PURPOSE: To demonstrate the relationship between epicardial fat accumulation and left atrial reverse remodeling by cardiac multi-detector CT (MDCT) after catheter ablation of atrial fibrillation (AF). MATERIALS AND METHODS: Seventy-six patients underwent cardiac MDCT before and after catheter ablation of AF. Left atrial volume (LAV) and epicardial fat volume (EFV) were measured. LAV and EFV before and after catheter ablation of AF were respectively compared and the change percentages (CPs) were evaluated. RESULTS: The LAV after catheter ablation of AF was significantly less than the baseline LAV (107.5 ± 50.2 mL vs. 144.9 ± 62.6 mL, p < 0.001). The EFV after catheter ablation of AF was significantly greater than the baseline EFV (105.0 ± 35.6 mL vs. 90.1 ± 31.9 mL, p < 0.001). Mean CPs of LAV and EFV were −23.3% ± 20.8% and 15.9% ± 20.9%, respectively. There was a significantly negative relationship between the CPs of LAV and EFV (R = −0.53, p < 0.001). CONCLUSION Catheter ablation of AF may result in a reduction in LAV and an increase in EFV. Left atrial reverse remodeling with a reduction in LAV may be associated with epicardial fat accumulation in patients who undergo catheter ablation of AF.

Catheter ablation of atrial fibrillation (AF) is one of the most complex interventional electrophysiological procedures. The success of AF ablation is based in large part on freedom from AF recurrence based on electrocardiography (ECG) monitoring. Arrhythmia monitoring can be performed with the use of noncontinuous or continuous ECG monitoring tools. AF ablation is an invasive procedure that entails risks, most of which are present during the acute procedural period. However, complications can also occur in the weeks or months following ablation. Recognizing common symptoms after AF ablation and distinguishing those that require urgent evaluation and referral to an electrophysiologist is an important part of follow-up after AF ablation. This section reviews the complications associated with catheter ablation procedures performed to treat AF. The types and incidence of complications are presented, their mechanisms are explored, and the optimal approach to prevention and treatment is discussed. Finally, surgical and hybrid AF ablation technology and the indications for concomitant open or closed surgical ablation of AF, stand-alone and hybrid surgical ablation of AF are covered in this section.
Arrhythmias, Cardiac ; Atrial Fibrillation ; Catheter Ablation ; Catheters ; Electrocardiography ; Follow-Up Studies ; Freedom ; Incidence ; Recurrence ; Referral and Consultation

In this part the writing group will cover strategies, techniques, and endpoints of atrial fibrillation (AF) ablation. Prior to all, electrical isolation of the pulmonary veins is recommended during all AF ablation procedures. In addition, techniques to be used for ablation of persistent and long-standing persistent AF, adjunctive ablation strategies, nonablative strategies to improve outcomes of AF ablation, and endpoints for ablation of paroxysmal, persistent, and long-standing persistent AF will be reviewed. Currently many technologies and tools are employed for AF ablation procedures. Radiofrequency energy, cryoablation, and other energy sources and tools are in various stages of development and/or clinical investigation. Finally, anticoagulation strategies pre-, during, and postcatheter ablation of AF and technical aspects of ablation to maximize safety are discussed in this section.
Atrial Fibrillation ; Catheter Ablation ; Catheters ; Cryosurgery ; Pulmonary Veins ; Writing

Catheter and surgical ablation of atrial fibrillation (AF) have evolved from investigational procedures to their current role as effective treatment options for patients with AF. Surgical ablation of AF is available in most major hospitals throughout the world. Catheter ablation of AF is even more widely available, and is now the most commonly performed catheter ablation procedure. Management of patients with AF has traditionally consisted of three main components: (1) anticoagulation for stroke prevention; (2) rate control; and (3) rhythm control. With the emergence of large amounts of data, which have both defined and called attention to the interaction between modifiable risk factors and the development of AF and outcomes of AF management, we believe it is time to include risk factor modification as the fourth pillar of AF management. Catheter and surgical ablation of AF are highly complex procedures, therefore a decision to perform catheter or surgical AF ablation should only be made after a patient carefully considers the risks, benefits, and alternatives to the procedure.
Atrial Fibrillation ; Catheter Ablation ; Catheters ; Humans ; Risk Factors ; Stroke

