality Of Life in Childhood Epilepsy (QOLCE) questionnaire was administered when CBD treatment began and again after 6 months. Adaptive behavior was measured using the Korean versions of the Child Behavior Checklist (K-CBCL) and the second edition of the Vineland Adaptive Behavior Scales (Vineland-II). @*Results@#This study included 41 patients (11 with Dravet syndrome and 30 with LennoxGastaut syndrome), of which 25 were male. The median age was 4.1 years. After 6 months, 26.8% (11/41) of patients experienced a ≥50% reduction in the number of seizures. The total score for the QOLCE questionnaire did not change from baseline to after 6 months of CBD treatment (85.71±39.65 vs. 83.12±48.01, respectively; p=0.630). The score in the motor skills domain of Vineland-II reduced from 48.67±13.43 at baseline to 45.18±14.08 after 6 months of treatment (p=0.005). No other Vineland-II scores and no K-CBCL scores had changed after 6 months of CBD treatment. @*Conclusions@#CBD is an efficacious antiseizure drug used to treat Dravet syndrome and Lennox-Gastaut syndrome. However, it did not improve the patient QOL in our study, possibly because all of our patients had profound intellectual disabilities.

Establishment of Patient-Derived Pancreatic Cancer Organoids from Endoscopic Ultrasound-Guided Fine-Needle Aspiration Biopsies

Background/Aims@#Three-dimensional cultures of human pancreatic cancer tissue also known as “organoids” have largely been developed from surgical specimens. Given that most patients present with locally advanced and/or metastatic disease, such organoids are not representative of the majority of patients. Therefore, we used endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) to collect pancreatic cancer tissues from patients with advanced pancreatic cancer to create organoids, and evaluated their utility in pancreatic cancer research. @*Methods@#Single-pass EUS-FNA samplings were employed to obtain the tissue for organoid generation. After establishment of the organoid, we compared the core biopsy tissues with organoids using hematoxylin and eosin staining, and performed whole exome sequencing (WES) to detect mutational variants. Furthermore, we compared patient outcome with the organoid drug response to determine the potential utility of the clinical application of such organoid-based assays. @*Results@#Organoids were successfully generated in 14 of 20 tumors (70%) and were able to be passaged greater than 5 times in 12 of 20 tumors (60%). Among them, we selected eight pairs of organoid and core biopsy tissues for detailed analyses. They showed similar patterns in hematoxylin and eosin staining. WES revealed mutations in KRAS, TP53, CDKN2A, SMAD4, BRCA1, and BRCA2 which were 93% homologous, and the mean nonreference discordance rate was 5.47%. We observed moderate drug response correlations between the organoids and clinical outcomes in patients who underwent FOLFIRINOX chemotherapy. @*Conclusions@#The established organoids from EUS-FNA core biopsies can be used for a suitable model system for pancreatic cancer research

Risk factors of recurrence following common bile duct exploration for choledocholithiasis

Purpose@#The purpose of this study was to investigate the recurrence factors of choledocholithiasis after common bile duct (CBD) exploration. @*Methods@#From January 2000 to December 2018, we retrospectively reviewed 253 patients who underwent CBD exploration surgery. We excluded 100 cases who had residual stone, combined major surgery, or follow-up loss after surgery. Total of 153 patients were included, and we investigated the recurrence factors of choledocholithiasis. Various variables such as patients’ demographics, gallstones, preoperative endoscopic treatment, and laboratory data were analyzed to find factors related to recurrent choledocholithiasis. @*Results@#The median follow-up period was 20.6 months (range 4.7–219 months), and 27 patients (17.6%) had experienced recurrent choledocholithiasis. Univariate analysis showed that the following variables were associated with recurrence of choledocholithiasis; preoperative leukocytosis (white blood cell ≥ 11,000/µL), open procedure, T tube insertion, long hospital duration, and long operation time. Logistic regression multivariate analysis identified preoperative leukocytosis (odds ratio [OR], 3.43; 95% confidence interval [CI], 1.21–9.73; p = 0.021), open procedure (OR, 5.54; 95% CI, 4.73–6.35; p = 0.037), and T-tube insertion (OR, 2.82; 95% CI, 1.04–7.65; p = 0.042) as independent predictors of recurrent choledocholithiasis. @*Conclusion@#Because of delayed recurrence of choledocholithiasis, it is recommended to continue follow-up of patients after CBD exploration surgery. Laparoscopic surgery was observed to be associated with a reduction in recurrence. The preoperative leukocytosis and clinical conditions in which open surgery is performed could be associated with recurrence of choledocholithiasis. However, further study is necessary to validate the result.