Purpose: We investigated the consistent efficacy and safety of eflapegrastim, a novel long-acting granulocyte-colony stimulating factor (G-CSF), in Koreans and Asians compared with the pooled population of two global phase 3 trials. Materials and Methods: Two phase 3 trials (ADVANCE and RECOVER) evaluated the efficacy and safety of fixed-dose eflapegrastim (13.2 mg/0.6 mL [3.6 mg G-CSF equivalent]) compared to pegfilgrastim (6 mg based on G-CSF) in breast cancer patients who received neoadjuvant or adjuvant docetaxel/cyclophosphamide. The primary objective was to demonstrate non-inferiority of eflapegrastim compared to pegfilgrastim in mean duration of severe neutropenia (DSN) in cycle 1, in Korean and Asian subpopulations. Results: Among a total of 643 patients randomized to eflapegrastim (n=314) or pegfilgrastim (n=329), 54 Asians (29 to eflapegrastim and 25 to pegfilgrastim) including 28 Koreans (14 to both eflapegrastim and pegfilgrastim) were enrolled. The primary endpoint, DSN in cycle 1 in the eflapegrastim arm was non-inferior to the pegfilgrastim arm in Koreans and Asians. The DSN difference between the eflapegrastim and pegfilgrastim arms was consistent across populations: –0.120 days (95% confidence interval [CI], –0.227 to –0.016), –0.288 (95% CI, –0.714 to 0.143), and –0.267 (95% CI, –0.697 to 0.110) for pooled population, Koreans and Asians, respectively. There were few treatment-related adverse events that caused discontinuation of eflapegrastim (1.9%) or pegfilgrastim (1.5%) in total and no notable trends or differences across patient populations. Conclusion This study may suggest that eflapegrastim showed non-inferior efficacy and similar safety compared to pegfilgrastim in Koreans and Asians, consistently with those of pooled population.

OBJECTIVE: Most patients with head trauma require brain computed tomography (CT) in the emergency department. However, the requirement for facial CT remains controversial. The aim of this study was to evaluate the diagnostic value of brain CT alone for detection of facial fractures and its ability to determine the requirement for additional facial CT. METHODS: This retrospective multicenter study was conducted in two tertiary hospitals in Seoul, Republic of Korea, between January 2014 and December 2015. Data were collected from the medical records of adult patients (aged over 18 years) who had undergone both brain and facial CT on the same day as their presentation to the emergency department with blunt trauma to the head and face. The same radiologist analyzed all brain and facial CT images. RESULTS: Eight hundred and sixty patients (668 men, 192 women; mean age 48.60±18.2 years) were identified to have had facial fractures. There was a statistically significant predominance of men but not of any particular age group. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of brain CT were 83.72%, 98.87%, 97.17%, 92.92%, and 94.08%, respectively. CONCLUSION: These findings suggest that brain CT has high diagnostic value for detection of upper facial bone fractures with high accuracy and can aid emergency physicians when determining the requirement for additional facial CT.
Adult ; Brain* ; Craniocerebral Trauma ; Diagnosis ; Emergencies ; Emergency Service, Hospital ; Facial Bones* ; Female ; Head ; Humans ; Male ; Medical Records ; Republic of Korea ; Retrospective Studies ; Sensitivity and Specificity ; Seoul ; Skull ; Tertiary Care Centers

