Cardiotoxicity is a well-known complication following treatment with anthracyclines. However, they are still widely used in chemotherapy for breast cancer, lymphoma, leukemia, and sarcoma, among others. Patient clinical characteristics, such as age, sex, comorbidities, anthracycline dose and infusion schedule, and the combined anti-cancer agents used, are diverse among cancer types. It is difficult to recommend guidelines for the prevention or management of anthracycline-induced cardiotoxicity applicable to all cancer types. Therefore, anthracycline-induced cardiotoxicity remains a major limitation in the proper management of cancer patients treated with an anthracycline-combined regimen. Efforts have been extensive to determine the mechanism and treatment of anthracycline-induced cardiotoxicity. Because cardiotoxicity causes irreversible damage to the myocardium, prevention is a more effective approach than treatment of cardiotoxicity after symptomatic or asymptomatic cardiac dysfunction develops. This article will review the pathophysiological mechanisms of anthracycline-induced cardiotoxicity and strategies for protecting the myocardium from anthracycline.

Macrophage migration inhibitory factor (MIF) is originally identified in the culture medium of activated T lymphocytes as a soluble factor that inhibits the random migration of macrophages. MIF is now recognized as a multipotent cytokine involved in the regulation of immune and inf lammatory responses. In rheumatoid arthritis (RA), MIF promotes inf lammatory responses by inducing proinflammatory cytokines and tissue-degrading molecules, promoting the proliferation and survival of synovial fibroblasts, stimulating neutrophil chemotaxis, and regulating angiogenesis and osteoclast differentiation. Expression of MIF in synovial tissue and synovial fluid levels of MIF are elevated in RA patients. Specifically, MIF levels correlate with RA disease activity and high levels are associated with bone erosion. In animal models of RA, the genetic and therapeutic inhibition of MIF has been shown to control inflammation and bone destruction. Based on the role of MIF in RA pathogenesis, small molecular inhibitors targeting it or its receptor pathways could provide a new therapeutic option for RA patients.

Aging processes are inevitably accompanied by structural and functional changes in vital organs. Skeletal muscle, which accounts for 40% of total body weight, deteriorates quantitatively and qualitatively with aging. Skeletal muscle is known to play diverse crucial physical and metabolic roles in humans. Sarcopenia is a condition characterized by significant loss of muscle mass and strength. It is related to subsequent frailty and instability in the elderly population. Because muscle tissue is involved in multiple functions, sarcopenia is closely related to various adverse health outcomes. Along with increasing recognition of the clinical importance of sarcopenia, several international study groups have recently released their consensus on the definition and diagnosis of sarcopenia. In practical terms, various skeletal muscle mass indices have been suggested for assessing sarcopenia: appendicular skeletal muscle mass adjusted for height squared, weight, or body mass index. A different prevalence and different clinical implications of sarcopenia are highlighted by each definition. The discordances among these indices have emerged as an issue in defining sarcopenia, and a unifying definition for sarcopenia has not yet been attained. This review aims to compare these three operational definitions and to introduce an optimal skeletal muscle mass index that reflects the clinical implications of sarcopenia from a metabolic perspective.

Background/Aims: Although it is generally known that the risk for all types of cancer increases with adult height, combined and for several common site-specific cancers (including colon and rectal), evidence is limited for adenomas, which are precursors to colorectal cancer. We evaluated the association between height and risk of colorectal adenoma at various stages of the adenoma-carcinoma pathway. Methods: We conducted a retrospective study using data from patients who had undergone a complete colonoscopy as part of a health examination at the Health Promotion Center of Samsung Medical Center between October 13, 2009 and December 31, 2011. A total of 1,347 male subjects were included in our study. Multivariate logistic regression analysis was used to evaluate the association between height and colorectal adenoma. Results: Each 5-cm increase in height was associated with 1.6% and 5.3% higher risks of advanced colorectal adenoma and high-risk colorectal adenoma, respectively, but associations were not significant after adjusting for age, body mass index, metabolic syndrome, alcohol intake, smoking, family history of colorectal cancer, and regular aspirin use (p = 0.840 and p = 0.472, respectively). Conclusions: No clear association was found between colorectal adenoma risk and height. Unlike other site-specific tumors reported to have a consistent relationship with height, the association between colorectal tumor and height remains controversial.

