Middle East Respiratory Syndrome coronavirus (MERS-CoV) was first isolated from a patient with severe pneumonia in 2012. The 2015 Korea outbreak of MERSCoV involved 186 cases, including 38 fatalities. A total of 83% of transmission events were due to five superspreaders, and 44% of the 186 MERS cases were the patients who had been exposed in nosocomial transmission at 16 hospitals. The epidemic lasted for 2 months and the government quarantined 16,993 individuals for 14 days to control the outbreak. This outbreak provides a unique opportunity to fill the gap in our knowledge of MERS-CoV infection. Therefore, in this paper, we review the literature on epidemiology, virology, clinical features, and prevention of MERS-CoV, which were acquired from the 2015 Korea outbreak of MERSCoV.

Antimicrobial resistance is becoming one of the greatest challenges to public health worldwide. Infections by antimicrobial-resistant organisms could result in the failure of treatment, increased medical costs, prolonged hospital stays, and an increased socioeconomic burden. Antimicrobial usage in Korea remains heavy, even after much effort to reduce their use. According to the Korean antimicrobial resistance surveillance system, the resistance rates of many bacteria are increasing. The resistance rate of Acinetobacter baumannii to imipenem in Korea increased to 85% in 2015, representing a major public threat. The reports of increased carbapenem resistance in Enterobacteriaceae are worrisome. More importantly, some carbapenem-resistant Enterobacteriaceae may result from the production of carbapenemases, which break down carbapenems. There are relatively few treatment options for extensively drug-resistant A. baumannii and carbapenem-resistant Enterobacteriaceae. Most reports are retrospective observational studies. Because there are little published data from randomized controlled trials, more data assessing antimicrobial treatment for extensively drug-resistant A. baumannii and carbapenem-resistant Enterobacteriaceae are needed to make treatment recommendations.

Hematopoietic stem cell transplantation (HSCT) is a treatment for hematologic malignancies, immune deficiencies, or genetic diseases, ect. Recently, the number of HSCTs performed in Korea has increased and the outcomes have improved. However, infectious complications account for most of the morbidity and mortality after HSCT. Post-HSCT infectious complications are usually classified according to the time after HSCT: pre-engraftment, immediate post-engraftment, and late post-engraftment period. In addition, the types and risk factors of infectious complications differ according to the stem cell source, donor type, conditioning intensity, region, prophylaxis strategy, and comorbidities, such as graft-versus-host disease and invasive fungal infection. In this review, we summarize infectious complications after HSCT, focusing on the Korean perspectives.

The number of medical studies being published is increasing exponentially, and clinicians must routinely process large amounts of new information. Moreover, the results of individual studies are often insufficient to provide confident answers, as their results are not consistently reproducible. A meta-analysis is a statistical method for combining the results of different studies on the same topic and it may resolve conflicts among studies. Meta-analysis is being used increasingly and plays an important role in medical research. This review introduces the basic concepts, steps, advantages, and caveats of meta-analysis, to help clinicians understand it in clinical practice and research. A major advantage of a meta-analysis is that it produces a precise estimate of the effect size, with considerably increased statistical power, which is important when the power of the primary study is limited because of a small sample size. A meta-analysis may yield conclusive results when individual studies are inconclusive. Furthermore, meta-analyses investigate the source of variation and different effects among subgroups. In summary, a meta-analysis is an objective, quantitative method that provides less biased estimates on a specific topic. Understanding how to conduct a meta-analysis aids clinicians in the process of making clinical decisions.

Systemic lupus erythematosus (SLE), an autoimmune disease of unknown etiology, is characterized by the production of autoantibodies and end-organ damage. Lupus nephritis affects up to 70% of patients with SLE and is the most critical predictor of morbidity and mortality. The immunopathogenesis of SLE is complex and most clinical trials of biologics targeting immune cells or their mediators have failed to show efficacy in SLE patients. It has therefore become increasingly clear that additional, local factors give rise to the inflammation and organ damage. In this review, we describe recent advances in the role of renal resident cells, including podocytes, mesangial cells, and epithelial cells, in the pathogenesis of lupus nephritis.

