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Background: In patients with metastatic renal cell carcinoma (mRCC), sites of metastatic involvement have been reported to be associated with a difference in survival. However, the frequency and survival according to different sites of metastases in Korean patients with mRCC remain unclear. Therefore, this study aimed to assess the frequency of metastatic site involvement and the association between sites of metastatic involvement and survival in Korean patients with mRCC., Methods: This retrospective study used the multicenter cohort of the Korean Renal Cancer Study Group mRCC database to identify patients who started targeted therapy between December 2005 and March 2018. Data on the frequency of metastatic organ involvement at the time of mRCC diagnosis and oncologic outcomes according to different sites of metastasis were analyzed., Results: A total of 1,761 patients were eligible for analysis. Of the 1,761 patients, 1,564 (88.8%) had clear cell RCC, and 1,040 (59.1%) had synchronous metastasis. The median number of metastasis sites was 2 (interquartile range [IQR], 1-6). The median age at the initiation of systemic therapy was 60 years (IQR, 29-88), 1,380 (78.4%) were men, and 1,341 (76.1%) underwent nephrectomy. Based on the International Metastatic Renal Cell Carcinoma Database Consortium model, patients were stratified into favorable-, intermediate-, and poor-risk groups with 359 (20.4%), 1,092 (62.0%), and 310 (17.6%) patients, respectively. The lung (70.9%), lymph nodes (37.9%), bone (30.7%), liver (12.7%), adrenal gland (9.8%), and brain (8.2%) were the most common sites of metastasis, followed by the pancreas, pleura, peritoneum, spleen, thyroid, and bowel. Among the most common sites of metastasis (> 5%), the median cancer-specific survival (CSS) ranged from 13.9 (liver) to 29.1 months (lung). An association was observed between liver, bone, and pleural metastases and the shortest median CSS (< 19 months)., Conclusion: In Korean patients with mRCC, metastases to the lung, lymph nodes, bone, liver, adrenal gland, and brain were more frequent than those to other organs. Metastases to the liver, bone, and pleura were associated with poor CSS. The findings of this study may be valuable for patient counseling and guiding future study designs., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Fourteen azaphilone-type polyketides ( 1 - 14 ), including nine new ones ( 1 - 6 and 8 - 10 ), were isolated from cultures of Vitex rotundifolia -associated Penicillium sp. JVF17, and their structures were determined by spectroscopic analysis together with computational methods and chemical reactions. Neuroprotective effects of the isolated compounds were evaluated against glutamate-induced neurotoxicity. Treatment with compounds 3 , 6 , 7 , and 11 - 14 increased cell viabilities of hippocampal neuronal cells damaged by glutamate, with compound 12 being the most potent. Compound 12 markedly decreased intracellular Ca 2+ and nuclear condensation levels. Mechanistically, molecular markers of apoptosis induced by treatment with glutamate, i.e., phosphorylation of MAPKs and elevated Bax/Bcl-2 expression ratio, were significantly lowered by compound 12 . The azaphilones with an isoquinoline core structure were more active than those with pyranoquinones, but N -substitution decreased the activity. This study, including the structure-activity relationship, indicates that the azaphilone scaffold is a promising lead toward the development of novel neuroprotective agents.

Background and Aim: We aimed to measure the natural killer (NK) cell activity and pro-inflammatory cytokine levels in the peripheral blood of pancreatic cancer patients and investigate the correlation of NK cell activity and cytokines with cancer status and clinical outcomes., Methods: We prospectively enrolled patients who were pathologically diagnosed with pancreatic ductal adenocarcinoma (PDAC) between 2016 and 2017 at a tertiary hospital in Seoul, South Korea. As a control group, healthy participants were enrolled by mobile application recruitment., Results: A total of 203 patients were enrolled for this study (PDAC, n = 102; healthy participants, n = 101). The peripheral blood NK cell activity of PDAC patients was significantly lower than that of healthy participants (median level, 95 pg/mL vs 2000 pg/mL, P < 0.001), and decreased NK cell activity was correlated to poor clinical outcome in terms of response to chemotherapy, tumor progression, and survival. The pro-inflammatory cytokine interleukin-6 had a strong negative correlation with NK cell activity., Conclusions: In pancreatic cancer patients, NK cell activity decreased as cancer progressed, and decreased NK cell activity was associated with poor clinical outcomes., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Locally advanced pancreatic cancer (LAPC) is one of the most aggressive malignancies. Irreversible electroporation (IRE) is a novel technique that uses a non-thermal ablation to avoid vessel or duct injury., Purpose: To investigate the safety and efficacy of IRE for the management of LAPC in a Korean population., Material and Methods: Twelve patients (median age 64 years; age range 46-73 years) treated between December 2015 and March 2017 underwent intraoperative IRE for LAPC. Technical success and clinical outcomes, including complications, serum pancreatic enzyme levels, overall survival (OS), and progression-free survival (PFS), were evaluated., Results: Tumors were located in the pancreas head in 7 (58.3%) patients and in the body/tail in 5 (41.7%) patients. The median tumor diameter in the longest axis was 3.1 cm. Vascular invasion was observed in all patients and bowel abutment in 3 (25%) patients. Technical success was achieved in all patients. The median serum levels of amylase and lipase were 55 U/L and 31 U/L, respectively, at baseline, increased to 141.5 U/L ( P  = 0.008) and 53 U/L ( P  = 0.505), respectively, one day after IRE, and normalized after one week. The rate of 30-day mortality of unknown relation was 8.3% (one individual experienced massive hematemesis 12 days after IRE). The median OS from diagnosis and IRE was 24.5 months and 13.5 months, respectively. The median PFS from diagnosis and IRE was 19.2 months and 8.6 months, respectively., Conclusion: For patients with LAPC, IRE appears to be a promising treatment modality with an acceptable safety profile.

