Hereditary hemolytic anemia (HHA) is considered a group of rare hematological diseases in Korea, primarily because of its unique ethnic characteristics and diagnostic challenges.Recently, the prevalence of HHA has increased in Korea, reflecting the increasing number of international marriages and increased awareness of the disease. In particular, the diagnosis of red blood cell (RBC) enzymopathy experienced a resurgence, given the advances in diagnostic techniques. In 2007, the RBC Disorder Working Party of the Korean Society of Hematology developed the Korean Standard Operating Procedure for the Diagnosis of Hereditary Hemolytic Anemia, which has been continuously updated since then. The latest Korean clinical practice guidelines for diagnosing HHA recommends performing nextgeneration sequencing as a preliminary step before analyzing RBC membrane proteins and enzymes. Recent breakthroughs in molecular genetic testing methods, particularly nextgeneration sequencing, are proving critical in identifying and providing insight into cases of HHA with previously unknown diagnoses. These innovative molecular genetic testing methods have now become important tools for the management and care planning of patients with HHA. This review aims to provide a comprehensive overview of recent advances in molecular genetic testing for the diagnosis of HHA, with particular emphasis on the Korean context.

BACKGROUND: Immunohistochemical demonstration of CD20 in diffuse large B-cell lymphoma (DLBCL) is prerequisite not only for the diagnosis but also for assigning patients to rituximab-containing chemotherapy. However, little is known about the impact of abundance of CD20 expression assessed by immunohistochemistry on the clinical outcome of DLBCL. We performed a semi-quantitative immunohistochemical analysis of CD20 expression in DLBCL to examine the prognostic implication of the level of CD20 expression. METHODS: Pre-treatment diagnostic tissue samples from 48 DLBCL patients who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen were represented in a tissue microarray and immunostained for CD20. The relative abundance of CD20 expression was semi-quantitatively scored using a web-based ImmunoMembrane plug-in. Receiver operating characteristic curve analysis was used to determine a prognostically relevant cut-off score in order to dichotomize the patients into CD20-high versus CD20-low groups. RESULTS: The levels of CD20 expression were heterogeneous among the patients, with a wide and linear distribution of scores. Patients in CD20-low group showed significantly poor clinical outcome. CONCLUSIONS: The levels of CD20 expression in DLBCL are heterogeneous among the patients with DLBCL. A subgroup of the patients with CD20 expression levels below the cut-off score showed poor clinical outcome.
Antigens, CD20 ; B-Lymphocytes* ; Cyclophosphamide ; Diagnosis ; Doxorubicin ; Drug Therapy ; Humans ; Immunohistochemistry ; Lymphoma, B-Cell* ; Prednisone ; ROC Curve ; Tissue Array Analysis ; Vincristine ; Rituximab

PURPOSE: To determine the long-term patency of percutaneous intravascular metallic stent placement in patients with chronic iliac artery stenosis. MATERIALS AND METHODS: Intravascular metallic stents were placed percutaneously in 41 limbs of 38 patients with chronic iliac artery stenosis who presented with intermittent claudication in 40 limbs and gangrene in the other. Preoperative angiography showed that complete occlusion occurred in one limb, and luminal stenosis of over 50% in 34 and of less than 50% in six. The mean length of stenoses was 3.1 (range, 1 -8) cm, and in all cases the systolic pressure gradient was over 10 (range, 12 -100, mean, 43) mmHg. Stent placement was indicated by failed balloon angioplasty in 35 limbs, primary stenting in five, and restenosis after balloon angioplasty in one. Technical and clinical success were evaluated in terms of immediate results and stent patency over a period of 1 -49 (mean, 19) months (Kaplan-Meier method). RESULTS: Stent placement was successful in all cases in which residual stenosis was less than 10% and systolic pressure gradient less than 2 mmHg. One to three days after the procedure, clinical symptoms had improved in 40 limbs and ABI (n=23) had increased from 0.64 +/-0.20 to 0.92 +/-0.17. Follow-up studies demonstrated patency rates of 94.1% at 6 months, 90.7% at 1 year, 86.6% at 2 years, and 86.6% at 4 years. CONCLUSION: Our results showed that in patients with chronic iliac artery stenosis, percutaneous intravascular metallic stent placement led to patency rates which were similar over a period of between six months and four years.
Angiography ; Angioplasty, Balloon ; Blood Pressure ; Constriction, Pathologic* ; Extremities ; Follow-Up Studies ; Gangrene ; Humans ; Iliac Artery* ; Intermittent Claudication ; Phenobarbital ; Stents*

