Objective: Atomoxetine and fluoxetine are psychopharmacologic agents associated with loss of appetite and weight. Adenosine monophosphate-activated protein kinase (AMPK) is the cellular energy sensor that regulate metabolism and energy, being activated by fasting and inhibited by feeding in the hypothalamus. Methods: Human brain cell lines (SH-SY5Y and U-87 MG cells) were used to study the outcome of atomoxetine and fluoxetine treatment in the activity of AMPK-acetyl-CoA carboxylase (ACC)- carnitine palmitoyl transferase 1 (CPT1) pathway and upstream regulation by calcium/calmodulin-dependent kinase kinase β (CaMKKβ) using immunoblotting and CPT1 enzymatic activity measures. Results: Phosphorylation of AMPK and ACC increased significantly after atomoxetine and fluoxetine treatment in the first 30–60 minutes of treatment in the two cell lines. Activation of AMPK and inhibition of ACC was associated with an increase by 5-fold of mitochondrial CPT1 activity. Although the neuronal isoform CPT1C could be detected by immunoblotting, activity was not changed by the drug treatments. In addition, the increase in phospho-AMPK and phospho-ACC expression induced by atomoxetine was abolished by treatment with STO-609, a CaMKKβ inhibitor, indicating that AMPK-ACC-CPT1 pathway is activated through CaMKKβ phosphorylation. Conclusion These findings indicate that at the cellular level atomoxetine and fluoxetine treatments may activate AMPK-ACC-CPT1 pathways through CaMKKβ in human SH-SY5Y and U-87 MG cells.

Purpose: Only a few Asian studies have discussed the impact of statin intensity on clinical outcomes in patients with peripheral artery disease (PAD). We aimed to investigate the clinical impact of statin intensity in patients with PAD after endovascular revascularization. Materials and Methods: From April 2009 to June 2019, 376 patients with lower extremity PAD treated with endovascular revascularization were enrolled. They were classified into three groups according to statin intensity: no-statin, low-to-moderate intensity (LMI), and high-intensity (HI). The primary outcomes were major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Results: During the 40-month follow-up, MACE occurred less frequently in the HI and LMI groups than the no-statin group (11.4% vs. 16.0% vs. 39%, p<0.001). In adjusted Cox models, the HI group had the fewest MACE [hazard ratio (HR): 0.447; 95% confidence interval (CI): 0.244–0.834; p=0.018] and MALE (HR: 0.360; 95% CI: 0.129–1.006; p=0.051) events, while the LMI group had fewer MACE (HR: 0.571; 95% CI: 0.326–1.0; p=0.050) events than the no-statin group. HI statin therapy was associated with better outcomes in terms of MALE (HR: 0.432; 95% CI: 0.223–0.837; p=0.003) than LMI statin therapy after inverse probability treatment weighting analysis. Conclusion HI and LMI statin use is associated with a significant reduction in MACE events than no-statin use. HI statin use was associated with better MALE outcomes than no-statin or LMI statin use.

Background: Although regular physical activity benefits cardiovascular health, there is a concern that intense exer‑ cise is linked to the promotion of atrial fibrillation (AF) and coronary plaque rupture. However, the impact of physical activity on the outcomes of patients with concomitant AF and coronary artery disease (CAD) remains unclear. This study aimed to evaluate the association with clinical outcomes according to the level of physical activity in patients with concomitant AF and CAD. Methods: We assessed 551 patients with AF and CAD (mean age, 67.1 ± 9.8 years) who completed a self-reported questionnaire for physical activity from 2015 to 2020 in a single tertiary-care hospital. Physical activity levels were con‑ verted into metabolic equivalent of task (MET) per week and categorized to correspond with multiple public health recommendations. We examined the association between physical activity, all-cause mortality, and major adverse cardiac and cerebrovascular events (MACCE). Results: The risks of all-cause mortality (P for linear trend = 0.017) and MACCE (P for linear trend = 0.05) appeared inverse trend with a greater level of physical activity. Compared with inactive patients, patients who met the recom‑ mended target range of physical activity (500–1,000 MET-min/week: unadjusted hazard ratio [HR] = 0.58, 95% confi‑ dence interval [CI] = 0.36–0.99) and highly active patients who exceeded the minimum recommended level (≥ 1,000 MET-min/week: unadjusted HR = 0.47, 95% CI = 0.25–0.88) had a lower risk of all-cause mortality in the unadjusted model; however, these associations did not remain significant after adjusting for the model. There was no evidence of increased risk of all-cause mortality and MACCE at levels of physical activity above the recommended target range, even with vigorous-intensity physical activity exceeding the recommended target range. Conclusions There appears to be an inverse trend between physical activity levels and all-cause mortality and MACCE in patients with concomitant AF and CAD. No excess risk of mortality or MACCE was found at exercise levels above the recommended target range. Further large-scale studies are warranted to create an improved evidence base concerning the effects of physical activity in patients with AF and CAD.

