Search

Background: Late hospital arrival keeps patients with stroke from receiving recanalization therapy and is associated with poor outcomes. This study used a nationwide acute stroke registry to investigate the trends and regional disparities in prehospital delay and analyze the significant factors associated with late arrivals., Methods: Patients with acute ischemic stroke or transient ischemic attack between January 2012 and December 2021 were included. The prehospital delay was identified, and its regional disparity was evaluated using the Gini coefficient for nine administrative regions. Multivariate models were used to identify factors significantly associated with prehospital delays of >4.5 h., Results: A total of 144,014 patients from 61 hospitals were included. The median prehospital delay was 460 min (interquartile range, 116-1912), and only 36.8% of patients arrived at hospitals within 4.5 h. Long prehospital delays and high regional inequality (Gini coefficient > 0.3) persisted throughout the observation period. After adjusting for confounders, age > 65 years old (adjusted odds ratio [aOR] = 1.23; 95% confidence interval [CI], 1.19-1.27), female sex (aOR = 1.09; 95% CI, 1.05-1.13), hypertension (aOR = 1.12; 95% CI, 1.08-1.16), diabetes mellitus (aOR = 1.38; 95% CI, 1.33-1.43), smoking (aOR = 1.15, 95% CI, 1.11-1.20), premorbid disability (aOR = 1.44; 95% CI, 1.37-1.52), and mild stroke severity (aOR = 1.55; 95% CI, 1.50-1.61) were found to independently predict prehospital delays of >4.5 h., Conclusion: Prehospital delays were lengthy and had not improved in Korea, and there was a high regional disparity. To overcome these inequalities, a deeper understanding of regional characteristics and further research is warranted to address the vulnerabilities identified., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Importance: Limited data suggest that early palliative care (EPC) improves quality of life (QOL) and survival in patients with advanced cancer., Objective: To evaluate whether comprehensive EPC improves QOL; relieves mental, social, and existential burdens; increases survival rates; and helps patients develop coping skills., Design, Setting, and Participants: This nonblinded randomized clinical trial (RCT) recruited patients from 12 hospitals in South Korea from September 2017 to October 2018. Patients aged 20 years or older with advanced cancer who were not terminally ill but for whom standard chemotherapy has not been effective were eligible. Participants were randomized 1:1 to the control (receiving usual supportive oncological care) or intervention (receiving EPC with usual oncological care) group. Intention-to-treat data analysis was conducted between September and December 2022., Interventions: The intervention group received EPC through a structured program of self-study education materials, telephone coaching, and regular assessments by an integrated palliative care team., Main Outcomes and Measures: The primary outcome was the change in overall QOL score (assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Care) from baseline to 24 weeks after enrollment, with evaluations also conducted at 12 and 18 weeks. Secondary outcomes were social and existential burdens (assessed with the McGill Quality of Life Questionnaire) as well as crisis-overcoming capacity and 2-year survival., Results: A total of 144 patients (83 males [57.6%]; mean [SD] age, 60.7 (7.2) years) were enrolled, of whom 73 were randomized to the intervention group and 71 to the control group. The intervention group demonstrated significantly greater changes in scores in overall health status or QOL from baseline, especially at 18 weeks (11.00 [95% CI, 0.78-21.22] points; P = .04; effect size = 0.42). However, at 12 and 24 weeks, there were no significant differences observed. Compared with the control group, the intervention group also showed significant improvement in self-management or coping skills over 24 weeks (20.51 [95% CI, 12.41-28.61] points; P < .001; effect size = 0.93). While the overall survival rate was higher in the intervention vs control group, the difference was not significant. In the intervention group, however, those who received 10 or more EPC interventions (eg, telephone coaching sessions and care team meetings) showed a significantly increased probability of 2-year survival (53.6%; P < .001)., Conclusions and Relevance: This RCT demonstrated that EPC enhanced QOL at 18 weeks; however, no significant improvements were observed at 12 and 24 weeks. An increased number of interventions sessions was associated with increased 2-year survival rates in the intervention group., Trial Registration: ClinicalTrials.gov Identifier: NCT03181854.

Objective: To develop a deep-learning-based bone age prediction model optimized for Korean children and adolescents and evaluate its feasibility by comparing it with a Greulich-Pyle-based deep-learning model., Materials and Methods: A convolutional neural network was trained to predict age according to the bone development shown on a hand radiograph (bone age) using 21036 hand radiographs of Korean children and adolescents without known bone development-affecting diseases/conditions obtained between 1998 and 2019 (median age [interquartile range {IQR}], 9 [7-12] years; male:female, 11794:9242) and their chronological ages as labels (Korean model). We constructed 2 separate external datasets consisting of Korean children and adolescents with healthy bone development (Institution 1: n = 343; median age [IQR], 10 [4-15] years; male: female, 183:160; Institution 2: n = 321; median age [IQR], 9 [5-14] years; male: female, 164:157) to test the model performance. The mean absolute error (MAE), root mean square error (RMSE), and proportions of bone age predictions within 6, 12, 18, and 24 months of the reference age (chronological age) were compared between the Korean model and a commercial model (VUNO Med-BoneAge version 1.1; VUNO) trained with Greulich-Pyle-based age as the label (GP-based model)., Results: Compared with the GP-based model, the Korean model showed a lower RMSE (11.2 vs. 13.8 months; P = 0.004) and MAE (8.2 vs. 10.5 months; P = 0.002), a higher proportion of bone age predictions within 18 months of chronological age (88.3% vs. 82.2%; P = 0.031) for Institution 1, and a lower MAE (9.5 vs. 11.0 months; P = 0.022) and higher proportion of bone age predictions within 6 months (44.5% vs. 36.4%; P = 0.044) for Institution 2., Conclusion: The Korean model trained using the chronological ages of Korean children and adolescents without known bone development-affecting diseases/conditions as labels performed better in bone age assessment than the GP-based model in the Korean pediatric population. Further validation is required to confirm its accuracy., Competing Interests: Jaewon Lee, Jinkyeong Sung, and Byeonguk Bae are employee of VUNO, and Kyu-Hwan Jung is shareholder of VUNO Inc., however this do not affect to publish this manuscript. All remaining authors have declared no conflicts of interest., (Copyright © 2023 The Korean Society of Radiology.)

Purpose: The treatment of male breast cancer (MBC) has been extrapolated from female breast cancer (FBC) because of its rarity despite their different clinicopathologic characteristics. We aimed to investigate the distribution of intrinsic subtypes based on immunohistochemistry, their clinical impact, and treatment pattern in clinical practice through a multicenter study in Korea., Materials and Methods: We retrospectively analyzed clinical data of 248 MBC patients from 18 institutions across the country from January 1995 to July 2016., Results: The median age of MBC patients was 63 years (range, 25 to 102 years). Among 148 intrinsic subtype classified patients, 61 (41.2%), 44 (29.7%), 29 (19.5%), and 14 (9.5%) were luminal A, luminal B, human epidermal growth factor receptor 2, and triple-negative breast cancer, respectively. Luminal A subtype showed trends for superior survival compared to other subtypes. Most hormone receptor-positive patients (166 patients, 82.6%) received adjuvant endocrine treatment. Five-year completion of adjuvant endocrine treatment was associated with superior disease-free survival (DFS) in patients classified with an intrinsic subtype (hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.04 to 0.49; p=0.002) and in all patients (HR, 0.16; 95% CI, 0.05 to 0.54; p=0.003)., Conclusion: Distribution of subtypes of MBC was similar to FBC and luminal type A was most common. Overall survival tended to be improved for luminal A subtype, although there was no statistical significance. Completion of adjuvant endocrine treatment was associated with prolonged DFS in intrinsic subtype classified patients. MBC patients tended to receive less treatment. MBC patients should receive standard treatment according to guidelines as FBC patients.

Objective: Many pharmacokinetic studies of lacosamide (LCM) have been reported, but no large-scale clinical study has been conducted on genetic polymorphisms that affect the metabolism of LCM. Therefore, we designed a pharmacogenetic study of LCM to explore the effect of genetic polymorphisms on serum LCM concentration. We evaluated the pharmacodynamic characteristics of LCM, including clinical efficacy and toxicity., Methods: Adult patients with epilepsy who received LCM at Seoul National University Hospital were enrolled. Blood samples were obtained from 115 patients taking LCM for more than 1 month with unchanged doses and were used to analyze the serum LCM concentration, the concentration/dose (C/D) ratio and the single nucleotide polymorphisms (SNPs) of the cytochrome P450 (CYP)2C9 and CYP2C19 genes. In addition, clinical information-including efficacy, toxicity, and concomitant drugs-was collected., Results: The serum LCM concentration showed a linear correlation with the daily dose (r = .66, p < .001). In genetic analysis, 43 patients (38.7%) were extensive metabolizers (EMs), 51 (45.9%) were intermediate metabolizers (IMs), and 17 (15.3%) were poor metabolizers (PMs). In the group comparison, mean serum concentrations and the C/D ratio showed significant differences between the three groups (p = .01 and p < .001, respectively). The C/D ratios of IM (27.78) and PM (35.6) were 13% and 39% higher than those of EM (25.58), respectively. In the pharmacodynamic subgroup analysis, patients in the ineffective LCM group had significantly lower serum concentrations (6.39 ± 3.25 vs. 8.44 ± 3.68 μg/ml, p = .024), whereas patients with adverse events had higher serum concentrations than those without adverse events (11.03 ± 4.32 vs. 7.4 ± 3.1 μg/ml, p < .001). Based on this, we suggest a reference range for LCM in the Korean population (6-9 μg/ml)., Significance: Genetic polymorphisms of the CYP2C19 gene affect the serum LCM concentration. Because efficacy and toxicity are apparently related to serum LCM levels, the genetic phenotype of CYP2C19 should be considered when prescribing LCM for patients with epilepsy., (© 2022 International League Against Epilepsy.)

