Induced pluripotent stem cells (iPSCs) were first described in 2006 and have since emerged as a promising cell source for clinical applications. The rapid progression in iPSC technology is still ongoing and directed toward increasing the efficacy of iPSC production and reducing the immunogenic and tumorigenic potential of these cells. Enormous efforts have been made to apply iPSC-based technology in the clinic, for drug screening approaches and cell replacement therapy. Moreover, disease modeling using patient-specific iPSCs continues to expand our knowledge regarding the pathophysiology and prospective treatment of rare disorders. Furthermore, autologous stem cell therapy with patient-specific iPSCs shows great propensity for the minimization of immune reactions and the provision of a limitless supply of cells for transplantation. In this review, we discuss the recent updates in iPSC technology and the use of iPSCs in disease modeling and regenerative medicine.

The epidemiology, genetics, and clinical manifestations of Crohn's disease (CD) vary considerably among geographic areas and ethnic groups. Thus, identifying the characteristics of Korean CD is important for establishing management strategies appropriate for Korean patients. Since the mid-2000s, many studies have investigated the characteristic features of Korean CD. The incidence and prevalence rates of CD have been increasing rapidly in Korea, especially among the younger population. Unlike Western data, Korean CD shows a male predominance and a lower proportion of isolated colonic disease. Perianal lesions are more prevalent than in Western countries. Genome-wide association studies have confirmed that genetic variants in TNFSF15, IL-23R, and IRGM, but not ATG16L1, are associated with CD susceptibility in the Korean population. Studies of the associations between genetic mutations and the clinical course of CD are underway. Although it has been generally accepted that the clinical course of Korean CD is milder than that in Western countries, recent studies have shown a comparable rate of intestinal resection in Korean and Western CD patients. An ongoing nationwide, hospital-based cohort study is anticipated to provide valuable information on the natural history and prognosis of Korean CD in the near future.

Background/Aims: Protein disulfide isomerase (PDI) has been implicated in the survival and progression of some cancer cells, by compensating for endoplasmic reticulum stress by upregulating the protein-folding capacity. However, its prognostic role in patients with hepatocellular carcinoma (HCC) has not been investigated. Methods: We collected HCC tissues from 83 HCC patients who underwent surgical resection for an immunohistochemical study of PDI. Overall survival (OS) was measured from the date of surgical resection until the date of death from any cause. Radiological progression was evaluated using the modified Response Evaluation Criteria in Solid Tumors in an independent radiological assessment. Results: PDI expression was found to be increased in human HCC compared to adjacent nontumor tissues. Increased immunopositivity for PDI was associated with a high Edmondson-Steiner grade (p = 0.028). Univariate analysis of patients who had undergone surgical resection for HCC showed that tumor PDI upregulation is a significant risk factor for poor OS (p = 0.016; hazard ratio [HR], 1.980) and time to progression (TTP; p = 0.007; HR, 1.971). Multivariate analyses revealed that high PDI expression was an independent predictor of a shorter TTP (p = 0.015; HR, 1.865) and poor OS (p = 0.012; HR, 2.069). Conclusions: Upregulated PDI expression is associated with aggressive clinicopathological features of HCC; thus, PDI might serve as an independent prognostic factor and a potential therapeutic target for HCC patients.

Background/Aims: Most current knowledge regarding amiodarone toxicity derives from clinical trials. This study was performed to investigate the incidence and risk factors of overall adverse effects of amiodarone in real-world practice using a large sample size. Methods: Between January 1, 2000 and March 10, 2012, a total of 930 consecutive patients who had been treated with amiodarone for arrhythmia were reviewed retrospectively. An amiodarone-associated adverse event was considered in cases of discontinuation or drug dose reduction due to an unexpected clinical response. Results: The mean daily dose of amiodarone was $227{\pm}126mg$, and the mean duration was $490{\pm}812days$. During the mean follow-up duration of $982{\pm}1,137days$, a total of 154 patients (16.6%) experienced adverse effects related to amiodarone, the most common being bradycardia or conduction disturbance (9.5%). Major organ toxicities in the thyroid (2.5%), liver (2.2%), eyes (0.6%), and lungs (0.3%) were rare. All patients recovered fully without complications after amiodarone discontinuation or dose reduction. The only independent predictor of adverse effects was the duration of amiodarone treatment (odds ratio, 1.21; 95% confidence interval, 1.03 to 1.41; p = 0.016, per year). Conclusions: Low-dose amiodarone is well tolerated in a real-world clinical population. Further studies with a prospective design are needed to confirm this finding.

