Although safe and effective vaccines for hepatitis B virus (HBV) have been available for nearly three decades, this virus kills at least 600,000 people annually worldwide and remains the leading global cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Because the HBV reverse transcriptase lacks a proofreading function, many HBV genotypes, subgenotypes, mutants, and recombinants exist. At least 10 HBV genotypes (HBV-A through J) with distinct geographic distributions have been identified; by definition, their complete genomic sequences diverge by more than 8%. HBV genotype is increasingly becoming recognized as an important factor in the progression and clinical outcome of HBV-induced disease. Infections by HBV-C or -D are significantly more likely to lead to cirrhosis and hepatocellular carcinoma than are infections by HBV-A or -B. Additionally, the hepatitis B e antigen seroconversion response to standard or pegylated interferon is more favorable in patients with HBV-A or -B than in those with HBV-C or -D. However, therapeutic responses to nucleos(t)ide analogues are generally comparable among HBV genotypes. In conclusion, genotyping of HBV is useful in identifying chronic hepatitis B patients who are at increased risk of disease progression, thereby enabling physicians to optimize antiviral therapy for these patients.

The incidence of allergic diseases in most industrialized countries has increased. Although the exact mechanisms behind this rapid increase in prevalence remain uncertain, a variety of air pollutants have been attracting attention as one causative factor. Epidemiological and toxicological research suggests a causative relationship between air pollution and the increased incidence of asthma, allergic rhinitis, and other allergic disorders. These include ozone, nitrogen dioxide and, especially particulate matter, produced by traffic-related and industrial activities. Strong epidemiological evidence supports a relationship between air pollution and the exacerbation of asthma and other respiratory diseases. Recent studies have suggested that air pollutants play a role in the development of asthma and allergies. Researchers have elucidated the mechanisms whereby these pollutants induce adverse effects; they appear to affect the balance between antioxidant pathways and airway inflammation. Gene polymorphisms involved in antioxidant pathways can modify responses to air pollution exposure. While the characterization and monitoring of pollutant components currently dictates pollution control policies, it will be necessary to identify susceptible subpopulations to target therapy/prevention of pollution-induced respiratory diseases.

Background/Aims: Sleep disorder (SD) is associated with an increased risk of cardiovascular disease and is more prevalent among individuals with type 2 diabetes mellitus. These health problems not only frequently coexist but also exacerbate each other. We conducted a cross-sectional study to estimate the prevalence of SD among diabetic patients and to investigate the relationship between SD and cardiovascular risk among these patients. Methods: We recruited 784 patients with type 2 diabetes and conducted a self-administered questionnaire. We assessed sleep quality using the Pittsburgh Sleep Quality Index and the risk of obstructive sleep apnea (OSA) using the Berlin Questionnaire. Additional information included blood pressure and metabolic profiles. Results: Of the 784 diabetic patients, 301 (38.4%) patients had poor sleep quality, and 124 (15.8%) were at high risk for OSA. Patients at increased risk for OSA were more obese; they also had higher blood pressure, fasting plasma insulin levels, insulin resistance assessed by homeostasis model assessment (HOMA-IR), and serum triglycerides levels (p < 0.05). The frequency of risk for OSA was higher among obese patients compared with non-obese patients (34.8% vs. 9.4%, p < 0.05). Logistic regression analysis revealed that male sex and bone mass index were independent predictors of risk for OSA. Conclusions: SD was prevalent among type 2 diabetic patients, and OSA could aggravate their risk for cardiovascular disease. Clinical treatment of these patients should include evaluation and intervention for SD.

