Angiogenesis is a complex biological phenomenon that forms new blood vessels from the pre-existing vasculature. Aberrant angiogenesis has been implicated in a variety of diseases such as cancer, atherosclerosis, arthritis, obesity, pulmonary hypertension, diabetic retinopathy, and age-related macular degeneration. These conditions collectively affect nearly 10% of the global population. Much effort has focused on identifying new therapeutic agents that inhibit pathological angiogenesis since 1971, when Judah Folkman published the hypothesis that tumor growth is angiogenesis-dependent and that its inhibition may be therapeutic. In 2004, the U.S. Food and Drug Administration approved the first antiangiogenic drug for the treatment of metastatic colon cancer, bevacizumab (Avastin, Genentech). This drug is a humanized monoclonal antibody that neutralizes the vascular endothelial growth factor. It is used in combination with chemotherapy, and its use began the era of antiangiogenesis therapy. Several new therapeutic agents have been added to the list of approved drugs, and clinical trials of new therapeutic options and antiangiogenic agents are ongoing. This review describes the progress made in the first decade of antiangiogenesis therapy, and addresses both validated and possible targets for future drug development.

S100A8 and S100A9 are major leukocyte proteins, known as damage-associated molecular patterns, found at high concentrations in the synovial fluid of patients with rheumatoid arthritis (RA). A heterodimeric complex of S100A8/A9 is secreted by activated leukocytes and binds to Toll-like receptor 4, which mediates downstream signaling and promotes inflammation and autoimmunity. Serum and synovial fluid levels of S100A8/A9 are markedly higher in patients with RA than in patients with osteoarthritis or miscellaneous inflammatory arthritis. Serum levels of S100A8/A9 are significantly correlated with clinical and laboratory markers of inf lammation, such as C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, and the Disease Activity Score for 28 joints. Significant correlations have also been found between S100A8/A9 and radiographic and clinical assessments of joint damage, such as hand radiographs and the Rheumatoid Arthritis Articular Damage score. In addition, among known inflammatory markers, S100A8/A9 has the strongest correlation with total sum scores of ultrasonography assessment. Furthermore, baseline levels of S100A8/A9 are independently associated with progression of joint destruction in longitudinal studies and are responsive to change during conventional and biologic treatments. These findings suggest S100A8/A9 to be a valuable diagnostic and prognostic biomarker for RA.

Background/Aims: Oxidative stress increases the risk of cardiovascular complications of metabolic syndrome (MetS). This study was conducted to examine the difference in antioxidant capacity according to the presence of MetS, and to characterize the association between antioxidant capacity and MetS-related factors. Methods: We used the biological antioxidant potential (BAP) test to estimate antioxidant capacity. The BAP test has recently been used as an indicator of antioxidant capacity. We measured BAP levels in 45 patients with MetS (mean age, $44.6{\pm}1.1$ years) and 47 age- and sex-matched controls (mean age, $42.7{\pm}1.1$ years). To evaluate the association between antioxidant capacity and MetS, adiponectin, high-sensitivity C-reactive protein (hs-CRP), interleukin-6, tumor necrosis factor-${\alpha}$, and homeostatic model assessment for insulin resistance (HOMA-IR), linear regression and logistic analyses were performed. Results: The mean BAP of the MetS group ($1,937.3{\pm}36.5{\mu}mol/L$) was significantly lower than that of the non-MetS group ($2,101.7{\pm}29.5{\mu}mol/L$). Also, the mean BAP was low in persons having low high density lipoprotein and high triglyceride. Reduced antioxidant capacity was significantly associated with adiponectin, HOMA-IR and hs-CRP after adjusting for age and sex. The odds ratios for MetS with BAP, log adiponectin, log HOMA-IR, and log hs-CRP were 0.63 (95% confidence interval [CI], 0.49 to 0.82), 0.22 (0.10 to 0.51), 14.24 (4.35 to 46.58), and 1.93 (1.36 to 2.75), respectively. Conclusions: Persons with MetS showed reduced antioxidant capacity. We identified relationships between antioxidant capacity measured by BAP test and MetS, as well as MetS-related factors, such as insulin resistance, hs-CRP, and adiponectin.