PURPOSE: Obtaining brain tissue is critical to definite diagnosis and to furthering understanding of neurodegenerative diseases. The present authors have maintained the National Neuropathology Reference and Diagnostic Laboratories for Dementia in South Korea since 2016. We have built a nationwide brain bank network and are collecting brain tissues from patients with neurodegenerative diseases. We are aiming to facilitate analyses of clinic-pathological and image-pathological correlations of neurodegenerative disease and to broaden understanding thereof. MATERIALS AND METHODS: We recruited participants through two routes: from memory clinics and the community. As a baseline evaluation, clinical interviews, a neurological examination, laboratory tests, neuropsychological tests, and MRI were undertaken. Some patients also underwent amyloid PET. RESULTS: We recruited 105 participants, 70 from clinics and 35 from the community. Among them, 11 died and were autopsied. The clinical diagnoses of the autopsied patients included four with Alzheimer's disease (AD), two with subcortical vascular dementia, two with non-fluent variant primary progressive aphasia, one with leukoencephalopathy, one with frontotemporal dementia (FTD), and one with Creutzfeldt-Jakob disease (CJD). Five patients underwent amyloid PET: two with AD, one with mixed dementia, one with FTD, and one with CJD. CONCLUSION: The clinical and neuropathological information to be obtained from this cohort in the future will provide a deeper understanding of the neuropathological mechanisms of cognitive impairment in Asia, especially Korea.
Alzheimer Disease ; Amyloid ; Aphasia, Primary Progressive ; Asia ; Brain* ; Cognition Disorders ; Cohort Studies ; Creutzfeldt-Jakob Syndrome ; Dementia ; Dementia, Vascular ; Diagnosis ; Frontotemporal Dementia ; Humans ; Korea* ; Leukoencephalopathies ; Magnetic Resonance Imaging ; Memory ; Neurodegenerative Diseases ; Neurologic Examination ; Neuropathology ; Neuropsychological Tests

PURPOSE: The aim of this study was to identify the pathogens of blood stream infection (BSI) in children with hemato-oncologic disorders, to analyze susceptibility patterns of microorganisms to guide empirical antimicrobial therapy, and to compare temporal trends of the pathogen and antimicrobial susceptibility with those of previous studies. METHODS: We retrospectively analyzed the medical records of children with hemato-oncologic disorders whose blood culture grew pathogens at the Seoul National University Children's Hospital between 2011 and 2015. RESULTS: A total of 167 patients developed 221 episodes of bacteremia. Among 229 pathogens, gram-negative bacteria (GNB) accounted for 69.0% (64.0% in 2002 to 2005, 63.4% in 2006 to 2010); gram-positive bacteria (GPB) accounted for 28.8% (31.3% in 2002 to 2005, 34.6% in 2006 to 2010); and fungus accounted for 2.2%. Among GNB, Klebsiella species (53.2%, 84/158) and Escherichia coli (19.6%, 31/158) were common. Staphylococcus aureus (48.5%, 32/66) and viridans streptococci (21.2%, 14/66) were frequently isolated among GPB. The susceptibilities of oxacillin and vancomycin in GPB were 54.8% and 96.9% (51.5% and 95.5% in 2002 to 2005; 34.1% and 90.5% in 2006 to 2010), respectively, whereas in GNB, the susceptibilities of cefotaxime, piperacillin/tazobactam, and imipenem were 73.2%, 77.2%, and 92.6% (75.9%, 82.8%, and 93.4% in 2002 to 2005; 62.8%, 82.9%, 93.8% and in 2006 to 2010), respectively. There were no significant differences in the proportion of etiologic agents or the antimicrobial susceptibilities between the current study and that of the previous two studies from 2002 to 2010. Overall fatality rate was 13.1%. CONCLUSIONS: GNB predominated in BSI among children with hemato-oncologic disorders. The etiology of bacteremia and antimicrobial susceptibility were comparable to those of the previous studies. Thus, piperacillin/tazobactam can be used as the initial empirical antimicrobial agent in febrile neutropenia.
Bacteremia* ; Cefotaxime ; Child* ; Escherichia coli ; Febrile Neutropenia ; Fungi ; Gram-Negative Bacteria ; Gram-Positive Bacteria ; Humans ; Imipenem ; Klebsiella ; Korea ; Medical Records ; Oxacillin ; Retrospective Studies ; Rivers ; Seoul ; Staphylococcus aureus ; Vancomycin ; Viridans Streptococci