Background/Aims: Non-pancreatic elevations of serum lipase have been reported, and differential diagnosis is necessary for clinical practice. This study aimed to evaluate the clinical efficacy of serum lipase subtype analysis for the differential diagnosis of pancreatic and non-pancreatic lipase elevation. Methods: Patients who were referred for the serum lipase elevation were prospectively enrolled. Clinical findings and serum lipase subtypes were analyzed and compared by dividing the patients into pancreatitis and non-pancreatitis groups. Results: A total of 34 patients (12 pancreatitis vs. 22 non-pancreatitis cases) were enrolled. In univariate analysis, the fraction of pancreatic lipase (FPL) in the total amount of serum lipase subtypes was statistically higher in patients with pancreatitis ([median, 0.004; interquartile range [IQR], 0.003 to 0.011] vs. [median, 0.002; IQR, 0.001 to 0.004], p = 0.04). Based on receiver operating characteristic curve analysis for the prediction of acute pancreatitis, FPL was the most valuable predictor (area under the receiver-operating characteristic curve [AUROC], 0.72; 95% confidence interval [CI], 0.54 to 0.86; sensitivity, 83.3%; specificity, 63.6%; positive predictive value, 55.6%; negative predictive value, 97.5%). In multivariate analysis, a cut-off value higher than 0.0027 for the FPL was associated with acute pancreatitis (odds ratio, 8.3; 95% CI, 1.3 to 51.7; p = 0.02). Conclusions: The results did not support that serum lipase subtype analysis could replace standard lipase measurement for the diagnosis of acute pancreatitis. However, the test demonstrated adequate sensitivity for use in triage or as an add-on test for serum lipase elevation.

Background/Aims: Angiodysplasia is important in the differential diagnosis of upper gastrointestinal bleeding (UGIB), but the clinical features and outcomes associated with UGIB from angiodysplasia have not been characterized. We aimed to analyze the clinical characteristics and outcomes of angiodysplasia presented as UGIB. Methods: Between January 2004 and December 2013, a consecutive series of patients admitted with UGIB were retrospectively analyzed. Thirty-five patients with bleeding from angiodysplasia were enrolled. We compared them with an asymptomatic control group (incidental finding of angiodysplasia in health screening, n = 58) and bleeding control group (simultaneous finding of angiodysplasia and peptic ulcer bleeding, n = 28). Results: When patients with UGIB from angiodysplasia were compared with the asymptomatic control group, more frequent rates of nonantral location and large sized lesion (${\geq}1cm$) were evident in multivariate analysis. When these patients were compared with the bleeding control group, they were older (mean age: $67.94{\pm}9.16years$ vs.$55.07{\pm}13.29years$, p = 0.03) and received less transfusions (p = 0.03). They also had more frequent rate of recurrence (40.0% vs. 20.7%, p = 0.02). Conclusions: Non-antral location and large lesions (${\geq}1cm$) could be risk factors of UGIB of angiodysplasia. UGIB due to angiodysplasia was more common in older patients. Transfusion requirement would be less and a tendency of clinical recurrence might be apparent.

Background/Aims: To compare the clinical outcomes of 'on-label' and 'off-label' drug-eluting stents (DESs) over a 5-year follow-up period. Methods: A total of 929 patients that underwent percutaneous coronary intervention with DESs were enrolled. Patients were divided into two groups according to on-label (n = 449) and off-label (n = 480) indications. Off-label use was defined as implantation of DESs for acute myocardial infarction (MI), very small vessel, a long stenotic lesion, chronic total occlusion, a bifurcation lesion, an ostial lesion, left main coronary artery disease, multivessel disease, a saphenous vein graft lesion, and a lesion with thrombus. Endpoints were composite of major adverse cardiac events (MACEs), which included all-cause death, ischemic-driven target vessel revascularization (Id-TVR), MI, and stent thrombosis (ST). Clinical outcomes in the two groups were compared for up to 5 years postimplantation. Results: At 1 year postimplantation, the off-label group had higher incidences of total MACEs (8.2% vs. 3.7%, p = 0.005), Id-TVR (5.0% vs. 1.6%, p = 0.004), and ST (1.7% vs. 0.3%, p = 0.042), and at 5 years postimplantation, the off-label group continued to have higher incidences of total MACEs (17.5% vs. 9.4%, p < 0.001), Id-TVR (13.1% vs. 5.8%, p = 0.024), and ST (2.1% vs. 0.3%, p = 0.021). Multivessel disease and diabetes were found to be independent risk factors of MACE in patients with an off-label indication. Conclusions: Patients treated with an on-label DES had better long-term clinical outcomes than those treated with an off-label DES.

