The prevalence of hepatitis C virus (HCV) in Asia is 0.5% to 4.7%, with three different genotypes predominating, depending on the geographic region: genotype 1b in East Asia, genotype 3 in South and Southeast Asia, and genotype 6 in Indochina. Official approval for direct-acting antiviral agents (DAAs) in Asia lags significantly behind that in the West, such that in most countries the mainstay of therapy is still pegylated interferon and ribavirin (PR). Because the interleukin-28B genetic variant, associated with a high sustained virologic response (SVR), is common in Asians, this treatment is still acceptable in Asian patients with HCV infections. A roadmap for HCV therapy that starts with PR and takes into account those DAAs already approved in some Asian countries can provide guidance as to the best strategies for management, particularly of genotype 1 and 3 infections, based on SVR rates. Sofosbuvir and PR are likely to be the initial therapies for genotype 1 and 3 disease, although in the former these drugs may be suboptimal in patients with cirrhosis (62% SVR) and the extension of treatment to 24 weeks may be required. For difficult to treat genotype 3 infections in treatment-experienced patients with cirrhosis, a combination of sofosbuvir and PR result in an 83% SVR and is, therefore, currently the optimal treatment regimen. Treatment failure is best avoided since data on rescue therapies for DAA failure are still incomplete.

Infective endocarditis (IE) has been increasingly diagnosed in patients without previously detected predisposing heart disease, but its clinical features have yet to be fully determined. A recent single-center study including echocardiographic images and surgical findings investigated the incidence of undiagnosed, clinically silent valvular or congenital heart diseases and healthcare-associated infective endocarditis (HAIE). The study confirmed that a large proportion of patients with IE have no previous history of heart disease. Analysis of underlying disease in these patients showed that undetected mitral valve prolapse was the most common disease, followed by an apparently structurally normal valve. The patients who developed IE of apparently structurally normal valves had different clinical characteristics and worse outcomes. IE involving a structurally normal valve was associated with both nosocomial and non-nosocomial HAIE, whereas community-acquired IE was more frequent than HAIE. The pathophysiologic mechanism involving the development of non-HAIE or community-acquired IE due to predominantly staphylococcal infection in an apparently structurally normal valve is not yet clearly understood. Structurally normal valves are not necessarily free of regurgitation or abnormal turbulence and, given the dynamic nature and fluctuating hemodynamic effects of conditions such as poorly controlled hypertension, end-stage renal disease, and sleep apnea, further investigation is necessary to evaluate the potential role of these diseases in the development of IE. An apparently normal-looking valve is associated with IE development in patients without previously recognized predisposing heart disease, warranting repartition of at-risk groups to achieve better clinical outcomes.

Many patients with asthma or chronic obstructive pulmonary disease (COPD) have overlapping characteristics of both diseases. By spirometric definition, patients with both fixed airflow obstruction (AO) and bronchodilator reversibility or fixed AO and bronchial hyperresponsiveness can be considered to have asthma-COPD overlap syndrome (ACOS). However, patients regarded to have ACOS by spirometric criteria alone are heterogeneous and can be classified by phenotype. Eosinophilic inflammation, a history of allergic disease, and smoke exposure are important components in the classification of ACOS. Each phenotype has a different underlying pathophysiology, set of characteristics, and prognosis. Medical treatment for ACOS should be tailored according to phenotype. A narrower definition of ACOS that includes both spirometric and clinical criteria is needed.

Background/Aims: Although pyogenic liver abscesses (PLAs) can be successfully treated, the visual prognosis of patients with endogenous endophthalmitis (EE) associated with a PLA is poor. Early diagnosis and prompt intervention may salvage useful vision. Therefore, we investigated risk factors for EE in patients with PLA, to facilitate early diagnosis. Methods: Data from 626 patients diagnosed with PLA between January 2004 and July 2013 were analyzed retrospectively. Patients were divided into two groups: those with liver abscess-associated endogenous endophthalmitis (LAEE) and non-LAEE. Results: The prevalence of EE in PLA patients was 1.92%. The mean age for all patients (373 males, 59.6%) was 62.8 years. Upon multivariate logistic regression, a liver abscess or another systemic infection (odds ratio [OR], 5.52; p = 0.005), an abscess in the right superior segment (OR, 5.26; p = 0.035), and Klebsiella pneumoniae infection (OR, 3.68; p = 0.039), were risk factors for LAEE. The final visual outcomes of patients with LAEE included no light perception in seven, hand motion only in three, and decreased visual acuity in two. Vitrectomy and early intravitreal injections of antibiotics improved visual acuity and preserved useful vision. Conclusions: PLA patients with other systemic infections, abscesses in the right superior segment, and K. pneumoniae infection require close monitoring and early intervention to treat LAEE. Intravitreal antibiotic injections or early vitrectomy may salvage useful vision.

