Resistance to hypomethylating agents (HMAs) in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is a concerning problem. Polo-like kinase 1 (PLK1) is a key cell cycle modulator and is known to be associated with an activation of the PI3K pathway, which is related to the stabilization of DNA methyltransferase 1 (DNMT1), a target of HMAs. We investigated the effects of volasertib on HMA-resistant cell lines (MOLM/AZA-1 and MOLM/DEC-5) derived from MOLM-13, and bone marrow (BM) samples obtained from patients with MDS (BM blasts >5%) or AML evolved from MDS (MDS/AML). Volasertib effectively inhibited the proliferation of HMA-resistant cells with suppression of DNMTs and PI3K/AKT/mTOR and ERK pathways. Volasertib also showed significant inhibitory effects against primary BM cells from patients with MDS or MDS/AML, and the effects of volasertib inversely correlated with DNMT3B expression. The DNMT3B-overexpressed AML cells showed primary resistance to volasertib treatment. Our data suggest that volasertib has a potential role in overcoming HMA resistance in patients with MDS and MDS/ AML by suppressing the expression of DNMT3 enzymes and PI3K/AKT/mTOR and ERK pathways. We also found that DNMT3B overexpression might be associated with resistance to volasertib.

Background and Objectives: De-escalation of dual-antiplatelet therapy through dose reduction of prasugrel improved net adverse clinical events (NACEs) after acute coronary syndrome (ACS), mainly through the reduction of bleeding without an increase in ischemic outcomes. Whether the benefits of de-escalation are sustained in highly thrombotic conditions such as ST-elevation myocardial infarction (STEMI) is unknown. We aimed to assess the efficacy and safety of de-escalation therapy in patients with STEMI or non-STsegment elevation ACS (NSTE-ACS). Methods: This is a pre-specified subgroup analysis of the HOST-REDUCE-POLYTECH-ACS trial. ACS patients were randomized to prasugrel de-escalation (5 mg daily) or conventional dose (10 mg daily) at 1-month post-percutaneous coronary intervention. The primary endpoint was a NACE, defined as a composite of all-cause death, non-fatal myocardial infarction, stent thrombosis, clinically driven revascularization, stroke, and bleeding events of grade ≥2 Bleeding Academic Research Consortium (BARC) criteria at 1 year. Results: Among 2,338 patients included in the randomization, 326 patients were diagnosed with STEMI. In patients with NSTE-ACS, the risk of the primary endpoint was significantly reduced with de-escalation (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.48– 0.89; p=0.006 for de-escalation vs. conventional), mainly driven by a reduced bleeding. However, in those with STEMI, there was no difference in the occurrence of the primary outcome (HR, 1.04; 95% CI, 0.48–2.26; p=0.915; p for interaction=0.271). Conclusions Prasugrel dose de-escalation reduced the rate of NACE and bleeding, without increasing the rate of ischemic events in NSTE-ACS patients but not in STEMI patients.

OBJECTIVE: To evaluate the value of airway computed tomography (CT) in patients with obstructive sleep apnea (OSA) as a predictor of cerebrocardiovascular disease (CCVD) clinically, by quantitatively analyzing carotid arterial calcification (CarAC). MATERIALS AND METHODS: This study included 287 patients aged 40–80 years, who had undergone both polysomnography (PSG) and airway CT between March 2011 and October 2015. The carotid arterial calcium score (CarACS) was quantified using the modified Agatston method on each upper airway CT. The OSA severity was categorized as normal, mild, moderate, and severe using the PSG results. Clinical characteristics, comorbid diseases, and lipid profiles of all patients were analyzed, and the prevalence of CCVDs was investigated during the follow up period (52.2 ± 16.0 months). RESULTS: CCVD occurred in 27 patients (9.3%) at the end of follow-up, and the CCVD-present groups showed a significantly older mean age (57.5 years vs. 54.2 years), higher prevalence of hypertension (59% vs. 34%) and CarAC (51.9% vs. 20.8%), whereas sex, other comorbid diseases, and severity of OSA were not significantly different from the CCVD-absent group. A univariate analysis showed that age, hypertension, incidence of CarAC, and CarACS were risk factors for the occurrence of CCVD events. In a multivariate analysis, the incidence of CarAC was the only independent risk factor for CCVD. CONCLUSION: CarAC is an independent risk factor for CCVD, whereas the severity of OSA is not a contributory risk factor in patients with OSA. Therefore, additional analysis of CarACS based on airway CT scans may be useful for predicting CCVD.
Calcium ; Carotid Arteries ; Fluorouracil ; Follow-Up Studies ; Humans ; Hypertension ; Incidence ; Methods ; Multivariate Analysis ; Polysomnography ; Prevalence ; Risk Factors ; Sleep Apnea, Obstructive ; Tomography, X-Ray Computed