Background/Aims: The smoking rates and patterns in the North Korean population are not well known. More than 20,000 North Korean defectors have settled in South Korea; thus, we can estimate the current North Korean smoking situation using this group. Methods: All North Korean defectors spend their first 3 months in a South Korean facility learning to adapt to their new home. We retrospectively analyzed the results from a questionnaire conducted among North Korean male defectors in this facility from August 2012 to February 2014. Results: Of 272 men, 84.2% were current smokers, 12.5% were ex-smokers, and 3.3% were non-smokers. The mean age of this group was $35.9{\pm}11.3years$, and smoking initiation occurred at a mean age of $18.2{\pm}4.7years$. Among the subjects, 78.1% had a family member who smoked. Of the 221 current smokers, 67.4% responded that they intended to quit smoking. $Fagerstr{\ddot{o}}m$ test and Kano test for social nicotine dependence (KTSND) results for current smokers were $3.35{\pm}2.26$ and $13.76{\pm}4.87$, respectively. Question 9 on the KTSND (doctors exaggerate the ill effects of smoking) earned a significantly higher score relative to the other questions and a significantly higher score in current smokers compared with non-smokers. Conclusions: The smoking rate in North Korean male defectors was higher than that indicated previously. However, interest in smoking cessation was high and nicotine dependence was less severe than expected. Further investigation is needed to identify an efficient method for North Korean smokers to stop smoking.

Background/Aims: It is not clear which tests are indicative of the activity and severity of tuberculosis (TB). This study aimed to investigate the predictive value of neuron-specific enolase (NSE) and to determine the origin of NSE in TB patients. Methods: A single-center retrospective analysis was conducted on newly diagnosed TB patients between January and December 2010. Patients were categorized into one of two disease groups (focal segmental or extensive) based on chest X-ray. Pre- and post-treatment NSE concentrations were evaluated. To determine the origin of serum NSE concentration, NSE staining was compared with macrophage-specific CD68 staining in lung tissues and with a tissue microarray using immunohistochemistry and immunofluorescence. Results: A total of 60 newly diagnosed TB patients were analyzed. In TB patients, NSE serum concentration was significantly increased and NSE level decreased after treatment (p < 0.001). In proportion to serum high-sensitivity C-reactive protein concentration, the mean serum concentration of NSE in the extensive group (25.12 ng/mL) was significantly higher than that in the focal segmental group (20.23 ng/mL, p = 0.04). Immunohistochemical staining revealed a large number of macrophages that stained positively for both NSE and CD68 in TB tissues. In addition, NSE signals mostly co-localized with CD68 signals in the tissue microarray of TB patients. Conclusions: Our results suggest that NSE may be a practical parameter that can be used to monitor TB activity and treatment response. Elevated serum NSE level originates, at least in part, from macrophages in granulomatous lesions.

