The introduction of drug-eluting stents (DES) in the practice of percutaneous coronary intervention (PCI) has substantially reduced angiographic and clinical restenosis but is associated with an increasing propensity for very late stent thrombosis (ST). Among several clinical, lesion, or procedure-related predictors of ST, early discontinuation of dual antiplatelet therapy (DAPT) is the most important factor for DES-associated late thrombosis; therefore, the optimal duration of DAPT is a major issue to be critically considered in the current DES era. Given that the benefit and risk of longer duration DAPT should be simultaneously considered, the optimal DAPT period following DES implantation has been controversial. Several small-to-medium sized randomized clinical trials and observational registries have indicated that short-term DAPT (< 6 months) is not inferior to 12-month DAPT with fewer bleeding events, whereas prolonged duration of DAPT (> 12 months) failed to prove its superiority. However, compelling evidence from a landmark DAPT trial has clearly demonstrated the efficacy of prolonged DAPT up to 30 months in terms of preventing ST and major cardiovascular adverse events at the expense of major bleeding. In addition, coupled with various risk algorithms, a more individualized approach to balance the efficacy and safety of optimal DAPT duration has been emphasized. In this review article, we systematically summarize the cumulative evidence from key clinical studies and try to help the physician make decisions on the optimal duration of DAPT in contemporary PCI practice.

Thyroid cancer is one of the most common malignancies of endocrine organs, and its incidence rate has increased steadily over the past several decades. Most differentiated thyroid tumors derived from thyroid epithelial cells exhibit slow-growing cancers, and patients with these tumors can achieve a good prognosis with surgical removal and radioiodine treatment. However, a small proportion of patients present with advanced thyroid cancer and are unusually resistant to current drug treatment modalities. Thyroid tumorigenesis is a complex process that is regulated by the activation of oncogenes, inactivation of tumor suppressors, and alterations in programmed cell death. Mitochondria play an essential role during tumor formation, progression, and metastasis of thyroid cancer. Recent studies have successfully observed the mitochondrial etiology of thyroid carcinogenesis. This review focuses on the recent progress in understanding the molecular mechanisms of thyroid cancer relating to altered mitochondrial metabolism.

The radiocephalic arteriovenous fistula (AVF) provides optimal vascular access for hemodialysis; it has a higher long-term patency rate and fewer complications than other vascular access methods. However, the AVF has a high primary failure rate. The presence of small-diameter vessels at anastomosis sites is an important risk factor for AVF failure. However, in a recent study, despite selecting an adequate artery and vein for creating an AVF by routine preoperative vascular mapping, AVF maturation and primary failure occurred. Thus, pre-existing arteriosclerosis at AVF anastomosis sites likely contributes to AVF failure. In this review, we discuss the relationship between pathologic changes and AVF patency in hemodialysis patients. Because arteriosclerosis of the major arteries such as the coronary and carotid arteries is associated with cardiovascular mortality, we also review the impact of arteriosclerosis of upper arm arteries at AVF anastomosis sites on cardiovascular mortality in hemodialysis patients.

Epithelial ovarian cancer is the eighth most common cause of cancer-related deaths in women because most patients present with advanced stage disease at the time of diagnosis. Although cytoreductive surgery and platinum-based chemotherapy remain the gold standards of treatment, the recurrence rate of ovarian cancer remains high. Attempts to improve this standard two-drug chemotherapy by adding a third cytotoxic drug have failed to affect either progression-free survival or overall survival and have resulted in an increase in toxic side effects. Some anti-angiogenic agents, poly(ADP-ribose) polymerase, and immune checkpoint inhibitors have shown efficacy in early stages of development for the treatment of epithelial ovarian cancer. As demonstrated in recent clinical trials, the use of bevacizumab, cediranib, pazopanib, olaparib, and rucaparib, either alone or in combination with conventional cytotoxic agents, improves progression-free survival. Trials on immune checkpoint inhibitors such as nivolumab have revealed prolonged responses in a small set of ovarian cancer cases but require further exploration. In this review, we discuss the role of targeted therapies against ovarian cancer, including the use of immune checkpoint inhibitors.