Background/Aims: Sunitinib is an oral multitargeted tyrosine kinase inhibitor used mainly for the treatment of metastatic renal cell carcinoma. The renal adverse effects (RAEs) of sunitinib have not been investigated. The aim of this study was to determine the incidence and risk factors of RAEs (proteinuria [PU] and renal insufficiency [RI]) and to investigate the relationship between PU and antitumor efficacy. Methods: We performed a retrospective review of medical records of patients who had received sunitinib for more than 3 months. Results: One hundred and fifty-five patients (mean age, $58.7{\pm}12.6$ years) were enrolled, and the mean baseline creatinine level was 1.24 mg/dL. PU developed in 15 of 111 patients, and preexisting PU was aggravated in six of 111 patients. Only one patient developed typical nephrotic syndrome. Following discontinuation of sunitinib, PU was improved in 12 of 17 patients but persisted in five of 17 patients. RI occurred in 12 of 155 patients, and the maximum creatinine level was 3.31 mg/dL. RI improved in two of 12 patients but persisted in 10 of 12 patients. Risk factors for PU were hypertension, dyslipidemia, and chronic kidney disease. Older age was a risk factor for RI. The median progression-free survival was significantly better for patients who showed PU. Conclusions: The incidence of RAEs associated with sunitinib was lower than those of previous reports. The severity of RAEs was mild to moderate, and partially reversible after cessation of sunitinib. We suggest that blood pressure, urinalysis, and renal function in patients receiving sunitinib should be monitored closely.

Background/Aims: To enable appropriate antimicrobial treatment for community-onset infections in emergency departments (EDs), data are needed on the resistance profiles of Escherichia coli and Klebsiella pneumoniae, which are the main pathogens of community-onset bacteremia. Methods: Records were reviewed of 734 patients with E. coli and K. pneumoniae bacteremia who visited the Daegu Fatima Hospital ED, Daegu, Korea between 2003 and 2009. We investigated the demographic data, clinical findings, and antimicrobial susceptibility patterns of the organisms. Results: Of 1,208 cases of community-onset bacteremia, 62.8% were caused by E. coli or K. pneumoniae in an ED of a secondary care hospital. Five hundred and forty-eight cases of E. coli (75%) and 183 cases of K. pneumoniae (25%) were analyzed. Urinary tract infection (43.1%) was most common, followed by intra-abdominal infection (39%) and pneumonia (7.2%). Trimethoprim/sulfamethoxazole, fluoroquinolone, third-generation cephalosporin (3GC) and amikacin resistance rates among E. coli and K. pneumoniae were 22.8%, 19.6%, 6.2%, and 1.3%, respectively. In 2009, the rate of 3GC resistance (10.6%) was significantly higher, compared to the annual averages of 2003 to 2008 (6.1%; p = 0.03). Previous exposure to antibiotics was an independent risk factor for 3GC resistance in multivariate logistic regression analysis. Conclusions: The rate of 3GC resistance increased in community-onset infections, and previous exposure to antibiotics was an independent risk factor. Despite the increased 3GC resistance in community-onset infections, an amikacin combination therapy could provide an option for treatment of bacteremic patients with previous antibiotic exposure in an ED.

Background/Aims: In patients with liver cirrhosis, drugs acting on the central nervous system can lead to hepatic encephalopathy and the effects may be prolonged. Recently, misuse of propofol has been reported and the associated risk of death have become an issue. Propofol is commonly used during sedative endoscopy; therefore, its safety in high-risk groups must be further investigated. We performed a pilot study of the safety and efficacy of propofol during endoscopy in Korean patients with cirrhosis. Methods: Upper gastrointestinal endoscopy was performed under sedation with propofol along with careful monitoring in 20 patients with liver cirrhosis and 20 control subjects. The presence or development of hepatic encephalopathy was assessed using the number connection test and neurologic examination. Results: Neither respiratory depression nor clinically significant hypotension were observed. Immediate postanesthetic recovery at 5 and 10 minutes after the procedure was delayed in the cirrhotic patients compared with the control group; however, at 30 minutes, the postanesthetic recovery was similar in both groups. Baseline psychomotor performance was more impaired in cirrhotic patients, but propofol was not associated with deteriorated psychomotor function even in cirrhotic patients with a minimal hepatic encephalopathy. Conclusions: Sedation with propofol was well tolerated in cirrhotic patients. No newly developed hepatic encephalopathy was observed.