PURPOSE: Previous retrospective studies suggest that anaplastic lymphoma kinase (ALK) mutation-positive (ALK+) non-small cell lung cancer (NSCLC) patients are sensitive to pemetrexed. To determine its efficacy, we retrospectively evaluated clinical outcomes of pemetrexed-based chemotherapy in patients with ALK+ NSCLC. MATERIALS AND METHODS: We identified 126 patients with advanced, ALK+ NSCLC who received first-line cytotoxic chemotherapy. We compared response, progression-free survival (PFS), and overall survival (OS) rates according to chemotherapy regimens. Furthermore, we evaluated intracranial time to tumor progression (TTP) and proportion of ALK+ cells as prognostic factors. RESULTS: Forty-eight patients received pemetrexed-based chemotherapy, while 78 received other regimens as first-line treatment. The pemetrexed-based chemotherapy group showed superior overall response (44.7% vs. 14.3%, p < 0.001) and disease control (85.1% vs. 62.3%, p=0.008) rates. The pemetrexed-based chemotherapy group also exhibited longer PFS (6.6 months vs. 3.8 months, p < 0.001); OS rates were not significantly different. The lack of exposure to second-generation ALK inhibitors and intracranial metastasis on initial diagnosis were independent negative prognostic factors of OS. Intracranial TTP was similar between the treatment groups (32.7 months vs. 35.7 months, p=0.733). Patients who harbored a greater number of ALK+ tumor cells (≥70%) showed prolonged OS on univariate analysis (not reached vs. 44.8 months, p=0.041), but not on multivariate analysis (hazard ratio: 0.19, 95% confidence interval: 0.03–1.42; p=0.106). CONCLUSION: Pemetrexed-based regimens may prolong PFS in patients with ALK+ NSCLC as a first-line treatment, but are not associated with prolonged OS. Exposure to second-generation ALK inhibitors may improve OS rates in patients with ALK+ NSCLC.
Adult ; Aged ; Antineoplastic Agents/*therapeutic use ; Carcinoma, Non-Small-Cell Lung/*drug therapy/enzymology/mortality ; Disease-Free Survival ; Female ; Humans ; Lung Neoplasms/*drug therapy/enzymology/mortality ; Male ; Middle Aged ; Mutation ; Pemetrexed/*therapeutic use ; Receptor Protein-Tyrosine Kinases/genetics ; Retrospective Studies ; Survival Rate ; Treatment Outcome

Target cells differentiation techniques from stem cells are developed rapidly. Recently, direct conversion techniques are introduced in various categories. Unlike pluripotent stem cells, this technique enables direct differentiation into the other cell types such as neurons, cardiomyocytes, insulin-producing cells, and hepatocytes without going through the pluripotent stage. However, the function of these converted cells reserve an immature phenotype. Therefore, we modified the culture conditions of mouse direct converted hepatocytes (miHeps) to mature fetal characteristics, such as higher AFP and lower albumin (ALB) expression than primary hepatocytes. First, we generate miHeps from mouse embryonic fibroblasts (MEFs) with two transcription factors HNF4α and Foxa3. These cells indicate typical epithelial morphology and express hepatic proteins. To mature hepatic function, DMSO is treated during culture time for more than 7 days. After maturation, miHeps showed features of maturation such as exhibiting typical hepatocyte-like morphology, increased up-regulated ALB and CYP enzyme gene expression, down-regulated AFP expressions, and acquired hepatic function over time. Thus, our data provides a simple method to mature direct converted hepatocytes functionally and these cells enable them to move closer to generating functional hepatocytes.
Animals ; Dimethyl Sulfoxide ; Fibroblasts* ; Gene Expression ; Hepatocytes* ; Methods ; Mice ; Myocytes, Cardiac ; Neurons ; Phenotype ; Pluripotent Stem Cells ; Stem Cells ; Transcription Factors

We developed an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of acetaminophen concentration in human plasma. Following protein precipitated extraction, the analytes were separated and analyzed using an UPLC-MS/MS in the multiple reaction monitoring (MRM) mode with the respective [M+H]+ ions, m/z 152.06 → 110.16 for acetaminophen and m/z 180.18 → 138.12 for phenacetin (internal standard, IS). The method showed a linear response from 1 to 100 µg/mL (r > 0.9982). The limit of quantitation for acetaminophen in plasma was 1 µg/mL. The intra- and inter-day accuracy ranged in the ranges of 94.40–99.56% and 90.00–99.20%, respectively. The intra- and inter-day precision ranged in the ranges of 2.64–10.76% and 6.84–15.83%, respectively. This method was simple, reliable, precise and accurate and can be used to determine the concentration of acetaminophen in human plasma. Finally, this fully validated method was successfully applied to a pharmacokinetic study of acetaminophen in healthy volunteers following oral administration.
Acetaminophen* ; Administration, Oral ; Healthy Volunteers ; Humans* ; Ions ; Mass Spectrometry ; Phenacetin ; Plasma*

