Background: Hereditary hemolytic anemia (HHA) is a rare disease characterized by premature red blood cell (RBC) destruction due to intrinsic RBC defects. The RBC Disorder Working Party of the Korean Society of Hematology established and updated the standard operating procedure for making an accurate diagnosis of HHA since 2007. The aim of this study was to investigate a nationwide epidemiology of Korean HHA. Methods: We collected the data of a newly diagnosed pediatric HHA cohort (2007–2016) and compared this cohort's characteristics with those of a previously surveyed pediatric HHA cohort (1997–2006) in Korea. Each participant's information was retrospectively collected by a questionnaire survey. Results: A total of 369 children with HHA from 38 hospitals distributed in 16 of 17 districts of Korea were investigated. RBC membranopathies, hemoglobinopathies, RBC enzymopathies, and unknown etiologies accounted for 263 (71.3%), 59 (16.0%), 23 (6.2%), and 24 (6.5%) of the cases, respectively. Compared to the cohort from the previous decade, the proportions of hemoglobinopathies and RBC enzymopathies significantly increased (P < 0.001 and P = 0.008, respectively). Twenty-three of the 59 hemoglobinopathy patients had immigrant mothers, mostly from South-East Asia. Conclusion In Korea, thalassemia traits have increased over the past 10 years, reflecting both increased awareness of this disease and increased international marriages. The enhanced recognition of RBC enzymopathies is due to advances in diagnostic technique; however, 6.5% of HHA patients still do not have a clear diagnosis. It is necessary to improve accessibility of diagnosing HHA.

Background: Hodgkin's lymphoma (HL) constitutes 10%–20% of all malignant lymphomas and has a high cure rate (5-year survival, around 90%). Recently, interest has increased concerning preventing secondary complications (secondary cancer, endocrine disorders) in long-term survivors. We aimed to study the epidemiologic features and therapeutic outcomes of HL in children, adolescents, and young adults in Korea. Methods: We performed a multicenter, retrospective study of 224 patients aged < 25 years diagnosed with HL at 22 participating institutes in Korea from January 2007 to August 2016. Results: A higher percentage of males was diagnosed at a younger age. Nodular sclerosis histopathological HL subtype was most common, followed by mixed cellularity subtype.Eighty-one (36.2%), 101 (45.1%), and 42 (18.8%) patients were classified into low, intermediate, and high-risk groups, respectively. Doxorubicin, bleomycin, vinblastine, dacarbazine was the most common protocol (n = 102, 45.5%). Event-free survival rate was 86.0% ± 2.4%, while five-year overall survival (OS) rate was 96.1% ± 1.4%: 98.7% ± 1.3%, 97.7% ± 1.6%, and 86.5% ± 5.6% in the low, intermediate, and high-risk groups, respectively (P = 0.021). Five-year OS was worse in patients with B-symptoms, stage IV disease, highrisk, splenic involvement, extra-nodal lymphoma, and elevated lactate dehydrogenase level.In multivariate analysis, B-symptoms and extra-nodal involvement were prognostic factors for poor OS. Late complications of endocrine disorders and secondary malignancy were observed in 17 and 6 patients, respectively. Conclusion This is the first study on the epidemiology and treatment outcomes of HL in children, adolescents, and young adults in Korea. Future prospective studies are indicated to develop therapies that minimize treatment toxicity while maximizing cure rates in children, adolescents, and young adults with HL.

PURPOSE: Enolase is a cytoplasmic enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate in the glycolytic pathway. The aim of this study was to investigate whether the overexpression of neuron-specific enolase (NSE) can serve as a prognostic factor in patients with gastric cancer (GC). MATERIALS AND METHODS: To assess its prognostic value in GC, NSE expression was measured by immunohistochemistry in a clinically annotated tissue microarray comprising of 327 human GC specimens. Cytoplasmic NSE expression was scored from 0 to 4, reflecting the percentage of NSE-positive cells. RESULTS: In terms of histology as per the World Health Organization criteria (P=0.340), there were no differences between the NSE overexpression (NSE-OE) and NSE underexpression (NSE-UE) groups. The NSE-OE group showed a significantly lower rate of advanced GC (P<0.010), lymph node metastasis (P=0.010), advanced stage group (P<0.010), cancer-related death (P<0.010), and cancer recurrence (P<0.010). Additionally, a Kaplan-Meier survival analysis revealed that the NSE-OE group had longer cumulative survival times than the NSE-UE group (log-rank test, P<0.010). However, there were no significant differences in the serum levels of NSE expression in patients with GC and healthy volunteers (P=0.280). CONCLUSIONS: Patients with NSE overexpressing GC tissues showed better prognostic results, implying that NSE could be a candidate biomarker of GC.
Cytoplasm ; Healthy Volunteers ; Humans ; Immunohistochemistry ; Lymph Nodes ; Neoplasm Metastasis ; Phosphoenolpyruvate ; Phosphopyruvate Hydratase* ; Prognosis ; Recurrence ; Stomach Neoplasms* ; World Health Organization