Background/Aims: Although complex bifurcation stenting in patients with non-left main (LM) bifurcation lesions has not yielded better clinical outcomes than simpler procedures, the utility of complex bifurcation stenting to treat LM bifurcation lesions has not yet been adequately explored. Methods: In the present study, patients who underwent LM-to-left anterior descending (LAD) coronary artery simple crossover stenting to treat significant de novo distal LM or ostial LAD disease, in the absence of angiographically significant ostial left circumflex (LCX) coronary artery disease, were consecutively enrolled. The frequencies of 3-year major adverse cardiovascular events (MACEs; cardiac death, myocardial infarction, and target lesion revascularization), were analyzed. Results: Of 105 eligible consecutive patients, only 12 (11.4%) required additional procedures to treat ostial LCX disease after main vessel stenting. The mean percentage diameter of ostial LCX stenosis increased from $22.5%{\pm}15.2%$ to $32.3%{\pm}16.3%$ (p < 0.001) after LM-to-LAD simple crossover stenting. The 3-year incidence of MACEs was 9.7% (cardiac death 2.2%; myocardial infarction 2.2%; target lesion revascularization 8.6%), and that of stent thrombosis 1.1%. Of seven cases (7.5%) requiring restenosis, pure ostial LCX-related repeat revascularization was required by only two. Conclusions: Simple crossover LM-to-LAD stenting without opening of a strut on the LCX ostium was associated with acceptable long-term clinical outcomes.

Background/Aims: The clinical outcomes of some patients with pleural infection may be favorable with medical treatment alone, but in others, the disease progresses and requires additional surgical treatment. However, little is known about the factors affecting this difference. The aim of this study was to investigate the factors predictive of failure of medical treatment in patients with pleural infection. Methods: A cohort of 127 consecutive patients who were admitted to the hospital with pleural infection was studied. Clinical manifestations and laboratory findings in patients in whom medical treatment succeeded or failed were reviewed. Results: In univariate analysis, the significant factors associated with medical treatment outcome were age, smoking history, duration of chief complaint, serum albumin level, and pleural fluid glucose and lactate dehydrogenase levels (p <0.05). Multivariate logistic regression analysis identified age and duration of chief complaint as independent predictive factors for failure of medical treatment, with odds ratios of 0.871 (p = 0.013) and 0.797 (p = 0.026), respectively. Receiver operating characteristic curve analysis determined cutoff values of 50.5 years for age and 4.5 days for duration of chief complaint. Conclusions: We demonstrated that a younger age < 50.5 years and shorter duration of chief complaint < 4.5 days were independent predictive factors for the failure of medical treatment in patients with pleural infection. This suggests their role as evaluative criteria in setting indications for the optimal treatment in patients with pleural infection. A larger, prospective study is required to confirm these findings.

Background/Aims: Smoking is widely acknowledged as the single most important risk factor for chronic obstructive pulmonary disease (COPD). However, the risk of COPD in nonsmokers exposed to secondhand smoke remains controversial. In this study, we investigated the association of secondhand smoke exposure with COPD prevalence in nonsmokers who reported never smoking. Methods: This study was based on data obtained from the Korean National Health and Nutrition Examination Surveys (KNHANES) conducted from 2008 to 2010. Using nationwide stratified random sampling, 8,596 participants aged ${\geq}40$ years of age with available spirometry results were recruited. After selecting participants who never smoked, the duration of exposure to secondhand smoke was assessed based on the KNHANES questionnaire. Results: The prevalence of COPD was 6.67% in participants who never smoked. We divided the participants who had never smoked into those with or without exposure to secondhand smoke. The group exposed to secondhand smoke was younger with less history of asthma and tuberculosis, higher income, and higher educational status. Multivariate logistic regression analysis determined that secondhand smoke did not increase the prevalence of COPD. Conclusions: There was no significant difference in the prevalence of COPD between participants who had never smoked with or without exposure to secondhand smoke in our study. Thus, secondhand smoke may not be an important risk factor for the development of COPD in patients who have never smoked.