Background/Aims: While drug-eluting stents (DESs) have shown favorable outcomes in ST-segment elevation myocardial infarction (STEMI) compared to bare metal stents (BMSs), there are concerns about the risk of stent thrombosis (ST) with DESs. Because intravascular ultrasound (IVUS) guidance may help optimize stent placement and improve outcomes in percutaneous coronary intervention (PCI) patients, we evaluated the impact of IVUS-guided BMS versus DES implantation on long-term outcomes in primary PCI. Methods: In all, 239 STEMI patients received DES (n = 172) or BMS (n = 67) under IVUS guidance in primary PCI. The 3-year incidence of major adverse cardiac events (MACEs) including death, myocardial infarction (MI), target vessel revascularization (TVR), and ST was evaluated. Results: There was no difference in all cause mortality or MI. However, the incidence of TVR was 23.9% with BMS versus 9.3% with DES (p = 0.005). Thus, the number of MACEs was significantly lower with DES (11.0% vs. 29.9%; p = 0.001). The incidence of definite or probable ST was not different (1.5% vs. 2.3%; p = 1.0). IVUS-guided DES implantation (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.08 to 0.78; p = 0.017), stent length (HR, 1.03; 95% CI, 1.00 to 1.06; p = 0.046), and multivessel disease (HR, 3.01; 95% CI, 1.11 to 8.15; p = 0.030) were independent predictors of MACE. Conclusions: In patients treated with primary PCI under IVUS guidance, the use of DES reduced the incidence of 3-year TVR versus BMS. However, all cause mortality and MI were similar between the groups. The incidence of ST was low in both groups.

Background/Aims: We investigated the agreement between the QuantiFERON-TB Gold (QFT-Gold) test and the tuberculin skin test (TST) in the diagnosis of latent tuberculosis infection in patients with rheumatoid arthritis (RA), compared with healthy controls, in Korea. Methods: We recruited 64 patients with RA and 79 healthy controls at two university hospitals in South Korea. The participants underwent both the QFT-Gold test and the TST simultaneously between August 2006 and February 2009. All patients were diagnosed using the classification criteria for RA revised in 1987 by the American College of Rheumatology. Bacillus Calmette-Gu$\acute{e}$rin vaccination status and current medications were evaluated, and disease activities were assessed using the Disease Activity Score in 28 joints. Eleven patients with RA produced indeterminate QFT-Gold test results and were thus excluded from the kappa analysis. Results: Based on an induration of 10 mm in diameter as the TST cutoff value, the QFT-Gold test and TST demonstrated 75.0% agreement (${\kappa}$= 0.23) in patients with RA and 75.9% agreement (${\kappa}$= 0.19) in healthy controls. Among the 56 patients with RA who had negative TST results, 11 patients (17.2%) also yielded indeterminate QFT-Gold results. Conclusions: Our study showed poor agreement between the results of the QFT-Gold test and the TST in both RA patients and healthy controls. Based on these findings, we emphasize the importance of making clinical decisions in the diagnosis of latent tuberculosis in Koreans with or without RA.