Background/Aims: The objective of this study was to determine whether insulin resistance is associated with gallbladder stone formation in Korean women based on menopausal status. Methods: The study included 4,125 consecutive Korean subjects (30-79 years of age). Subjects who had a medical history of diabetes, hypertension, dyslipidemia, other cardiovascular disorders, or hormone replacement therapy were excluded. The women were subdivided into two groups according to their menopausal status. Results: Analysis of premenopausal women showed no significant differences in the homeostasis model of assessment-insulin resistance (HOMA-IR) index between the two groups in terms of gallstone disease. The associations between the occurrence of gallbladder stones and age, obesity, abdominal obesity, hyperinsulinemia, and high HOMA-IR index were statistically significant in the analysis with postmenopausal women. In a multiple logistic regression analysis, low high density lipoprotein-cholesterol was an independent predictor of gallbladder stone formation in premenopausal women. However, the multiple logistic regression analysis also showed that age and HOMA-IR were significantly associated with gallbladder stone formation in postmenopausal women. In an additional analysis stratified by obesity, insulin resistance was a significant risk factor for gallbladder stone formation only in the abdominally obese premenopausal group. Conclusions: Insulin resistance may be associated with gallbladder stone formation in Korean postmenopausal women with abdominal obesity.

Background/Aims: A controversy exists about which statin is preferable for patients with acute myocardial infarction (AMI), and clinical impacts of different statins according to lipophilicity have not been established. Methods: The 1,124 patients with AMI included in the present study were divided into hydrophilic- and lipophilic-statin groups. In-hospital complications (defined as death, cardiogenic shock, ventricular arrhythmia, infection, bleeding, and renal insufficiency, and other fatal arrhythmias), major adverse cardiac events (MACE), all-cause death, re-myocardial infarction, re-percutaneous coronary intervention (re-PCI), and surgical revascularization were analyzed during a 1-year clinical follow-up. Results: Baseline characteristics were similar between the two groups, and in-hospital complication rates showed no between-group differences (11.7% vs. 12.8%, p = 0.688). Although MACE at the 1- and 6-month clinical follow-ups occurred more in hydrophilic statin group I (1 month: 10.0% vs. 4.4%, p = 0.001; 6 month: 19.9% vs. 14.2%, p = 0.022), no significant difference in MACE was observed at the 1-year follow-up (21.5% vs. 17.9%, p = 0.172). Both statin groups showed similar efficacy for reducing serum lipid concentrations. A Cox-regression analysis showed that the use of a hydrophilic statin did not predict 1-year MACE, all-cause death, AMI, or re-PCI. Conclusions: Although short-term cardiovascular outcomes were better in the lipophilic-statin group, 1-year outcomes were similar in patients with AMI who were administered hydrophilic and lipophilic statins. In other words, the type of statin did not influence 1-year outcomes in patients with AMI.

Background/Aims: Oxidative stress results in protein oxidation and is implicated in carcinogenesis. Sulfiredoxin (Srx) is responsible for the enzymatic reversal of inactivated peroxiredoxin (Prx). Nuclear factor E2-related factor 2 (Nrf2) binds to antioxidant responsive elements and upregulates the expression of Srx and Prx during oxidative stress. We aimed to elucidate the biological functions and potential roles of Srx in lung cancer. Methods: To study the roles of Srx and Prx III in lung cancer, we compared the protein levels of Nrf2, Prxs, thioredoxin, and Srx in 40 surgically resected human lung cancer tissues using immunoblot and immunohistochemical analyses. Transforming growth factor-${\beta}_1$, tumor necrosis factor-${\alpha}$, and camptothecin treatment were used to examine Prx III inactivation in Mv1Lu mink lung epithelial cells and A549 lung cancer cells. Results: Prx I and Prx III proteins were markedly overexpressed in lung cancer tissues. A significant increase in the oxidized form of a cysteine sulfhydryl at the catalytic site of Prxs was found in carcinogenic lung tissue compared to normal lung tissue. Densitometric analyses of immunoblot data revealed significant Srx expression, which was higher in squamous cell carcinoma tissue (60%, 12/20) than in adenocarcinoma (20%, 4/20). Also, Nrf2 was present in the nuclear compartment of cancer cells. Conclusions: Srx and Prx III proteins were markedly overexpressed in human squamous cell carcinoma, suggesting that these proteins may play a protective role against oxidative injury and compensate for the high rate of mitochondrial metabolism in lung cancer.