BACKGROUND AND OBJECTIVES: In this second report from Korean percutaneous coronary intervention (K-PCI) registry, we sought to describe the updated information of PCI practices and Korean practice pattern of PCI (KP3). METHODS: In addition to K-PCI registry of 2014, new cohort of 2016 from 92 participating centers was appended. Demographic and procedural information, as well as in-hospital outcomes, of PCI was collected using a web-based reporting system. KP3 class C was defined as any strategy with less evidence from randomized trials and more aggressive for PCI than medical therapy or bypass-surgery. RESULTS: In 2016, total 48,823 PCI procedures were performed at 92 participating centers. Mean age of the patients was 65.7±11.6 years, and 71.7% were males. Overall patient characteristics and PCI practices in 2016 were similar to those in 2014. The biggest change was the decrease in the in-hospital occurrence of myocardial infarction (MI;1.6%→0.7%, p<0.001). Many associations between PCI volumes and demographic/procedural characteristics observed in 2014 have disappeared. The median of door-to-balloon time was 62 minutes, and 83.3% of ST-elevation MI patients received primary PCI within 90 minutes, while the median of total ischemic time was 168 minutes and patients who had total ischemic time within 120 and 180 minutes were 29.1% and 54.1%, respectively. The proportion of KP3 class C cases in non-acute coronary syndrome patients decreased from 13.5% in 2014 to 12.1% in 2016 (p<0.001). CONCLUSIONS: In this second report from K-PCI registry, we described the current practices of PCI and changes from 2014 to 2016 in Korea.
Cohort Studies ; Coronary Artery Disease ; Humans ; Korea ; Male ; Myocardial Infarction ; Percutaneous Coronary Intervention

BACKGROUND AND OBJECTIVES: In this second report from Korean percutaneous coronary intervention (K-PCI) registry, we sought to describe the updated information of PCI practices and Korean practice pattern of PCI (KP3). METHODS: In addition to K-PCI registry of 2014, new cohort of 2016 from 92 participating centers was appended. Demographic and procedural information, as well as in-hospital outcomes, of PCI was collected using a web-based reporting system. KP3 class C was defined as any strategy with less evidence from randomized trials and more aggressive for PCI than medical therapy or bypass-surgery. RESULTS: In 2016, total 48,823 PCI procedures were performed at 92 participating centers. Mean age of the patients was 65.7±11.6 years, and 71.7% were males. Overall patient characteristics and PCI practices in 2016 were similar to those in 2014. The biggest change was the decrease in the in-hospital occurrence of myocardial infarction (MI;1.6%→0.7%, p<0.001). Many associations between PCI volumes and demographic/procedural characteristics observed in 2014 have disappeared. The median of door-to-balloon time was 62 minutes, and 83.3% of ST-elevation MI patients received primary PCI within 90 minutes, while the median of total ischemic time was 168 minutes and patients who had total ischemic time within 120 and 180 minutes were 29.1% and 54.1%, respectively. The proportion of KP3 class C cases in non-acute coronary syndrome patients decreased from 13.5% in 2014 to 12.1% in 2016 (p<0.001). CONCLUSIONS In this second report from K-PCI registry, we described the current practices of PCI and changes from 2014 to 2016 in Korea.

