Cytomegalovirus (CMV) reactivation is common in patients with severe ulcerative colitis (UC), and may reflect exacerbation of mucosal inflammation and/or administration of immunosuppressants. The question of whether CMV is an active pathogen or 'an innocent bystander' in the exacerbation of UC remains controversial. Patients with UC exacerbated by reactivated CMV experience worse prognoses than those without CMV reactivation and antiviral therapy significantly reduces the need for colectomy in patients with severe UC and high-grade CMV infection, indicating that CMV plays a role in UC prognosis. Therefore, the CMV status of patients on immunosuppressants, particularly those with steroid-refractory or -dependent UC, should be tested. When CMV is detected, be performed based on should adequate treatment the extent of the viral load and the presence of certain clinical features including a large ulcer. Anti-tumor necrosis factor agents may be useful for treating CMV colitis complicating UC.

Peripartum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy that causes systolic heart failure (HF) in previously healthy young women. Despite latest remarkable achievement, unifying pathophysiologic mechanism is not well established. Considering close temporal relationship to pregnancy, the recent prolactin theory is promising. Abnormal short form of 16-kDa prolactin may be produced in the oxidative stress milieu, show anti-angiogenic effect and damage cardiovascular structure in late pregnancy. Future study is needed to determine whether abnormal prolactin system is useful as a biomarker for diagnosis and therapy of PPCM. Diagnosis is made based on the finding of left ventricular systolic dysfunction after excluding other causes of HF. A multidisciplinary team approach is essential for acute HF, antepartum, labor and postpartum care. Recovery from left ventricular dysfunction is critical for prognosis. As PPCM can recur and cause serious clinical events, subsequent pregnancy is not recommended. This review focuses on the practical management of PPCM.

The global burden of diabetes mellitus and its related complications are currently increasing. Diabetes mellitus affects the heart through various mechanisms including microvascular impairment, metabolic disturbance, subcellular component abnormalities, cardiac autonomic dysfunction, and a maladaptive immune response. Eventually, diabetes mellitus can cause functional and structural changes in the myocardium without coronary artery disease, a disorder known as diabetic cardiomyopathy (DCM). There are many diagnostic tools and management options for DCM, although it is difficult to detect its development and effectively prevent its progression. In this review, we summarize the current research regarding the pathophysiology and pathogenesis of DCM. Moreover, we discuss emerging diagnostic evaluation methods and treatment strategies for DCM, which may help our understanding of its underlying mechanisms and facilitate the identification of possible new therapeutic targets.

An exon 19 deletion and a L858R mutation in exon 21 of the epidermal growth factor receptor (EGFR) are the two most common mutations that predict favorable efficacy of EGFR tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). Many retrospective and prospective studies, as well as meta-analyses including patients with NSCLC with various lines of EGFR TKI treatment, have demonstrated longer progression-free survival and sometimes more favorable overall survival in patients with an exon 19 deletion than those with the L858R or other mutations. In contrast, some clinical studies, including phase III trials, have demonstrated no difference in the efficacy of EGFR TKIs according to the EGFR mutation type. Therefore, the existence of clinically significant differences in sensitivity to EGFR-TKIs among different EGFR mutation subtypes remains controversial. In this review, we summarize the evidence suggesting different outcomes according to the type of EGFR mutation in patients with advanced NSCLC who were treated with EGFR-TKIs, along with their clinical significance. We also discuss possible mechanisms that can explain the different sensitivities to EGFR TKIs between cases with an exon 19 deletion and those with the L858R mutation.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with diverse manifestations, and its pathogenesis is unclear and complicated. Infection and SLE are similar in that they both cause inf lammatory reactions in the immune system; however, one functions to protect the body, whereas the other is activated to damage the body. Infection is known as one of the common trigger factors for SLE; there are a number of reports on infectious agents that provoke autoimmune response. Several viruses, bacteria, and protozoa were revealed to cause immune dysfunction by molecular mimicry, epitope spreading, and bystander activation. In contrast, certain pathogens were revealed to protect from immune dysregulation. Infection can be threatening to patients with SLE who have a compromised immune system, and it is regarded as one of the common causes of mortality in SLE. A clinical distinction between infection and lupus f lare up is required when patients with SLE present fevers. With a close-up assessment of symptoms and physical examination, C-reactive protein and disease activity markers play a major role in differentiating the different disease conditions. Vaccination is necessary because protection against infection is important in patients with SLE.