Background/Aims: Churg-Strauss syndrome (CSS) is a rare systemic necrotizing small-vessel vasculitis, with accompanying bronchial asthma, eosinophilia, and eosinophilic infiltration of various tissues. The purposes of our study were to characterize the clinical features of CSS and to identify factors associated with CSS prognosis in Koreans. Methods: Medical records were reviewed retrospectively for all physician-diagnosed CSS patients in the Seoul National University Hospital between January 1990 and March 2011. Results: Data from 52 CSS patients were analyzed. The respiratory tract was the most commonly involved organ (90.4%). Renal involvement was less frequent in antineutrophilic cytoplasmic antibody (ANCA)(-) patients than in ANCA(+) patients (p = 0.048). Clinical remission occurred in 95.3% of patients, but 16.3% of them relapsed. Patients who maintained remission for more than 6 months were relatively older (median, 51 years) at diagnosis (p = 0.004), had been diagnosed in earlier stages (p = 0.027), showed more frequent respiratory involvement (p = 0.024) and generalized symptoms (p = 0.039), and showed less frequent cutaneous involvement (p = 0.030) than those who did not achieve persistent (> 6 months) remission. Patients who achieved persistent remission also showed higher C-reactive protein (CRP) levels (p = 0.031) than those who did not. Conclusions: ANCA(-) CSS patients showed less frequent renal involvement. Characteristics of good responders were older age, diagnosis at earlier stages, less cutaneous involvement, more respiratory involvement, high CRP values, and more generalized symptoms.

Primary duodenal adenocarcinoma is a rare malignant neoplasm accounting for 0.3% of all gastrointestinal tract carcinomas. We herein present one case of duodenal adenocarcinoma after duodenal neuroendocrine carcinoma. Poorly differentiated duodenal neuroendocrine carcinoma with liver metastasis ($TxNxM_1$) was confirmed, and eight cycles of palliative chemotherapy (5-fluorouracil/etoposide/cisplatin) were administered. The patient was then in a clinically complete response status. About 1 year later, newly developed adenocarcinoma was detected at the same site. It was completely surgically resected, and the patient was cured.

A 71-year-old male patient was readmitted to our hospital 1 month after discharge because of relapse of abdominal pain. He had been diagnosed with hepatocellular carcinoma (HCC) 1 year prior and had undergone repeated transcatheter arterial chemoembolization and radiotherapy. During the last hospitalization, he was diagnosed with a liver abscess complicated by previous treatments for HCC and was treated with intravenous antibiotics and abscess aspiration. Follow-up abdominal computed tomography revealed a liver abscess with a duodenal fistula, which was successfully treated with endoscopic Histoacryl injection into the fistula. Liver abscesses with duodenal fistulas rarely occur, but they are intractable and possibly fatal in patients with HCC. In the literature, they have frequently been managed only with abscess treatment without fistula management. We herein report the first case of a patient with a liver abscess complicated by a fistula between the duodenum and the abscess, which was treated with endoscopic Histoacryl injection.

Spontaneous coronary artery dissection is a rare cause of acute coronary syndrome and sudden cardiac death. The incidence, causes, pathogenesis, and treatment have not been defined clearly, but spontaneous coronary artery dissection should be considered in young patients without major cardiovascular risk factors or in patients in the peripartum period who present with acute coronary syndrome. The treatment is often challenging. Medical treatment is usually considered, and percutaneous coronary intervention or coronary artery bypass surgery may be possible in some patients. We herein report two cases of middle-aged males with myocardial infarction who were treated with percutaneous coronary angioplasty.

Hypothermia, defined as an unintentional decline in the core body temperature to below $35^{\circ}C$, is a life-threatening condition. Patients with malnutrition and diabetes mellitus as well as those of advanced age are at high risk for accidental hypothermia. Due to the high mortality rates of accidental hypothermia, proper management is critical for the wellbeing of patients. Accidental hypothermia was reported to be associated with acute kidney injury (AKI) in over 40% of cases. Although the pathogenesis remains to be elucidated, vasoconstriction and ischemia in the kidney were considered to be the main mechanisms involved. Cases of AKI associated with hypothermia have been reported worldwide, but there have been few reports of hypothermia-induced AKI in Korea. Here, we present a case of hypothermia-induced AKI that was treated successfully with rewarming and supportive care.