BACKGROUND: The natural course of cytologically benign thyroid nodules remains unclear. The aim of this study was to evaluate whether ultrasonographic (US) changes are associated with changes in nodule volume during follow-up. METHODS: We retrospectively reviewed over 4 years of clinical records of patients with benign thyroid nodules as confirmed by fine needle aspiration (FNA). In total, 186 patients with 202 benign thyroid nodules were included for study. We assessed for changes in nodule volume and examined the cystic portion of the nodule as well as four US features (echogenicity, margin, calcification pattern, and shape). RESULTS: During follow-up (mean, 21.7+/-10.7 months) and using 50% as a cutoff value, nodule volumes increased in 11.8%, exhibited no change in 79.9%, and decreased in 8.3% of patients. Proportion of nodules demonstrating at least one US change was 20.8% (42/202). The most common US changes (in descending order of frequency) were cystic change, margin change, and calcification pattern change. Nodule shape and echogenicity rarely changed. Increased nodule volume was not significantly associated with any US features or with the number of FNAs but was associated with younger age at time of diagnosis. CONCLUSION: Although a portion of thyroid nodules confirmed as benign showed US changes or volume changes during the follow-up period, these findings may only represent the natural course of benign nodules. Frequent follow-up with US might be needed for only a small number of cases with suspicious US findings.
Biopsy, Fine-Needle ; Follow-Up Studies ; Humans ; Retrospective Studies ; Thyroid Gland ; Thyroid Nodule ; Tumor Burden

BACKGROUND: Epithelial mesenchymal transition (EMT) has an important role in invasion and metastasis of tumor cells. The purpose of this study was to evaluate the roles of EMT-associated proteins on progression and metastasis as a prognostic/predictive factor in curatively-resected (R0) head and neck squamous cell carcinoma (HNSCC). METHODS: A total of 118 patients who received curative surgery for HNSCC at Inha University Hospital between January 1996 and December 2011 were included. We used protein immunohistochemistry to evaluate the expression of E-cadherin, vimentin, and EZH2 on tissue microarrays. Also, we reviewed all medical records and analyzed the relationship between the expression of EMT-associated proteins and prognosis. RESULTS: The E-cadherin-negative group showed more moderate/poor differentiation of cancer cell type than the higher E-cadherin-expressing group (p=.016) and high EZH2 expression was significantly correlated with nodal metastasis (p=.012). Our results demonstrate a significant association between high expression of EZH2 and vimentin and presence of distant progression (p=.026). However, expression of E-cadherin, vimentin, and EZH2 was not significantly associated with overall survival. CONCLUSIONS: These findings suggest that an EMT-associated protein expression profile is correlated with aggressiveness of disease and prognosis, and could be a useful marker for determination of additional treatment in curatively-resected HNSCC patients.
Cadherins ; Carcinoma, Squamous Cell* ; Epithelial-Mesenchymal Transition* ; Head* ; Humans ; Immunohistochemistry ; Medical Records ; Neck* ; Neoplasm Metastasis ; Prognosis ; Vimentin

Coxsackievirus B3 (CVB3) is a non-enveloped virus that has a single-stranded RNA genome. CVB3 induces myocarditis, and ultimately, dilated cardiomyopathy. A myocarditis variant of CVB3 (CVB3 H3) and its antibody-escape mutant (CVB3 10A1) were studied previously; H3 was found to induce myocarditis and 10A1 was found to be attenuated in infected mice. Although amino acid residue 165, located in a puff region of VP2, was found to be altered (i.e., the H3 asparagine was altered to aspartate in 10A1), the detailed mechanism of attenuation was not clearly elucidated. Here, DNA microarray technology was used to monitor changes in mRNA levels of infected mouse hearts after CVB3 H3 and 10A1 infection. This tool was used to elucidate the pathogenic mechanisms of viral infection by understanding virus-host interactions. We identified several genes, including protein tyrosine kinases, Ddr2 and Ptk2, as well as Clqb and Crry, involved in complement reactions, which may be involved in these viral processes. Thus, gene profiling can provide an opportunity to understand host immune responses to viral infection for gene therapy and may contribute to the identification of the target gene that is modified during treatment of viral myocarditis.
Animals ; Asparagine ; Aspartic Acid ; Cardiomyopathy, Dilated ; Complement System Proteins ; Genetic Therapy ; Genome ; Heart* ; Mice* ; Myocarditis ; Oligonucleotide Array Sequence Analysis ; Protein-Tyrosine Kinases ; RNA ; RNA, Messenger