Background/Aims: The gastroesophageal junction is an important barrier against gastroesophageal reflux. Endoscopic grading of gastroesophageal flap valve is simple, reproducible, and may predict reflux activity. We investigated the correlation between gastroesophageal flap valve grade and the gastroesophageal junction's structural properties using abdominal computed tomography. Methods: A total of 138 patients with early gastric cancer who underwent both pre-treatment esophagogastroduodenoscopy and water-distended stomach two-phase computed tomography were enrolled. Endoscopic gastroesophageal flap valve grade and abdominal computed tomography findings were analyzed to assess anatomical factors including the gastroesophageal junction and related organs. Results: The angle of His increased significantly with gastroesophageal flap valve grade (grade I, $65.2^{\circ}{\pm}19.6^{\circ}$; grade II, $66.6^{\circ}{\pm}19.8^{\circ}$; grade III, $76.7^{\circ}{\pm}11.9^{\circ}$; grade IV, $120.0^{\circ}{\pm}30.3^{\circ}$; p < 0.001), as did the size of the diaphragmatic hiatus (grade I, $213.0{\pm}53.8mm^2$; grade II, $232.6{\pm}71.0mm^2$; grade III, $292.3{\pm}99.2mm^2$; grade IV, $584.4{\pm}268.3$; p < 0.001). The length of the abdominal esophagus decreased as gastroesophageal flap valve grade increased (grade I, $34.6{\pm}5.8mm$; grade II, $32.0{\pm}6.5mm$; grade III, $24.6{\pm}7.8mm$; grade IV, $-22.6{\pm}38.2mm$; p < 0.001). There was no significant relationship between gastroesophageal flap valve grade and visceral and subcutaneous fat areas (p = 0.877 and p = 0.508, respectively). Conclusions: Endoscopic grading of the gastroesophageal flap valve is well correlated with anatomical changes around the gastroesophageal junction on abdominal computed tomography, and it can provide useful information about the anti-reflux barrier.

Background/Aims: Gastrointestinal (GI) bleeding is a life-threatening complication in critically ill patients. The aim of this study was to determine the efficacy of bedside endoscopy in an intensive care unit (ICU) setting, and to compare the outcomes of early endoscopy (within 24 hours of detecting GI bleeding) with late endoscopy (after 24 hours). Methods: We retrospectively reviewed the medical records of patients who underwent bedside endoscopy for nonvariceal upper GI bleeding and lower GI bleeding that occurred after ICU admission at Seoul National University Hospital from January 2010 to May 2015. Results: Two hundred and fifty-three patients underwent bedside esophagogastroduodenoscopy (EGD) for upper GI bleeding (early, 187; late, 66) and 69 underwent bedside colonoscopy (CS) for lower GI bleeding (early, 36; late, 33). Common endoscopic findings were peptic ulcer, and acute gastric mucosal lesion in the EGD group, as well as ischemic colitis and acute hemorrhagic rectal ulcers in the CS group. Early EGD significantly increased the rate of finding the bleeding focus (82% vs. 73%, p = 0.003) and endoscopic hemostasis (32% vs. 12%, p = 0.002) compared with late EGD. However, early CS significantly decreased the rate of identifying the bleeding focus (58% vs. 82%, p = 0.008) and hemostasis (19% vs. 49%, p = 0.011) compared with late CS due to its higher rate of poor bowel preparation and blood interference (38.9% vs. 6.1%, p = 0.035). Conclusions: Early EGD may be effective for diagnosis and hemostatic treatment in ICU patients with GI bleeding. However, early CS should be carefully performed after adequate bowel preparation.

Background/Aims: NADPH (nicotinamide adenine dinucleotide phosphate) oxidase (NOX)-mediated oxidative stress plays a key role in promotion of oxidative injury in the cardiovascular system. The aim of this study is to evaluate the status of NOX in endothelial progenitor cells (EPCs) of hyperlipidemic patients and to assess the correlation between NOX activity and the functions EPCs. Methods: A total of 30 hyperlipidemic patients were enrolled for this study and 30 age-matched volunteers with normal level of plasma lipids served as controls. After the circulating EPCs were isolated, the EPC functions (migration, adhesion and tube formation) were evaluated and the status of NOX (expression and activity) was examined. Results: Compared to the controls, hyperlipidemic patients showed an increase in plasma lipids and a reduction in EPC functions including the attenuated abilities in adhesion, migration and tube formation, concomitant with an increase in NOX expression ($NOX_2$ and $NOX_4$), NOX activity, and reactive oxygen species production. The data analysis showed negative correlations between NOX activity and EPC functions. Conclusions: There is a positive correlation between the NOX-mediated oxidative stress and the dysfunctions of circulating EPCs in hyperlipidemic patients, and suppression of NOX might offer a novel strategy to improve EPCs functions in hyperlipidemia.