Candida species is indigenous fungus of healthy individuals, and frequently found in sputum culture. Candida isolation from the respiratory tract is not generally considered as a marker of lung infection, and definitive diagnosis of Candida pneumonia is confirmed by tissue biopsy. A few cases of Candida pneumonia pathologically confirmed by transthoracic needle aspiration of mycetoma have been reported. In Korea, a case of Candida pneumonia diagnosed by bronchial washing and blood culture was reported, but there is no case report diagnosed by biopsy. We report a case of Candida pneumonia diagnosed by endobronchial biopsy, and antifungal therapy resulted in successful resolution of the pneumonia.
Biopsy* ; Candida albicans* ; Candida* ; Diagnosis ; Fungi ; Korea ; Lung ; Mycetoma ; Needles ; Pneumonia* ; Respiratory System ; Sputum

Epidemiological studies have demonstrated an increased risk for cardiovascular events in relation to both short- and long-term exposure to ambient particulate matter (PM). Several plausible mechanistic pathways have been described, including an enhanced propensity for arrhythmias, systemic inflammatory responses, and the chronic promotion of atherosclerosis. On the basis of this review, several new findings were reached, including the following: exposure to PM including PM <2.5 microm in diameter can trigger cardiovascular disease-related mortality; longer-term exposure (e.g., a few years) increases the risk for cardiovascular mortality; reductions in PM levels are associated with decreases in cardiovascular mortality within a period as short as a few years; and many credible pathological mechanisms have been elucidated that lend biological plausibility to these findings. It is the opinion of the writing group that the overall evidence is consistent with a causal relationship between PM exposure and cardiovascular morbidity and mortality. Finally, PM exposure is deemed a modifiable factor that contributes to cardiovascular morbidity and mortality. The purpose of this statement is to develop evidence-based practical guidelines for healthcare professionals and regulatory agencies with a comprehensive review of the literature on air pollution and cardiovascular disease and a specific focus on the clinical implications.
Air Pollution ; Arrhythmias, Cardiac ; Atherosclerosis ; Cardiovascular Diseases* ; Delivery of Health Care ; Dust* ; Epidemiologic Studies ; Mortality ; Particulate Matter ; Writing

Previous researches have proved that Pueraria lobata up-regulates bone mineral contents and bone mineral density in bone-loss model, ovariectomized mice and orchidectomized rats. However, the precise effects and mechanisms of Pueraria lobata on osteoclast differentiation and bone resorbing activity of mature osteoclasts still remains unknown. Therefore, we investigated the effect and mechanism of Pueraria lobata on receptor activator of nuclear factor-kappaB ligand (RANKL) and macrophage colony stimulation factor (M-CSF)-induced osteoclast differentiation in bone marrow macro-phages (BMMs). First of all, we treated BMMs derived from mice with various concentrations of Pueraria lobata in order to perform screening by tartrate-resistant acid phosphatase (TRAP) staining. Also, we conducted western blotting and RT-PCR for the purpose of verifying the treatment mechanism of Pueraria lobata and lastly, we used hydroxyapatite-coated plate to evaluate the effects of Pueraria lobata on bone resorbing activity of mature osteoclasts. As a result, Pueraria lobata has inhibitory effect on phosphorylation of p38, Akt, c-Jun N-terminal kinase (JNK), and IkappaB which are essential early signaling pathway of osteoclastogenesis. Also, the inactivation of nuclear factor of activated T cells (NFAT)c1, and c-Fos which is caused by Pueraria lobata is followed by the suppression effects of Pueraria lobata on osteoclast-related various genes, osteoclast-associated receptor (OSCAR), TRAP, Integrin beta3, osteoclast stimulatory transmembrane protein (OC-STAMP), and dendritic cell-specific transmembrane protein (DC-STAMP). Particularly, Pueraria lobata blocks the formation of pit area on hydroxyapatite-coated plate in a dose-dependent manner as well as the mRNA expression of Cathepsin K, which is associated with bone resorbing activity. These results demonstrate the molecular mechanism relating to anti-osteoclastogenesis effect of Pueraria lobata as well as the inhibitory effect of Pueraria lobata on mature osteoclast formation and bone resorbing activity.
Acid Phosphatase ; Animals ; Blotting, Western ; Bone Density ; Bone Marrow ; Bone Remodeling ; Bone Resorption* ; Cathepsin K ; Integrin beta3 ; JNK Mitogen-Activated Protein Kinases ; Macrophages ; Mass Screening ; Mice ; Osteoclasts* ; Osteoporosis ; Phosphorylation ; Pueraria* ; RANK Ligand ; Rats ; RNA, Messenger ; T-Lymphocytes