Background/Aims: Hyponatremia is a well-known risk factor for poor outcomes in Western studies of heart failure (HF) patients. We evaluated the predictive value of hyponatremia in hospitalized Asian HF patients. Methods: The Clinical Characteristics and Outcomes in the Relation with Serum Sodium Level in Asian Patients Hospitalized for Heart Failure (the COAST) study enrolled hospitalized patients with systolic HF (ejection fraction < 45%) at eight centers in South Korea, Taiwan, and China. The relationship between admission sodium level and clinical outcomes was analyzed in 1,470 patients. Results: The mean admission sodium level was $138{\pm}4.7mmol/L$, and 247 patients (16.8%) had hyponatremia defined as $Na^+$ < 135 mmol/L. The 12-month mortality was higher in hyponatremic patients (27.9% vs. 14.6%, p < 0.001), and hyponatremia was an independent predictor of 12-month mortality (hazard ratio, 1.72; 95% confidence interval, 1.12 to 2.65). During hospital admission, 57% of hyponatremic patients showed improvement without improvement in their clinical outcomes (p = 0.620). The proportion of patients with optimal medical treatment was only 26.5% and 44.2% at admission and discharge, respectively, defined as the combined use of angiotensin-converting-enzyme inhibitor/angiotensin receptor blocker and ${\beta}-blocker$. Underuse of optimal medical treatment was more pronounced in hyponatremic patients. Conclusions: In hospitalized Asian HF patients, hyponatremia at admission is common and is an independent predictor of poor clinical outcome. Furthermore, hyponatremic patients receive less optimal medical treatment than their counterparts.

Background/Aims: The modified early warning score (MEWS) is used to predict patient intensive care unit (ICU) admission and mortality. Lactate (LA) in the blood lactate (BLA) is measured to evaluate disease severity and treatment efficacy in patients with severe sepsis/septic shock. The usefulness of a combination of MEWS and BLA to predict ICU transfer in severe sepsis/septic shock patients is unclear. We evaluated whether use of a combination of MEWS and BLA enhances prediction of ICU transfer and mortality in hospitalized patients with severe sepsis/septic shock. Methods: Patients with severe sepsis/septic shock who were screened or contacted by a medical emergency team between January 2012 and August 2012 were enrolled at a university-affiliated hospital with ~2,700 beds, including 28 medical ICU beds. Results: One hundred patients were enrolled and the rate of ICU admittance was 38%. MEWS (7.37 vs. 4.85) and BLA concentration (5 mmol/L vs. 2.19 mmol/L) were significantly higher in patients transferred to ICU than those in patients treated in general wards. The combination of MEWS and BLA was more accurate than MEWS alone in terms of ICU transfer (C-statistics: 0.898 vs. 0.816, p = 0.019). The 28-day mortality rate was 19%. MEWS was the only factor significantly associated with 28-day mortality rate (odds ratio, 1.462; 95% confidence interval, 1.122 to 1.905; p = 0.005). Conclusions: The combination of MEWS and BLA may enhance prediction of ICU transfer in patients with severe sepsis/septic shock.

Background/Aims: The clinical outcomes of patients with hematologic malignancies who were treated with extracorporeal membrane oxygenation (ECMO) after the failu re of optimal conventional therapy were determined. Methods: The medical records of all patients administered ECMO during their stay in a medical intensive care unit of Seoul St. Mary's Hospital between February 2010 and July 2013 were reviewed retrospectively. Results: In total, 15 patients with hematologic malignancies were compared to 33 immunocompetent patients with documented cardiorespiratory failure. Underlying hematologic malignancies were significantly associated with lower overall survival (0.0% vs. 24.2%, p = 0.044). Mortality was significantly associated with a higher 24 hours ECMO inspired fraction of oxygen ($0.71{\pm}0.24$ vs. $0.47{\pm}0.13$, p = 0.015), the development of infection after ECMO (87.5% vs. 25.0%, p = 0.001), and the presence of hyperbilirubinemia (70.0% vs. 0.0%, p < 0.001). Matching of the patients based on their Acute Physiology and Chronic Health Evaluation II scores confirmed the greater risk of mortality in patients with hematologic malignancies (survival: 0.0% vs. 40.0%, p = 0.017). The mean difference in inotropic-equivalent scores after ECMO was significantly lower in the immunocompetent patients than in those with hematologic malignancies ($-59.22{\pm}97.83$ vs. $53.87{\pm}164.46$, p = 0.026). Conclusions: Patients with hematologic malignancies who require ECMO for respiratory support have poor outcomes. The incidence of complications in these patients did not significantly differ from that in immunocompetent patients.