Background/Aims: Scrub typhus is known as a self-limited infectious disease. Cardiac complication is uncommon and usually not life-threatening. Until now, few cases of fulminant myocarditis by scrub typhus have been reported. So, we investigated incidence and predictors of acute myocarditis in severe scrub typhus. Methods: We retrospectively reviewed 89 patients among 91 scrub typhus confirmed patients who examined an echocardiogram and cardiac biomarkers from 2005 to 2015 in the intensive care unit at our hospital. We excluded two patients who didn't have electrocardiography. Patients were divided into two groups and compared between scrub typhus with (n = 13) and without (n = 76) acute myocarditis. Results: Age, sex, and underlying diseases were similar between the groups. The existence of eschar and duration of general ache and fever were similar between the groups. However, patients with acute myocarditis had more elevated total bilirubin, high incidence of ST elevations and paroxysmal atrial fibrillation (PAF) than those without acute myocarditis. Receiver operating characteristic analysis showed that the PAF was a predictor of myocarditis with a sensitivity of 70% and specificity of 84%. Predictive power of combination of ST-segment elevation and PAF was significantly associated with myocarditis in the multivariate analysis (odds ratio, 1.57; 95% confidence interval [CI], 1.21 to 11.7; p = 0.041) and area under the curve was 0.947 (95% CI, 0.878 to 0.983; p < 0.001). Conclusions: Acute myocarditis with scrub typhus may be more common than previously reported. Patients with high bilirubin and PAF are at increased risk of acute myocarditis with scrub typhus. These patients warrant closer follow-up and echocardiogram would be needed.

Background/Aims: Both diaphragmatic excursion and change in muscle thickening are measured using ultrasonography (US) to assess diaphragm function and mechanical ventilation weaning outcomes. However, which parameter can better predict successful extubation remains to be determined. The aim of this study was to compare the clinical utility of these two diaphragmatic parameters to predict extubation success. Methods: This study included patients subjected to extubation trial in the medical or surgical intensive care unit of a university-affiliated hospital from May 2015 through February 2016. Diaphragm excursion and percent of thickening change (${\Delta}tdi%$tdi%) were measured using US within 24 hours before extubation. Results: Sixty patients were included, and 78.3% (47/60) of these patients were successfully extubated, whereas 21.7% (13/60) were not. The median degree of excursion was greater in patients with extubation success than in those with extubation failure (1.65 cm vs. 0.8 cm, p < 0.001). Patients with extubation success had a greater ${\Delta}tdi%$ than those with extubation failure (42.1% vs. 22.5%, p = 0.03). The areas under the receiver operating curve for excursion and ${\Delta}tdi%$ were 0.836 (95% confidence interval [CI], 0.717 to 0.919) and 0.698 (95% CI, 0.566 to 0.810), respectively (p = 0.017). Conclusions: Diaphragm excursion seems more accurate than a change in the diaphragm thickness to predict extubation success.

Background/Aims: Brain and bone metastases are common in patients with lung cancer. The development of metastasis is associated with poor survival in lung cancer patients. Although tumor morphologic features on radiographs are routinely assessed for differentiation between benign and malignant lung nodules, they are not used to predict metastasis. We assessed morphologic features of pulmonary adenocarcinomas with brain/bone metastasis on computed tomography (CT) to identify related factors for metastasis. Methods: We performed a retrospective analysis of initial chest CT findings (size, type of contour, percentage of necrosis, enhancement, presence or absence of calcification, and air cavity) from 2009 to 2010 of patients with brain or bone metastasis and compared the findings with those of patients without metastases. Results: In total, 128 patients were included (78 men, 52 women; mean age 69 years; range, 36 to 87). Nineteen patients had brain metastases and 32 had bone metastases. Morphologic features associated with brain metastasis included size ${\geq}50mm$ (odds ratio [OR], 3.37; 95% confidence interval [CI], 1.24 to 9.17; p = 0.013), necrosis ${\geq}30%$ (OR, 4.51; 95% CI, 1.62 to 12.55; p =0.002), and presence of calcification (OR, 3.97; 95% CI, 1.16 to 13.55; p = 0.035). Morphologic features associated with bone metastasis included necrosis ${\geq}30%$ (OR, 4.639; 95% CI, 1.98 to 10.82; p < 0.001) and T 3 to 4 stage (OR, 2.53; 95% CI, 1.07 to 6.00; p = 0.031). Conclusions: We found that necrosis ${\geq}30%$ was associated with pulmonary adenocarcinoma with brain and bone metastasis at initial chest CT morphologic feature. To validate these results, further research should be conducted.