Background/Aims: Overt hypothyroidism is frequently found in patients with type 2 diabetes mellitus (T2DM), but it remains unknown the relationship between subclinical hypothyroidism (SCH) and T2DM. We attempt to evaluate the difference in prevalence of SCH between patients with T2DM and general population, and the association between SCH and glycemic control status ofdiabetic patients. Methods: This was cross-sectional study. Total 8,528 subjects who visited for health check-up were recruited. SCH was defined as an elevated level of serum thyroid stimulating hormone (> 4.0 mIU/L) with a normal level of free thyroxine. T2DM group was categorized into three groups by glycosylated hemoglobin (HbA1c): < 7% (reference), ${\geq}7%$ and < 9%, ${\geq}9%$. Results: Finally, 7,966 subjects were included. The prevalence of SCH was not different between healthy controls and subjects with T2DM (8.1% vs. 7.4%, p = 0.533; in men, 5.7% vs. 5.1%, p = 0.573; in women, 10.9% vs. 11.7%, p = 0.712), but it was increased with highest HbA1c group more than well controlled group, especially in women. The risk of SCH was increased by group with poorer glycemic control; the odds ratio for HbA1c ${\geq}9%$ compared to < 7% was 2.52 (95% confidence interval [CI], 1.09 to 5.86; p = 0.031), and 4.58 (95% CI, 1.41 to 14.87; p = 0.011) in women, but not significant in men. Conclusions: The prevalence of SCH was similar between T2DM and healthy group. Poor glycemic control in T2DM was obviously associated with the risk of SCH, especially in elderly women. These results suggest SCH as comorbidity may be considered in elderly women with poor glycemic control.

Background/Aims: The prevalence of single-person households has rapidly increased in Korea. Individuals living alone and in rural areas may have a higher risk of various metabolic diseases due to differences in lifestyle. However, few studies have investigated the association of household size and residential area with health-related problems. This study aimed to evaluate the association of household size and residential area with risk of osteoporosis in postmenopausal women. Methods: This cross-sectional study enrolled 3,058 postmenopausal women from the 2008 to 2011 Korea National Health and Nutrition Examination Survey (KNHANES). We examined the association between bone mineral density (BMD) and household size and residential area. Results: Individuals living in rural areas had significantly lower BMD of the lumbar spine than those living in an urban area. Subsequently, we divided the participants into four groups according to household size and residential areas. Lumbar spine BMD was significantly lower in individuals living in rural single-person households than those in urban households with two or more individuals, even after adjustment for multiple confounding factors. In addition, individuals in rural single-person households had significantly greater odds of osteoporosis in the lumbar spine than those in urban households with two or more residents. Conclusions: Individuals in rural single-person households had significantly lower BMD and greater odds of osteoporosis in lumbar spine than urban households with two or more individuals. The results of this study suggest that individuals living in rural single-person households may benefit from more careful screening for osteoporosis.

Background/Aims: It has been shown that circulating tumor necrosis factor ${\alpha}$ ($TNF-{\alpha}$) is elevated in end stage renal disease patients; however, the relationship between $TNF-{\alpha}$ and the development of infection in these patients is unknown. In this study, we investigated the association of plasma $TNF-{\alpha}$ and interleukin 6 (IL-6) with infection in peritoneal dialysis (PD) patients. We also evaluated the association of their plasma levels with the production by peripheral blood mononuclear cells (PBMC), and with various clinical parameters. Methods: We enrolled 32 patients on maintenance PD and 10 healthy controls. Plasma and PBMC were isolated from blood. PBMC were stimulated with lipopolysaccharide in vitro. Results: Mean follow-up duration was 775 days. Six patients developed organ infections (five pneumonia and one liver abscess), and six patients developed PD peritonitis and eight developed exit site infection. Plasma $TNF-{\alpha}$ and IL-6 levels were significantly elevated in organ infections but not in peritonitis or in exit site infection. Plasma $TNF-{\alpha}$ was the only significant risk factor for organ infections and pneumonia in multivariate regression analysis. Patients with high plasma $TNF-{\alpha}$ levels showed a significantly greater cumulative hazard rate for organ infections compared to those with low $TNF-{\alpha}$ levels. Plasma $TNF-{\alpha}$ levels correlated with $TNF-{\alpha}$ production by PBMC and showed an inverse association with Kt/V. Conclusions: This is the first study showing that plasma $TNF-{\alpha}$ is a significant risk factor for infection in PD patients.