Objective: The risk of gastric cancer based on a family history of gastric cancer remains unclear. The purpose of this study was to investigate the relationship between gastric cancer and family history of gastric cancer within a large cohort in Korea., Methods: In total 211 708 participants were recruited in the Korean Genome and Epidemiology Study during 2001-2013, and divided into a group with a self-reported personal history of gastric cancer ( n  = 930) and a 1:40 matched control group ( n  = 37 200). We examined the family history of gastric cancer in first-degree relatives for cross-sectional analysis. Logistic regression was used to estimate the odds ratios (ORs) of gastric cancer according to family history, using four models that were adjusted for different confounding variables, including the interaction among a family history of gastric cancer., Results: After matching the two groups for age and sex, the gastric cancer group had a significantly higher proportion of family history in each relative than the controls ( P  < 0.001). In the adjusted model, the ORs [95% confidence interval (CI)] for gastric cancer with a history of an affected father, mother and sibling were 1.80 (1.38-2.34), 1.95 (1.42-2.69) and 2.98 (2.31-3.83), respectively, compared with those in the control group. There was no statistically significant interaction among a family history of gastric cancer in each relative., Conclusion: A history of gastric cancer in siblings, among first-degree relatives, is strongly associated with an increased risk of gastric cancer. Regular follow-up and early treatment are recommended for those with a family history of gastric cancer., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has led to changes in stroke patients' healthcare use. This study evaluated changes in Korean stroke patients' health-seeking behaviors and stroke care services using data from the Korean Stroke Registry (KSR)., Methods: We reviewed data from patients with acute stroke and transient ischemic attack (TIA) during 2019 (before COVID-19 period) and 2020 (COVID-19 period). Outcomes included patient characteristics, time from stroke onset to hospital arrival, and in-hospital stroke pathways. Subgroup analyses were performed for an epidemic region (Daegu city and Gyeongsangbuk-do region, the D-G region)., Results: The study included 1,792 patients from the pre-COVID-19 period and 1,555 patients from the COVID-19 period who visited hospitals that contribute to the KSR. During the COVID-19 period, the D-G region had two-thirds the number of cases (vs. the pre-CO-VID-19 period) and a significant decrease in the proportion of patients with TIA (9.97%-2.91%). Unlike other regions, the median onset-to-door time increased significantly in the D-G region (361 min vs. 526.5 min, p = 0.016), and longer onset-to-door times were common for patients with mild symptoms and who were in their 60s or 70s. The number of patients who underwent intravenous thrombolysis also decreased during the COVID-19 period, although the treatment times were not significantly different between the 2 periods., Discussion/conclusion: Korean stroke patients in a CO-VID-19 epidemic region exhibited distinct changes in health-seeking behaviors. Appropriate triage system and public education regarding the importance of early treatment are needed during the COVID-19 pandemic., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Background Previous studies assessing the effects of computer-aided detection on observer performance in the reading of chest radiographs used a sequential reading design that may have biased the results because of reading order or recall bias. Purpose To compare observer performance in detecting and localizing major abnormal findings including nodules, consolidation, interstitial opacity, pleural effusion, and pneumothorax on chest radiographs without versus with deep learning-based detection (DLD) system assistance in a randomized crossover design. Materials and Methods This study included retrospectively collected normal and abnormal chest radiographs between January 2016 and December 2017 ( https://cris.nih.go.kr/ ; registration no. KCT0004147) . The radiographs were randomized into two groups, and six observers, including thoracic radiologists, interpreted each radiograph without and with use of a commercially available DLD system by using a crossover design with a washout period. Jackknife alternative free-response receiver operating characteristic (JAFROC) figure of merit (FOM), area under the receiver operating characteristic curve (AUC), sensitivity, specificity, false-positive findings per image, and reading times of observers with and without the DLD system were compared by using McNemar and paired t tests. Results A total of 114 normal (mean patient age ± standard deviation, 51 years ± 11; 58 men) and 114 abnormal (mean patient age, 60 years ± 15; 75 men) chest radiographs were evaluated. The radiographs were randomized to two groups: group A ( n = 114) and group B ( n = 114). Use of the DLD system improved the observers' JAFROC FOM (from 0.90 to 0.95, P = .002), AUC (from 0.93 to 0.98, P = .002), per-lesion sensitivity (from 83% [822 of 990 lesions] to 89.1% [882 of 990 lesions], P = .009), per-image sensitivity (from 80% [548 of 684 radiographs] to 89% [608 of 684 radiographs], P = .009), and specificity (from 89.3% [611 of 684 radiographs] to 96.6% [661 of 684 radiographs], P = .01) and reduced the reading time (from 10-65 seconds to 6-27 seconds, P < .001). The DLD system alone outperformed the pooled observers (JAFROC FOM: 0.96 vs 0.90, respectively, P = .007; AUC: 0.98 vs 0.93, P = .003). Conclusion Observers including thoracic radiologists showed improved performance in the detection and localization of major abnormal findings on chest radiographs and reduced reading time with use of a deep learning-based detection system. © RSNA, 2021 Online supplemental material is available for this article.

Background: Although international guidelines recommend palliative care approaches for many serious illnesses, the palliative needs of patients with serious illnesses other than cancer are often unmet, mainly due to insufficient prognosis-related discussion. We investigated physicians' and the general public's respective attitudes toward prognostic disclosure for several serious illnesses., Methods: We conducted a cross-sectional survey of 928 physicians, sourced from 12 hospitals and the Korean Medical Association, and 1,005 members of the general public, sourced from all 17 administrative divisions in Korea., Results: For most illnesses, most physicians (adjusted proportions - end-organ failure, 99.0%; incurable genetic or neurologic disease, 98.5%; acquired immune deficiency syndrome [AIDS], 98.4%; stroke or Parkinson's disease, 96.0%; and dementia, 89.6%) and members of the general public (end-organ failure, 92.0%; incurable genetic or neurologic disease, 92.5%; AIDS, 91.5%; stroke or Parkinson's disease, 92.1%; and dementia, 86.9%) wanted to be informed if they had a terminal prognosis. For physicians and the general public, the primary factor to consider when disclosing terminal status was "the patient's right to know his/her condition" (31.0%). Yet, the general public was less likely to prefer prognostic disclosure than physicians. Particularly, when their family members were patients, more than 10% of the general public did not want patients to be informed of their terminal prognosis. For the general public, the main reason for not disclosing prognosis was "psychological burden such as anxiety and depression" (35.8%), while for the physicians it was "disclosure would have no beneficial effect" (42.4%)., Conclusion: Most Physicians and the general public agreed that disclosure of a terminal prognosis respects patient autonomy for several serious illnesses. The low response rate of physicians might limit the generalizability of the results., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2020 The Korean Academy of Medical Sciences.)

Importance: An increasing number of patients with breast cancer receiving neoadjuvant chemotherapy (NACT) undergo immediate breast reconstruction (IBR) with nipple-sparing mastectomy (NSM) or skin-sparing mastectomy (SSM) as surgical treatment. However, the oncologic efficacy and safety of this treatment sequencing strategy is unclear., Objective: To compare the long-term oncologic outcomes of IBR with NSM/SSM and conventional mastectomy (CM) alone for breast cancer in the NACT setting., Design, Setting, and Participants: A retrospective, propensity score-matched case-control study was conducted at Asan Medical Center, Seoul, Korea. A total of 1266 patients with breast cancer who underwent NACT followed by mastectomy with or without breast reconstruction between January 1, 2010, and November 30, 2016, were included. Data analysis was performed from July 1, 2019, to January 24, 2020. After propensity score matching, 323 patients who underwent IBR with NSM/SSM and 323 who underwent CM alone were selected for comparison of long-term oncologic outcomes., Main Outcomes and Measures: The 5-year local recurrence-free survival, disease-free survival, distant metastasis-free survival, and overall survival rates were calculated using the Kaplan-Meier method and compared using log-rank tests. Hazard ratios (HRs) and 95% CIs were estimated using the Cox proportional hazards regression model., Results: After matching, the median follow-up periods were 67 (range, 17-125) months for the IBR group and 68 (range, 17-126) months for the CM-alone group. Median age of the women in the IBR group was 42 (range, 23-72) years; median age of those in the CM-alone group was 46 (range, 30-75) years. No significant differences were observed between the IBR and CM-alone groups in local recurrence (3.7% vs 3.4%; P = .83), regional recurrence (7.1% vs 5.3%; P = .33), or distant metastasis (17.3% vs 18.6%; P = .68) rates. There was also no significant difference between the IBR and CM-alone groups in 5-year local recurrence-free survival (95.6% vs 96.7%; HR, 1.124; 95% CI, 0.495-2.549; P = .78), disease-free survival (76.5% vs 79.9%; HR, 1.089; 95% CI, 0.790-1.500; P = .60), distant metastasis-free survival (82.5% vs 82.5%; HR, 0.941; 95% CI, 0.654-1.355; P = .74), or overall survival (92.0% vs 89.3%; HR, 0.847; 95% CI, 0.530-1.353; P = .49) rates., Conclusions and Relevance: The long-term oncologic outcomes of IBR with NSM/SSM for breast cancer in this study appeared to be comparable to those of CM alone after NACT, suggesting the feasibility of IBR with NSM/SSM in the NACT setting.