Background/Aims: Non-alcoholic fatty liver disease is associated with insulin resistance. Compound K (CK) is the final metabolite of panaxadiol ginsenosides that have been shown to exert antidiabetic effects. However, the molecular mechanism of the antidiabetic effects in the liver have not been elucidated; further, whether CK has beneficial effects in hepatosteatosis remains unclear. Therefore, we evaluated the effect of CK on hepatosteatosis as well as its mechanism in high-fat diet (HFD)-fed type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Methods: Twenty-four-week-old male OLETF rats were assigned to four groups: control (saline), CK 10 mg/kg, CK 25 mg/kg, or metformin 300 mg/kg (positive control); all treatments were administered orally for 12 weeks. Results: Fasting glucose levels of the CK25 group were significantly lower than those of the control group during the 12 weeks. The results of the oral glucose tolerance test showed that both the glucose concentration after glucose loading and the fasting insulin levels of the CK25 group were significantly lower than those of the control. Hepatosteatosis was significantly improved by CK25. CK25 and metformin significantly increased the phosphorylation of hepatic adenosine monophosphate-activated protein kinase (AMPK). CK25 significantly inhibited the expression of sterol regulatory element-binding protein-1c and fatty acid synthase, while upregulating that of peroxisome proliferator-activated receptor-${\alpha}$ and carnitine palmitoyltransferase-1. Conclusions: CK improved glucose intolerance and hepatosteatosis in HFD-fed OLETF rats through AMPK activation, which has dual mode of action that involves decreasing the synthesis of fatty acids and increasing fatty acid oxidation.

Background/Aims: Kidney transplantation (KT) reportedly provides a significant survival advantage over dialysis in diabetic patients. However, KT outcome in diabetic patients compared with that in non-diabetic patients remains controversial. In addition, owing to recent improvements in the outcomes of KT and management of cardiovascular diseases, it is necessary to analyze outcomes of recently performed KT in diabetic patients. Methods: We reviewed all diabetic patients who received living donor KT between January 2008 and December 2011. Each patient was age- and sex-matched with two non-diabetic patients who received living donor KT during the same period. The outcomes of living donor KT were compared between diabetic and non-diabetic patients. Results: Among 887 patients, 89 diabetic patients were compared with 178 non-diabetic patients. The incidence of acute rejection was not different between the diabetic and non-diabetic patients. Urinary tract infection and other infections as well as cardiovascular events occurred more frequently in diabetic patients. However, diabetes, cardiovascular disease, and infection were not significant risk factors of graft failure. Late rejection (acute rejection after 1 year of transplantation) was the most important risk factor for graft failure after adjusting for diabetes mellitus (DM), human leukocyte antigen mismatch, rejection and infection (hazard ratio, 56.082; 95% confidence interval, 7.169 to 438.702; p < 0.001). Mortality was not significantly different between diabetic and non-diabetic patients (0 vs. 2, p = 0.344 by log-rank test). Conclusions: End-stage renal disease patients with DM had favorable outcomes with living donor kidney transplantation.

