Background/Aims: We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL). Methods: We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up. Results: The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis. Conclusions Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.

Venous thromboembolism (VTE), which includes pulmonary embolism and deep vein thrombosis, is a condition characterized by abnormal blood clot formation in the pulmonary arteries and the deep venous vasculature. It is often serious and sometimes even fatal if not promptly and appropriately treated. Moreover, the later consequences of VTE may result in reduced quality of life. The treatment of VTE depends on various factors, including the type, cause, and patient comorbidities. Furthermore, bleeding may occur as a side effect of VTE treatment. Thus, it is necessary to carefully weigh the benefits versus the risks of VTE treatment and to actively monitor patients undergoing treatment. Asian populations are known to have lower VTE incidences than Western populations, but recent studies have shown an increase in the incidence of VTE in Asia. A variety of treatment options are currently available owing to the introduction of direct oral anticoagulants.The current VTE treatment recommendation is based on evidence from previous studies, but it should be applied with careful consideration of the racial, genetic, and social characteristics in the Korean population.

Ischemic stroke results from arterial occlusion and can cause irreversible brain injury. A non-human primate (NHP) model of ischemic stroke was previously developed to investigate its pathophysiology and for efficacy testing of therapeutic candidates; however, fine motor impairment remains to be well-characterized. We evaluated hand motor function in a cynomolgus monkey model of ischemic stroke. Endovascular transient middle cerebral artery occlusion (MCAO) with an angiographic microcatheter induced cerebral infarction. In vivo magnetic resonance imaging mapped and measured the ischemia-induced infarct lesion. In vivo diffusion tensor imaging (DTI) of the stroke lesion to assess the neuroplastic changes and fiber tractography demonstrated three-dimensional patterns in the corticospinal tract 12 weeks after MCAO. The hand dexterity task (HDT) was used to evaluate fine motor movement of upper extremity digits. The HDT was modified for a home cage-based training system, instead of conventional chair restraint training. The lesion was localized in the middle cerebral artery territory, including the sensorimotor cortex. Maximum infarct volume was exhibited over the first week after MCAO, which progressively inhibited ischemic core expansion, manifested by enhanced functional recovery of the affected hand over 12 weeks after MCAO. The total performance time decreased with increasing success rate for both hands on the HDT. Compensatory strategies and retrieval failure improved in the chronic phase after stroke. Our findings demonstrate the recovery of fine motor skill after stroke, and outline the behavioral characteristics and features of functional disorder of NHP stroke model, providing a basis for assessing hand motor function after stroke.

Microorganisms play important roles in obesity; however, the role of the gut microbiomes in obesity is controversial because of the inconsistent findings. This study investigated the gut microbiome communities in obese and lean groups of captive healthy cynomolgus monkeys reared under strict identical environmental conditions, including their diet. No significant differences in the relative abundance of Firmicutes, Bacteroidetes and Prevotella were observed between the obese and lean groups, but a significant difference in Spirochetes (p < 0.05) was noted. Microbial diversity and richness were similar, but highly variable results in microbial composition, diversity, and richness were observed in individuals, irrespective of their state of obesity. Distinct clustering between the groups was not observed by principal coordinate analysis using an unweighted pair group method. Higher sharedness values (95.81% ± 2.28% at the genus level, and 79.54% ± 5.88% at the species level) were identified among individual monkeys. This paper reports the association between the gut microbiome and obesity in captive non-human primate models reared under controlled environments. The relative proportion of Firmicutes and Bacteroidetes as well as the microbial diversity known to affect obesity were similar in the obese and lean groups of monkeys reared under identical conditions. Therefore, obesity-associated microbial changes reported previously appear to be associated directly with environmental factors, particularly diet, rather than obesity.
Bacteroidetes ; Diet ; Environment, Controlled ; Firmicutes ; Gastrointestinal Microbiome ; Haplorhini ; Macaca fascicularis ; Methods ; Microbiota ; Obesity ; Prevotella ; Primates ; Spirochaetales