Perampanel (PER) is a new-generation antiepileptic drug that has an occasional but significant shortcoming, psychiatric adverse effects (PAEs). Recently, antiepileptic drug-related adverse reactions, such as skin rash and even PAEs, have been discovered to be correlated with certain human leukocyte antigen (HLA) types. Thus, we aimed to analyze specific HLA alleles as risk factors for PER-PAEs. We prospectively enrolled 17 patients with epilepsy who were prescribed PER between May 2016 and Jul 2018 at Seoul National University Hospital and developed PAEs while taking PER. Their HLA types were analyzed compared to those of 19 patients in the PAE-tolerant group and the general Korean population. In silico docking was performed with two different computational programs, AutoDock Vina and SwissDock, to theoretically evaluate the binding affinity of PER in the grooves of the specific HLA alleles. The HLA-DQB1*06:01, DRB1*08:03, and B*54:01 alleles were significantly associated with the patients who developed PER-PAEs compared with the general Korean population (odds ratio [OR] 3.94, p = 0.008, OR 9.24, p = 0.037, and OR 3.25, p = 0.041, respectively). As a haplotype, the combination of the three alleles was significantly more frequent in the PER-PAE group than in both the PER-tolerant group and the general Korean population. DQB1*06:01 and B*54:01 also demonstrated higher docking scores with PER than other alleles. This is the first study to analyze the association of PER-PAEs with specific HLA genotypes. Our results suggest that an HLA-associated genetic predisposition and a possible immunological mechanism are involved in the occurrence of PER-PAEs.

Background: Lifestyle changes and evolving healthcare practices in Korea have influenced disease patterns and medical care. Since strokes have high disease burden in countries with aging populations, it is necessary to evaluate the associated recent disease characteristics and patient care patterns. The Korean Stroke Registry is a nationwide, multicenter, prospective, hospital-based stroke registry in Korea used to monitor these changes across the population., Aims: We aimed to evaluate the recent status of clinical characteristics and management of stroke cases in order to identify changes in the Korean population across time., Methods: This study used Korean Stroke Registry data from patients experiencing ischemic stroke or transient ischemic attack patients, between 2014 and 2018. We analyzed data on demographics, risk factors, stroke subtypes, and treatments that included thrombolysis., Results: A total of 39,291 patients (mean age 68.0 ± 13.0, 58.3% male) were analyzed. The proportions of hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, and prior stroke were 63.4%, 30.9%, 27.7%, 19.4%, and 17.1%, respectively. In the stroke subtype analysis, the frequency of large artery atherosclerosis was highest (32.6%), followed by cardioembolism (21.3%) and small vessel occlusion (19.9%). Acute reperfusion therapy was conducted in 15.3% of cases (11.7% using intravenous tPA and 7.3% using intra-arterial thrombectomy). Intra-arterial thrombectomy also demonstrated a steep increasing trend over time (RR 1.095 (1.060-1.131), p  < 0.001)., Conclusions: This study provided analysis of nationwide, hospital-based, quality-controlled data from the Korean Stroke Registry database regarding changes in the characteristics, risk factors, and treatments of strokes in Korea.

Objective: Epidemiological studies on inflammatory myopathies (IMs) show widely variable results, and studies on Asians are lacking. Despite emerging interest in the cardiovascular disease (CVD) risk associated with IMs, the prevalence of CVD in IM patients and its impact on mortality remain unclear. We conducted a nationwide, population-based study on the incidence, mortality, and associated major CVD events of IMs in the Republic of Korea over 11 years., Method: Using the nationwide, population-based National Health Insurance claims database and the Rare Intractable Disease registration programme, we estimated incidence, mortality, and CVD occurrence. Survival was examined using the Kaplan-Meier method. Mortality rate in IMs with CVD was analysed by Cox proportional hazards regression., Results: There were 3014 incident cases, 640 of whom died during the study period. The mean annual incidence was 7.16/10 6 . Dermatomyositis (DM) and polymyositis (PM) had 5 year survival rates of 76.8% and 79.3%, respectively. Cardiovascular events occurred in 155 patients and 40.6% of IM patients with CVD died. Acute myocardial infarction in men had the highest risk of any CVD event in both DM [standardized incidence ratio (SIR) 4.2, 95% confidence interval (95% CI) 2.4-7.2] and PM (SIR 3.5, 95% CI 1.8-7.0). Haemorrhagic stroke had the highest hazard ratio (HR) in both DM (HR 2.31, 95% CI 1.13-4.70) and PM patients (HR 2.10, 95% CI 1.03-4.27) compared with the general population with CVD., Conclusion: We found persistently low incidence, poor survival, and high major CVD incidence in IMs, and increased mortality in IMs with CVD.

Background: Neurocritical care by dedicated neurointensivists may improve outcomes of critically ill patients with severe brain injury. In this study, we aimed to validate whether neurointensive care could improve the outcome in patients with critically ill acute ischemic stroke using the linked big dataset on stroke in Korea., Methods: We included 1,405 acute ischemic stroke patients with mechanical ventilator support in the intensive care unit after an index stroke. Patients were retrieved from linking the Clinical Research Center for Stroke Registry and the Health Insurance Review and Assessment Service data from the period between January 2007 and December 2014. The outcomes were mortality at discharge and at 3 months after an index stroke. The main outcomes were compared between the centers with and without dedicated neurointensivists., Results: Among the included patients, 303 (21.6%) were admitted to the centers with dedicated neurointensivists. The patients treated by dedicated neurointensivists had significantly lower in-hospital mortality (18.3% vs. 26.8%, P = 0.002) as well as lower mortality at 3-month (38.0% vs. 49.1%, P < 0.001) than those who were treated without neurointensivists. After adjusting for confounders, a treatment without neurointensivists was independently associated with higher in-hospital mortality (odds ratio [OR], 1.59; 95% confidence intervals [CIs], 1.13-2.25; P = 0.008) and 3-month mortality (OR, 1.48; 95% CIs, 1.12-1.95; P = 0.005)., Conclusion: Treatment by dedicated neurointensivists is associated with lower in-hospital and 3-month mortality using the linked big datasets for stroke in Korea. This finding stresses the importance of neurointensivists in treating patients with severe ischemic stroke., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2020 The Korean Academy of Medical Sciences.)

Background/aims: Although the diarrheal disease caused by Campylobacter bacteria has been continuously increasing in Korea, there has been limited study on the clinical aspects of Campylobacter enteritis in adults in Korea. The purpose of this study was to analyze the clinical features and characteristics of adult patients with Campylobacter enteritis., Methods: This retrospective study included patients diagnosed with Campylobacter enterocolitis at Nowon Eulji University Hopsital between January 2016 and December 2017. Campylobacter enterocolitis was diagnosed through polymerase chain reaction of stools from patients with acute diarrhea., Results: Among 630 hospitalized patients with acute diarrhea, Campylobacter enterocolitis was diagnosed in 88 patients (14.0%). The mean age was 37.9±19.1 years. Campylobacter enterocolitis was most prevalent in the summer (52 patients, 59.1%). Patients exhibited more than 10 times of diarrhea in 36 (40.9%), high fever above 39°C in 19 (21.59%), and abdominal pain above 5 points on the numeric rating scale in 23 (26.14%) cases. In abdominal CT scan, pancolitis was found in 58 patients (65.9%). Small intestine was involved in 37 patients (42.4%). Mean CRP was 10.14 mg/dL (range 0.72-32.27 mg/dL). The duration of diarrhea after antibiotics treatment was 2.34±1.51 days in the ciprofloxacin treatment group and 2.26±1.71 days in the 3rd cephalosporin treatment group., Conclusions: Campylobacter enterocolitis was common during summer. Commonly healthy young adults were hospitalized due to severe symptoms of Campylobacter enterocolitis. Whole colon and small bowel were frequently involved. Most patients were treated with antibiotics, and the efficacy of 3rd cephalosporin treatment was not inferior to that of ciprofloxacin treatment.

The clinical utility of BRCA1/2 genotyping was recently extended from the selection of subjects at high risk for hereditary breast and ovary cancer to the identification of candidates for poly (ADP-ribose) polymerase (PARP) inhibitor treatment. This underscores the importance of accurate interpretation of BRCA1/2 genetic variants and of reducing the number of variants of uncertain significance (VUSs). Two recent studies by Findlay et al. and Starita et al. introduced high-throughput functional assays, and proactively analyzed variants in specific regions regardless of whether they had been previously observed. We retrospectively reviewed all BRCA1 and BRCA2 germline genetic test reports from patients with breast or ovarian cancer examined at Asan Medical Center (Seoul, Korea) between September 2011 and December 2018. Variants were assigned pathogenic or benign strong evidence codes according to the functional classification and were reclassified according to the ACMG/AMP 2015 guidelines. Among 3684 patients with available BRCA1 and BRCA2 germline genetic test reports, 429 unique variants (181 from BRCA1) were identified. Of 34 BRCA1 variants intersecting with the data reported by Findlay et al., three missense single-nucleotide variants from four patients (0.11%, 4/3684) were reclassified from VUSs to likely pathogenic variants. Four variants scored as functional were reclassified into benign or likely benign variants. Three variants that overlapped with the data reported by Starita et al. could not be reclassified. In conclusion, proactive high-throughput functional study data are useful for the reclassification of clinically observed VUSs. Integrating additional evidence, including functional assay results, may help reduce the number of VUSs.