Background/Aims: The potential physiologic roles of Klotho in acute kidney injury (AKI) have recently been demonstrated in animal models. However, to date, there have been no human studies investigating the expression of renal Klotho in AKI. Methods: We retrospectively collected biopsy specimens and clinical data of AKI patients between January 2001 and December 2012. Klotho expression was determined by immunohistochemical staining, and the clinical-pathological correlation was examined. Results: Among the 34 patients diagnosed with acute tubular necrosis or acute tubulointerstitial nephritis, 21 patients without chronic histological lesions were included. The mean age was $37.3{\pm}18.5$ years and the mean peak creatinine level was $8.2{\pm}5.5mg/dL$. In total, 10 patients (47.6%) received temporary renal replacement therapy (RRT); however, 17 patients (81%) showed functional recovery with creatinine levels of < 1.3 mg/dL after 1 month. The intensity of Klotho expression was scored as a percentage of Klotho-positive area. The renal Klotho score showed a significant negative correlation with the initial or peak creatinine level. When the patients were divided into three groups according to the Klotho score (low, middle, high), the low group had a significantly higher peak creatinine level and a more frequent requirement for RRT. However, the Klotho score was not a significant predictor of renal recovery. Conclusions: The results demonstrated that renal Klotho expression in humans decreased significantly according to the severity of AKI, regardless of the etiology, and that low expression was associated with a poor short-term outcome.

Background/Aims: The gastrointestinal (GI) tract often becomes involved in patients with systemic amyloidosis. As few GI amyloidosis data have been reported, we describe the clinical features and outcomes of patients with pathologically proven GI amyloidosis. Methods: We identified 155 patients diagnosed with systemic amyloidosis between April 1995 and April 2013. Twenty-four patients (15.5%) were diagnosed with GI amyloidosis using associated symptoms, and the diagnoses were confirmed by direct biopsy. Results: Among the 24 patients, 20 (83.3%) had amyloidosis light chain (AL), three (12.5%) had amyloid A, and one (4.2%) had transthyretin-related type amyloidosis. Their median age was 57 years (range, 37 to 72), and 10 patients were female (41.7%). The most common symptoms of GI amyloidosis were diarrhea (11 patients, 45.8%), followed by anorexia (nine patients, 37.5%), weight loss, and nausea and/or vomiting (seven patients, 29.2%). The histologically confirmed GI tract site in AL amyloidosis was the stomach in 11 patients (55.0%), the colon in nine (45.0%), the rectum in seven (35.0%), and the small bowel in one (5.0%). Patients with GI involvement had a greater frequency of organ involvement (p = 0.014). Median overall survival (OS) in patients with GI involvement was shorter (7.95 months; range, 0.3 to 40.54) than in those without GI involvement (15.84 months; range, 0.0 to 114.53; p = 0.069) in a univariate analysis. A multivariate analysis of prognostic factors for AL amyloidosis revealed that GI involvement was not a significant predictor of OS (p = 0.447). Conclusions: The prognosis of patients with AL amyloidosis and GI involvement was poorer than those without GI involvement, and they presented with more organ involvement and more advanced disease than those without organ involvement.

Background/Aims: Infections are major causes of both early and late death after lung transplantation (LT). The development of prophylaxis strategies has altered the epidemiology of post-LT infections; however, recent epidemiological data are limited. We evaluated infections after LT at our institution by time of occurrence, site of infections, and microbiologic etiologies. Methods: All consecutive patients undergoing lung or heart-lung transplantation between October 2008 and August 2014 at our institution were enrolled. Cases of infections after LT were initially identified from the prospective registry database, which was followed by a detailed review of the patients' medical records. Results: A total of 108 episodes of post-LT infections (56 bacterial, 43 viral, and nine fungal infections) were observed in 34 LT recipients. Within 1 month after LT, the most common bacterial infections were catheter-related bloodstream infections (42%). Pneumonia was the most common site of bacterial infection in the 2- to 6-month period (28%) and after 6 months (47%). Cytomegalovirus was the most common viral infection within 1 month (75%) and in the 2- to 6-month period (80%). Respiratory viruses were the most common viruses after 6 months (48%). Catheter-related candidemia was the most common fungal infection. Invasive pulmonary aspergillosis developed after 6 months. Survival rates at the first and third years were 79% and 73%, respectively. Conclusions: Although this study was performed in a single center, we provide valuable and recent detailed epidemiology data for post-LT infections. A further multicenter study is required to properly evaluate the epidemiology of post-LT infections in Korea.