BACKGROUND/AIMS: The aim of our study was to determine the incidence and clinical features of severe pulmonary complications in patients receiving cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab plus CHOP (R-CHOP) as the initial treatment for lymphoma. METHODS: A retrospective analysis of pulmonary infection and drug-induced interstitial pneumonitis (DIIP) was performed using lymphoma registry data. R-CHOP was administered in 71 patients and CHOP in 29 patients. RESULTS: The severe pulmonary adverse events tended to occur more frequently with R-CHOP (18.3%) than CHOP alone (13.8%), although the difference was not significant (p = 0.771). DIIP occurred in five patients in the R-CHOP arm (7%) and in one in the CHOP arm (3%). The continuous use of steroids for conditions other than lymphoma significantly increased the risk of pulmonary infection including Pneumocystis jiroveci pneumonia (p = 0.036) in the multivariate analysis. International prognostic index, tumor stage, smoking, previous tuberculosis, chronic obstructive pulmonary disease, and lymphoma involvement of lung parenchyma were not related to pulmonary adverse events. Patients who experienced severe pulmonary events showed shorter survival when compared to those without complications (p = 0.002). CONCLUSIONS: Our experiences with serial cases with DIIP during chemotherapy and the correlation of continuous steroid use with pulmonary infection suggest that the incidence of pulmonary complications might be high during lymphoma treatment, and careful monitoring should be performed.
Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal/administration & dosage/*adverse effects ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*adverse effects ; Cyclophosphamide/administration & dosage/adverse effects ; Doxorubicin/administration & dosage/adverse effects ; Female ; Humans ; Incidence ; Lung Diseases, Interstitial/*chemically induced/mortality ; Lymphoma, Non-Hodgkin/*drug therapy/mortality ; Male ; Middle Aged ; Pneumocystis jirovecii ; Pneumonia, Bacterial/mortality ; Pneumonia, Pneumocystis/mortality ; Prednisone/administration & dosage/adverse effects ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; Tuberculosis, Pulmonary/mortality ; Vincristine/administration & dosage/adverse effects ; Young Adult

Although the prevalence of hereditary hemolytic anemia (HHA) is relatively low in Korea, it has been gradually increasing in recent decades due to increment in the proportions of hemoglobinopathies from immigrants of South East Asia, raising awareness of the disease among clinicians, and advances in diagnostic technology. As such, the red blood cell (RBC) Disorder Working Party (WP), previously called HHA WP, of the Korean Society of Hematology (KSH) developed the Korean Standard Operating Procedures (SOPs) for the diagnosis of HHA in 2007. These SOPs have been continuously revised and updated following advances in diagnostic technology [e.g., flow cytometric osmotic fragility test (FOFT) and eosin-5-maleimide (EMA) binding test], current methods for membrane protein or enzyme analysis [e.g., liquid chromatography-tandem mass spectrometry (LC-MS/MS), ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), high-performance liquid chromatography (HPLC)], and molecular genetic tests using next-generation sequencing (NGS). However, the diagnosis and treatment of HHA remain challenging as they require considerable experience and understanding of the disease. Therefore, in this new Korean Clinical Practice Guidelines for the Diagnosis of HHA, on behalf of the RBC Disorder WP of KSH, updated guidelines to approach patients suspected of HHA are summarized. NGS is proposed to perform prior to membrane protein or enzyme analysis by LC-MS/MS, UPLC-MS/MS or HPLC techniques due to the availability of gene testing in more laboratories in Korea. We hope that this guideline will be helpful for clinicians in making diagnostic decisions for patients with HHA in Korea.

OBJECTIVES: It is increasingly thought that the human cerebellum plays an important role in emotion and cognition. Although recent evidence suggests that the cerebellum may also be implicated in fear learning, only a limited number of studies have investigated the cerebellar abnormalities in panic disorder. The aim of this study was to evaluate the cerebellar gray matter deficits and their clinical correlations among patients with panic disorder. METHODS: Using a voxel-based morphometry approach with a high-resolution spatially unbiased infratentorial template, regional cerebellar gray matter density was compared between 23 patients with panic disorder and 33 healthy individuals. RESULTS: The gray matter density in the right posterior-superior (lobule Crus I) and left posterior-inferior (lobules Crus II, VIIb, VIIIa) cerebellum was significantly reduced in the panic disorder group compared to healthy individuals (p < 0.05, false discovery rate corrected, extent threshold = 100 voxels). Additionally, the gray matter reduction in the left posterior-inferior cerebellum (lobule VIIIa) was significantly associated with greater panic symptom severity (r = -0.55, p = 0.007). CONCLUSIONS: Our findings suggest that the gray matter deficits in the posterior cerebellum may be involved in the pathogenesis of panic disorder. Further studies are needed to provide a comprehensive understanding of the cerebro-cerebellar network in panic disorder.
Cerebellum* ; Cognition ; Humans ; Learning ; Panic ; Panic Disorder*

BACKGROUND: To standardize renal biopsy reporting and diagnosis, The Renal Pathology Study Group of the Korean Society of Pathologists (RPSKSP) has developed a renal pathology reporting format for the native and allograft kidney. METHODS: A consensus checklist of a provisional renal biopsy format was sent to all members of the RPSKSP. Feed back opinions regarding the practical application of the checklist to the diagnostic work were received. RESULTS: Kidney biopsies require three essential examinations: by light microscopy, immunofluorescence (IF), and electron microscopy (EM). A final report of a renal biopsy should include information on specimen adequacy and a description of the morphologic change using a systematic semiquantitative method for each of the compartments, with optional separate IF and EM reports. CONCLUSIONS: A standard renal biopsy report format is important in establishing clinicopathologic correlations, making reliable prognostic considerations, comparing the findings in sequential biopsies and evaluating the effects of therapy.
Biopsy ; Checklist ; Consensus ; Kidney ; Light ; Microscopy, Electron ; Microscopy, Fluorescence ; Transplantation, Homologous