Methods for distinguishing catheter-related candidemia (CRC) from non-CRC before catheter removal remain limited. We thus evaluated the diagnostic performance of differential time to positivity (DTP) to diagnose CRC in neutropenic cancer patients with suspected CRC. Of the 35 patients enrolled, 15 (43%) with CRC (six definite and nine probable) and 17 (49%) with non-CRC were finally analyzed. Based on the receiver operating characteristic curve, the optimal cutoff value of DTP for diagnosing CRC was ≥1.45 hours with the sensitivity 80% (95% confidence interval [CI], 51-95) and specificity 100% (95% CI, 80-100), respectively., (© The Author(s) 2019. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

As the prevalence of gout and hyperuricemia increases, the comorbidities of gout and hyperuricemia have become a public health burden. In particular, risks of cardiovascular disease (CVD)-related complications are increasing. However, a few guidelines exist for the management of hyperuricemia. This cross-sectional study aimed to investigate the association of serum uric acid with CVD risk in the general population of Korean adults. We examined cross-sectional data from the first and second years of the seventh Korea National Health and Nutrition Examination Survey 2016-2017. Among 16,277 participants, 8781 were analyzed. We estimated the CVD risk using a 10-year CVD risk score prediction formula. There was a significant association of serum uric acid with 10-year CVD risk scores after adjusting for physical activity, body mass index, serum creatinine, and alcohol consumption in both sexes ( p < 0.001). In the fitted fractional polynomial model, an approximate U-shaped association between serum uric acid levels and 10-year CVD risk scores was found in men. At the serum uric acid level of 6.9 mg/dL, the CVD risk was lowest. An approximate J-shaped association between serum uric acid levels and 10-year CVD risk scores was found in women. Our study showed that hyperuricemia was associated with an increased CVD risk. Hypouricemia was also associated with an increased CVD risk in men. We, therefore, recommend proper management of uric acid levels in the general population to reduce CVD risks.

Strain IMCC1322 was isolated from a surface water sample from the East Sea of Korea. Based on 16S rRNA analysis, IMCC1322 was found to belong to the OCS28 sub-clade of SAR116. The cells appeared as short vibrioids in logarithmic-phase culture, and elongated spirals during incubation with mitomycin or in aged culture. Growth characteristics of strain IMCC1322 were further evaluated based on genomic information; proteorhodopsin (PR), carbon monoxide dehydrogenase, and dimethylsulfoniopropionate (DMSP)-utilizing enzymes. IMCC1322 PR was characterized as a functional retinylidene protein that acts as a light-driven proton pump in the cytoplasmic membrane. However, the PR-dependent phototrophic potential of strain IMCC1322 was only observed under CO-inhibited and nutrient-limited culture conditions. A DMSP-enhanced growth response was observed in addition to cultures grown on C 1 compounds like methanol, formate, and methane sulfonate. Strain IMCC1322 cultivation analysis revealed biogeochemical processes characteristic of the SAR116 group, a dominant member of the microbial community in euphotic regions of the ocean. The polyphasic taxonomy of strain IMCC1322 is given as Candidatus Puniceispirillum marinum, and was confirmed by chemotaxonomic tests, in addition to 16S rRNA phylogeny and cultivation analyses.

Osteoarthritis (OA) has a multifactorial etiology that includes oxidative stress. Oxidative balance score (OBS) is a well-known indicator of oxidative stress. However, the association between OBS and OA has not been assessed. Thus, this study aimed to investigate the associations of OBS with OA and quality of life (QOL) in patients with OA.By using data from the Korea National Health and Nutrition Examination Survey VI, patients previously diagnosed and/or treated by a physician were considered to have OA regardless of the affected joints. The control group was defined as participants without any form of chronic arthritis. OBS was calculated by combining 10 pro-oxidant and antioxidant factors through a baseline nutritional and lifestyle assessment. Higher OBS scores indicated a predominance of antioxidant exposure. Multivariable logistic regression was used to estimate the adjusted odds ratios (ORs) for OA, and the EuroQoL five-dimensional questionnaire (EQ5D) was used in patients with OA after adjusting for demographic factors and comorbidities.Among the 14,930 participants, 296 patients with OA, and 1,309 controls were included in the analysis. In the age- and sex-adjusted model, the OR of the total OBS for OA was significant. In the full model adjusted for age, sex, education, income, and comorbidities, the total OBS for OA was not significant. Only the non-dietary pro-oxidant OBS had a significant inverse association with OA. The patients with OA who had a high EQ5D score had a higher total OBS than those with a low EQ5D score. The OR of the total OBS for a high EQ5D score was 1.14 in the multivariable logistic regression model. As we analyzed the OBS as a categorical variable (reference = Q1), the ORs of the Q2, Q3, and Q4 (highest) total OBS were 1.43, 2.71, and 2.22, respectively.In the fully adjusted model, the total OBS was not associated with OA. However, a positive association was observed between the total OBS and QOL in the patients with OA, indicating that antioxidative status was associated with better QOL in patients with OA.

The prevalence of human taeniasis has decreased in Korea. The stool egg positive proportion decreased from 1.9% in 1971 to 0% in 2004 in nationwide surveys. The neurocysticercosis (NCC) is also presumed to decrease. However, detailed information regarding the recent status of NCC in Korea is lacking. We retrospectively reviewed NCC cases from 1990 to 2016 at Asan Medical Center, a 2700-bed tertiary referral hospital in Korea. We identified patients based on clinical symptoms, brain imaging, pathology and serological assay. The cases were classified as parenchymal, extraparenchymal, and mixed NCC. Eighty-one patients were included in the analysis. The mean age was 54.5 years, and 79.0% were male. The number of NCC cases was highest from 1995 to 1999, and continuously decreased thereafter. Forty (49.4%) patients had parenchymal NCC, while 25 (30.9%) patients had extraparenchymal NCC, and 16 (19.8%) patients had mixed NCC. The seizure and headache were most common symptom of parenchymal NCC and extraparenchymal NCC respectively. Hydrocephalus was more common in extraparenchymal NCC, and patients with extraparenchymal NCC were more likely to require a ventriculoperitoneal shunt. Cases of NCC are decreasing accordingly with human taeniasis and lesion location was the most important determinant of clinical presentation and outcome of NCC in Korea.

Background: A phase II clinical trial of the comparison between eribulin plus gemcitabine (EG) and paclitaxel plus gemcitabine (PG) as first-line chemotherapy for patients with metastatic breast cancer (MBC) found that the EG regimen was less neurotoxic, but was similar in efficacy to the PG regimen. In the present study, we analyzed functional assessment of cancer therapy-taxane (FACT-Taxane) questionnaires from patients in this clinical trial to determine their quality of life (QoL)., Methods: QoL was assessed using the Korean version of the FACT-Taxane questionnaires. After baseline assessment, QoL was assessed every 2 cycles for 12 cycles and every 3 cycles thereafter. The linear mixed model was used to evaluate the difference in QoL between the EG and PG arms., Results: Of the 118 enrolled patients, 117 responded to the FACT-Taxane questionnaires at baseline, 1 in the PG arm did not. Baseline QoL scores were not different between the EG and PG arms. During treatment, taxane subscale scores were significantly higher in the PG arm than in the EG arm after 2-13 cycles of chemotherapy (all P < 0.05), except for the 11th cycle. Neuropathy-specific analysis showed that patients in the PG arm had earlier and more severe neuropathic symptoms than those in the EG arm (P < 0.001)., Conclusions: In our QoL analysis, the EG regimen delayed and decreased neuropathy as compared with the PG regimen. Therefore, eribulin would be a reasonable substitute for paclitaxel as first-line chemotherapy for MBC.