Mitochondria continuously fuse and divide to maintain homeostasis. An impairment in the balance between the fusion and fission processes can trigger mitochondrial dysfunction. Accumulating evidence suggests that mitochondrial dysfunction is related to neurodegenerative diseases such as Parkinson's disease (PD), with excessive mitochondrial fission in dopaminergic neurons being one of the pathological mechanisms of PD. Here, we investigated the balance between mitochondrial fusion and fission in the substantia nigra of a non-human primate model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. We found that MPTP induced shorter and abnormally distributed mitochondria. This phenomenon was accompanied by the activation of dynamin-related protein 1 (Drp1), a mitochondrial fission protein, through increased phosphorylation at S616. Thereafter, we assessed for activation of the components of the cyclin-dependent kinase 5 (CDK5) and extracellular signal-regulated kinase (ERK) signaling cascades, which are known regulators of Drp1(S616) phosphorylation. MPTP induced an increase in p25 and p35, which are required for CDK5 activation. Together, these findings suggest that the phosphorylation of Drp1(S616) by CDK5 is involved in mitochondrial fission in the substantia nigra of a non-human primate model of MPTP-induced PD.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Cyclin-Dependent Kinase 5 ; Cyclin-Dependent Kinases ; Dopaminergic Neurons ; Homeostasis ; Mitochondria ; Mitochondrial Dynamics ; Neurodegenerative Diseases ; Parkinson Disease ; Phosphorylation ; Phosphotransferases ; Primates ; Substantia Nigra

The function of microglia/macrophages after ischemic stroke is poorly understood. This study examines the role of microglia/macrophages in the focal infarct area after transient middle cerebral artery occlusion (MCAO) in rhesus monkeys. We measured infarct volume and neurological function by magnetic resonance imaging (MRI) and non-human primate stroke scale (NHPSS), respectively, to assess temporal changes following MCAO. Activated phagocytic microglia/macrophages were examined by immunohistochemistry in post-mortem brains (n=6 MCAO, n=2 controls) at 3 and 24 hours (acute stage), 2 and 4 weeks (subacute stage), and 4, and 20 months (chronic stage) following MCAO. We found that the infarct volume progressively decreased between 1 and 4 weeks following MCAO, in parallel with the neurological recovery. Greater presence of cluster of differentiation 68 (CD68)-expressing microglia/macrophages was detected in the infarct lesion in the subacute and chronic stage, compared to the acute stage. Surprisingly, 98~99% of transforming growth factor beta (TGFβ) was found colocalized with CD68-expressing cells. CD68-expressing microglia/macrophages, rather than CD206⁺ cells, may exert anti-inflammatory effects by secreting TGFβ after the subacute stage of ischemic stroke. CD68⁺ microglia/macrophages can therefore be used as a potential therapeutic target.
Brain ; Haplorhini ; Immunohistochemistry ; Infarction, Middle Cerebral Artery ; Inflammation ; Macaca mulatta ; Magnetic Resonance Imaging ; Microglia ; Middle Cerebral Artery ; Primates ; Stroke ; Transforming Growth Factor beta

OBJECTIVES: The aim of this 7-year study was to examine regional differences in scaling experience rate. METHODS: This study used data on scaling experience rate from the Community Health Survey (CHS) obtained between 2008 and 2014. The standardized frequency of scaling experience rate was analyzed using the SPSS 20.0 program, and shown as a Box Plot. Using the Map Wizard for Excel 10.0, the scaling experience rate in each region was illustrated using Geographic Information System (GIS). RESULTS: The scaling experience rate in 2008 was 18.6% and in 2014, was 34.9%. From 2008 to 2014, the annual rate of scaling experience increased approximately 1.8 times. The scaling experience appeared to form clustering on GIS, and there were differences in scaling experience rate between cities, towns, and districts. Although the scaling experience rate increased, the gap between regions seems consistent. CONCLUSIONS: The Scaling Experience rate increased annually, but regional differences did not decrease. Therefore, oral health care professionals in each community should strive to improve the scaling experience rate.
Geographic Information Systems ; Health Surveys ; Oral Health