The type III histone deacetylase silent information regulator 1 (SIRT1) is an enzyme that is critical for the modulation of immune and inflammatory responses. However, the data on its role in rheumatoid arthritis (RA) are limited and controversial. To better understand how SIRT1 regulates adaptive immune responses in RA, we evaluated collagen-induced arthritis (CIA) in myeloid cell-specific SIRT1 knockout (mSIRT1 KO) and wild-type (WT) mice. Arthritis severity was gauged on the basis of clinical, radiographic and pathologic scores. Compared with their WT counterparts, the mSIRT1 KO mice exhibited less severe arthritis, which was less destructive to the joints. The expression levels of inflammatory cytokines, matrix metalloproteinases and ROR-γT were also reduced in the mSIRT1 KO mice compared with the WT mice and were paralleled by reductions in the numbers of Th1 and Th17 cells and CD80- or CD86-positive dendritic cells (DCs). In addition, impaired DC maturation and decreases in the Th1/Th17 immune response were observed in the mSIRT1 KO mice. T-cell proliferation was also investigated in co-cultures with antigen-pulsed DCs. In the co-cultures, the DCs from the mSIRT1 KO mice showed decreases in T-cell proliferation and the Th1/Th17 immune response. In this study, myeloid cell-specific deletion of SIRT1 appeared to suppress CIA by modulating DC maturation. Thus, a careful investigation of DC-specific SIRT1 downregulation is needed to gauge the therapeutic utility of agents targeting SIRT1 in RA.
Animals ; Arthritis ; Arthritis, Experimental* ; Arthritis, Rheumatoid ; Coculture Techniques ; Cytokines ; Dendritic Cells* ; Down-Regulation ; Histone Deacetylases ; Joints ; Matrix Metalloproteinases ; Mice* ; T-Lymphocytes ; Th17 Cells

BACKGROUND: The number of patients diagnosed with hereditary hemolytic anemia (HHA) has increased since the advent of novel diagnostic techniques that accurately identify this disorder. Here, we report data from a survey on the prevalence and characteristics of patients diagnosed with HHA in Korea from 2007 to 2011. METHODS: Information on patients diagnosed with HHA in Korea and their clinical and laboratory results were collected using a survey questionnaire. Globin gene and red blood cell (RBC) enzyme analyses were performed. In addition, we analyzed data collected by pediatricians. RESULTS: In total, 195 cases of HHA were identified. Etiologies identified for HHA were RBC membranopathies, hemoglobinopathies, and RBC enzymopathies, which accounted for 127 (64%), 39 (19.9%), and 26 (13.3%) cases, respectively. Of the 39 patients with hemoglobinopathies, 26 were confirmed by globin gene analysis, including 20 patients with beta-thalassemia minor, 5 patients with alpha-thalassemia minor, and 1 patient with unstable hemoglobin disease. CONCLUSION: The number of patients diagnosed with hemoglobinopathies and RBC enzymopathies has increased considerably since the previous survey on HHA in Korea, dated from 1997 to 2006. This is likely the result of improved diagnostic techniques. Nevertheless, there is still a need for more sensitive diagnostic tests utilizing flow cytometry and for better standardization of test results to improve the accuracy of diagnosis of RBC membranopathies in Korea. Additionally, more accurate assays for the identification of RBC enzymopathies are warranted.
alpha-Thalassemia ; Anemia, Hemolytic, Congenital ; beta-Thalassemia ; Diagnostic Tests, Routine ; Erythrocytes ; Flow Cytometry ; Globins ; Hematology ; Hemoglobinopathies ; Hemoglobins ; Humans ; Korea ; Prevalence ; Spherocytosis, Hereditary ; Thalassemia ; Surveys and Questionnaires

BACKGROUND AND OBJECTIVES: S100 calcium-binding proteins are known to play multiple roles in progression and invasion of various carcinomas. In this study, we focused on two kinds of these proteins, S100A4 and S100A2, and investigated their expressions in thyroid neoplasm. SUBJECTS AND METHOD: We investigated S100A4 and S100A2 expressions in 75 thyroid neoplasms by immunohistochemistry. RESULTS: S100A4 and S100A2 were not expressed in normal thyroid follicles or follicular carcinomas. Positive relationships were established between S100A4 expression and size (p=.014), invasiveness (p=.029) and T stage (p=.004) of papillary carcinomas. Especially, the S100A4 expression was observed more frequently in the peripheral area (p=.046). But there was no correlation between S100A4 expression with multiple tumor formation and lymph node metastasis. Positive relationships were established between S100A2 expression and size (p=.041), invasiveness (p=.008) and T stage (p<.001) of papillary carcinomas. S100A4 expression was also observed more frequently in the peripheral area (p=.001). CONCLUSION: These findings suggest that S100A4 and S100A2 contribute to the progression and local invasion of thyroid carcinoma.
Calcium-Binding Proteins ; Carcinoma, Papillary ; Immunohistochemistry ; Lymph Nodes ; Neoplasm Metastasis ; Thyroid Gland* ; Thyroid Neoplasms*