Background/Aims: Recent epidemiological studies revealed a striking inverse relationship between vitamin D levels, glucose intolerance/insulin resistance (IR), and cardiovascular disease. However, few interventional studies have evaluated the effect of vitamin D supplementation on cardiovascular risk, such as IR and arterial stiffness, in diabetes. We investigated the role of vitamin D supplementation on cardiovascular risk in type 2 diabetes patients, including metabolic parameters, IR, and arterial stiffness. Methods: We enrolled patients who were taking antidiabetic medications or managed their diabetes using lifestyle changes. We excluded patients who were taking vitamin D or calcium supplements. We randomized participants into the vitamin D group (cholecalciferol 2,000 IU/day + calcium 200 mg/day, n = 40) or the placebo group (calcium 200 mg/day, n = 41). We compared their IR (homeostasis model of assessment [HOMA]-IR) and arterial stiffness (brachial-ankle pulse wave velocity and radial augmentation index) before and after 24 weeks of intervention. Results: The baseline characteristics of the two groups were similar. A total of 62 participants (placebo, 30; vitamin D, 32) completed the study protocol. At the end of the study period, the 25-hydroxyvitamin D [25(OH)D] levels were significantly higher in the vitamin D group than in the placebo group ($35.4{\pm}8.5ng/mL$ vs. $18.4{\pm}7.3ng/mL$, p < 0.001). There was no difference in HOMA-IR or changes in arterial stiffness (placebo, 21, vitamin D, 24) between the groups. Conclusions: Our data suggest that high-dose vitamin D supplementation might be effective in terms of elevating 25(OH)D levels. However, we identified no beneficial effects on cardiovascular risk in type 2 diabetes, including IR and arterial stiffness.

Background/Aims: The treatment for steroid-refractory acute graft versus host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT) needs to be standardized. We report our clinical experience with etanercept for steroid-refractory acute GVHD. Methods: Eighteen patients who underwent allo-SCT and presented with steroid-refractory acute GVHD at Ajou University Hospital were studied retrospectively. They were given 25 mg of etanercept subcutaneously twice weekly for 4 weeks. The clinical responses were evaluated with regard to the severity of acute GVHD. Results: The median patient age was 43.5 years. Using nonparametric tests, etanercept had a down-grading effect on acute GVHD (p = 0.005), although no patient experienced complete remission. Partial responses were seen in 80%, 17%, and 57% of grade II to IV patients, respectively. Skin and gut GVHD were well controlled with etanercept, whereas hepatic GVHD was not. Four patients died of fatal infections. No factors affecting the clinical outcome of etanercept were identified. Conclusions: Etanercept has a modest effect on steroid-refractory acute GVHD after allo-SCT, with tolerable side effects.

Background/Aims: We examined the prevalence of extended-spectrum ${\beta}$-lactamase (ESBL) production and the impact of ESBL on clinical outcomes in cancer patients with Enterobacter spp. bacteremia. Methods: Using prospective cohort data on Enterobacter bacteremia obtained between January 2005 and November 2008 from a tertiary care center, the prevalence and clinical impact of ESBL production were evaluated. Results: Two-hundred and three episodes of Enterobacter spp. bacteremia were identified. Thirty-one blood isolates (15.3%, 31/203) scored positive by the double-disk synergy test. Among 17 isolates in which ESBL genes were detected by polymerase chain reaction and sequencing, CTX-M (n = 12), SHV-12 (n = 11), and TEM (n = 4) were the most prevalent ESBL types. Prior usage of antimicrobial agents (77.4% vs. 54.0%, p = 0.02) and inappropriate empirical antimicrobial therapy (22.6% vs. 3.0%, p < 0.001) were more commonly encountered in the ESBL-positive group than in the extended-spectrum cephalosporin-susceptible ESBL-negative group, respectively. Clinical outcomes did not differ significantly between the two groups (30-day mortality rate, 19.4% vs. 17.0%, p = 0.76; median length of hospital stay, 24.0 days vs. 30.5 days, p = 0.97). Initial presentation of severe sepsis/septic shock, pneumonia, and intra-abdominal infection were independently associated with 30-day mortality. Conclusions: The prevalence of ESBL-producing isolates was 15.3% in cancer patients with Enterobacter bacteremia. Although inappropriate empirical therapy was more common in the ESBL-positive group, ESBL production was not associated with poorer outcomes.

