Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in all countries and all age groups. DLBCL is potentially curable, and the outcome of patients with DLBCL has completely changed with the introduction of therapy involving the monoclonal antibody rituximab in combination with chemotherapy. Nonetheless, relapse is detected after treatment with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone in approximately 30% of patients. It has recently become clear that DLBCL represents a heterogeneous admixture of quite different entities. Gene expression profiling has uncovered DLBCL subtypes that have distinct clinical behaviors and prognoses; however, incorporation of this information into treatment algorithms awaits further investigation. Future approaches to DLBCL treatment will use this new genetic information to identify potential biomarkers for prognosis and targets for treatment.

Rheumatoid arthritis (RA) is a progressive inflammatory disease with severe symptoms of pain and stiffness. Chronic persistent inflammation of RA often leads to joint destruction, deformity and limitation of function, which ultimately results in significant deterioration of quality of life (QoL). RA is characterized pathogenetically by immunologically driven, chronic synovitis, and production of autoantibodies, such as rheumatoid factor and anti-cyclic citrullinated peptide antibodies. Although the cause of RA is yet unknown, advances in the molecular biology led to in-depth understanding of its pathogenesis, and have fostered the recent development of novel treatments. The last decade has seen the dramatic change in the landscape of RA treatment with more aggressive therapy early in the disease course and with treatment guided by a structured assessment of disease activity, with the ultimate goal of reaching remission. In addition, prevention and control of joint damage and improvement in QoL are important goals. To achieve these goals, a multidisciplinary approach to reduce disease activity with disease modifying antirheumatic drugs and biological therapy is needed. We also need to find ways to identify those patients who are at risk for more rapid disease progression who would benefit from intensive therapy early in the course of disease.

Background/Aims: To determine which drug-eluting stents are more effective in acute myocardial infarction (MI) patients with chronic kidney disease (CKD). Methods: This study included a total of 3,566 acute MI survivors with CKD from the Korea Acute Myocardial Infarction Registry who were treated with stenting and followed up for 12 months: 1,845 patients who received sirolimus-eluting stents (SES), 1,356 who received paclitaxel-eluting stents (PES), and 365 who received zotarolimus-eluting stents (ZES). CKD was defined as an estimated glomerular filtration rate < $60mL/min/1.73m^2$ calculated by the modification of diet in renal disease method. Results: At the 12-month follow-up, patients receiving ZES demonstrated a higher incidence (14.8%) of major adverse cardiac events (MACEs) compared to those receiving SES (10.1%) and PES (12%, p = 0.019). The ZES patients also had a higher incidence (3.9%) of target lesion revascularization (TLR) compared to those receiving SES (1.5%) and PES (2.4%, p = 0.011). After adjusting for confounding factors, ZES was associated with a higher incidence of MACE and TLR than SES (adjusted hazard ratio [HR], 0.623; 95% confidence interval [CI], 0.442 to 0.879; p = 0.007; adjusted HR, 0.350; 95% CI, 0.165 to 0.743; p = 0.006, respectively), and with a higher rate of TLR than PES (adjusted HR, 0.471; 95% CI, 0.223 to 0.997; p = 0.049). Conclusions: Our findings suggest that ZES is less effective than SES and PES in terms of 12-month TLR, and has a higher incidence of MACE due to a higher TLR rate compared with SES, in acute MI patients with CKD.

Background/Aims: The relationship between Runt-related transcription factor 3 (RUNX3) gene inactivation and various solid tumors has been reported; however, little information is available about RUNX3 in thyroid cancers. Methods: We evaluated the DNA methylation of RUNX3 in 13 papillary thyroid cancer tissues and four thyroid cancer cell lines. Additionally, using reverse transcriptase-polymerase chain reaction, we analyzed RUNX3 gene expression in several thyroid cancer cell lines after treating with the demethylating agent 5-aza-2'-deoxycytidine (DAC). Results: RUNX3 was hypermethylated in many thyroid cancer cell lines and in 10 of the 12 papillary thyroid cancer tissues. Treatment with DAC increased the expression of RUNX3 in some thyroid cancer cell lines. Conclusions: We suggest that RUNX3 is associated with thyroid carcinogenesis, and RUNX3 methylation is a potentially useful diagnostic marker for papillary thyroid cancer.