BACKGROUND: Melanomas need to be differentiated from benign melanocytic lesions during diagnosis. However, it is difficult to differentiate them using histopathology alone, since both neoplasms have broad morphological spectrums and subtle differentiating features. OBJECTIVE: To evaluate the usefulness of Ki-67/Melan-A double staining for differentiating melanoma from benign melanocytic nevi. METHODS: We selected 20 cases of intradermal nevi, 20 cases of compound nevi, 5 cases of dysplastic nevi, and 25 cases of melanoma from clinicopathologically proven cases reviewed by the Department of Dermatology at our medical center. Ki-67/Melan-A double staining was performed, and the Melan-A verified Ki-67 index (Ki-67-M index) and Ki-67 index were measured. The immunopositivity was measured in the deepest third of the lesions. RESULTS: The Ki-67-M index of intradermal nevi, compound nevi, dysplastic nevi, and melanoma were 0.4+/-0.9%, 1.0+/-1.1%, 4.3+/-1.7%, and 24.1+/-10.9%, respectively. The best Ki-67/Melan-A cut-off point to distinguish melanomas from benign melanocytic nevi was 5%; the sensitivity and specificity were 100% and 97.7%, respectively. Immunopositivity in the deepest third of the intradermal nevi, compound nevi, and melanoma, were 10.5%, 20%, and 100%, respectively; the sensitivity and specificity for diagnosing melanoma were 100% and 84.6%, respectively. The sensitivity and specificity of combined Ki-67-M and immunopositivity in the deepest third for diagnosing melanoma were 100% and 97.7%, respectively. CONCLUSION: The Ki-67-M index and immunopositivity in the deepest third of melanoma were significantly higher than that of benign melanocytic nevi. Therefore, Ki-67/Melan-A double staining is a potentially valuable diagnostic tool for differentiating melanoma from benign melanocytic nevi.
Dermatology ; Diagnosis ; Dysplastic Nevus Syndrome ; MART-1 Antigen ; Melanoma* ; Nevus ; Nevus, Intradermal ; Nevus, Pigmented* ; Sensitivity and Specificity

F-18 FDG PET is a metabolic imaging modality that is efficacious in staging and assessment of treatment response for variety of lymphomas. We report usefulness of F-18 FDG PET/CT in evaluating severity of the disease and response to therapy in a patient with subcutaneous panniculitis- like T-cell lymphoma (SPTCL). Here we describe a case of SPTCL in 24-year-old man who had wide spread firm and tender nodular lesions with increased F-18 FDG uptake. After chemotherapy follow up F-18 FDG PET/CT image shows disseminated malignancy and then the patient died with hemophagocytic syndrome. This report suggests that F-18 FDG PET/CT may be useful in determining disease activity at the time of initial diagnosis, after treatment, and evaluating a suspected outcome of SPTCL.
Follow-Up Studies ; Humans ; Lymphohistiocytosis, Hemophagocytic ; Lymphoma ; Lymphoma, T-Cell ; Panniculitis ; Young Adult

OBJECTIVES: It is now conventional practice to use human chorionic gonadotropin (hCG) as the marker of tumor activity in gestational trophoblastic disease (GTD). The interpretation of serial serum beta-hCG regression patterns is important in monitoring the course of the disease. The purpose of this study was to establish a regression time and pattern of the serum beta-hCG in which GTD is divided into hydatidiform mole and malignant trophoblastic disease. MATERIALS & METHODS: During the period from January 1990 through December 2000, 46 patients with GTD were histopathologically diagnosed and treated at the department of Obstetrics and Gynecology in Hanyang University Hospital. For the purpose of analysis and comparison, patients were divided into 19 cases of hydatidiform mole and 27 cases of malignant trophoblastic disease which was subdivided into nonmetastatic (17) and metastatic (10). Patients were followed clinically and by weekly estimations of quantitative serum beta-hCG until negative (<3 mIU/ml). After three consecutive negative beta-hCG, serum beta-hCG were drawn monthly in all patients for one year. The level of serum beta-hCG was detected by two-site sandwich immunoassay (Chiron Diagnostics Automated Chemiluminescence System 180). The obtained data were analyzed using t test and ANOVA test by SPSS. RESULTS: The incidence of the GTD compared with delivery was one per 182.7 deliveries. The mean value of serum beta-hCG regression time in hydatidiform mole was 12.8+/-1.1 (SEM) weeks (7.0-26.0 weeks) and 17.9+/-1.4 (SEM) weeks (8.0-34.0 weeks) in malignant trophoblastic disease. The regression time was significantly shorter in hydatidiform mole than that of malignant trophoblastic disease (P<0.01). The differences of mean value of serum beta-hCG regression time between the groups with nonmetastatic (18.0 weeks) and metastatic (17.8 weeks) were not statistically significant(P =0.946). The mean values of serum beta-hCG in both hydatidiform mole and malignant trophoblastic disease declined following a log-normal distribution. CONCLUSIONS: The regression pattern of serum beta-hCG in present study was similar to that of which in Western and also similar to that of which in Korea in 1980s. The present study supports the continued use of individual patients serum beta-hCG regression curve to make treatment decision and to recognize malignant trophoblastic disease promptly.
Chorionic Gonadotropin ; Female ; Gestational Trophoblastic Disease* ; Gynecology ; Humans ; Hydatidiform Mole ; Immunoassay ; Incidence ; Korea ; Luminescence ; Obstetrics ; Pregnancy ; Trophoblasts