Invasive aspergillosis (IA) is one of the most common life-threatening complications in immunocompromised patients. Voriconazole is currently the drug of choice for IA treatment. However, some patients with IA suffer clinical deterioration despite voriconazole therapy. Management of voriconazole-refractory IA remains challenging; no useful recommendations have yet been made. Voriconazole-refractory IA can be further categorized as disease attributable to misdiagnosis or co-infection with another mold; inadequate blood voriconazole blood; inadequate tissue drug concentrations attributable to angioinvasion; immune reconstitution inflammatory syndrome; or infection with voriconazole-resistant Aspergillus. Hence, when encountering a case of voriconazole-refractory IA, it is necessary to schedule sequential tests to decide whether medical treatment or surgical intervention is appropriate; to adjust the voriconazole dose via drug monitoring; to seek CYP2C19 polymorphisms; to monitor serum galactomannan levels; and to examine the drug susceptibility of the causative Aspergillus species.

Background/Aims: Some people have difficulty tolerating upper endoscopy. The cause of and risk factors for this are not well known. The aim of this study was to investigate the factors involved in poor cooperation during screening upper endoscopy. Methods: A total of 4,422 subjects who underwent a health inspection with upper endoscopy carried out by a single experienced endoscopist were included. We retrospectively investigated subjects' self-reporting questionnaires and medical records, including endoscopic and histologic findings. The examinees' cooperation and the completeness of endoscopic examination were evaluated based on the operator's subjective judgment. Results: Examinee cooperation during the endoscopic procedure was poor in 358 out of 4,422 subjects (8.1%). Of the subjects with poor cooperation, the endoscopic examination was incomplete in 36 subjects (10.1%). Multivariate analysis revealed that young age (< 40 years), female sex, high body mass index (${\geq}25$), hiatal hernia, and procedural sedation using midazolam were independent risk factors for poor cooperation. Conclusions: Cooperation during screening upper endoscopy was poor in a considerable number of examinees. Endoscopists must keep in mind that examinee cooperation is more likely to be poor in the young, obese people, women, patients with hiatal hernias, and those who receive procedural sedation.

Background/Aims: Duodenitis is not infrequent finding in patient undergoing endoscopy. However, hospitalized patients have a higher incidence of secondary duodenal mucosal lesions that might be related with inflammatory bowel disease (IBD), cytomegalovirus (CMV) infection, tuberculosis, immunologic disorders, or other rare infections. We aimed to identify clinicopathologic features of duodenal mucosal lesions in hospitalized patients. Methods: All hospitalized patients having duodenal mucosal lesions were identified by endoscopic registration data and pathologic data query from 2011 to 2014. The diagnostic index was designed to be sensitive; however, a detailed review of medical record and endoscopic findings was undertaken to improve specificity. Secondary duodenal lesion was defined as having specific reason to explain the duodenal lesion. Results: Among 6,334 hospitalized patients have undergone upper endoscopy, endoscopic duodenal mucosal lesions was detected in 475 patients. Secondary duodenal lesions was 21 patients (4.4%) and the most frequent secondary cause was IBD (n = 7). The mean age of secondary group was significantly lower than that in primary group ($42.3{\pm}18.9years$ vs. $58.5{\pm}16.8years$, p = 0.00), and nonsteroidal anti-inflammatory drugs were less frequently used in secondary group, but there was no differences of gender or presence of Helicobacter pylori. The involvement of distal part of duodenum including postbulbitis or panduodenitis was more frequently detected in secondary group than in primary group. By multivariate regression analysis, younger age of 29 years and the disease extent were significant predictors for the secondary mucosal lesions. Conclusions: Secondary duodenal mucosal lesions with different pathophysiology, such as IBD or CMV infection, are rare. Disease extent and age seems the most distinctive feature of secondary duodenal mucosal lesions.

Background/Aims: Coronary vasospasms are one of the important causes of sudden cardiac death (SCD). Provocation of coronary vasospasms can be useful, though some results may lead to false positives, with patients potentially experiencing recurrent SCD despite appropriate medical treatments. We hypothesized that it is not coronary vasospasms but inherited primary arrhythmia syndromes (IPAS) that underlie the development of SCD. Methods: We analyzed 74 consecutive patients (3.8%) who survived out-of-hospital cardiac arrest among 1,986 patients who had angiographically proven coronary vasospasms. Electrical abnormalities were evaluated in serial follow-up electrocardiograms (ECGs) during and after the index event for a 3.9 years median follow-up. Major clinical events were defined as the composite of death and recurrent SCD events. Results: Forty five patients (60.8%) displayed electrocardiographic abnormalities suggesting IPAS: Brugada type patterns in six (8.2%), arrhythmogenic right ventricular dysplasia patterns in three (4.1%), long QT syndrome pattern in one (2.2%), and early repolarization in 38 (51.4%). Patients having major clinical events showed more frequent Brugada type patterns, early repolarization, and more diffuse multivessel coronary vasospasms. Brugada type pattern ECGs (adjusted hazard ratio [HR], 4.22; 95% confidence interval [CI], 1.16 to 15.99; p = 0.034), and early repolarization (HR, 2.97; 95% CI, 1.09 to 8.10; p = 0.034) were ultimately associated with an increased risk of mortality. Conclusions: Even though a number of aborted SCD survivors have coronary vasospasms, some also have IPAS, which has the potential to cause SCD. Therefore, meticulous evaluations and follow-ups for IPAS are required in those patients.