Background/Aims: Hypoalbuminemia occurs frequently in renal transplant recipients immediately after renal transplantation. We studied the regulation of hepatic albumin synthesis by cyclosporin A (CsA) in Huh7 cells. Methods: Huh7 cells were incubated with various concentrations of CsA for 4, 8, 16, and 24 hours. Albumin was measured in Huh7 cell-conditioned medium by sandwich enzyme-linked immunosorbent assay and Western blot. Albumin mRNA expression was analyzed by Northern blotting in CsA-treated cells. Results: CsA ($10^{-7}-10^{-4}$ M) inhibited albumin synthesis in Huh7 cells in a dose- dependent manner. A Western blot analysis for albumin in the conditioned medium released from CsA-treated ($10^{-7}-10^{-5}$ M) cells also showed significant inhibition of albumin synthesis in a dose-dependent manner. Vehicle (olive oil) did not affect albumin synthesis. In contrast, a Northern blot analysis revealed no inhibition of albumin mRNA expression by CsA at any time point from 1-24 hours, indicating that the inhibition of albumin synthesis occurred at the translational level. Conclusions: Our results suggest that inhibition of hepatic albumin synthesis by high dose CsA contributes to the hypoalbuminemia in renal transplant recipients.

Background/Aims: We assessed changes in hemodynamic and arterial stiffness parameters following reductions of dialysate calcium concentrations in patients undergoing hemodialysis. Methods: In this prospective study, 20 patients on maintenance hemodialysis (10 females, 10 males) with dialysate calcium concentrations of 1.75 mmol/L were enrolled. At the start of the study, the dialysate calcium level was lowered to 1.50 mmol/L. Serial changes in biochemical, hemodynamic, and arterial stiffness parameters, including pulse wave velocity (PWV) and augmentation index (AIx), were assessed every 2 months for 6 months. We also examined changes in the calcification-inhibitory protein, serum fetuin-A. Results: During the 6-month study period, serum total calcium and ionized calcium decreased consistently (9.5 ${\pm}$ 1.0 to 9.0 ${\pm}$ 0.7, p = 0.002 vs. 1.3 ${\pm}$ 0.1 to 1.1 ${\pm}$ 0.1, p = 0.035). Although no apparent changes in blood pressure were observed, heart-femoral PWW (hf-PWV) and AIx showed significant improvement (p = 0.012, 0.043, respectively). Repeated-measures ANOVA indicated a significant effect of lowering dialysate calcium on hf-PWV (F = 4.58, p = 0.004) and AIx (F = 2.55, p = 0.049). Accompanying the change in serum calcium, serum fetuin-A levels significantly increased (95.8 ${\pm}$ 45.8 pmol/mL at baseline to 124.9 ${\pm}$ 82.2 pmol/mL at 6 months, p = 0.043). Conclusions: Lowering dialysate calcium concentration significantly improved arterial stiffness parameters, which may have been associated with upregulation of serum fetuin-A.

Background/Aims: We investigated the clinical characteristics and prognosis of elderly patients with acute lymphoblastic leukemia (ALL). Methods: We reviewed the clinical data, laboratory findings, bone marrow findings, and cytogenetic analysis of elderly patients (${\geq}$ 60 years) with ALL, and data of an additional 101 younger adult patients (< 60 years) with ALL were reviewed for comparison. Results: Twenty-six elderly patients (${\geq}$ 60 years) and 101 younger adult patients (< 60 years) with ALL were retrospectively enrolled. The median follow-up duration was 6.0 months (range, 0.4 to 113.2) in the elderly patients and 21.7 months (range, 1.0 to 122.7) in the adult patients. In total, 34.6% (9 patients) of the elderly patients and 24.8% (25 patients) of the adult patients had Philadelphia chromosome positive ALL. The overall complete remission (CR) rate was much higher in the younger than in the elderly patients (94.1% vs. 57.7%, p < 0.001). The median overall survival (OS) of the younger patients (< 60 years) was 26.3 months, whereas that of the elderly patients (${\geq}$ 60 years) was 10.3 months (p = 0.003). In the elderly patients with ALL, T cell lineage and the presence of lymphadenopathy were significant prognostic factors for OS in a univariate analysis (p = 0.033 and 0.041, respectively). Conclusions: The outcomes of Korean elderly patients with ALL were poor, and the shorter OS was mainly due to the low CR rate. T-cell lineage and the presence of lymphadenopathy were significant prognostic factors in Korean elderly patients with ALL.