Background: A biopsy of first recurrence or metastatic disease is recommended to re-evaluate oestrogen receptor status in patients with breast cancer and to select appropriate treatment. However, retesting for oestrogen receptor status with rebiopsy is not always feasible, depending on lesion location and the risk associated with biopsy, and in these cases clinicians continue to treat patients according to the oestrogen receptor status of the primary tumour. Consequently suboptimal therapy might be offered to these patients. We assessed the diagnostic accuracy and safety of 16α-[ 18 F]fluoro-17β-oestradiol ( 18 F-FES) PET-CT to assess oestrogen receptor status in patients with recurrent or metastatic breast cancer., Methods: We did a prospective cohort study at the Asan Medical Center, Seoul, South Korea. Eligible patients had breast cancer, with first recurrence or metastatic disease at presentation, were 19 years or older, and had an Eastern Cooperative Oncology Group performance status of 0-2. The primary objective was to show the agreement between qualitative 18 F-FES PET-CT interpretation and the results of oestrogen receptor expression by immunohistochemical assay, a non-reference standard test. Whole-body 18 F-FES PET-CT imaging was done after intravenous injection of 111-222 MBq of 18 F-FES, with dosing primarily determined by radiation dosimetry analysis. 18 F-FES uptake above background intensity was interpreted as positive. Efficacy was assessed in all patients with histologically confirmed recurrent or metastatic breast cancer who received 18 F-FES and had PET-CT images available (intention-to-diagnose analysis), and safety was assessed in all patients who received 18 F-FES. This study is registered with ClinicalTrials.gov, number NCT01986569., Findings: Between Nov 27, 2013, and Nov 10, 2016, 93 patients were enrolled. Of the 85 patients included in the efficacy analysis, 47 (55%) were oestrogen receptor-positive and 38 (45%) were oestrogen receptor-negative. Positive status percent agreement between the 18 F-FES PET-CT results and oestrogen receptor status by immunohistochemical assay was 76·6% (95% CI 62·0-87·7) and the negative status percent agreement was 100·0% (90·8-100·0). Patients who were oestrogen receptor-positive and had a positive 18 F-FES PET-CT result had a significantly higher progesterone receptor expression than those who were oestrogen receptor-positive and had a negative 18 F-FES PET-CT result (23 [68%] of 34 patients vs 0 of 11 patients; p<0·0001). The most common adverse event was procedural pain in nine (10%) of 90 patients injected with 18 F-FES. No adverse events were related to the study drug except injection site pain in one (1%) patient. No serious adverse events were recorded., Interpretation: The high negative percent agreement between 18 F-FES PET-CT and oestrogen receptor status by immunohistochemical assay in this cohort suggests that positive 18 F-FES uptake by recurrent or metastatic oestrogen receptor-positive breast cancer lesions could be an alternative to oestrogen receptor assays in this setting. Staging assessment should include 18 F-FES PET-CT when retesting oestrogen receptor status is not feasible., Funding: Asan Institute for Life Sciences, Ministry of Health and Welfare, South Korea., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Essential thrombocythemia (ET) is known to be associated with an increased vascular event, but the stroke patterns and prognosis have not been studied., Methods: Between January 2013 and December 2017, acute ischemic stroke patients with ET who were admitted to two tertiary hospital stroke centers in Seoul, Korea were included. We retrospectively reviewed their clinical, laboratory and imaging data. Stroke mechanism was determined as ET-only when no atherosclerotic, cardioembolic, or lacunar stroke etiology was demonstrated and as ET-plus group when any specific etiology was combined. Each group was analyzed to ascertain stroke patterns and outcomes., Results: A total of 26 patients were included, and their mean age was 66 ± 17 years, including 12 female patients. There were 12 ET-only cases and 14 ET-plus cases per stroke mechanism. The ET-plus group included 7 large artery atherosclerosis, 5 small vessel occlusion, and 2 cardioembolic cases. Multiple scattered lesions involving multiple vascular territories were more prevalent in the ET-only group. Poor outcome (modified Rankin scale >2 at discharge) was noted in 13 cases (50.0%), and old age, female sex, prior diagnosis of ET to stroke and low hemoglobin level were associated with poor outcome., Conclusion: ET-related stroke displayed a characteristic infarction pattern, such as multiple embolisms., (Copyright © 2019. Published by Elsevier B.V.)

Purpose: With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data., Materials and Methods: To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared., Results: We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration., Conclusion: In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.

Although the introduction of human epidermal growth factor receptor (HER)2-directed therapy including trastuzumab, pertuzumab, lapatinib and trastuzumab emtansine (T-DM1) in the treatment of HER2-positive metastatic breast cancers (mBCs) favorably changed the natural history of this disease, most cases of HER2-positive mBC will eventually progress. Poziotinib is an oral pan-HER kinase inhibitor showing potent activity through irreversible inhibition of these kinases. This open-label, multicenter phase II study was designed to evaluate the efficacy and safety of poziotinib monotherapy in patients with HER2-positive mBC who had progressed from more than two HER2-directed therapies. Patients received 12 mg poziotinib once daily on a 14-day on/7-day off schedule. Progression-free survival (PFS) as the primary endpoint, the objective response rate (ORR), overall survival (OS) and safety were evaluated. From April 2015 to February 2016, 106 patients were enrolled in the trial from seven institutes in South Korea. They had a median age of 51 years (range 30-76) and had received a median of four prior therapies including two HER2-directed therapies for advanced or metastatic cancers. The median follow-up duration was 12 months. The median PFS was 4.04 months (95% confidence interval [CI], 2.94-4.40 months), and median overall survival has not been reached. The most common treatment-related adverse events were (total/grade ≥3) diarrhea (96.23%/14.15%), stomatitis (92.45%/12.26%) and rashes (63.21%/3.77%). Poziotinib showed meaningful activity in these heavily treated HER2-positive mBCs. Diarrhea and stomatitis were the major toxicities. Biomarker studies analyzed are warranted to support further evaluation of this treatment in such cases., (© 2018 UICC.)

Background: It is difficult to decide whether to inform the child of the incurable illness. We investigated attitudes of the general population and physicians toward prognosis disclosure to children and associated factors in Korea., Methods: Physicians working in one of 13 university hospitals or the National Cancer Center and members of the general public responded to the questionnaire. The questionnaire consisted of the age appropriate for informing children about the prognosis and the reason why children should not be informed. This survey was conducted as part of research to identify perceptions of physicians and general public on the end-of-life care in Korea., Results: A total of 928 physicians and 1,241 members of the general public in Korea completed the questionnaire. Whereas 92.7% of physicians said that children should be informed of their incurable illness, only 50.7% of the general population agreed. Physicians were also more likely to think that younger children should know about their poor prognosis compared with the general population. Physicians who opposed incurable illness disclosure suggested that children might not understand the situation, whereas the general public was primarily concerned that disclosure would exacerbate the disease. Physicians who were women or religious were more likely to want to inform children of their poor prognosis. In the general population, gender, education, comorbidity, and caregiver experience were related to attitude toward poor prognosis disclosure to children., Conclusion: Our findings indicate that physicians and the general public in Korea differ in their perceptions about informing children of poor prognosis., Competing Interests: Disclosure: The authors have no potential conflicts of interest to disclose.

Background: This study aimed to describe patterns of long-term antithrombotic use in acute ischemic stroke (AIS) patients with non-valvular atrial fibrillation (NVAF) in Korea and their impacts on clinical events before introduction of non-vitamin K antagonist oral anticoagulants (NOAC) into practice in 2015., Methods: Patients with NVAF who were admitted due to the AIS and discharged no later than 2008 were enrolled retrospectively. Data were collected at 11 time points during the first 3 years of follow-up. The primary outcome event was a composite of stroke recurrence, major bleeding, and death. Vitamin K antagonist (VKA) users were categorized into a well-controlled INR group and a poorly-controlled INR group (modified TTR ≥47.0% vs <47.0%)., Results: Of 1,350 patients enrolled in this study, 95% were on antithrombotic medications at discharge. The rate of VKA usage decreased over time (77% and 40% at discharge and 3 years, respectively). The cumulative event rates of the primary outcome differed by treatment patterns. Among the 10 most frequent treatment types, the highest outcome rate was observed in patients who started with VKA-only therapy but discontinued VKAs during follow-up without restarting (70.2%); this was followed by those starting with antiplatelet-only therapy and stopping it without restart (66.7%). Among VKA users, the 3-year cumulative primary outcome rates were higher in the poorly-controlled INR group than the well-controlled INR group (24.5% vs 15.7%; p = 0.015)., Conclusion: Our study revealed that, in pre-NOAC era, there was a wide spectrum of long-term antithrombotic use. The incidence of the composite outcome also varied by patterns of antithrombotic use., Competing Interests: We have the following interests: This research was sponsored by BMS/Pfizer Pharmaceuticals Korea Ltd. The Authors, B-J Seo, Y-J Kim, and S-S Kang, who are employees of Pfizer contributed in the study design, data analysis, decision to publish, or preparation of the manuscript. We declare that the authors have no other competing interests. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis is a rare autoimmune condition presenting mainly as altered mental state, cognitive dysfunction, and seizure. Antiepileptic drugs (AEDs) are usually initiated to control seizures despite their limited efficacy; however, accumulating clinical experience suggests a high incidence of adverse reactions to AEDs in anti-LGI1 encephalitis. We reviewed the medical records of patients who were diagnosed with anti-LGI1 encephalitis to analyze the adverse effects of AEDs in these patients. Among the 20 patients who were treated with AEDs, 10 (50%) changed their AEDs due to adverse cutaneous drug reaction. Eight of them presented with maculopapular eruption, one with drug rash with eosinophilia and systemic symptoms syndrome, and one with eczema. Causative agents mostly consisted of aromatic AEDs. Oxcarbazepine was discontinued in two additional patients due to hyponatremia. Six patients (30%) discontinued their dose of levetiracetam because of psychiatric manifestations including irritability/aggressive behavior (four patients), insomnia (one patient), and depressive mood (one patient). Clinicians should consider adverse cutaneous drug reaction, psychiatric adverse events, and hyponatremia when selecting AEDs for the treatment of anti-LGI1 encephalitis., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.)