Recently, we reported that Artemisia annua (AA) has anti-adipogenic properties in vitro and in vivo. Reduction of adipogenesis by AA treatment may dampen systemic inflammation and protect neurons from cytokine-induced damage. Therefore, the present study was undertaken to assess whether AA increases neuronal maturation by reducing inflammatory responses, such as those mediated by cyclooxygenase 2 (COX-2). Mice were fed normal chow or a high-fat diet with or without chronic daily oral administration of AA extract (0.2 g/10 mL/kg) for 4 weeks; then, changes in their hippocampal dentate gyri were measured via immunohistochemistry/immunofluorescence staining for bromodexoxyuridine, doublecortin, and neuronal nuclei, markers of neuronal maturation, and quantitative western blotting for COX-2 and Iba-1, in order to assess correlations between systemic inflammation (interleukin-6) and food type. Additionally, we tested the effect of AA in an Alzheimer's disease model of Caenorhabditis elegans and uncovered a potential benefit. The results show that chronic AA dosing significantly increases neuronal maturation, particularly in the high-fat diet group. This effect was seen in the absence of any changes in COX-2 levels in mice given the same type of food, pointing to the possibility of alternate anti-inflammatory pathways in the stimulation of neurogenesis and neuro-maturation in a background of obesity.
Adipogenesis ; Administration, Oral* ; Alzheimer Disease ; Animals ; Artemisia annua ; Blotting, Western ; Caenorhabditis elegans ; Cyclooxygenase 2* ; Dentate Gyrus* ; Diet, High-Fat ; In Vitro Techniques ; Inflammation ; Mice* ; Neurogenesis ; Neurons* ; Obesity* ; Prostaglandin-Endoperoxide Synthases*

BACKGROUND/AIMS: Peritoneal micrometastasis is known to play an important role in the recurrence of gastric cancer. However, its effects remain equivocal. Herein, we examine the messenger RNA (mRNA) as tumor markers, carcinoembryonic antigen (CEA), and cytokeratin 20 (CK20), in peritoneal washing fluid. Moreover, we evaluate whether these results could predict the recurrence of gastric cancer following curative resection. METHODS: We prospectively enrolled 132 patients with gastric cancers, who had received an operation, between January 2010 and January 2013. The peritoneal lavage fluid was collected at the operation field and semi-quantitative PCR was performed using the primers for CEA and CK20. We excluded patients with stage IA (n=28) early gastric cancer, positive cytologic examination of peritoneal washings (n=7), and those who were lost during follow up (n=18). RESULTS: A total of 79 patients with gastric cancers were enrolled, and the mean follow-up period was 39.95±19.25 months (range, 5-72 months). According to the multivariate analysis, T4 stage at the initial diagnosis was significantly associated with recurrence. All cases of recurrence were CEA positive and 6 cases were CK20 positive. The positive and negative predictive values of CEA were 32.0% and 100%, respectively, whereas those of CK20 were 37.5% and 71.4%, respectively. Disease free survival of CK20-negative cases was 36.17±20.28 months and that of CK20-positive cases was 32.06±22.95 months (p=0.39). CONCLUSIONS: It is unlikely that the real time polymerase chain reaction results of mRNA for CEA and CK20 in peritoneal washing fluid can predict recurrence. However, negative results can convince surgeons to perform curative R0 resection.
Biomarkers, Tumor ; Carcinoembryonic Antigen* ; Diagnosis ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Keratin-20* ; Keratins* ; Multivariate Analysis ; Neoplasm Micrometastasis ; Peritoneal Lavage ; Polymerase Chain Reaction ; Prospective Studies ; Real-Time Polymerase Chain Reaction ; Recurrence ; RNA, Messenger* ; Stomach Neoplasms* ; Surgeons