BACKGROUND: The aim of this study was to investigate the prevalence, clinical and laboratory findings of hereditary hemolytic anemia (HHA) in Korea from 1997 to 2006 and to develop the appropriate diagnostic approach for HHA. METHODS: By the use of questionnaires, information on the clinical and laboratory findings ofHHA diagnosed from 1997 to 2006 in Korea was collected and analyzed retrospectively. A total of 431 cases were enrolled in this study from 46 departments of 35 hospitals. RESULTS: The overall frequency of HHA did not change through the 10-year period for pediatrics but did show an increasing tendency for internal medicine. The overall male to female sex ratio did not show sex predominance (1.17:1), but a significant male predominance with a ratio of 1.49:1 was seen for pediatrics while a significant female predominance with a ratio of 1:1.97 was seen forinternal medicine. Of the total cases, 74.2% (282/431) were diagnosed before the age of 15 years. The etiologies of HHA were classified as red cell membrane defects, hemoglobinopathies, red cell enzyme deficiencies and unknown causes. There were 382 cases (88.6%) of red cell membrane defects with 376 cases (87.2%) of hereditary spherocytosis and 6 cases (1.4%) of hereditary elliptocytosis, 20 cases (4.6%) of hemoglobinopathies with 18 cases (4.2%) of beta-thalassemia, a case (0.2%) of alpha-thalassemia and a case (0.2%) of Hemoglobin Madrid, 7 cases (1.6%) of red cell enzyme deficiencies with 5 cases (1.2%) of glucose-6- phosphate dehydrogenase (G-6-PD) deficiency, a case (0.2%) of pyruvate kinase (PK) deficiency and a case (0.2%) of enolase deficiency, and 22 cases (5.1%) of unknown causes. The most common chief complaint in pediatric patients was pallor and that in adult patients was jaundice. In the red cell membrane defect group of patients, the level of hemoglobin was significantly higher than in adult patients. The mean corpuscular volume, mean corpuscular hemoglobin, corrected reticulocyte count, total and indirect bilirubin level and lactate dehydrogenase levels in the hemoglobinopathy group of patients were significantly lower than the values in the red cell membrane defect group of patients. The mean concentration of G-6-PD was 0.8+/-0.7U/1012RBC in the G-6-PD deficient patients, PK was 1.7U/1010 RBC in the PK deficient patient, and the level of enolase was 0.04U/g of Hb in the enolase deficient patient. CONCLUSION: The most prevalent cause of HHA in Korea during 1997 to 2006 was hereditary spherocytosis, but HHA by other causes such as hemoglobinopathy and red cell enzyme deficiency gradually increased with the development of molecular diagnostic methods and increasing general interest. However, the etiologies of HHA need to be pursued further in 5.1% of the patients. An systematic standard diagnostic approach is needed in a nationwide prospective study for correct diagnoses and appropriate management of HHA.
Adult ; alpha-Thalassemia ; Anemia, Hemolytic, Congenital* ; beta-Thalassemia ; Bilirubin ; Cell Membrane ; Diagnosis ; Elliptocytosis, Hereditary ; Erythrocyte Indices ; Female ; Hemoglobinopathies ; Humans ; Internal Medicine ; Jaundice ; Korea* ; L-Lactate Dehydrogenase ; Male ; Oxidoreductases ; Pallor ; Pathology, Molecular ; Pediatrics ; Phosphopyruvate Hydratase ; Prevalence ; Pyruvate Kinase ; Reticulocyte Count ; Retrospective Studies* ; Sex Ratio ; Surveys and Questionnaires

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that may affect many organ systems including the nervous system. The immune response in patients with SLE can cause inflammation and other damage that can cause significant injury to the arteries and tissues. A 48-year-old woman was admitted to the hospital because of transient monocular blindness. Magnetic resonance imaging and conventional angiography showed severe stenosis of the distal intracranial internal carotid artery. The patient was diagnosed as having SLE but the antiphospholipid antibodies were negative. Amaurosis fugax has not been previously reported as an initial manifestation of SLE in Korea. We report a patient with a retinal transient ischemic attack as the first manifestation of SLE.
Amaurosis Fugax* ; Angiography ; Antibodies, Antiphospholipid* ; Arteries ; Autoimmune Diseases ; Blindness* ; Carotid Artery, Internal ; Constriction, Pathologic ; Female ; Humans ; Inflammation ; Ischemic Attack, Transient ; Korea ; Lupus Erythematosus, Systemic* ; Magnetic Resonance Imaging ; Middle Aged ; Nervous System ; Retinaldehyde

A 59 year-old woman who had suffered daily headaches was diagnosed with leptomeningeal metastasis. Leptomeningeal metastasis is uncommon but devastating form of metastatic spread. Cerebral venous thrombosis is a disease sometimes associated with systemic cancer. Rarely, cerebral sinus occlusion accompanies leptomeningeal cancer. We report a patient who had cerebral sinus thrombosis and leptomeningeal metastasis.
Female ; Headache ; Humans ; Middle Aged ; Neoplasm Metastasis* ; Sinus Thrombosis, Intracranial ; Venous Thrombosis*