Background: Endobiliary radiofrequency ablation (EB-RFA) has emerged as a palliative treatment for malignant biliary strictures (MBSs); however, concerns about complications related to thermal injury remain. In this study, we evaluated the efficacy and safety of EB-RFA with a novel catheter for MBS., Methods: Patients with inoperable cancer causing MBS were randomly assigned to either the radiofrequency ablation (RFA) group or the non-RFA group. The RFA group underwent EB-RFA at the stricture site with a temperature-controlled catheter (ELRA™; STARmed Co., Goyang, Korea) followed by deployment of a self-expanding metal stent (SEMS). For the non-RFA group, only SEMS placement was performed. The duration of stent patency, overall survival (OS), and 30-day complication rate were evaluated. This trial was registered at ClinicalTrials.gov (number NCT02646514)., Results: A total of 48 patients were enrolled (24 in each group). During a median follow-up period of 135.0 days (RFA group) and 119.5 days (non-RFA group), the 90-day stent patency rate, median duration of stent patency, and median OS were not different between the groups (58.3% vs. 45.8% [P = 0.386], 132.0 days vs. 116.0 days [P = 0.440], and 244.0 days vs. 180.0 days [P = 0.281], respectively). In the RFA group, procedure-related complications including thermal injury-related complications, such as bile duct perforation or hemobilia, were not reported. The early complication (< 7 days) rates were not different between the groups (4.2% vs. 12.5%, P = 0.609), and there were no late complications (7-30 days) in both groups., Conclusion: EB-RFA with a temperature-controlled catheter followed by SEMS placement for patients with inoperable MBS can be safe and feasible with acceptable biliary patency.

Morning stiffness is known to exert a significant impact on functional ability, quality of life, and employment status. There is an increasing need for a valid, reliable tool to comprehensively assess morning stiffness. The purpose of this study was to develop and verify a Morning Stiffness Assessment Scale. Items were developed on the basis of a framework of the conceptual attributes of morning stiffness. Validity and reliability tests were conducted on the devised scale. Eighty-five patients with rheumatoid arthritis were included to verify the devised scale. A 10-item Morning Stiffness Assessment Scale was developed. Its content and construct validities were well supported. The scale was found to have good reliability. The devised scale is simple and brief, but it provides a more comprehensive means of evaluation for morning stiffness. We believe this scale offers a clinically useful means of properly assessing morning stiffness and has potential utility for evaluating the effects of morning stiffness treatments., Competing Interests: No conflict of interest has been declared by the authors., (Copyright © 2021 by National Association of Orthopaedic Nurses.)

Objective: To investigate the prevalence of complex regional pain syndrome (CRPS), post-herpetic neuralgia (PHN), trigeminal neuralgia (TN), and diabetic neuropathy (DN), common causes of neuropathic pain encountered in pain clinics., Methods: We investigated the period prevalence rate of CRPS, PHN, TN, and DN using data from a Korean national electronic database from 2009 to 2013., Results: The prevalence of CRPS decreased slightly throughout the study period, while the prevalence of PHN increased from 2009 to 2013. The prevalence of TN was reduced over the same period. The prevalence of DN increased from 2009 to 2012 but decreased in 2013. All four neuropathic diseases were more prevalent in individuals aged over 70 years. The prevalence of CRPS, PHN, and TN were more common in women than in men, but DN showed no gender difference., Conclusion: While the prevalence of CRPS and TN has decreased in Korea, that of PHN and DN has increased. With the exception of DN, the neuropathic diseases were more prevalent in women. Further studies are necessary to investigate the risk factors and socioeconomic burden for each disease, and national efforts are essential to limit the development of these preventable neuropathic diseases.