Background/Aims: Chronic hepatitis B infection is a common cause of secondary membranous nephropathy (MN) in endemic areas. Lamivudine treatment improves renal outcome in patients with hepatitis B virus-associated MN (HBVMN), but prolonged use leads to the emergence of lamivudine-resistant variants. We describe our experience treating lamivudine-resistant and other strains of HBV-MN with new antiviral drugs. Methods: Of the 89 patients biopsied and diagnosed with MN from 1996 to 2011, 10 positive for hepatitis B surface antigen were recruited for this study. We investigated the clinical courses, therapeutic responses, and prognoses of patients with HBV-MN. Results: The incidence of HBV-MN among the original 89 patients was 11.2%. Of these patients, four were treated with supportive care and six with antiviral drugs. One of the four patients treated with supportive care had a spontaneous remission. Four of the six patients treated with antiviral drugs were given lamivudine, and the other two were given entecavir. Two of the four patients treated with lamivudine achieved complete remission with seroconversion (i.e., development of anti-hepatitis B e antigen antibodies), whereas the other two had lamivudine-resistant strains, which were detected at 22 and 23 months after lamivudine treatment, respectively. We added adefovir to the treatment regimen for one of these patients, and for the other patient we substituted clevudine for lamivudine. Both of these patients experienced complete remission, as did the two patients initially treated with entecavir, neither of whom showed resistance to the drug. Conclusions: New nucleoside analogues, such as entecavir, adefovir, and clevudine, can be effective for treatment of HBV-MN, including lamivudine-resistant strains.

Background/Aims: Falls among older people are a major public health problem and may result in fracture, medical complications that require hospitalization, and fear of additional falls. Given the prevalence and impact of the fear of falling again, reducing the incidence of falls is important to prevent additional falls. This study analyzed whether exercise programs decrease the fear of future falls in elderly patients who have fallen previously. Methods: A randomized controlled study was performed that included 65 elderly community-dwelling subjects who had fallen in the previous year. Subjects were randomized into two groups: an exercise group (EG, n = 36) and a control group (CG, n = 29). The EG participated in three exercise sessions per week for 12 weeks. Muscle strength, balance, agility, flexibility, and muscular endurance were measured at baseline and after 12 weeks. Results: After the 12-week exercise program, the subjects in the EG demonstrated remarkable improvement in their walking speed, balance (p = 0.003), back strength (p = 0.08), lower extremity strength (p = 0.004), and flexibility (p < 0.001). When asked whether they were afraid of falling, more participants in the EG than in the CG responded "not at all" or "a little." Conclusions: The 12-week exercise program described here reduced the fear of falling (p = 0.02). It also improved the balance, flexibility, and muscle strength of the participants and was associated with improved quality of life.

Background/Aims: Patients with chronic obstructive pulmonary disease (COPD) experience more problematic respiratory symptoms and have more trouble performing daily activities in the morning. The aim of this study was to assess the perception of COPD symptoms related to morning activities in patients with severe airflow limitation. Methods: Data of 133 patients with severe airflow limitation were analyzed in a prospective, non-interventional study. A clinical symptom questionnaire was completed by patients at baseline. In patients having morning symptoms, defined by at least one or more prominent or aggravating symptom during morning activities, a morning activity questionnaire was also completed at baseline and following 2 months of COPD treatment. Results: The most frequently reported COPD symptom was breathlessness (90.8%). Morning symptoms were reported in 76 (57%) patients; these had more frequent and severe clinical COPD symptoms. The most frequently reported morning activity was getting out of bed (82.9%). The long acting muscarinic antagonist (odds ratio [OR], 6.971; 95% confidence interval [CI], 1.317 to 11.905) and chest tightness (OR, 0.075; 95% CI, 0.011 to 0.518) were identified as significantly related to absence of morning symptoms. There was no significant correlation between the degree of forced expiratory volume in 1 second improvement and severity score differences of all items of morning activity after 2-month treatment. Conclusions: Fifty-seven percent of COPD patients with severe airflow limitation have morning symptoms that limit their morning activities. These patients also have more prevalent and severe COPD symptoms. The results of this study therefore provide valuable information for the development of patient-reported outcomes in COPD.