PURPOSE: Pentraxin 3 (PTX3) has been suggested to be a prognostic marker of mortality in severe sepsis. Currently, there are limited data on biomarkers including PTX3 that can be used to predict mortality in severe sepsis patients who have undergone successful initial resuscitation through early goal-directed therapy (EGDT). MATERIALS AND METHODS: A prospective cohort study was conducted among 83 severe sepsis patients with fulfillment of all EGDT components and the achievement of final goal. Plasma PTX3 levels were measured by sandwich ELISA on hospital day (HD) 0, 3, and 7. The data for procalcitonin, C-reactive protein and delta neutrophil index were collected by electric medical record. The primary outcome was 28-day all-cause mortality. RESULTS: 28-day all-cause mortality was 19.3% and the median (interquartile range) APHCH II score of total patients was 16 (13–19). The non-survivors (n=16) had significantly higher PTX3 level at HD 0 [201.4 (56.9–268.6) ng/mL vs. 36.5 (13.7–145.3) ng/mL, p=0.008]. PTX3 had largest AUC(ROC) value for the prediction of mortality among PTX3, procalcitonin, delta neutrophil index, CRP and APACHE II/SOFA sore at HD 0 [0.819, 95% confidence interval (CI) 0.677–0.961, p=0.008]. The most valid cut-off level of PTX3 at HD 0 was 140.28 ng/mL (sensitivity 66.7%, specificity 73.8%). The PTX3 and procalcitonin at HD 0 showed strong correlation (r=0.675, p<0.001). However, PTX3 at HD 0 was the only independent predictive marker in Cox's proportional hazards model (≥140 ng/mL; hazard rate 7.16, 95% CI 2.46–15.85, p=0.001). CONCLUSION: PTX3 at HD 0 could be a powerful predictive biomarker of 28-day all-cause mortality in severe septic patients who have undergone successful EGDT.
APACHE ; Biomarkers ; C-Reactive Protein ; Cohort Studies ; Enzyme-Linked Immunosorbent Assay ; Humans ; Medical Records ; Mortality* ; Neutrophils ; Plasma ; Proportional Hazards Models ; Prospective Studies ; Resuscitation ; Sensitivity and Specificity ; Sepsis

PURPOSE: Chronic kidney disease (CKD) patients tend to have higher serum magnesium values than healthy population due to their positive balance of magnesium in kidney. Recent studies found that magnesium level is positively correlated with endothelial function. Therefore, this study was conducted to define the relationship between magnesium level and endothelial dysfunction in end stage renal disease (ESRD) patients on hemodialysis (HD). MATERIALS AND METHODS: A total of 27 patients were included in this cross-sectional study. Iontophoresis with laser-Doppler flowmetry, flow mediated dilation (FMD), and carotid intima-media thickness were measured. Patients' average serum magnesium levels were measured over previous three months, including the examination month. Pearson's correlation coefficient analysis and multivariate regression model were used to define the association between magnesium and endothelial function. RESULTS: In the univariate analysis, higher magnesium levels were associated with better endothelium-dependent vasodilation (EDV) of the FMD in ESRD patients on HD (r=0.516, p=0.007). When the participants were divided into two groups according to the median magnesium level (3.47 mg/dL), there was a significant difference in EDV of FMD (less than 3.47 mg/dL, 2.8±1.7%; more than 3.47 mg/dL, 5.1±2.0%, p=0.004). In multivariate analysis, magnesium and albumin were identified as independent factors for FMD (β=1.794, p=0.030 for serum magnesium; β=3.642, p=0.012 for albumin). CONCLUSION: This study demonstrated that higher serum magnesium level may be associated with better endothelial function in ESRD patients on HD. In the future, a large, prospective study is needed to elucidate optimal range of serum magnesium levels in ESRD on HD patients.
Carotid Intima-Media Thickness ; Cross-Sectional Studies ; Endothelium ; Humans ; Iontophoresis ; Kidney ; Kidney Failure, Chronic* ; Laser-Doppler Flowmetry ; Magnesium* ; Microcirculation ; Multivariate Analysis ; Prospective Studies ; Renal Dialysis* ; Renal Insufficiency, Chronic ; Vasodilation