Background/Aims: Approximately 30% of esophageal cancer (EC) patients cannot complete endoscopic ultrasonography (EUS) due to malignant stricture (EUS non-traversability). This study examines clinical implications of EUS non-traversability in patients with advanced locoregional squamous EC receiving preoperative chemoradiotherapy (CRT) followed by esophagectomy. Methods: We retrieved data on 89 consecutive patients with advanced locoregional squamous EC (stage II or III). Relevant clinical and tumor-specific parameters were reviewed retrospectively. Significant factors affecting survival was determined by Cox regression analysis. Results: EUS non-traversable EC was observed in 26 of 89 patients (29.2%). Median serum albumin level (3.6 g/dL vs. 3.9 g/dL, p = 0.028), tumor length (6.0 cm vs. 4.0 cm, p = 0.002), and percentage of clinical stage III disease (65.4% vs. 38.1%, p = 0.019) were significantly different between the patients with EUS non-traversable and traversable EC, respectively. Patients with EUS non-traversable EC demonstrated a significantly lower 5-year overall survival than patients with EUS traversable EC (30.8% vs. 49.3%, p = 0.023). In multivariate analysis, weight loss ${\geq}10%$ (p = 0.033), EUS non-traversability (p = 0.003), non-response to preoperative CRT (p = 0.002), and incompletion of esophagectomy (p = 0.002) were significant negative factors of survival. Conclusions: EUS non-traversability has significant negative prognostic implications in patients with advanced locoregional squamous EC receiving preoperative CRT followed by esophagectomy.

Background/Aims: Neuroendocrine tumors (NETs) may originate from heterogeneous neuroendocrine cells. The incidence is increasing worldwide, and World Health Organization (WHO) updated its classification in 2010. We investigated clinical characteristics of gastroenteropancreatic NETs in a single center. Methods: Clinicopathologic characteristics of patients with pathologically confirmed gastroenteropancreatic NET in Seoul St. Mary Hospital from March 2009 to August 2011 were retrospectively analyzed. The grade and stage were determined according to WHO 2010 classification and TNM Staging System for Neuroendocrine Tumors (7th ed., 2010) of American Joint Committee on Cancer. Results: One hundred and twenty-five patients (median age, 50; male, 61.3%) were analyzed. Among 100,000 patients who visited the hospital, incidence was 24.1. Only two patients (1.6%) had a functional NET. The rectum (n = 99, 79.8%) was most common primary site and found in early stage. The prevalence by stages was 84.7% stage I, 8.9% stage IV, 4.8% stage II, and 1.6% stage III. The pathology grading was 74.5% grade 1, 12.7% grade 2, and 12.7% grade 3. Tumor stage correlated positively with pathologic grade (Spearman's rank correlation coefficient, 0.644). Conclusions: Wide range of clinicopathological features of Korean gastroenteropancreatic NETs were demonstrated using WHO 2010 classification. Rectal NET was most frequent and found in early stage.

Background/Aims: Multiple myeloma (MM)-associated cardiac damage, particularly according to the type of monoclonal (M) protein has not been elucidated. We sought to investigate relationship between elevated serum M protein levels and echocardiographic indices of cardiac structure and function in patients with MM. Methods: We evaluated a total of 184 consecutive MM patients who underwent echocardiography for bone marrow pre-transplant screening. Serum levels of intact immunoglobulin M protein and free light chain kappa/lambda ($FLC-{\kappa}/-{\lambda}$) were measured. Results: One hundred thirty-nine patients were non-light chain MM (non-LCMM) and 45 patients belonged to LCMM. In patients with non-LCMM, significant correlations were found between serum M protein and left atrial volume index (LAVi; r = 0.720, p < 0.0001), E/e' (r = 0.511, p < 0.0001), and systolic pulmonary arterial pressure (r = 0.485, p < 0.0001). In patients with LCMM, log-transformed $FLC-{\lambda}$ (${\log}-{\lambda}$) was correlated with left ventricular ejection fraction (LVEF, r = -0.536, p = 0.010), left ventricular (LV) end-systolic dimension (r = 0.500, p = 0.018), and LV end-systolic volume (r = 0.444, p = 0.038). On multivariate analyses, hematocrit and serum M protein were independent predictors of LAVi in patients with non-LCMM. In patient with LCMM, $FLC-{\lambda}$ isotype was only found to be an independent determinant of LVEF. Conclusions: An increase in serum M protein was associated with LV diastolic dysfunction, whereas an increase in serum $FLC-{\lambda}$ concentration showed a negative correlation with the echocardiographic parameters of LV systolic function. These findings also suggest that serum M protein has different effects on LV function according to the type of paraproteins in patients with MM.