Background/Aims: To evaluate the geographic and demographic variabilities of the quantitative parameters of computed tomography perfusion (CTP) of the left ventricular (LV) myocardium in patients with normal coronary artery on computed tomography angiography (CTA). Methods: From a multicenter CTP registry of stress and static computed tomography, we retrospectively recruited 113 patients (mean age, 60 years; 57 men) without perfusion defect on visual assessment and minimal (< 20% of diameter stenosis) or no coronary artery disease on CTA. Using semiautomatic analysis software, quantitative parameters of the LV myocardium, including the myocardial attenuation in stress and rest phases, transmural perfusion ratio (TPR), and myocardial perfusion reserve index (MPRI), were evaluated in 16 myocardial segments. Results: In the lateral wall of the LV myocardium, all quantitative parameters except for MPRI were significantly higher compared with those in the other walls. The MPRI showed consistent values in all myocardial walls (anterior to lateral wall: range, 25% to 27%; p = 0.401). At the basal level of the myocardium, all quantitative parameters were significantly lower than those at the mid- and apical levels. Compared with men, women had significantly higher values of myocardial attenuation and TPR. Age, body mass index, and Framingham risk score were significantly associated with the difference in myocardial attenuation. Conclusions: Geographic and demographic variabilities of quantitative parameters in stress myocardial CTP exist in healthy subjects without significant coronary artery disease. This information may be helpful when assessing myocardial perfusion defects in CTP.

Background/Aims: Pulmonary endarterectomy (PEA) is the gold standard for treating chronic thromboembolic pulmonary hypertension (CTEPH) in Western countries. The aim of this study was to investigate the long-term outcomes of performing PEA on CTEPH patients in comparison with medical therapy at a single Korean center. Methods: This retrospective study included 88 CTEPH patients. These patients were classified into the PEA group (n = 37) or non-PEA group (i.e., medical therapy; n = 51). The clinical characteristics, hemodynamic data, and long-term survival rates were compared. Independent prognostic factors for CTEPH were also investigated. Results: CTEPH was not associated with either gender, and the mean age at diagnosis was $53.3{\pm}13.7years$. Echocardiography revealed that the mean peak velocity of the tricuspid regurgitation jet was $4.2{\pm}0.7m/sec$ and the mean pulmonary arterial pressure was $51.7{\pm}15.1mmHg$. The PEA and non-PEA groups demonstrated no significant differences, except in terms of the right ventricular end-diastolic diameter. The survival rates of the PEA group were significantly higher than the non-PEA group at 1, 3, 5, and 10 years (p = 0.032). Multivariate analyses indicated that World Health Organization class IV and PEA were significant predictors of poorer and better outcomes, respectively. Conclusions: PEA demonstrates more favorable effects on long-term survival than medical therapy in Korean CTEPH patients who were considered operable.

Background/Aims: Diesel exhaust particles (DEPs) lead to elevation of reactive oxygen species, which can activate the nucleotide-binding oligomerization domain-like receptor (NLR) family members containing the pyrin domain 3 (NLRP3)-inflammasome. In this study, we elucidated whether NLRP3-inflammasome is activated by DEPs and whether antioxidants (N-acetylcysteine [NAC]) could inhibit such activation. Methods: RAW 264.7 cells and ex vivo lung tissues explants obtained from elastase-induced emphysema animal models were stimulated with cigarette smoking extract (CSE), DEPs, and lipopolysaccharide, and levels of $interleukin-1{\beta}$ ($IL-1{\beta}$), caspase-1 and nucleotide-binding oligomerization domain-like receptor (NLR) family members containing the pyrin domain (NLRP3)-inflammasome were assessed by Western blotting and immunohistochemistry. Results: NAC and caspase-1 inhibitor suppressed CSE- and DEP-induced secretion of $IL-1{\beta}$ in RAW 264.7 cells. The expression levels of the NLRP3-inflammasome and caspase-1 were upregulated in RAW 264.7 cells by stimulation with CSE and DEPs and were inhibited by NAC. CSE and DEPs increased the secretion of $IL-1{\beta}$ in lung tissues from both the normal and elastase-induced emphysema groups. The secretion of $IL-1{\beta}$ by CSE and DEPs was increased in the elastin-induced emphysema group more than that in the normal group (CSE: $309{\pm}19pg/mL$ vs. $151{\pm}13pg/mL$, respectively, p < 0.05; DEP: $350{\pm}24pg/mL$ vs. $281{\pm}15pg/mL$, respectively, p < 0.05). NAC inhibited CSE- and DEP-induced $IL-1{\beta}$ secretion in both the normal and elastase-induced emphysema groups. NLRP3-inflammasome expression as determined by immunohistochemistry was increased by CSE and DEPs in both the normal and elastin-induced emphysema groups, and was suppressed by NAC. Conclusions: The NLRP3-inflammasome is activated by DEPs in ex vivo tissue explants from elastase-induced emphysema animal model, and this activation is inhibited by NAC.