Objectives: This study determined attitudes of four groups-Korean patients with cancer, their family caregivers, physicians and the general Korean population-towards five critical end-of-life (EOL) interventions-active pain control, withdrawal of futile life-sustaining treatment (LST), passive euthanasia, active euthanasia and physician-assisted suicide., Design and Setting: We enrolled 1001 patients with cancer and 1006 caregivers from 12 large hospitals in Korea, 1241 members of the general population and 928 physicians from each of the 12 hospitals and the Korean Medical Association. We analysed the associations of demographic factors, attitudes towards death and the important components of a 'good death' with critical interventions at EoL care., Results: All participant groups strongly favoured active pain control and withdrawal of futile LST but differed in attitudes towards the other four EoL interventions. Physicians (98.9%) favoured passive euthanasia more than the other three groups. Lower proportions of the four groups favoured active euthanasia or PAS. Multiple logistic regression showed that education (adjusted OR (aOR) 1.77, 95% CI 1.33 to 2.36), caregiver role (aOR 1.67, 95% CI 1.34 to 2.08) and considering death as the ending of life (aOR 1.66, 95% CI 1.05 to 1.61) were associated with preference for active pain control. Attitudes towards death, including belief in being remembered (aOR 2.03, 95% CI 1.48 to 2.79) and feeling 'life was meaningful' (aOR 2.56, 95% CI 1.58 to 4.15) were both strong correlates of withdrawal of LST with the level of monthly income (aOR 2.56, 95% CI 1.58 to 4.15). Believing 'freedom from pain' negatively predicted preference for passive euthanasia (aOR 0.69, 95% CI 0.55 to 0.85). In addition, 'not being a burden to the family' was positively related to preferences for active euthanasia (aOR 1.62, 95% CI 1.39 to 1.90) and PAS (aOR 1.61, 95% CI 1.37 to 1.89)., Conclusion: Groups differed in their attitudes towards the five EoL interventions, and those attitudes were significantly associated with various attitudes towards death., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We described a novel multi-step retinal fundus image reading system for providing high-quality large data for machine learning algorithms, and assessed the grader variability in the large-scale dataset generated with this system., Methods: A 5-step retinal fundus image reading tool was developed that rates image quality, presence of abnormality, findings with location information, diagnoses, and clinical significance. Each image was evaluated by 3 different graders. Agreements among graders for each decision were evaluated., Results: The 234,242 readings of 79,458 images were collected from 55 licensed ophthalmologists during 6 months. The 34,364 images were graded as abnormal by at-least one rater. Of these, all three raters agreed in 46.6% in abnormality, while 69.9% of the images were rated as abnormal by two or more raters. Agreement rate of at-least two raters on a certain finding was 26.7%-65.2%, and complete agreement rate of all-three raters was 5.7%-43.3%. As for diagnoses, agreement of at-least two raters was 35.6%-65.6%, and complete agreement rate was 11.0%-40.0%. Agreement of findings and diagnoses were higher when restricted to images with prior complete agreement on abnormality. Retinal/glaucoma specialists showed higher agreements on findings and diagnoses of their corresponding subspecialties., Conclusion: This novel reading tool for retinal fundus images generated a large-scale dataset with high level of information, which can be utilized in future development of machine learning-based algorithms for automated identification of abnormal conditions and clinical decision supporting system. These results emphasize the importance of addressing grader variability in algorithm developments., Competing Interests: Disclosure: Sang Jun Park, Joo Young Shin, Sangkeun Kim, Jaemin Son, and Kyu-Hwan Jung hold the Korean patent (No. 10-1848321 and 20-2848322). Sang Jun Park and Kyu-Hwan Jung is a shareholder of VUNO Inc., Seoul, Korea. The authors alone are responsible for the content and writing of the paper.

Levetiracetam (LEV) is effective for focal and generalized epilepsy and is used worldwide because of its relatively few drug interactions and favorable tolerability. However, some psychiatric adverse events (PAEs) have been reported, resulting in drug withdrawal. The pathophysiology of LEV-induced PAE has not yet been elucidated. In this study, we investigated the relationship between PAEs and human leukocyte antigen (HLA) genes. Eleven epilepsy patients, who developed PAEs after the administration of LEV and spontaneously improved after drug withdrawal, were enrolled retrospectively. Genomic DNA from the peripheral blood was extracted, and four-digit allele genotyping of HLA genes was performed. The genotype frequencies of HLA genes were compared to those of 80 patients in which LEV was well tolerated, as well as to 485 individuals from the general Korean population. The frequency of the HLA-A*1101 allele was significantly higher in the LEV-induced PAEs group compared to both the LEV-tolerant group (p = 0.021, OR 4.80, 95% CI 1.30-17.74) and the general Korean population (p = 0.015, OR 4.62, 95% CI 1.38-15.45). This study is the first attempt at investigating the relationship between the HLA system and LEV-induced PAE. The results of this study suggest that the HLA-A*1101 allele could be a risk factor for the development of PAEs., Competing Interests: The authors have declared that no competing interests exist.

Integrated early palliative care (EPC) improves quality of life and reduces psychological distress in adult patients with cancer and caregivers, but attitudes toward EPC have been poorly studied. We aimed to investigate attitudes toward EPC in a nationwide survey of patients with cancer and caregivers. From July to October 2016, we administered nationwide questionnaires examining attitudes toward EPC in patients with cancer (n = 1001) and their families (n = 1006) from 12 Korean hospitals. When an individual considered EPC unnecessary, the reasons were collected and analyzed. Factors associated with perception of EPC were examined. A majority of patients (84.5%) and caregivers (89.5%) had positive attitudes toward EPC. The most common reasons for deeming EPC unnecessary were that EPC may be an obstacle to cancer treatment (patients: 37%; caregivers: 23%; respectively) or that they were not sure if EPC is beneficial (patients: 21%; caregivers: 24%; respectively). Financial burden as a reason was more evident in caregivers (23%) than in patients (17%). Male gender, age <50, early stage, intensive care unit admission, and not believing that dying people should prepare to practice charity were associated with patients' negative attitudes. In caregivers, opposition to EPC was associated with not thinking death should be feared, not thinking people should be remembered, and lower educational level. Our findings showed that significant numbers of patients with advanced cancer and family caregivers showed positive attitudes toward EPC. However, more than 10% of participants did not consider EPC necessary. Physicians' communication with patients and caregivers and financial support could help overcome the barriers of EPC., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Importance: Disruption of extracellular matrix integrity is critically involved in both intracranial aneurysm and bone fragility. Furthermore, both intracranial aneurysm and osteoporosis have a female predominance, and sex hormones are considered to affect this discrepancy., Objective: To evaluate the association between bone mineral density and intracranial aneurysm., Design, Setting, and Participants: A cross-sectional study conducted with 14 328 patients who underwent brain magnetic resonance angiography and bone mineral densitometry as a part of a health examination at a specialized center for comprehensive health examination in Seoul, the largest metropolitan area in the Republic of Korea, between December 2004 and November 2015. After excluding patients with insufficient clinical information (n = 1102) and with ambiguous intracranial arterial lesion (n = 441), 12 785 were included in the analysis., Exposures: Bone mineral density was measured at the lumbar vertebrae (L1 to L4), femur neck, and total hip using dual-energy x-ray absorptiometry., Main Outcomes and Measures: Multiple logistic regression or linear regression was used to examine the association between tertiles of bone mineral density and the presence, size, and multiplicity of intracranial aneurysms. In secondary analyses, we analyzed postmenopausal women and men 50 years and older (n = 8722) because they are particularly at risk of decreased bone mineral density., Results: Among 12 785 patients in the study (7242 women [56.6%]; mean [SD] age, 54.8 [10.1] years) intracranial aneurysms were found in 472 patients (3.7%). Lower bone mineral density was associated with an increased risk of harboring intracranial aneurysm. In multivariable logistic regression analyses, odds ratios for the highest compared with the lowest bone mineral density tertile were 1.30 (95% CI, 1.03-1.64) in the lumbar spine, 1.30 (95% CI, 1.03-1.64) in the femoral neck, and 1.27 (95% CI, 1.01-1.60) in the total hip after adjusting for age, sex, and vascular risk factors. In a linear regression model adjusted for age, sex, and vascular risk factors, the lowest tertile of bone mineral density in the lumbar spine was associated with an increased log-transformed size of aneurysm (β, 0.196; SE, 0.047). In secondary analyses, these associations were more definite and a low T score (<-1 SD) was additionally associated with multiple aneurysms (OR, 1.84; 95% CI, 1.05-3.30) after adjusting for age, sex, and vascular risk factors., Conclusions and Relevance: Bone mineral density may be associated with the presence, size, and multiplicity of intracranial aneurysm. The study findings provide evidence for shared pathophysiology between intracranial aneurysm and bone fragility.