Background/Aims: Patients with symptoms of coronary artery disease (CAD) often display normal tracings or only nonspecific changes on electrocardiography (ECG). The aim of this study was to explore strategic elements of the ECG and other potential factors that are predictive of CAD in this scenario. Methods: This was an observational study of 142 patients with the chief complaint of chest pain, each of whom presented with a normal ECG and was subjected to emergency coronary angiography (CAG). Two population subsets were identified: those patients (n = 97) with no significant stenotic lesions and those (n = 45) with the significant stenotic lesions of CAD. Results: Those patients with normal or nonspecific ECGs and CAD (15.8%) were more likely to have left circumflex artery involvement (20% vs. 7%). In patients with normal ECGs and CAD (vs. normal CAG), male sex (86.7% vs. 68%, p = 0.023), creatine kinase-MB (CK-MB) levels > 10 U/L (13 vs. 10, p = 0.025), and fragmented QRS (fQRS) (38.6% vs. 21.6%, p = 0.042) occurred with greater frequency. In multivariable analysis, the following variables were significant predictors of CAD, given a normal ECG: male sex (odds ratio [OR], 2.593; 95% confidence interval [CI], 1.068 to 5.839); CK-MB (OR, 2.497; 95% CI, 0.955 to 7.039); and W- or M-shaped QRS complex (OR, 2.306; 95% CI 0.988 to 5.382). Conclusions: In our view, male sex, elevated CK-MB (> 10 U/L), and fQRS complexes are suspects for CAD in patients with angina and unremarkable ECGs and should be considered screening tests.

Background/Aims: Pneumocystis jirovecii polymerase chain reaction (PCR) can be helpful in diagnosing Pneumocystis pneumonia (PCP); however it has limitations. We evaluated the prevalence of positive P. jirovecii PCR from non-human immunodeficiency virus (HIV) immunocompromised patients and tried to determine the risk of PCP development. Methods: Between May 2009 and September 2012, P. jirovecii PCR was performed in bronchoscopic specimens from 1,231 adult non-HIV immunocompromised patients suspected of respiratory infection. Only 169 patients (13.7%) who were tested positive for P. jirovecii PCR were enrolled. Retrospective chart review was performed. PCP was defined in patients with positive P. jirovecii PCR who were treated for PCP based on the clinical decision. Results: From 169 P. jirovecii PCR-positive patients, 90 patients were in the PCP group (53.3%) and 79 patients were in the non-PCP group (46.7%). In the PCP group, 38% of patients expired or aggravated after therapy, whereas the majority of patients (84%) in the non-PCP group recovered without treatment for PCP. Independent risk factors for PCP by binary logistic regression analysis were underlying conditions- hematological malignancies, solid tumors or solid organ transplantation, dyspnea, age < 60 years, and albumin < 2.9 g/dL. Conclusions: This study suggests that not all P. jirovecii PCR-positive patients need to be treated for PCP. Among P. jirovecii PCR-positive patients, those who are less than 60 years old, with hematological malignancies, solid tumors or solid organ transplantation, low albumin, and with symptoms of dyspnea, the possibility of PCP might be higher. Treatment should also be selected to these patients.

Background/Aims: The tuberculin skin test (TST) and interferon ${\gamma}$ release assay are currently used as diagnostic tools to detect latent tuberculosis (TB) infection; however, there are inconsistencies about the degree of agreement between the tests. We aimed to evaluate the concordance rate between the two tests in household contacts of a country with intermediate TB burden, where most people were vaccinated. Methods: We recruited household contacts who spent > 8 hours daily with patients with microbiologically confirmed active pulmonary TB, and received both TST and T-SPOT.TB (Oxford Immunotec) simultaneously. The degree of agreement was analysed according to TST cutoff and Bacille Calmette-Guerin (BCG) vaccination status. Relevant factors were analysed to establish the association with TST or T-SPOT.TB. Results: Among 298 household contacts, 122 (40.9%) were spouses, and 250 (83.9%) had received BCG vaccination. In the contact sources, 117 (39.3%) showed a positive result for acid-fast bacillus (AFB) sputum smear and 109 (36.6%) had cavities. The highest agreement rate of 69.5% and ${\kappa}$ value of 0.378 were found with a 10 mm cutoff. Spouse, time interval from TB diagnosis to test, and AFB sputum smear positivity were significantly associated with a positive result for T-SPOT.TB. Sex, BCG vaccination, and cavity on chest computed tomography were related to TST positivity. Conclusions: The present study suggested it was not possible for TST and T-SPOT.TB to replace each other because of considerable discrepancy between the two tests in household contacts in a country with intermediate TB prevalence.