Background/Aims: The aim of this study was to compare the progression of bone mass loss in chronic hemodialysis patients (CHPs) with that in general population patients (GPPs) over an 18-month period. Methods: The control group consisted of 60 patients (aged $57.5{\pm}10.9$ years) with a glomerular filtration rate > $60mL/min/1.73m^2$. The study group included 80 patients undergoing hemodialysis (aged $59.3{\pm}11.8$ years; duration of dialysis $5.47{\pm}5.16$ years). Bone mineral density (BMD) testing was conducted in both groups using dual energy X-ray absorptiometry at hip and lumbar spine regions at baseline and after 18 months. Biochemical parameters (albumin, C-reactive protein, calcium, ionized calcium, alkaline phosphatase, and parathyroid hormone) were determined in all participants using standard laboratory procedures. Results: The mean values of BMD (average hip + lumbar spine) were $0.900{\pm}0.14g/cm^2$ and $0.866{\pm}0.14g/cm^2$ in the GPP and $0.823{\pm}0.16g/cm^2$ and $0.769{\pm}0.13g/cm^2$ in the CHP groups at baseline and 18 months, respectively. The statistical significance (p value) of hip bone loss progression over 18 months was 0.0577 for GPP and 0.0002 for CHP, whereas that of lumbar spine bone loss progression was 0.6820 for GPP and 0.5389 for CHP. Conclusions: The of progression bone mass loss was significantly greater in CHP than in GPP. Bone mass loss was evident even over 1 month, albeit in only the CHP with accelerated osteoporosis.

Background/Aims: Spontaneous reporting systems have several weak points, such as low reporting rates and insufficient clinical information. Active surveillance programs, such as ward rounds and a clinical data repository (CDR), may supplement the weak points of such systems. We developed active surveillance programs and compared them with existing spontaneous reporting. Methods: We collected adverse drug event (ADE) cases, which comprised 1,055 cases of spontaneous reporting, 309 reported by ward rounds, and 229 found using a CDR. The clinical features and causative drugs were evaluated. Results: Active surveillance programs detected additional serious ADEs compared to those of spontaneous reporting programs. The ADEs identified by CDR (22.9%) were more likely to be classified as "serious" than those reported spontaneously (5.2%) or identified during ward rounds (10.3%). Causative drugs also differed. Opioids, antibiotics, and contrast media were the most common drugs causing ADEs in the spontaneous reporting system, whereas the active surveillance programs identified antibiotics as the most common causative drug. Clinical features also differed. ADEs with gastrointestinal manifestations were reported most frequently by spontaneous reporting programs. ADEs reported from active surveillance more reliably identified events associated with changes in laboratory values, such as hepatobiliary toxicity, hematologic manifestations, and nephrologic manifestations, compared with spontaneous reporting programs. Conclusions: Our findings suggest that active surveillance programs can supplement spontaneous reporting systems in hospitals. ADEs related to laboratory abnormalities were monitored more closely by active surveillance programs and may be useful for identification of serious ADEs.

Eosinophilic gastroenteritis (EGE) is an uncommon disease characterized by eosinophilic infiltration of the gastrointestinal tract, which is usually associated with abdominal pain, diarrhea, ascites, and peripheral eosinophilia. Steroids remain the mainstay of treatment for EGE, but symptoms often recur when the dose is reduced. Macrolides have immunomodulatory effects as well as antibacterial effects. The immunomodulatory effect results in inhibition of T-lymphocyte proliferation and triggering of T-lymphocyte and eosinophil apoptosis. Macrolides also have a steroidsparing effect through their influence on steroid metabolism. We report a rare case of EGE, which relapsed on steroid reduction but improved following clarithromycin treatment.

We herein report a rare case of subaortic stenosis in association with a previous tetralogy of Fallot (TOF) surgical repair, which was not taken into account as a differential diagnosis. Echocardiography plays a pivotal role in identification of this rare combination. Therefore, echocardiography should be performed periodically during follow-up of patients with surgically corrected TOF. Given the clinical complications that can result from subaortic stenosis (i.e., aortic regurgitation and infective endocarditis), early and aggressive management of this rare combination should be performed.

A 22-year-old man was referred to our institution due to lower back pain and was diagnosed with Langerhans cell histiocytosis of the thoracic and lumbar spine. The patient achieved complete remission with radiotherapy and chemotherapy. One year later, right cervical lymphadenopathy was observed and Hodgkin's lymphoma was confirmed on biopsy. The patient was treated with chemotherapy and autologous stem cell transplantation, and experienced no further symptoms. Further, no evidence of recurrence was observed on follow-up imaging. This report discusses the association between Langerhans cell histiocytosis and Hodgkin's lymphoma.

Pseudomembranous necrotizing bronchial aspergillosis (PNBA) is a rare form of invasive aspergillosis with a very poor prognosis. The symptoms are non-specific, and the necrotizing plugs cause airway obstruction. Atelectasis and respiratory failure can be the initial manifestations. Recently, we treated an immunocompromised patient with PNBA, who presented with a sudden onset of atelectasis and acute respiratory failure. There were no preceding signs except for a mild cough and one febrile episode. Bronchoscopy revealed PNBA, and Aspergillus nidulans was cultured from the bronchial wash.