Background/Aims: Recent studies have suggested an important role of adipokines in the development of insulin resistance and diabetes mellitus. The clinical relevance of adipokines on long-term outcomes in patients with diabetes and chronic kidney disease is uncertain. The purpose of this study was to identify a predictable factor in patients with long-term diabetic complications. Methods: A total of 161 diabetic individuals were followed-up from 2002 to 2013. Circulating plasma levels of adiponectin, glypican-4, irisin, visfatin, and visit-to-visit glucose variability were measured in diabetic patients. Associations among adipokines and variable metabolic parameters and microvascular, and macrovascular complications were evaluated. Results: Plasma adiponectin and glypican-4 levels were significantly increased in patients with renal insufficiency. These adipokines were negatively associated with estimated glomerular filtration rate and positively associated with urinary albumin excretion. The relative risk of renal progression to dialysis increased independently with increasing level of adiponectin. Glypican-4 and visfatin were not predictive of any microvascular or macrovascular complications. Glucose variability increased the risk of diabetic nephropathy and cerebrovascular complications. Conclusions: Adiponectin and glypican-4 were associated with renal function and might be able to predict renal progression. Glucose variability was a predictable factor for diabetic nephropathy and cerebrovascular complications.

Background/Aims: Because of rarity, role of chemotherapy of bladder adenocarcinoma are still unidentified. Therefore, we performed a retrospective analysis of the clinical features and chemotherapy outcomes of bladder adenocarcinoma. Methods: Eligible patients for this retrospective analysis were initially diagnosed with bladder adenocarcinoma and presented with a clinically no other primary site of origin. The collected data included age, gender, performance status, stage, hemoglobin, albumin, initial date of diagnosis, treatment modality utilized, response to treatment, presence of relapse, last status of patient, and last date of follow-up. Results: We retrospectively reviewed 29 patients, who were treated with chemotherapy for bladder adenocarcinoma at 10 Korean medical institutions from 2004 to 2014. The median age of patients was 58 years (range, 17 to 78) and 51.7% of the patients were female. Urachal adenocarcinoma was identified in 15 patients. Of 27 symptomatic patients, 22 experienced gross hematuria. Twelve patients were treated with 5-f luorouracil based chemotherapy, five were gemcitabine based, three were taxane and others. Thirteen of them achieved complete response (10.3%) or partial response (34.5%). Median progression-free survival (PFS) and overall survival (OS) for all patients were 10.6 months (95% confidence interval [CI], 9.5 to 11.6) and 24.5 months (95% CI, 1.2 to 47.8), respectively. The cases of urachal adenocarcinoma exhibited worse tendency in PFS and OS (p = 0.024 and p = 0.046, respectively). Conclusions: Even though bladder adenocarcinoma had been observed moderate effectiveness to chemotherapy, bladder adenocarcinoma is a highly aggressive form of bladder cancer. PFS and OS were short especially in urachal carcinoma.

Background/Aims: Due to advances in diagnostic techniques, clinicians are more frequently performing influenza diagnostic tests and referring to their test results ahead of the administration of neuraminidase inhibitors (NAIs). To investigate the clinical significance of the time from symptom onset to laboratory diagnosis, we reviewed the clinical characteristics of adult patients with influenza who had an early laboratory diagnosis (ED) or a late laboratory diagnosis (LD) at one of four tertiary care centers during a seasonal outbreak of influenza. Methods: Clinical data were collected from 1,405 adults during the 2013 to 2014 influenza season. A patient was regarded as receiving an ED or LD if he/she received an influenza diagnostic test at 0 to 1 or 4 to 7 days after symptom onset, respectively. Early NAI therapy and late NAI therapy were defined as the administration of NAI ${\leq}2$ or > 2 days after symptom onset, respectively. Results: Nearly half of the patients (47.0%) received an ED (n = 661), whereas 13.5% (n = 190) received a LD. Patients with a LD had initial symptoms of cough, sputum production, and dyspnea and experienced pneumonia, antibiotic therapy, hospitalization, and admission to the intensive care unit more often than those with an ED. NAI therapy and early NAI therapy were less frequent in patients with a LD than those with an ED. Of the analyzed baseline characteristics, age ${\geq}50$ years, influenza B infection, and diagnosis using a polymerase chain reaction test were significantly associated with a LD. Conclusions: LD was associated with inappropriate antiviral therapy and complicated presenting features in adult patients with seasonal influenza. ED of influenza should be emphasized, especially for older adults.