Background/Aims: We evaluated whether serum bilirubin levels can predict the development of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM). Methods: This was a retrospective observational longitudinal study of patients presenting at the Pusan National University Hospital. A total of 349 patients with T2DM and preserved kidney function (estimated glomerular filtration rate ${\geq}60mL/min/1.73m^2$) were enrolled. The main outcome was the development of CKD stage 3 or greater. The patients were divided into four groups according to the quartiles of the total serum bilirubin levels at baseline. Results: The group with the lowest range of total serum bilirubin level (Q1) showed the highest cumulative incidence of CKD stage 3 or greater than that of the other lower quartiles (Q1 vs. Q4; hazard ratio [HR], 6.75; 95% confidence interval [CI], 1.54 to 29.47; p = 0.011). In multivariate analysis, the risk of developing CKD stage 3 or greater was higher in the second lowest quartile of the serum bilirubin level than that in the highest quartile of the serum bilirubin level (Q2 vs. Q4; HR, 9.36; 95% CI, 1.33 to 65.73; p = 0.024). In the normoalbuminuria subgroup (n = 236), multivariate analysis showed that the risk of developing CKD stage 3 or greater was higher in the lowest quartile of the serum bilirubin level than that in the highest quartile of the serum bilirubin level (Q1 vs. Q4; HR, 7.36; 95% CI, 1.24 to 35.82; p = 0.019). Conclusions: Serum bilirubin might be an early clinical marker for predicting the progression of CKD in patients with T2DM and preserved renal function.

Background/Aims: We demonstrated the role of caveolin-1 involved in high glucose (HG)-induced glomerular mesangial cells (GMCs) senescence. Methods: HG was used to stimulate GMCs. The telomere lengths were analyzed by Southern blot. ${\beta}$-Galactosidase staining was determined. The expressions of caveolin-1 and P53 proteins were determined by Western blot. Results: Treatment with high concentrations of glucose induced GMC senescence accompanied by shortened telomere length and increase of ${\beta}$-galactosidase staining as well as P53 protein, which was abrogated after application of caveolin-1-siRNA. Conclusions: This study proved that HG induced cell senescence in GMCs. The caveolin-1 is involved in HG-induced mesangial cell senescence, and blocking caveolin-1 significantly reduced cell senescence. The effect of caveolin-1 is mediated by P53 pathway.

Background/Aims: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that typically presents in the form of skin manifestations with or without lymph node and bone marrow involvement. Given its rarity and recent recognition as a distinct pathological entity, no standard of treatment exists for this aggressive disease and its prognosis is particularly dismal. Methods: We retrospectively analyzed clinical features and treatment outcomes of patients who were diagnosed with BPDCN between 2000 and 2014. Results: Ten patients had a median age at diagnosis of 41 years (range, 18 to 79), and seven patients were male. Sites of disease involvement were the skin (n = 7), lymph node (n = 5), bone marrow (n = 2), liver (n = 2), spleen (n = 2), and soft tissue (n = 1). Intensified chemotherapy regimens such as hyperCVAD regimen (cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, cytarabine), and VPDL (vincristine, methylprednisolone, daunorubicin, L-asparaginase) were used as a first-line treatment. Although all patients treated with intensified chemotherapy showed an objective response (five patients with complete response) with median progression-free survival of 11.2 months (range 6.2 to 19.4), complete remission was not sustained for more than 2 years in any case. The response was relatively long-lived compared with previously reported CHOP (doxorubicin, cyclophosphamide, vincristine, prednisone)-like regimens, but the above regimens do not result in long-term remission. Conclusions: All patients treated with hyperCVAD or VPDL showed an objective response, but the duration of response was relatively short. Thus, the development of more effective induction as well as consolidation treatment strategy should be warranted to improve this rare disease entity.