Purpose: FOLFIRINOX is the standard therapy in patients with unresectable pancreatic cancer (PC). However, FOLFIRINOX frequently induces febrile neutropenia (FN) and neutropenia. The purpose of this study was to explore risk factors for FN and grade 4 neutropenia (NP G4) in patients receiving FOLFIRINOX for PC., Methods: We collected data on 106 patients with PC treated with first-line FOLFIRINOX between 2015 and 2017 using the Pancreatic Cancer Cohort Registry of Severance Hospital in Seoul, Korea., Results: Multivariate logistic regression analysis showed that female (OR, 3.24; P = 0.023), Eastern Cooperative Oncology Group performance status (OR, 3.70; P = 0.024), overweight (OR, 4.25; P = 0.022), and initial biliary stent insertion (OR, 4.22; P = 0.008) were significantly related to a high risk of FN. Time-dependent bias was reduced using Cox regression analysis, which revealed that female (OR, 2.29; P = 0.041), overweight (OR, 2.67; P = 0.022), and initial biliary stent insertion (OR, 2.59; P = 0.016) were statistically significant predictors. Regarding NP G4, female sex (OR, 2.90; P = 0.016) and overweight (OR, 4.07; P = 0.033) were identified as risk factors in multivariate analysis; however, in Cox regression analysis, tumor in the head of the pancreas (OR, 1.96; P = 0.027) and hemoglobin (g/dL < 12) (OR, 1.87; P = 0.049) were also identified as risk factors., Conclusion: Female sex, overweight, and initial biliary stent insertion were independent risk factors for the occurrence of FN in patients with unresectable PC treated with FOLFIRINOX.

The number of people who complain of sleep disturbances is steadily increasing. An understanding of sleep-related factors is required to address sleep problems. This survey study investigated the sleep habits and sleeping symptoms relating to the comfort and support characteristics of pillows and the relationship between sleep quality and pillow design factors. The study utilized data from 332 participating Korean adults aged 20-76 years (mean age ± SD: males, 40.4 ± 15.2; females, 42.9 ± 15.4). We developed a questionnaire that evaluated sleep habits (sleep duration, bedtime, wake-up time and sleeping position); sleeping symptoms (snoring or coughing, breathing and sleepiness during waking hours) based on the Korean version of the Pittsburgh Sleep Quality Index (PSQI-K) questionnaire; and pillow-related factors (support, comfort, fatigue, height and shape) from existing pillow studies. The average sleep duration was 6.8 h, with more than half (52%) of participants sleeping in the supine position. The overall score for sleep quality was considered poor (4.84 points on a seven-point Likert scale), with some degree of sleepiness during waking hours (4.4 points on a seven-point Likert scale). Females went to bed earlier than males and were more likely to sleep in the lateral position compared to males. The number of toss and turn or waking events during sleep increased with age, and older individuals went to sleep earlier and woke up earlier. Among the symptoms of fatigue, pain, discomfort with changing position, snoring, coughing and breathing discomfort, participants reported their highest levels of discomfort due to sleepiness after waking, and they experienced the least head pain. Participants who used a regular-type pillow had poorer satisfaction on multiple comfort and support factors (support, comfort, height suitability, shape suitability) compared with those who used a functional-type pillow. Less head fatigue, less neck fatigue and less shoulder pain had significant effects on sleep quality. To reduce neck fatigue and shoulder pain, designers should consider the height for neck support in the lateral position. To reduce neck fatigue, it is desirable to use materials like latex or memory foam that provide neck support, which can improve sleep quality. The findings of this study contribute to a better understanding of sleep habits and characteristics of pillow comfort and provide practical guidelines for better pillow designs.