Background/Aims: The aim of this study was to assess the efficacy and safety of monthly oral 150 mg ibandronate in women with postmenopausal osteoporosis (PMO). Methods: A systematic review and meta-analysis were performed to determine treatment efficacy and safety outcomes between monthly oral 150 mg ibandronate and weekly 70 mg alendronate, daily 2.5 mg ibandronate, and a placebo. Results: Eight randomized controlled trials were included in this systematic review and meta-analysis. Once-monthly 150 mg ibandronate therapy was clinically comparable to weekly 70 mg alendronate, showing increased bone mineral density (BMD) in both the lumbar spine and total hip. Pooled data from two cross-over trials showed that significantly more women with PMO preferred once-monthly ibandronate therapy to once-weekly alendronate therapy (relative risk [RR], 2.422; 95% confidence interval [CI], 2.111 to 2.825; p < $1\;{\times}\;10^{-8}$) and found the monthly ibandronate regimen more convenient than the weekly alendronate regimen (RR, 3.096; 95% CI, 2.622 to 3.622; p < $1\;{\times}\;10^{-8}$). Monthly 150 mg ibandronate therapy resulted in a significantly higher change in BMD of the lumbar spine than with the placebo. A once monthly 150 mg regimen produced greater increases in lumbar spine, total hip, femoral neck, and trochanter BMD than daily treatment, with a similar incidence of adverse events between the groups. Conclusions: Once monthly 150 mg ibandronate therapy was clinically comparable to weekly 70 mg alendronate, and patients strongly preferred the convenience of monthly ibandronate over weekly alendronate. Monthly 150 mg ibandronate was superior to, and as well tolerated as, the daily treatment.

The most common pancreatic cancer is adenocarcinoma. Primary adenosquamous cell carcinoma of the pancreas is very rare and aggressive. A 46-year-old man presented with a 3-month history of dyspepsia and a 7-kg weight loss. The physical examination showed tenderness of the right upper quadrant of the abdomen. There was no jaundice. Amylase and lipase were elevated. CA 19-9 was elevated to 566.7 U/mL. Gastroduodenoscopy showed a hard ulceroinfiltrative mass with a yellowish exudate that bled readily on touch in the second portion of the duodenum. Abdominal computed tomography showed a 7.1 ${\times}$ 6.3-cm heterogeneously enhancing mass in the pancreatic head. The pancreatic mass had invaded the duodenum wall, gastric antrum, and gastroduodenal artery sheath. Fine-needle aspiration biopsy of the pancreatic mass revealed adenosquamous cell carcinoma, anaplastic type. We concluded that an adenosquamous cell carcinoma of pancreas had invaded the duodenal mucosa causing ulceration.

Spontaneous retroperitoneal hemorrhage is a distinct clinical entity that can present in the absence of specific underlying pathology or trauma and is typically associated with anticoagulation therapy. We report a case of a 74-year-old female patient with a cerebral infarction related to atrial fibrillation who developed a spontaneous lumbar arterial hemorrhage complicating heparin therapy. The diagnosis was suggested by a computed tomography scan and confirmed by angiography. She was treated successfully with transcatheter embolization.

Idiopathic granulomatous mastitis (IGM) is a rare and chronic benign disease of the breast. Histologically, the disease presents as an intense inflammatory reaction with non-caseated granulomas that are the characteristic symptom of the disease. No consensus exists on the best treatment modality for this disease. In this report, we present a patient with granulomatous mastitis who was treated successfully with low-dose oral and topical steroids. Our aim here is to discuss various approaches for IGM in view of the literature and present treatment with topical steroids, which has not been reported.

Acute generalized exanthematous pustulosis is a rare severe pustular cutaneous adverse reaction characterized by a rapid clinical course with typical histological findings. It is accompanied by fever and acute eruption of non-follicular pustules overlying erythrodermic skin. The causative agents are most frequently antibacterial drugs. We present a patient with acute generalized exanthematous pustulosis caused by methylene blue and indigotin dyes.