Background/Aims: We evaluated the proposed clinical application of the combined interpretation of host factors and viral factors in two different cytomegalovirus (CMV) co-infection models. Methods: We prospectively enrolled all human immunodeficiency virus non-infected patients with confirmed Pneumocystitis jirovecii pneumonia (PCP) and those with suspected gastrointestinal CMV disease in a tertiary hospital. All patients underwent CMV interferon-${\gamma}$ releasing assay (IGRA) for CMV (T-track CMV, Lophius Biosciences). We created the 2-axis model with the CMV IGRA results as the x-axis and the results for CMV virus replication as the y-axis, and hypothesized that cases falling in the left upper quadrant (high viral load and low CMV-specific immunity) of the model would be true CMV infections. The CMV IGRA results were concealed from the attending physicians. Results: Of 39 patients with PCP, four (10%) were classified as combined CMV pneumonia, 13 (33%) as bystander activation, and the remaining 22 (56%) as no CMV infection. The data for all four patients with PCP and CMV pneumonia fell in the left upper quadrant of the 2-axis model. Of 24 patients with suspected gastrointestinal CMV disease, 12 (50%) were classified as gastrointestinal CMV disease and the remaining 12 (50%) as bystander activation with no gastrointestinal CMV disease. The data for 11 of the 12 patients (92%) with gastrointestinal CMV disease were located in the left upper quadrant of the 2-axis model. Conclusions: Cases yielding low CMV IGRA results and high CMV viral replication appear to be true CMV infections. Further studies with large number of cases in different types of CMV disease should be proposed.

Background/Aims: The Cough Symptom Score (CSS) is a simple, useful tool for measuring cough severity. However, there is no standard Korean version of the CSS. We developed a Korean version of the CSS and evaluated its clinical utility and validity for assessing chronic cough severity. Methods: The CSS was adapted for Korean use following a forward-backward translation procedure. Patients with chronic cough enrolled from five university hospitals were graded using the CSS and a 100-mm linear visual analog scale (VAS) of cough severity at each visit. Patients completed the Leicester Cough Questionnaire (LCQ) upon presentation and completed the LCQ and Global Rating of Change at follow-up visits after 2 to 4 weeks. The concurrent validity, repeatability, and responsiveness of the Korean version of the CSS were determined. Results: Correlation coefficients between the CSS and LCQ, and between the CSS and VAS, were -0.66 and 0.52, respectively. There was a weak correlation between the scores for night and day symptoms (r = 0.24, p = 0.0006). The repeatability of the CSS in patients with no change in cough (n = 23) was high (intra-class correlation coefficient, 0.75; 95% confidence interval [CI], 0.51 to 0.88). Patients who reported an improvement in cough (n = 30) at follow-up visits had a significant improvement in the CSS (median, -2; 95% CI, -3 to -1; p = 0.0003). Conclusions: The Korean version of the CSS correlated well with other tools for accessing cough severity in chronic cough patients. Therefore, it could be a reliable method for measuring chronic cough severity.

Background/Aims: In some Western countries, up to 50% of patients with ankylosing spondylitis (AS) have subclinical gut inflammation. This study was conducted to evaluate the prevalence and severity of gut inflammation and to determine clinical factors associated with colonic inflammation in Korean AS patients who performed ileocolonoscopy without evidence of established inflammatory bowel diseases before. Methods: One hundred and eight AS patients who underwent ileocolonoscopy were included in this study. Patients were divided into two groups based on gross ileocolonoscopic findings; patients with inflammatory lesions, and patients without inflammatory lesions. Results: Inflammatory lesions in ileocolonoscopic findings were found in 40 patients. The Ankylosing Spondylitis Disease Activity Score C-reactive protein was higher in the group with inflammatory lesions and gut lesions were found often in the terminal ileum. The risk of inflammatory lesions was higher for AS patients whose symptoms required ileocolonoscopy than for AS patients who underwent routine ileocolonoscopy screening (odds ratio, 3.96). However, abnormal lesions were detected also in 17.6% of the patients who underwent ileocolonoscopy for routine screening and most of them were erosion and ulcer. Among patients with inflammatory lesions (n = 40), 23 showed subclinical gut inflammation associated with AS and 17 were diagnosed finally as Crohn's disease (n = 12), intestinal tuberculosis (n = 4), and ulcerative colitis (n = 1). Conclusions: Our findings suggest that ileocolonoscopy might be recommended regularly in AS patients even without gastrointestinal symptoms, especially in the patients with high AS activity.