Background/Aims: Liver cirrhosis (LC) is an important problem in patients with end-stage renal disease (ESRD). Few studies have investigated the influence of LC on mortality in patients with ESRD. This study investigated the association between LC and mortality among patients with ESRD and compare mortality between two dialysis modalities. Methods: Adult patients (${\geq}18$ years of age) starting dialysis for ESRD were enrolled in the present study from 2000 to 2011. We analyzed 1,069 patients with ESRD; of these, 742 patients were undergoing hemodialysis (HD) and 327 patients were undergoing peritoneal dialysis (PD). Results: The prevalence of LC was 44 of 1,069 patients (4.1%). The cumulative 1-, 3-, and 5-year survival rates of noncirrhotic patients were 93%, 83%, and 73%, respectively, whereas the equivalent survival rates of cirrhotic patients were 90%, 68%, and 48%, respectively (p = 0.011). After adjustment, LC was an independent risk factor for death in patients with ESRD. No difference in mortality associated with LC was found between the HD and PD subgroups. Conclusions: Of the patients with ESRD, cirrhotic patients had poorer survival than noncirrhotic patients. Among patients with ESRD and LC, survival of patients undergoing PD may be comparable with that of patients undergoing HD.

Background/Aims: While surgical resection remains the standard of care in the treatment of upper urinary tract malignancies, nephrectomy is a risk factor for the development of chronic kidney disease (CKD). The aim of this study was to determine whether histologic evaluation of non-neoplastic kidney could enable early identification of unrecognized kidney disease and could be of prognostic value in predicting postoperative renal outcomes. Methods: We retrospectively analyzed 51 patients with upper urinary tract malignancies who received uninephrectomy or uninephroureterectomy. A thorough pathologic evaluation of non-neoplastic kidney including special stains, immunofluorescence, and electron microscopic studies was performed. The degree of parenchymal changes was graded from 0 to 15. Results: Of 51 patients, only 13 showed normal kidney pathology. Fifteen patients showed glomerular abnormalities, 14 showed diabetic nephropathy, and 11 showed vascular nephropathy. There was one case each of reflux nephropathy and chronic pyelonephritis. The median histologic score was 5 points. Only 25.4% of patients had ${\leq}3$ points. Score more than 5 was observed in 47.1% of patients. Postoperative estimated glomerular filtration rate (eGFR) at 3 to 36 months were obtained from 90.2% of patients, and of those, 34.8% had de novo CKD. Since no one had CKD in partial nephrectomized patients, we determined risk factors for CKD in radical nephrectomized patients. Cox regression analysis revealed that postoperative AKI, preoperative eGFR, and histologic score of non-neoplastic kidney were the independent predictors for CKD. Conclusions: We conclude that routine pathologic evaluation of non-neoplastic kidney provides valuable diagnostic and prognostic information.

Background/Aims: There is controversy about the prophylactic effect of anti-thymocyte globulin (ATG) on graft versus host disease (GVHD) in the setting of matched related-donor hematopoietic stem cell transplantation (HSCT). This study assessed the inf luences of ATG on the incidences of acute and chronic GVHD and other clinical outcomes in matched related-donor HSCT. Methods: Sixty-one patients received allogeneic HSCT from human leukocyte antigen-matched, related donors. Patients received busulfan/fludarabine conditioning regimens and standard GVHD prophylaxis with or without additional ATG. Results: There was no significant difference in the cumulative incidences of overall acute GVHD, grade II to IV acute GVHD at day 100, and chronic GVHD during the follow-up period between the ATG and non-ATG groups. Three-year overall survival rates were very similar, but three year disease-free survival of the non-ATG group was higher than that of the ATG group (56.2% for ATG vs. 63.1% for non-ATG, p = 0.597). Relapse rate at 3 years in the ATG group was slightly higher than that of the non-ATG group (37.5% vs. 20%, p = 0.29). Non-relapse mortality rate at 3 years was lower in the ATG group (6.25% vs. 15.6%, p = 0.668). Conclusions: Although the addition of ATG doesn't guarantee a reduction in the incidences of acute and chronic GVHD, pre-transplantation ATG may result in lower non-relapse mortality in the context of matched related-donor HSCT with a busulfan/fludarabine conditioning regimen. However, caution is needed when using ATG because of a possibility to increase relapse rate.