Background/Aims: Oxidative stress plays an important role in the pathogenesis and progression of diabetic complications and antagonists of renin-angiotensin system and amlodipine have been reported previously to reduce oxidative stress. In this study, we compared the changes in oxidative stress markers after valsartan and amlodipine treatment in type 2 diabetic patients with hypertension and compared the changes in metabolic parameters. Methods: Type 2 diabetic subjects with hypertension 30 to 80 years of age who were not taking antihypertensive drugs were randomized into either valsartan (n = 33) or amlodipine (n = 35) groups and treated for 24 weeks. We measured serum nitrotyrosine levels as an oxidative stress marker. Metabolic parameters including serum glucose, insulin, lipid profile, and urine albumin and creatinine were also measured. Results: After 24 weeks of valsartan or amlodipine treatment, systolic and diastolic blood pressure decreased, with no significant difference between the groups. Both groups showed a decrease in serum nitrotyrosine ($7.74{\pm}7.30nmol/L$ vs. $3.95{\pm}4.07nmol/L$ in the valsartan group and $8.37{\pm}8.75nmol/L$ vs. $2.68{\pm}2.23nmol/L$ in the amlodipine group) with no significant difference between the groups. Other parameters including glucose, lipid profile, albumin-to-creatinine ratio, and homeostasis model assessment of insulin resistance showed no significant differences before and after treatment in either group. Conclusions: Valsartan and amlodipine reduced the oxidative stress marker in type 2 diabetic patients with hypertension.

Background/Aims: There may be an association between vitamin D levels and allograft outcomes in kidney transplant recipients (KTRs). However, few studies have been conducted to determine the association between vitamin D levels and post-transplant infections. This study investigated the impact of vitamin D deficiency on the risk of infection after kidney transplantation. Methods: We measured 25-hydroxyvitamin D (25(OH)D) levels prior to kidney transplantation. Vitamin D deficiency was defined as a serum 25(OH)D level < 20 ng/mL. We examined the incidence of various post-transplant infections during follow-up period. We used Cox proportional hazards regression analysis to determine factors associated with increased risk of post-transplant infections during the follow-up period. Results: A total of 164 KTRs were followed up for a mean of $24.8{\pm}10.7$ months. Among them, 135 patients (82.3%) had vitamin D deficiency. Patients with vitamin D deficiency had a significantly higher incidence of urinary tract infection (p = 0.027) and any bacterial infection (p = 0.010) compared to those without vitamin D deficiency. Vitamin D deficiency was not significantly associated with incidence of viral or fungal infections. Cox proportional hazards regression analysis revealed that vitamin D deficiency (hazard ratio, 11.07; 95% confidence interval, 1.46 to 84.03; p = 0.020) was independent risk factor for post-transplant bacterial infections. Conclusions: Pre-transplant vitamin D deficiency was a significant risk factor for bacterial infections after kidney transplantation. Further studies are needed on possible benefits of vitamin D supplementation for preventing post-transplant bacterial infection.

Background/Aims: The predictive and prognostic value of KRAS mutation and its type of mutations in non-small cell lung cancer (NSCLC) are controversial. This clinical study was designed to investigate the predictive value of KRAS mutations and its mutation types to pemetrexed and gemcitabine based treatment. Methods: Advanced NSCLC patients tested for KRAS mutation (n = 334) were retrospectively reviewed and 252 patients with wild type epidermal growth factor receptor and no anaplastic lymphoma kinase fusion were enrolled for the analysis. KRAS mutations were observed in 45 subjects with mutation type as followed: G12C (n = 13), G12D (n = 12), G12V (n = 12), other (n = 8). Response rate (RR), progression-free survival (PFS), and overall survival (OS) of pemetrexed singlet and gemcitabine based chemotherapy were analysis. Results: Age, sex, performance status were well balanced between subjects with or without KRAS mutations. No difference was observed in RR. Hazard ratio (HR) of PFS for pemetrexed treated subjects with G12C mutation compared to subjects with KRAS wild type was 1.96 (95% confidential interval [CI], 1.01 to 3.79; p = 0.045), but other mutations failed to show clinical significance. By analysis done by PFS, compared to the subjects with transition mutation, HR was 1.48 (95% CI, 0.64 to 3.40; p = 0.360) for subjects with transversion mutation on pemetrexed treatment and 0.41 (95% CI, 0.19 to 0.87; p = 0.020) for subjects treated with gemcitabine based chemotherapy. No difference was observed in OS. Conclusions: In this study, different drug sensitivity was observed according to the type of KRAS mutation. NSCLC subpopulations with different KRAS mutation type should be considered as different subgroups and optimal chemotherapy regimens should be searched in further confirmative studies.