Perfluorinated compounds (PFCs) are widely distributed in nature and have many applications due to their unique chemical and physicochemical properties. While, PFCs are present in soil, water, and air, their pathway for entry into the human body is circumstantially via contaminated food. The demand for seafood has been increasing. In this study, we investigated via LC-MS/MS, the content of 19 different types of PFCs in 302 samples belonging to five different categories of the typical South Korean seafood. The highest levels of PFOA, PFTrDA, PFOS, and PFPeA were found in dried seafood, canned and salted seafood, processed fish food, and seasoned laver, respectively. The levels of PFOA and PFOS were compared on the basis of various criteria including the nomenclature, biological classification, and habitat of the source of seafood. High levels of PFOA and PFOS were detected in anchovy, sea squirt, and mackerel based on the nomenclature of raw seafood, in crustaceans based on the biological classification, and in demersal organisms based on the habitat. The human intake values of PFOA and PFOS from the processed marine products in South Korea were lower than the tolerable daily intake, indicating that the consumption of these processed seafood poses no immediate harm., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Pancreatic cancer has poor prognosis because of its rapid progression and treatment resistance. Based on the results of the Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT), a combination regimen of gemcitabine with nab-paclitaxel is currently used as standard therapy for the treatment of metastatic pancreatic cancer. However, because studies in Asian populations are lacking, we investigated the treatment efficacy and safety of this combination therapy in Korean population. Patients with metastatic pancreatic cancer (n=81) treated with gemcitabine and nab-paclitaxel (1,000 and 125 mg/m 2 , respectively) as the first-line chemotherapy from January 2016 were identified using the Severance Hospital Pancreatic Cancer Cohort Registry. Treatment efficacy and treatment-related adverse events (AEs) were analyzed. The median follow-up period was 10.7 months (range, 1.5-23.3 months). Median overall survival, progression-free survival, and objective response rates were 12.1 months (95% confidence interval [CI], 10.7-not estimable), 8.4 months (95% CI, 5.0-11.8), and 46.9%, respectively. The incidence of grade ≥3 neurotoxicity and neutropenia were 18.5% and 46.9%, respectively. Febrile neutropenia and grade ≥3 gastrointestinal AEs occurred in 13 (16.0%) and 16 (19.8%) patients, respectively. Dose reductions because of AEs were required in 60.5% of patients. The combination of gemcitabine with nab-paclitaxel is an effective anti-cancer regimen in Korean population of patients with metastatic pancreatic adenocarcinoma. However, careful monitoring and management are required because of occurrence of treatment-related AEs., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background/aims: We aimed to investigate the incidence of second primary pancreatic cancer (PC) after colorectal cancer (CRC) and to identify risk factors associated with subsequent PC., Methods: The observed incidence of a subsequent PC in patients with CRC was standardized using a population with CRC from the Korean Central Cancer Registry (KCCR). The expected incidence rate of PC was obtained by assuming that the select group experienced the same cancer incidence as the corresponding general population in the KCCR., Results: The registry included 4,822 patients with CRC aged 45 to 74 years, representing 16,725.1 person-years of follow-up. Thirteen patients (0.3%) were diagnosed with a subsequent PC, and the overall age-adjusted incidence of second primary PC was 269.6 per 100,000 cases. In contrast, the overall incidence of primary PC in the general population was 18.68 per 100,000 individuals. The standardized incidence ratio of subsequent PC was 14.44, which was significantly higher in patients with CRC than in the general population. Sex, diabetes mellitus, smoking, body mass index, and a history of receiving chemotherapy as a treatment for CRC did not increase the risk of subsequent development of PC., Conclusions: The risk of a second primary PC was higher in patients with CRC. Further studies are needed to identify the risk factors and generate a screening strategy for cancer survivors.

Wilson's disease (WD) is an autosomal recessive disorder caused by ATP7B gene mutation. The frequency of WD is about 1 in 30 000 worldwide. In the present study, we screened 14 835 dried blood spots (DBSs) from asymptomatic Korean neonates and retrospectively reviewed massively parallel sequencing of 1090 control individuals to estimate carrier frequency. TaqMan real-time PCR assays were conducted to detect six mutations that account for 58.3% of mutations in Korean WD patients: c.2333G>T (p.Arg778Leu), c.2621C>T (p.Ala874Val), c.3086C>T (p.Thr1029Ile), c.3247C>T (p.Leu1083Phe), c.3556G>A (p.Gly1186Ser) and c.3809A>G (p.Asn1270Ser). We also retrospectively reviewed data from 1090 individuals with various indications other than WD for whom whole-exome or panel sequencing data were available. Mutant allele frequency based on the six most common mutations was 0.0067 among the total of 14 835 DBSs screened. Given that these six mutations account for 58.3% of mutations in Korean WD patients, the corrected mutant allele frequency is 0.0115 (95% confidence interval (CI): 0.0103-0.0128). Corresponding incidence (q 2 ) and carrier frequency (2pq) were estimated to be 1:7561 and 1:44, respectively. In retrospective data analysis of 1090 control individuals, allele frequency of pathogenic or likely pathogenic variants was 0.0096 (95% CI: 0.0063-0.0146). Corresponding carrier frequency was estimated to be 1:53. Estimated allele and carrier frequencies based on DNA screening were relatively higher than those reported previously based on clinical ascertainment.