Background/Aims: This study aimed to evaluate the efficacy of computed tomography (CT)-guided bone biopsy for the diagnosis of spinal infection and compared the clinical outcomes between tuberculous and pyogenic spinal infections. Methods: The retrospective cohort study included patients who received CT-guided bone biopsy at a tertiary hospital over the 13 years. Results: Among 100 patients, 67 had pyogenic spondylitis and 33 had tuberculous spondylitis. Pathogens were isolated from bone specimens obtained by CT-guided biopsy in 42 cases, with diagnostic yields of 61% (20/33) for tuberculous spondylitis and 33% (22/67) for pyogenic spondylitis. For 36 culture-proven pyogenic cases, Staphylococcus aureus was the most commonly isolated organism. Patients with pyogenic spondylitis more frequently presented with fever accompanied by an increase in inflammatory markers than did those with tuberculosis. Among all patients who underwent surgery, the incidence of late surgery performed one month after diagnosis was higher in patients with tuberculous infection (56.3%) than in those with pyogenic disease (23.3%, p = 0.026). Conclusions: Results obtained by CT-guided bone biopsy contributed to prompt diagnoses of spinal infections, especially those caused by tuberculosis. Despite administration of anti-tuberculous agents, patients with tuberculous spondylitis showed an increased tendency to undergo late surgery.

Background/Aims: Increasing incidences of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected men who have sex were reported in the United States and Europe. However, few studies regarding the epidemiology of HCV infection in HIV-infected patients in Asian countries have been reported. Methods: To determine the prevalence and incidence of HCV infection in HIV-infected patients, a retrospective cohort study was conducted. All HIV-infected patients who visited a tertiary care hospital in Korea from 2000 to 2013 were identified. Patients with ${\geq}1HCV$ antibody (Ab) test were included and observed until December 2014. Results: Among 996 HIV-infected patients, 790 patients (79%) had baseline HCV Ab tests and 41 (5.2%) were positive at baseline and four at follow-up. Experience of injecting drug use (IDU; adjusted odds ratio, 16.20; 95% confidence interval [CI], 1.56 to 167.89; p < 0.01) was significantly associated with prevalent HCV infection. Conversion to HCV Ab positivity was observed in four of 384 included patients, with an incidence rate of 2.22 (95% CI, 0.60 to 5.80)/1,000 person-years (PYs); 164.89 (95% CI, 34.00 to 481.88)/1,000 PYs in patients with IDU, and 1.40 (95% CI, 0.35 to 7.79)/1,000 PYs in men who have sex with men who denied IDU. There was no significant increase in incidence rate of HCV in HIV-infected patients from 2009 to 2014 (p = 0.119). Among 19 patients who were positive for HCV RNA, genotype 1b (73%) was the most common following 2a/2c (20%). Conclusions: IDU was an independent risk factor for prevalent HCV infection. Prevalence of HCV infection was low and incidence of HCV infection was not significantly increased in HIV-infected patients in South Korea.

Background/Aims: To determine the efficacy and safety of low-dose tacrolimus in Korean rheumatoid arthritis (RA) subjects with an inadequate response to methotrexate (MTX). Methods: This was a multicenter, open-label study conducted at five Korean sites. Fifty-six patients with active RA, despite treatment for ${\geq}1month$ with a stable, maximally tolerated dosage of oral MTX (median dosage, 15 mg/wk), were enrolled and received 1.5 mg/day of tacrolimus as a single oral dose once per day for 16 weeks while continuing to receive MTX. All other disease-modifying anti-rheumatic drugs were discontinued, whereas stable dosages of nonsteroidal anti-inflammatory drugs and oral corticosteroids (${\leq}10mg/day$ of prednisone or an equivalent corticosteroid) were allowed. The primary clinical response criterion was the American College of Rheumatology's definition of 20% improvement (ACR20) at the end of treatment. Results: The ACR20 response rate was 42.9% (24 of 56 patients) in patients who had received tacrolimus at least once. The overall ACR50 and ACR70 responses at the end of treatment for all patients were 30.4% and 10.7%, respectively. Throughout the treatment period, 37 patients experienced 71 adverse events (AEs) in total, and four patients left the study because of AEs. In addition, 15 patients in total experienced treatment-related AEs. Throughout the treatment period, two patients were reported to experience two serious AEs, and one patient left the study because of a serious AE. Conclusions: In patients whose active RA persists despite treatment with MTX, low-dose tacrolimus in combination with MTX appears to be safe and well tolerated, and provides clinical benefit.