BACKGROUND AND OBJECTIVES: Although several multicenter registries have evaluated percutaneous coronary intervention (PCI) procedures in Korea, those databases have been limited by non-standardized data collection and lack of uniform reporting methods. We aimed to collect and report data from a standardized database to analyze PCI procedures throughout the country. MATERIALS AND METHODS: Both clinical and procedural data, as well as clinical outcomes data during hospital stay, were collected based on case report forms that used a standard set of 54 data elements. This report is based on 2014 Korean PCI registry cohort data. RESULTS: A total of 92 hospitals offered data on 44967 PCI procedures. The median age was 66.0 interquartile range 57.0-74.0 years, and 70.3% were men. Thirty-eight percent of patients presented with acute myocardial infarction and one-third of all PCI procedures were performed in an urgent or emergency setting. Non-invasive stress tests were performed in 13.9% of cases, while coronary computed tomography angiography was used in 13.7% of cases prior to PCI. Radial artery access was used in 56.1% of all PCI procedures. Devices that used PCI included drug-eluting stent, plain old balloon angioplasty, drug-eluting balloon, and bare-metal stent (around 91%, 19%, 6%, and 1% of all procedures, respectively). The incidences of in-hospital death, non-fatal myocardial infarction, and stroke were 2.3%, 1.6%, and 0.2%, respectively. CONCLUSION: These data may provide an overview of the current PCI practices and in-hospital outcomes in Korea and could be used as a foundation for developing treatment guidelines and nationwide clinical research.
Angiography ; Angioplasty, Balloon ; Cohort Studies* ; Data Collection ; Drug-Eluting Stents ; Emergencies ; Exercise Test ; Humans ; Incidence ; Korea* ; Length of Stay ; Male ; Myocardial Infarction ; Percutaneous Coronary Intervention* ; Radial Artery ; Registries ; Stents ; Stroke

BACKGROUND AND OBJECTIVES: Appropriate use criteria (AUC) was developed to improve the quality of percutaneous coronary intervention (PCI). However, these criteria should consider the current practice pattern in the country where they are being applied. MATERIALS AND METHODS: The algorithm for the Korean PCI practice pattern (KP3) was developed by modifying the United States-derived AUC in expert consensus meetings. KP3 class A was defined as any strategy with evidence from randomized trials that was more conservative for PCI than medical therapy or coronary artery bypass graft (CABG). Class C was defined as any strategy with less evidence from randomized trials and more aggressive for PCI than medical therapy or CABG. Class B was defined as a strategy that was partly class A and partly class C. We applied the KP3 classification system to the Korean PCI registry. RESULTS: The KP3 class A was noted in 67.7% of patients, class B in 28.8%, and class C in 3.5%. The median proportion of class C cases per center was 2.0%. The distribution of KP3 classes varied significantly depending on clinical and angiographic characteristics. The proportion of KP3 class C cases per center was not significantly dependent on PCI volume, but rather on the percentage of ACS cases in each center. CONCLUSION: We report the current PCI practice pattern by applying the new KP3 classification in a nationwide PCI registry. The results should be interpreted carefully with due regard for the complex relationships between the determining variables and the healthcare system in Korea.
Area Under Curve ; Classification ; Cohort Studies* ; Consensus ; Coronary Artery Bypass ; Delivery of Health Care ; Humans ; Korea* ; Percutaneous Coronary Intervention* ; Transplants

In the article, “The Practice Pattern of Percutaneous Coronary Intervention in Korea.Based on Year 2014 Cohort of Korean Percutaneous Coronary Intervention (K-PCI) Registry.” in Volume 47(3), page 320-327, indexed color of Class A and Class C has been changed.

Myocardial bridging (MB) occurs when the myocardium covers a segment of a major epicardial coronary artery, resulting in a tunneled arterial segment. Although MB is generally considered benign, it has been associated with myocardial ischemia. A 70-year-old man with MB (50% luminal narrowing during systole) at the mid-left anterior descending artery (LAD) on previous coronary angiography (CAG) visited our hospital with worsening chest pain. His blood pressure (BP) was not well controlled because of poor compliance. Follow-up CAG showed that MB at the mid-LAD progressed to severe stenosis (>90% luminal narrowing during systole) and the total length of tunneled artery extended from 22.5 to 23.9 mm. His chest pain was relieved by BP control. This is the first report of myocardial ischemia secondary to progression of MB demonstrated by CAG in Korea.
Aged ; Arteries ; Blood Pressure ; Chest Pain ; Compliance ; Constriction, Pathologic ; Coronary Angiography ; Coronary Vessels ; Follow-Up Studies ; Humans ; Hypertension ; Ischemia ; Korea ; Myocardial Bridging* ; Myocardial Ischemia* ; Myocardium ; Phenobarbital