Background/Aims: Eosinophilia has numerous diverse causes, and in many patients, it is not possible to establish the cause of eosinophilia. Recently, toxocariasis was introduced as one cause of eosinophilia. The aims of this study were to evaluate the prevalence of toxocariasis and the clinical impact of albendazole treatment for toxocariasis in patients suspected of eosinophilia of unknown origin. Methods: We performed a retrospective chart review. After evaluation of cause of eosinophilia, the patients suspected of eosinophilia of unknown origin performed immunoglobulin G antibody specific assay for the Toxocara canis larval antigen by enzyme-linked immunosorbent assay. Results: This study evaluated 113 patients, 69 patients (61%) were suspected of eosinophilia of unknown origin. Among these 69 patients, the frequency of T. canis infection was very high (45 patients, 65.2%), and albendazole treatment for 45 eosinophilia with toxocariasis was highly effective for a cure of eosinophilia than no albendazole group regardless of steroid (82.3%, p = 0.007). Furthermore, among the nonsteroid treated small group (19 patients), albendazole treatment for eosinophilia were more effective than no albendazole group, too (83.3% vs. 28.6 %, p = 0.045). Conclusions: The prevalence of toxocariasis was high among patients suspected of eosinophilia of unknown origin; therefore, evaluation for T. canis infection is recommended for patients with eosinophilia of unknown origin. Furthermore, for patients suspected of eosinophilia of unknown origin who have positive results for T. canis, albendazole treatment may be considered a valuable treatment option.

Background/Aims: Cat-scratch disease (CSD), caused by Bartonella henselae is one of the most common zoonosis. However, only several cases of B. henselae infection have been reported in Korea. This study investigated the seroprevalence of B. henselae in healthy adults and related risk factors. Methods: Serum samples from 300 healthy participants were analyzed using an immunoglobulin G immunofluorescence assay (IFA) for B. henselae isolated in Korea. Surveys on the risk factors for B. henselae infection were conducted simultaneously. Results: Of the participants, 47.7% and 15.0% raised dogs and cats, respectively. The overall seroprevalence of B. henselae was 15.0% (IFA titer ${\geq}1:64$). Participants who had raised cats showed 22.2% seropositivity against B. henselae, and those with no experience with cats showed 13.7% seroprevalence (p = 0.17). Participants who had cats as pets or been scratched by cats, showed 9.8% seropositivity against B. henselae (IFA titer ${\geq}1:256$). However, those who had not raised or been scratched by a cat showed 2.0% seropositivity (p = 0.015). Conclusions: In Korea, the seroprevalence of B. henselae is higher than expected, suggesting that Bartonella infection due to B. henselae is not uncommon. Cats are proposed to play a more important role than dogs in transmission of CSD.

Background/Aims: Biological agents (biologics) targeting proinflammatory signaling have emerged as an important treatment option in rheumatoid arthritis (RA). Despite the clinical effectiveness of biologics for patients with RA who do not respond to 'traditional' disease-modifying anti-rheumatic drugs (DMARDs), there are concerns regarding their cost and long-term safety. In this study, we aimed to compare the efficacy of various biologics and traditional DMARDs in RA patients refractory to methotrexate (MTX). Methods: Four DMARDs (hydroxychloroquine, sulfasalazine, MTX, lef lunomide) and five anti-tumor necrosis factor drugs (adalimumab, etanercept, golimumab, infliximab, and certolizumab) were selected. A systematic search of published studies was performed from inception through July 2013. Randomized trials of adults with MTX-refractory RA comparing two or more of the selected medications were included. Among 7,938 titles identified, in total, 16 head-to-head trials were selected. Two reviewers independently abstracted the study data and assessed methodological quality using the Cochrane Risk of Bias. Comparative efficacy was analyzed using a Bayesian mixed treatment comparison (MTC). Results: In total, 9, 4, and 11 studies were included for the outcome measures of the Health Assessment Questionnaire (HAQ), Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) < 2.6 (remission), and American College of Rheumatology (ACR) 70 response, respectively. The treatments with the highest efficacy for each outcome measure were certolizumab combined with MTX, golimumab combined with MTX, and certolizumab combined with MTX, respectively. Conclusions: Based on MTC analysis, using data from published randomized controlled trials, certolizumab and golimumab combined with MTX showed the highest efficacy in the three outcome measures (HAQ, DAS28-ESR < 2.6, and ACR 70 response) in MTX-refractory RA patients.