Background/Aims: To define the effect of statins on interleukin $1{\beta}$ (IL-$1{\beta}$)-induced osteoclastogenesis and elucidate the underlying mechanisms. Methods: Bone marrow cells were obtained from 5-week-old male ICR (Institute for Cancer Research) mice, and they were cultured to differentiate them into osteoclasts with macrophage colony-stimulating factor and the receptor activator of nuclear factor (NF)-${\kappa}B$ ligand in the presence or absence of IL-$1{\beta}$ or atorvastatin. The formation of osteoclasts was evaluated by tartrate-resistant acid phosphatase (TRAP) staining and resorption pit assay with dentine slice. The molecular mechanisms of the effects of atorvastatin on osteoclastogenesis were investigated using reverse transcription polymerase chain reaction and immunoblotting for osteoclast specific molecules. Results: Atorvastatin significantly reduced the number of TRAP-positive multinucleated cells as well as the bone resorption area. Atorvastatin also downregulated the expression of the NF of activated T-cell c1 messenger RNA and inhibited the expression of osteoclast-specific genes. A possible underlying mechanism may be that atorvastatin suppresses the degradation of the inhibitors of NF-${\kappa}B$ and blocks the activation of the c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38; thus, implicating the NF-${\kappa}B$ and mitogen-activated protein kinases pathway in this process. Conclusions: Atorvastatin is a strong inhibitor of inflammation-induced osteoclastogenesis in inflammatory joint diseases.

Background/Aims: To evaluate drug survival of the tumor necrosis factor ${\alpha}$ inhibitors (TNFi) and risk factors for the drug discontinuation in patients with ankylosing spondylitis (AS). Methods: We retrospectively evaluated 487 AS patients at a single tertiary hospital. Among the TNFi users, drug survival and risk factors of TNFi discontinuation were investigated. Results: Among 487 patients, 128 AS patients were treated with at least one TNFi. Patients who were treated with TNFi were younger at disease onset, had more peripheral manifestations, and had higher level of acute phase reactants and body mass index than those of TNFi non-users at baseline. Of 128 patients, 28 patients (21.9%) discontinued first TNFi therapy during the follow-up period of $65.1{\pm}27.9=;months$. In the multivariable analysis, female (hazard ratio [HR], 6.08; 95% confidence interval [CI], 2.27 to 16.27; p = 0.003), hip involvement (HR, 2.52; 95% CI, 1.08 to 5.87; p = 0.033) and a high C-reactive protein (CRP; HR, 1.10; 95% CI, 1.00 to 1.21; p = 0.044) were risk factors for drug discontinuation. Etanercept showed better survival rate than infliximab. The main reason for discontinuation of TNFi was inefficacy. Conclusions: TNFi discontinuation rate of Korean patients with AS seems to be similar to those with the European patients. Female sex, hip involvement, CRP, and the type of TNFi were associated with TNFi discontinuation.

Background/Aims: Pyomyositis is an infective condition with primary involvement of the skeletal muscles. There is sparse recent literature on patients with pyomyositis. Methods: This study was carried out at emergency services of a tertiary care center located in subtropical area of Indian subcontinent. Results: Sixty-two patients of primary pyomyositis formed the study cohort. Mean age of occurrence was $29.9{\pm}14.8years$. There were 54 men. Twelve patients had underlying medical diseases. Muscle pain was seen in all 62 patients. Forty-eight patients (77.4%) had the fever. Most common site of involvement was thigh muscles (n = 29, 46.8%). Forty-nine patients (79%) presented in the suppurative stage of illness. Patients with comorbidities were older (age: median 36 years [interquartile range (IQR), 25 to 47] vs. 24 years [IQR, 16 to 35], p = 0.024), had higher culture positivity with gram-negative organisms (8/9 [88.89%] vs. 6/29 [20.69%], p = 0.001). Importantly, higher number of these patients received inappropriate antibiotics initially. Patients with positive pus culture result had higher complication rate (32/38 [84.21%] vs. 10/18 [55.56%], p = 0.044). Six patients (9.7%) had in-hospital mortality. Lower first-day serum albumin, initial inappropriate antibiotic therapy, and advanced form of the disease at presentation were associated with increased in-hospital mortality. Conclusions: Primary pyomyositis is not an uncommon disease entity. Patients with comorbidities were more likely to receive initial inappropriate antibiotic therapy. Patients with positive pus culture report had the higher rate of complications. Lower first-day serum albumin, initial inappropriate antibiotic therapy and advanced form of the disease at presentation were associated with increased in-hospital mortality.