Background/Aims: Intranasal mupirocin and chlorhexidine bathing are candidate strategies to prevent healthcare-associated infections caused by methicillin-resistant Staphylococcus aureus (MRSA). In Korea, intranasal mupirocin is not available, and mupirocin ointment, an over-the-counter drug, has been used indiscriminately. Furthermore, because it is covered by health insurance, mupirocin is easy to prescribe within hospitals. Methods: We performed a mupirocin drug utilization review (DUR) within Hallym University Sacred Heart Hospital. Annual use of mupirocin was investigated between 2003 and 2013, and monthly consumption of mupirocin was assessed during the final 2-year period. The DUR focused on August 2012, the period of highest use of mupirocin. Also, we investigated trends in mupirocin resistance in MRSA between 2011 and 2013. Results: Annual consumption of mupirocin increased from 3,529 tubes in 2003 to 6,475 tubes in 2013. During August 2012, 817 tubes were prescribed to 598 patients; of these, 84.9% were prescribed to outpatients, and 77.6% at the dermatology department. The most common indication was prevention of skin infections (84.9%), and the ointment was combined with systemic antibiotics in 62.9% of cases. The average duration of systemic antibiotic administration was about 7.8 days. The rate of low-level mupirocin resistance in MRSA increased from 8.0% to 22.0%, and that of high-level mupirocin resistance increased from about 4.0% to about 7.5%. Conclusions: Inappropriate use of mupirocin is prevalent. Considering the increase in resistance and the future application of intranasal mupirocin, prophylactic use of mupirocin in dermatology departments should be reconsidered.

Background/Aims: Allopurinol is a urate-lowering agent that is commonly used to prevent chemotherapy-related hyperuricemia. Allopurinol hypersensitivity syndrome (AHS) is a disorder involving multiple organs, which may be accompanied by cutaneous adverse reactions. We identified the characteristics and clinical outcomes of chemotherapy-associated AHS in patients with hematological malignancies. Methods: This retrospective single-center study included 26 AHS patients (11 with and 15 without hematological malignancies) admitted to Seoul St. Mary's Hospital. AHS was defined using the criteria of Singer and Wallace. Comparisons were made using the Mann-Whitney U test and Fisher exact test as appropriate. Results: In patients with a hematological malignancy and AHS, statistically significant differences were observed in terms of younger age at onset; shorter duration of exposure; higher starting and maintenance doses of allopurinol; lower incidence of eosinophilia, leukocytosis, and underlying renal insufficiency; and more frequent occurrence of fever compared to AHS patients without a hematological malignancy. Two AHS patients with a hematological malignancy were examined for human leukocyte antigen (HLA)-B typing, but neither patient harbored the $HLA-B^*5801$ allele. All of the patients ceased allopurinol treatment, with most patients making a full recovery. Two patients in the study died; however, these deaths were unrelated to AHS. One patient developed serious sequelae of AHS that required hemodialysis. Conclusions: Physicians who prescribe allopurinol for the prevention of chemotherapy-related hyperuricemia should be aware of the unique risk of AHS, even in patients with hematological malignancies who do not have known risk factors for AHS. Novel urate-lowering agents should be considered alternative treatments.

Background/Aims: Nailfold capillaroscopy (NFC) has been used to examine morphological and functional microcirculation changes in connective tissue diseases. It has been demonstrated that NFC patterns reflect abnormal microvascular dynamics, which may play a role in fibromyalgia (FM) syndrome. The aim of this study was to determine NFC patterns in FM, and their association with clinical features of FM. Methods: A total of 67 patients with FM, and 30 age- and sex-matched healthy controls, were included. Nailfold capillary patterns were quantitatively analyzed using computerized NFC. The parameters of interest were as follows: number of capillaries within the central 3 mm, deletion score, apical limb width, capillary width, and capillary dimension. Capillary dimension was determined by calculating the number of capillaries using the Adobe Photoshop version 7.0. Results: FM patients had a lower number of capillaries and higher deletion scores on NFC compared to healthy controls ($17.3{\pm}1.7$ vs. $21.8{\pm}2.9$, p < 0.05; $2.2{\pm}0.9$ vs. $0.7{\pm}0.6$, p < 0.05, respectively). Both apical limb width (${\mu}m$) and capillary width (${\mu}m$) were significantly decreased in FM patients ($1.1{\pm}0.2$ vs. $3.7{\pm}0.6$; $5.4{\pm}0.5$ vs. $7.5{\pm}1.4$, respectively), indicating that FM patients have abnormally decreased digital capillary diameter and density. Interestingly, there was no difference in capillary dimension between the two groups, suggesting that the length or tortuosity of capillaries in FM patients is increased to compensate for diminished microcirculation. Conclusions: FM patients had altered capillary density and diameter in the digits. Diminished microcirculation on NFC may alter capillary density and increase tortuosity.