Background: Implantable loop recorders (ILRs) can provide an enhanced possibility to detect atrial fibrillation (AF), but the accuracy, especially the positive predictive value (PPV), is controversial. This study aimed to evaluate the accuracy of ILRs for detecting AF through a comparison with Holter. Method and results: Thirteen patients who underwent AF ablation were enrolled. ILRs were implanted in all patients, who were scheduled to have Holter monitorings after the procedure. The incidence of AF was compared between the two modalities and analyzed for any correlations. A total of 51 Holters (67,985.5 min) and concomitant ILRs were available for the comparison. The judgment of the presence of AF did not perfectly correlate between the ILR and Holter (Kappa = 0.866, P < 0.001). In the ILR data, the sensitivity of detecting AF on the Holter was 81.6% (95% confidence interval [CI] 0.812–0.820; P < 0.001). The specificity was 99.9% (95% CI 0.998–0.999; P < 0.001). When the ILR detected AF, the PPV was 99.5% (95% CI 0.994–0.995), but the ILR did not detect AF, and the negative predictive value was 94.2% (95% CI 0.941–0.944). A separate analysis of AF/atrial tachycardia (AT) showed that the AT detection rate of the ILR was 2.3%. Conclusion The ILR had a low false positive value and high PPV for AF events. However, it was limited in identifying AT.

BACKGROUND AND OBJECTIVES: This study was performed to describe clinical characteristics of patients with left ventriculars (LV) dysfunction and implantable cardioverter-defibrillator (ICD), and to evaluate the effect of ICD therapy on survival in Yeongnam province of Korea. SUBJECTS AND METHODS: From a community-based device registry (9 centers, Yeongnam province, from November 1999 to September 2012), 146 patients with LV dysfunction and an ICD implanted for primary or secondary prophylaxis, were analyzed. The patients were divided into two groups, based on the etiology (73 with ischemic cardiomyopathy and 73 with non-ischemic cardiomyopathy), and indication for the device implantation (36 for primary prevention and 110 for secondary prevention). The cumulative first shock rate, all cause death, and type and mode of death, were determined according to the etiology and indication. RESULTS: Over a mean follow-up of 3.5 years, the overall ICD shock rate was about 39.0%. ICD shock therapy was significantly more frequent in the secondary prevention group (46.4% vs. 16.7%, p=0.002). The cumulative probability of a first appropriate shock was higher in the secondary prevention group (p=0.015). There was no significant difference in the all-cause death, cardiac death, and mode of death between the groups according to the etiology and indication. CONCLUSION: Studies from this multicenter regional registry data shows that in both ischemic and non-ischemic cardiomyopathy patients, the ICD shock therapy rate was higher in the secondary prevention group than primary prevention group.
Cardiomyopathies ; Convulsive Therapy ; Death ; Defibrillators, Implantable* ; Follow-Up Studies ; Heart Failure* ; Heart* ; Humans ; Korea* ; Mortality ; Primary Prevention ; Secondary Prevention ; Shock ; Ventricular Dysfunction, Left