Background: The effect of vitamin D on allergic conditions is unclear. In particular, large-scale, population-based studies examining this relationship in adult Asian populations are lacking., Objective: To evaluate the association between serum vitamin D levels and allergic conditions in the general adult Korean population., Methods: A cross-sectional study was performed by using data collected from 15,212 individuals 19 years or older who participated in the Korean National Health and Nutrition Examination Survey from 2008 to 2010. The confounder-adjusted mean serum 25-hydroxyvitamin D (25[OH]D) levels of participants with and without allergic conditions (including atopic dermatitis, asthma, allergic rhinitis, and increased total and allergen-specific serum IgE) were compared by using multiple linear regression analyses. Multiple logistic regression analyses with confounder adjustment estimated the odds ratios (ORs) for developing each condition according to adequate, inadequate, or deficient serum 25(OH)D levels., Results: After adjusting for potential confounders, mean serum 25(OH)D levels were significantly lower in participants diagnosed with atopic dermatitis than in those without this diagnosis (mean ± SE, 18.58 ± 0.29 ng/mL vs 19.20 ± 0.15 ng/mL; P = .02). Compared with participants with adequate vitamin D levels (≥20 ng/mL), confounder-adjusted ORs of atopic dermatitis were significantly higher in those with inadequate (12-19.99 ng/mL) or deficient (<12 ng/mL) levels (OR [95% CI], 1.50 [1.10-2.06] and 1.48 [1.04-2.12], respectively; P = .02). This relationship was not observed in participants with the other allergic conditions., Conclusion: Vitamin D-insufficient adult individuals within the general Korean population have an increased likelihood of atopic dermatitis, but not asthma, allergic rhinitis, or IgE sensitization., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background and Aim: Transpapillary stent insertion is the standard treatment for palliating malignant biliary obstruction. However, luminal occlusion often occurs due to sludge formation, tumor ingrowth, or tumor overgrowth. Currently, influx of duodenal contents by duodenobiliary reflux is considered a mechanism of stent obstruction. The aim of the present study was to evaluate the efficacy and safety of a metal stent with an anti-reflux valve in distal malignant biliary obstruction., Methods: Thirty-two patients diagnosed with unresectable malignant biliary obstruction were enrolled. This trial was conducted at two tertiary hospitals in Korea from June 2009 to June 2011. An uncovered metal stent (M.I.Tech) with an S-type anti-reflux valve was placed., Results: A total of 32 patients were enrolled. The technical success rate of stent insertion was 100%. The median duration of stent patency was 14.4 months. Stent occlusion occurred in 11 cases, which was caused by sludge formation in six cases, tumor ingrowth in four cases, and migration of the stent membrane in one case. During the follow-up period, there were no episodes of ascending cholangitis, acute pancreatitis, or bleeding., Conclusions: The new metal stent with an S-shaped anti-reflux valve demonstrated a relatively long duration of stent patency. This was attributable to reductions in duodenobiliary reflux by the anti-reflux valve. Also, the stent with an S-shaped anti-reflux valve is technically feasible and very safe. However, further prospective, randomized comparison studies of stents with anti-reflux valves and conventional stents are needed to evaluate the duration of stent patency., (© 2012 The Authors. Digestive Endoscopy © 2012 Japan Gastroenterological Endoscopy Society.)

The stabilization efficiencies of arsenic (As) in contaminated soil were evaluated using various additives such as limestone, steel mill slag, granular ferric hydroxide (GFH), and mine sludge collected from an acid mine drainage treatment system. The soil samples were collected from the Chungyang area, where abandoned Au-Ag mines are located. Toxicity characteristic leaching procedure, synthetic precipitation leaching procedure, sequential extraction analysis, aqua regia digestion, cation exchange capacity, loss on ignition, and particle size distribution were conducted to assess the physical and chemical characteristics of highly arsenic-contaminated soils. The total concentrations of arsenic in the Chungyang area soil ranged up to 145 mg/kg. After the stabilization tests, the removal percentages of dissolved As(III) and As(V) were found to differ from the additives employed. Approximately 80 and 40% of the As(V) and As(III), respectively, were removed with the use of steel mill slag. The addition of limestone had a lesser effect on the removal of arsenic from solution. However, more than 99% of arsenic was removed from solution within 24 h when using GFH and mine sludge, with similar results observed when the contaminated soils were stabilized using GFH and mine sludge. These results suggested that GFH and mine sludge may play a significant role on the arsenic stabilization. Moreover, this result showed that mine sludge can be used as a suitable additive for the stabilization of arsenic.