Background/Aims: SKI306X, a mixed extract of three herbs, Clematis mandshurica (CM), Prunella vulgaris (PV), and Trichosanthes kirilowii (TK), is chondroprotective in animal models of osteoarthritis (OA). The objectives of this study were to investigate its effect on interleukin (IL)-$1{\beta}$-induced degradation of glycosaminoglycan (GAG) and the basis of its action in human OA cartilage, as well as to screen for the presence of inhibitors of matrix metalloproteinase (MMP)-13 and a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS)-4 in SKI306X and its component herbs, as well as in fractions from SKI306X. Methods: Human OA chondrocytes and cartilage explants were obtained during total knee replacements and incubated with IL-$1{\beta}{\pm}$ oncostatin M with or without SKI306X or its component herb extracts. GAG degradation was assayed in cartilage explants using a commercial kit. Expression of genes involved in cartilage destruction was measured by real-time polymerase chain reaction using chondrocyte RNA. SKI306X was fractionated by preparative liquid chromatography to test for the presence of inhibitors of MMP-13 and ADAMTS-4. Results: SKI306X and PV inhibited IL-$1{\beta}$-induced GAG release from cartilage explants, and SKI306X, CM, PV, and TK inhibited IL-$1{\beta}$-induced MMP gene expression. Unexpectedly, SKI306X greatly stimulated IL-$1{\beta}$ + oncostatin M-induced ADAMTS-4 gene expression, probably due to its TK component. Some fractions of SKI306X also inhibited ADAMTS-4 activity. Conclusions: SKI306X and its herbal components inhibit GAG degradation and catabolic gene expression in human OA chondrocytes and cartilage explants. SKI306X likely also contains one or more ADAMTS-4 inhibitor.

Background/Aims: The aim of this study was to assess the efficacy and safety of tofacitinib (5 and 10 mg twice daily) in patients with active rheumatoid arthritis (RA). Methods: A systematic review of randomized controlled trials (RCTs) that examined the efficacy and safety of tofacitinib in patients with active RA was performed using the Medline, Embase, and Cochrane Controlled Trials Register databases as well as manual searches. Results: Five RCTs, including three phase-II and two phase-III trials involving 1,590 patients, met the inclusion criteria. The three phase-II RCTs included 452 patients with RA (144 patients randomized to 5 mg of tofacitinib twice daily, 156 patients randomized to 10 mg of tofacitinib twice daily, and 152 patients randomized to placebo) who were included in this meta-analysis. The American College of Rheumatology 20% response rate was significantly higher in the tofacitinib 5- and 10-mg groups than in the control group (relative risk [RR], 2.445; 95% confidence interval [CI], 1.229 to 4.861; p = 0.011; and RR, 2.597; 95% CI, 1.514 to 4.455; p = 0.001, respectively). The safety outcomes did not differ between the tofacitinib 5- and 10-mg groups and placebo groups with the exception of infection in the tofacitinib 10-mg group (RR, 2.133; 95% CI, 1.268 to 3.590; p = 0.004). The results of two phase-III trials (1,123 patients) confirmed the findings in the phase-II studies. Conclusions: Tofacitinib at dosages of 5 and 10 mg twice daily was found to be effective in patients with active RA that inadequately responded to methotrexate or disease-modifying antirheumatic drugs, and showed a manageable safety profile.