PURPOSE: Chronic kidney disease (CKD) patients tend to have higher serum magnesium values than healthy population due to their positive balance of magnesium in kidney. Recent studies found that magnesium level is positively correlated with endothelial function. Therefore, this study was conducted to define the relationship between magnesium level and endothelial dysfunction in end stage renal disease (ESRD) patients on hemodialysis (HD). MATERIALS AND METHODS: A total of 27 patients were included in this cross-sectional study. Iontophoresis with laser-Doppler flowmetry, flow mediated dilation (FMD), and carotid intima-media thickness were measured. Patients' average serum magnesium levels were measured over previous three months, including the examination month. Pearson's correlation coefficient analysis and multivariate regression model were used to define the association between magnesium and endothelial function. RESULTS: In the univariate analysis, higher magnesium levels were associated with better endothelium-dependent vasodilation (EDV) of the FMD in ESRD patients on HD (r=0.516, p=0.007). When the participants were divided into two groups according to the median magnesium level (3.47 mg/dL), there was a significant difference in EDV of FMD (less than 3.47 mg/dL, 2.8±1.7%; more than 3.47 mg/dL, 5.1±2.0%, p=0.004). In multivariate analysis, magnesium and albumin were identified as independent factors for FMD (β=1.794, p=0.030 for serum magnesium; β=3.642, p=0.012 for albumin). CONCLUSION: This study demonstrated that higher serum magnesium level may be associated with better endothelial function in ESRD patients on HD. In the future, a large, prospective study is needed to elucidate optimal range of serum magnesium levels in ESRD on HD patients.
Carotid Intima-Media Thickness ; Cross-Sectional Studies ; Endothelium ; Humans ; Iontophoresis ; Kidney ; Kidney Failure, Chronic* ; Laser-Doppler Flowmetry ; Magnesium* ; Microcirculation ; Multivariate Analysis ; Prospective Studies ; Renal Dialysis* ; Renal Insufficiency, Chronic ; Vasodilation

PURPOSE: Endothelial dysfunction (ED) is a pivotal phenomenon in the development of cardiovascular disease (CVD) in patients receiving hemodialysis (HD). Indoxyl sulfate (IS) is a known uremic toxin that induces ED in patients with chronic kidney disease. The aim of this study was to investigate whether AST-120, an absorbent of IS, improves microvascular or macrovascular ED in HD patients. MATERIALS AND METHODS: We conducted a prospective, case-controlled trial. Fourteen patients each were enrolled in respective AST-120 and control groups. The subjects in the AST-120 group were treated with AST-120 (6 g/day) for 6 months. Microvascular function was assessed by laser Doppler flowmetry using iontophoresis of acetylcholine (Ach) and sodium nitroprusside (SNP) at baseline and again at 3 and 6 months. Carotid arterial intima-media thickness (cIMT) and flow-mediated vasodilation were measured at baseline and 6 months. The Wilcoxon rank test was used to compare values before and after AST-120 treatment. RESULTS: Ach-induced iontophoresis (endothelium-dependent response) was dramatically ameliorated at 3 months and 6 months in the AST-120 group. SNP-induced response showed delayed improvement only at 6 months in the AST-120 group. The IS level was decreased at 3 months in the AST-120 group, but remained stable thereafter. cIMT was significantly reduced after AST-120 treatment. No significant complications in patients taking AST-120 were reported. CONCLUSION: AST-120 ameliorated microvascular ED and cIMT in HD patients. A randomized study including a larger population will be required to establish a definitive role of AST-120 as a preventive medication for CVD in HD patients.
Acetylcholine ; Adult ; Carbon/*therapeutic use ; Cardiovascular Diseases/etiology/*prevention & control ; Carotid Intima-Media Thickness ; Endothelium, Vascular/*physiopathology ; Female ; Humans ; Iontophoresis ; Kidney Failure, Chronic/complications/*physiopathology/*therapy ; Laser-Doppler Flowmetry ; Male ; Microcirculation/physiology ; Middle Aged ; Nitroprusside ; Oxides/*therapeutic use ; Prospective Studies ; *Renal Dialysis ; Young Adult