Background and Aim: The aim of this study was to identify the effect of selective estrogen receptor modulator (SERM) on non-alcoholic fatty liver disease (NAFLD) in Asian women., Methods: We retrospectively evaluated fatty liver development and/or serum alanine aminotransferase (ALT) elevation during SERM treatment in 1061 women who were diagnosed and treated with breast cancer in 2005 at Asan Medical Center., Results: 45 of 618 SERM-treated patients with normal ALT at baseline experienced ALT elevation during SERM treatment. Among the 112 SERM-treated patients who underwent liver imaging test, fatty liver was observed in 47 and both fatty liver and ALT elevation developed in 16 of 102 SERM-treated patients with normal baseline ALT. The cumulative rates of ALT elevation (10.7 vs. 4.3%; P = 0.002), fatty liver (48.5 vs. 20.9%; P < 0.001), and both fatty liver and ALT elevation (17.7 vs. 7.1%; P = 0.02) at 60 months were significantly higher in the SERM group than non-SERM group. By multivariate analysis, SERM treatment increased the risk of ALT elevation (hazard ratio [HR], 2.20; P = 0.01), fatty liver development (HR, 3.59; P < 0.001), and both fatty liver and ALT elevation (HR, 4.98; P = 0.01). After discontinuation of SERM, elevated serum ALT normalized in 39 (92.9%) and there were no instances of liver-related death or progression to liver cirrhosis in patients who experienced fatty liver or ALT elevation., Conclusions: Although SERM treatment is significantly associated with NAFLD in Asian women, considering the tolerability and reversibility of NAFLD induced by SERM, it can be continued with liver function monitoring in relevant patients., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

We aimed to evaluate the prevalence of antineuronal antibodies in a nationwide cohort of patients with encephalopathy of unknown etiology. We screened 1699 patients with idiopathic encephalopathy who were referred from 70 hospitals across Korea for autoimmune synaptic and classic paraneoplastic antibodies. Those with cerebellar degeneration, sensory polyneuropathy or other paraneoplastic syndromes without encephalopathy were not included in this study. One-hundred and four patients (6.12%) had antibody-associated autoimmune encephalopathy. Autoimmune synaptic antibodies were identified in 89 patients (5.24%) and classic paraneoplastic antibodies were identified in 16 patients (0.94%). The patients with antibody-associated autoimmune encephalopathy comprised a small but significant portion of the total number of patients with encephalopathy of unknown cause., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Controversy surrounds appendectomy timings and their effects on postoperative outcomes. This study evaluated the influence of hospital delays on perforation rates and complications in patients with acute appendicitis. From January 2008 to December 2013, the cases of 4148 consecutive patients who had undergone appendectomies for suspected appendicitis were reviewed. The patients' demographic data, times from symptom onset to hospital arrival (prehospital delay), times from hospital arrival to surgery (hospital delay), histological findings, and postoperative outcomes were documented. Perforation rates and complications were assessed at each time interval between symptom onset and surgery. Perforation rates and complications increased with longer prehospital delays, but no correlations were evident between hospital delays and perforation rates or between hospital delays and complications. Although delaying appendectomies for >18 hours had no statistically significant impact on perforation rates (25.3 vs 19.4%, P = 0.133), it caused more complications (8.7 vs 3.8%, P = 0.023) compared with cases delayed for 12 to 18 hours. Multivariate analyses determined that hospital delays were not associated with increased risks of perforation, complications, wound infections, or intra-abdominal abscesses. However, a >18-hour hospital delay was associated with a significantly increased risk of postoperative ileus (odds ratio = 2.94, 95% confidence interval = 1.17-7.41, P = 0.022). Hospital delays were not associated with significantly increased risks of perforation and complications. However, patients with perforated appendicitis had higher risks of developing postoperative ileus if hospital delays were >18 hours. Therefore, hospital delays of ≤18 hours are safe, but caution is required if delays are >18 hours.

Objective: This study examined changes in health-related quality of life (HRQoL) and quality of care (QoC) as perceived by terminally ill cancer patients and a stratified set of HRQoL or QoC factors that are most likely to influence survival at the end of life (EoL)., Method: We administered questionnaires to 619 consecutive patients immediately after they were diagnosed with terminal cancer by physicians at 11 university hospitals and at the National Cancer Center in Korea. Subjects were followed up over 161.2 person-years until their deaths. We measured HRQoL using the core 30-item European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, and QoC using the Quality Care Questionnaire-End of Life (QCQ-EoL). We evaluated changes in HRQoL and QoC issues during the first three months after enrollment, performing sensitivity analysis by using data generated via four methods (complete case analysis, available case analysis, the last observation carried forward, and multiple imputation)., Results: Emotional and cognitive functioning decreased significantly over time, while dyspnea, constipation, and pain increased significantly. Dignity-conserving care, care by healthcare professionals, family relationships, and QCQ-EoL total score decreased significantly. Global QoL, appetite loss, and Eastern Cooperative Oncology Group Performance Status (ECOG-PS) scores were significantly associated with survival., Significance of Results: Future standardization of palliative care should be focused on assessment of these deteriorated types of quality. Accurate estimates of the length of life remaining for terminally ill cancer patients by such EoL-enhancing factors as global QoL, appetite loss, and ECOG-PS are needed to help patients experience a dignified and comfortable death.

Objective: The main aim of this study was to evaluate the antitumor activity and safety of vinorelbine and gemcitabine combination chemotherapy in patients with primary refractory or recurrent platinum-resistant epithelial ovarian and primary peritoneal cancers., Methods: Patients with platinum-resistant or primary refractory disease were eligible. Patients were allowed one prior chemotherapy for the treatment of platinum-resistant or refractory disease. Vinorelbine 25mg/m(2), followed by gemcitabine 1000mg/m(2), was administered intravenously on days 1 and 8 every 3weeks. Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 and cancer antigen 125 test (CA-125 criteria) were adopted to classify responses., Results: 44 patients received the median of 4 (range, 1-24) treatments with fifteen (34.1%) receiving six or more cycles. The overall objective response rate was 22.7%. One patient (2.3%) had complete while 9 patients (20.4%) had partial responses with median duration of response of 5.9months. 17 patients (38.6%) had stable disease for a median of 3.3months. Median progression-free survival (PFS) was 3.4months and overall survival (OS) was 14.5months. Four (9.1%) patients were not assessable. Neutropenia was the most frequently encountered toxicity, with grade 3 or 4 observed in 22 patients (50.0%). Fifteen patients (34.1%) needed immediate dose reduction. No treatment related death was reported., Conclusions: The combination chemotherapy with gemcitabine and vinorelbine achieved the primary end point of our clinical trial in management of platinum resistant recurrent ovarian cancer. However, further sophisticated dosing and scheduling of combination chemotherapy are needed because of a significant proportion of dose reduction., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: We tried to evaluate the association of self-leadership, effective health behaviors, and posttraumatic growth with health-related quality of life (HRQOL)., Methods: We recruited survivors of cancer from seven hospitals in Korea between 2011 and 2012. The patients completed the Seven Habits Profile (7HP) to evaluate leadership competency, the 10 rules for highly effective health behavior to evaluate health behavior, the Posttraumatic Growth Inventory (PTGI) to evaluate posttraumatic growth, the Short Form 36 (SF-36) to evaluate HRQOL, and the Hospital Anxiety and Depression Scale (HADS) to evaluate anxiety and depression. We performed multiple logistic regressions to identify significant associations., Results: A total of 668 patients with cancer participated in the study. Patients who scored high on the leadership subscales of Be Proactive, Begin with the End in Mind, Put First Things First, Think Win-Win, Synergize, and Sharpen the Saw in 7HP tried to practice and keep their health behaviors more. The Begin with the End in Mind, Put First Things First, Synergize, and Sharpen the Saw subscales of the 7HP were also significantly correlated with subscales on the PTGI. Patients who scored high on the leadership subscales of Life Balance, Be Proactive, Begin with the End in Mind, Think Win-Win, and Sharpen the Saw had higher physical and mental component scale scores on the SF-36 and lower anxiety and depression subscale scores on the HADS., Conclusion: Self-leadership, health behaviors, and posttraumatic growth are associated with QOL in survivors of cancer., (Copyright © 2014 John Wiley & Sons, Ltd.)

Although non-convulsive status epilepticus (NCSE) is an important type of epilepsy, it is not often recognized. In order to analyze the clinical characteristics and outcome in patients with NCSE, we examined the medical records of patients with NCSE admitted to the Seoul National University Hospital between June 2005 and October 2008. The clinical details and electroencephalography records of 34 adult NCSE patients (aged over 16 years) were collected. Their mean age was 47 years (standard deviation 20 years, range, 16-87 years), and 20 were female. Twenty-seven patients (79.4%) showed decreased awareness with acute onset, and seven (20.6%) were obtunded or comatose. Ten patients (29.4%) had a history of epilepsy, and four (11.8%) had a history of stroke. NCSE was etiologically attributed to acute medical or neurological problems in 25 patients (73.5%), was cryptogenic in three (8.8%), and was secondary to underlying epilepsy in six (17.7%). Acute symptomatic etiology was associated with poor recovery (p=0.048), with all unresponsive patients in this acute symptomatic group. Eight (23.5%) of the 34 NCSE patients did not recover or died, whereas nine (26.5%) recovered. Our study shows that the presence of acute symptoms or central nervous system infection is associated with poor outcome, suggesting that a high level of vigilance is required to identify and prevent complications., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: PM014 is a modified form of the Chung-Sang-Bo-Ha-Tang (CSBHT) herbal formula that has been used to treat chronic pulmonary diseases in Korea for centuries. Previously, we developed a formulation of PM014 based on a series of in vitro and in vivo screening efforts that comprises seven herbal extracts. The PM014 formula includes the root of Rehmannia glutinosa, the cortex of Paeonia suffruticosa, the fruit of Schizandra chinensis, the root of Asparagus cochinchinensis, seeds of Prunus armeniaca, the root of Scutellaria baicalensis and the root of Stemona sessilifolia. Asthma is a chronic inflammatory disease of the lungs that is characterized by wheezing, bronchial contraction, and chest tightness. In addition, the airway becomes hypersensitive and narrows through an inflammatory reaction mediated by Th2 cells. The present study was conducted to evaluate the ability of PM014 to prevent allergic airway inflammation and to attenuate airway responses in a cockroach allergen-induced mouse model., Materials and Methods: Mice sensitized to and challenged with cockroach allergen were treated with oral administration of PM014. Airway resistance was determined by whole body plethysmography. In addition, Th2 cytokines and immune cell profiles of bronchoalveolar lavage (BAL) fluid and inflammatory mediators in serum were analyzed by ELISA. A series of histological examinations were also conducted to demonstrate the effects of PM014 on airway remodeling, goblet cell hyperplasia and inflammatory responses in the lung., Results: PM014 significantly inhibited the number of total cells, eosinophils, neutrophils, macrophages and lymphocytes in the BAL fluid of mice that were challenged with cockroach allergen. In addition, PM014 reduced the levels of Th2 cytokines (IL-4, IL-5 and IL-13) in the BAL fluid and inflammatory mediators such as IgE in the serum, as measured by enzyme-linked immunosorbent assay (ELISA). Histopathological analysis also showed that PM014 substantially inhibited eosinophil infiltration into the airway, goblet cell hyperplasia and smooth muscle hypertrophy., Conclusions: In this study, our results indicate that PM014 has significant effects on allergic airway inflammation upon exposure to cockroach allergen in a mouse model. According to these outcomes, PM014 may have therapeutic potential as a treatment for allergic asthma., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Chronic, repetitive, and sublethal hypoperfusion by intra- or extracranial artery stenosis promotes collateral development and conditions the brain toward preventing subsequent lethal ischemia, although these latent properties have rarely been demonstrated in the clinical setting. This study assessed the previously unexplored role of subclavian steal syndrome (SSS) on inciting and protecting brain damage., Methods: We enrolled patients diagnosed with SSS associated with subclavian artery stenosis. Subclavian steal was determined by transcranial Doppler and/or digital subtraction angiography. We analyzed the prevalences and predictors of posterior ischemic symptoms and infarcts in SSS patients and also investigated individual cases to demonstrate a clinical evidence of brain conditioning, focusing on cytotoxic and vasogenic edema., Results: Of 54 SSS patients, 36 (66.7%) had been asymptomatic and incidentally diagnosed with SSS, whereas 18 (33.3%) patients had presented with posterior ischemic symptoms. Symptoms and infarcts including old silent lesions occurred more frequently as unstable hemodynamics of the anterior circulation were combined. Of 18 symptomatic patients, 13 patients (72.2%) had transient ischemic attack and 5 (27.8%) patients had an infarct in the posterior circulation territory. Four patients with cytotoxic edema had mild neurologic deficits and rapid and complete recovery, whereas 1 patient had prolonged, severe vasogenic edema after acute hypertension., Conclusions: Although we noted low rates of disabling or fatal strokes in patients with SSS, a variety of vascular and neural factors beyond severity of subclavian steal could influence the likelihood of brain damage., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Objective: Although it is hypothesized that inflammatory signals and/or hemodynamic stress resulting from carotid disease increase the risk of aneurysm formation and growth, a relationship between intracranial aneurysms and extracranial carotid artery disease (ECAD) has not been explored. Here, we examined the characteristics of intracranial aneurysms associated with ECAD., Methods: A total of 606 consecutive patients with stenosis of 50% or more of the proximal internal carotid artery (pICA) were enrolled. Stenosis was identified by conventional angiography between January 2003 and December 2009. We determined the prevalence of intracranial aneurysms in this population. The characteristics of the aneurysms were analyzed according to the degree and laterality of stenosis. The changes in the aneurysms were tracked for the evaluation of stability., Results: In 86 patients (14.2%), 120 aneurysms were detected in association with pICA stenosis. In this group, 97 were associated with unilateral pICA stenosis. The distribution of aneurysms was independent of the laterality of stenosis, but aneurysms were more prevalent in the contralateral side as the stenosis grade increased (P<0.001). All aneurysms with an imaging follow-up (28.9 ± 14.3 months) were stable, and the course was not affected by treatment of the carotid stenosis. In 23 aneurysms associated with bilateral pICA stenosis, there was only one case that increased in size during a 41-month period., Conclusion: Intracranial aneurysms were most likely associated with ECAD, but were evenly distributed irrespective of the laterality of the stenosis. The distribution was related to the severity of the contralateral pICA stenosis. The low incidence of aneurysm growth or rupture in patients with significant ECAD indicates that these aneurysms do not require immediate intervention more than other conditions., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Aims: Although use of antithrombotic agents is recommended after ischaemic stroke or transient ischaemic attack (TIA), long-term outcome of secondary prevention between stroke subtypes has not yet been explored., Methods and Results: We used data from the Korean Stroke Registry (KSR), a nationwide, multicentre, prospective registry for acute stroke patients. Patients with acute ischaemic stroke or TIA within 7 days of onset were consecutively enrolled between January 2002 and September 2010. A total of 46 108 patients with ischaemic stroke and TIA were included in this study. Among the major stroke subtypes, stroke due to small vessel occlusion (SVO) showed the lowest mortality, whereas cardioembolic stroke (CE) was associated with the fatal prognosis during the follow-up [for SVO: hazard ratio (HR) 0.66, 95% CI 0.62-0.71; for CE: HR 1.41, 95% CI 1.30-1.53; large artery atherosclerosis (LAA) group as a reference]. Regarding secondary prevention, antiplatelet polytherapy was better than monotherapy in the patients with LAA-related stroke in prognosis [HR 0.89, 95% CI 0.80-0.98]. Anticoagulant therapy was associated with better outcome than antiplatelet monotherapy in CE-related stroke [HR 0.66, 95% CI 0.59-0.74]. In SVO-related stroke group, antiplatelet polytherapy failed to show benefits over monotherapy. Additionally, the risk of death was higher with anticoagulant therapy in the patients with SVO-related stroke [HR 1.44, CI 95% 1.06-1.97]., Conclusions: Our study demonstrated that stroke subtype affects prognosis and also determines the effectiveness of secondary prevention.

Background and Purpose: We investigated the effect of celecoxib, a selective inhibitor of cyclo-oxygenase 2, in patients with intracerebral hemorrhage (ICH)., Methods: We conducted a multicenter, randomized, controlled, and open with blinded end-point trial of 44 Korean patients 18 years or older with ICH within 24 h of onset. The intervention group (n = 20) received celecoxib (400 mg twice a day) for 14 days. The control group (n = 24) received the standard medical treatment for ICH. The primary end-point was the number of patients with a change in the volume of perihematomal edema (PHE) from the 1st to the 7th ± 1 day (cut-off value, 20%)., Results: The time from onset to computed tomography scan slightly differed between groups (177 ± 160 min for control vs. 297 ± 305 min for the celecoxib group; P = 0.10). In the primary end-point analysis using cut-off values, there was a significant shift to reduced expansion of PHE in the celecoxib group (P = 0.005). With respect to the secondary end-points, there was also a significant shift to reduced expansion of ICH in the celecoxib group (P = 0.046). In addition, the expansion rate of PHE at follow-up tended to be higher in the control group than in the celecoxib group (90.6 ± 91.7% vs. 44.4 ± 64.9%; P = 0.058)., Conclusions: In our small, pilot trial, administration of celecoxib in the acute stage of ICH was associated with a smaller expansion of PHE than that observed in controls., (© 2013 The Author(s) European Journal of Neurology © 2013 EFNS.)

Purpose: The primary purpose of our study was to evaluate whether maintenance chemotherapy with paclitaxel/gemcitabine (PG) was superior to observation in improving progression-free survival (PFS) in patients with metastatic breast cancer (MBC) who achieved disease control with an initial six cycles of PG as their first-line treatment., Patients and Methods: The study was a prospective, randomized, multicenter, phase III trial. Patients MBC with who achieved disease control after six cycles of PG chemotherapy were randomly assigned to maintenance chemotherapy or observation until progression., Results: Of 324 patients from 10 centers enrolled, 231 patients with MBC exhibited disease control (complete response + partial response + stable disease) with first-line PG and were randomly assigned to maintenance chemotherapy (n = 116) or observation (n = 115). The median age was 48 years (range, 28 to 76 years), median follow-up was 33 months, and median number of chemotherapy cycles in the maintenance group after random assignment was six. The median PFS time after random assignment was longer in the maintenance group than in the observation group (7.5 v 3.8 months, respectively; P = .026). The median overall survival (OS) time was longer in the maintenance group than in the observation group (32.3 v 23.5 months, respectively; P = .047). The rate of grade 3 or higher neutropenia after random assignment was higher in the maintenance group than in the observation group (61% v 0.9%, respectively; P < .001)., Conclusion: In patients with MBC who achieved disease control with an initial six cycles of PG chemotherapy, maintenance PG chemotherapy resulted in better PFS and OS compared with observation.