BACKGROUND AND OBJECTIVES: Due to recent studies that have shown an association between the genetic variation of SCN5A and sick sinus syndrome (SSS), we sought to determine if a similar correlation existed in Korean patients with SSS. SUBJECTS AND METHODS: We enrolled 30 patients with SSS who showed a sinus pause (longer than 3.0 s) in Holter monitoring, in addition to 80 controls. All exons including the putative splicing sites of the SCN5A gene were amplified by polymerase chain reaction and sequenced either directly or following subcloning. Wild-type and single nucleotide polymorphisms were expressed in human embryonic kidney cells, and the peak sodium current (I(Na)) was analyzed using the whole-cell patch-clamp technique. RESULTS: A total of 9 genetic variations were identified: 7 variations (G87A-A29A, IVS9-3C>A, A1673G-H558R, G3823A-D1275N, T5457C-D1819D, T5963G-L1988R, and C5129T-S1710L) had been previously reported, and 2 variants (A3075T-E1025D and T4847A-F1616Y) were novel; the potential structural effects of F1616Y were analyzed in a three-dimensional model of the SCN5A domain. Patch-clamp studies at room temperature demonstrated that the peak I(Na) was significantly increased by 140% in HEK cells transfected with F1616Y compared with wild-type (-335.13 pA/pF+/-24.04, n=8 vs. -139.95 pA/pF+/-23.76, n=7, respectively). Furthermore, the voltage dependency of the activation and steady-state inactivation of F1616Y were leftward-shifted compared with wild-type (V(h) activation=-55.36 mv+/-0.22, n=8 vs. V(h) activation=-44.21 mV+/-0.17, n=7; respectively; V(h) inactivation=-104.47 mV+/-0.21, n=7 vs. V(h) inactivation=-84.89 mV+/-0.09, n=12, respectively). CONCLUSION: F1616Y may be associated with SSS.
Electrocardiography, Ambulatory ; Exons ; Genetic Variation* ; Humans ; Kidney ; Patch-Clamp Techniques ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Sick Sinus Syndrome* ; Sodium

PURPOSE: The hepatic resection is the gold-standard treatment for patients with colorectal-cancer liver metastases (CLM). This study aimed to identify prognostic factors in patients with synchronous CLM who underwent a surgical curative (R0) resection with respect to the number of metastatic nodules. METHODS: Of 1,261 CLM patients treated between January 1991 and December 2010, 339 who underwent a R0 resection for synchronous CLM were included in this retrospective analysis. Patients were grouped according to the number of CLM nodules: 1-2 CLM nodules, n = 272 (group 1) and 3-8 CLM nodules, n = 67 (group 2). RESULTS: The 5-year progression-free survival (PFS) rate in group 1was better than that in group 2 (P = 0.020). The multivariate analysis identified lymph-node metastasis (N2), lymphovascular invasion (LVI), and three or more CLM nodules as independent poor prognostic factors for PFS in all patients and lymph-node metastasis (N2) and LVI as independent poor prognostic factors for patients in group 1. No independent prognostic factors were identified for patients in group 2. CLM treatment method and neoadjuvant chemotherapy were not associated with survival. CONCLUSION: Three or more metastatic nodules, lymph-node metastasis (N2), and LVI were independent poor prognostic factors for PFS in patients with synchronous CLM who underwent a R0 resection. The latter 2 factors were also independent prognostic factors for PFS in patients with less than 3 CLM nodules; however, in patients with three or more CLM nodules, the prognosis for PFS may be related only to liver metastasis.
Colorectal Neoplasms* ; Disease-Free Survival ; Drug Therapy ; Humans ; Liver* ; Methods ; Multivariate Analysis ; Neoplasm Metastasis* ; Prognosis ; Retrospective Studies

OBJECTIVE: Epidural injection of hyaluronic acid may prevent adhesion formation after spine surgery, but the compounds used to stabilize hyaluronidase could interfere with its anti-adhesion effects. The present study was conducted as a clinical trial to evaluate the efficacy and safety of an experimental medical gel in preventing adhesion formation. METHODS: This study was designed as a multicenter, randomized, double-blind, and comparative controlled clinical trial with an observation period of 6 weeks. Subjects were randomly assigned into two groups: group A with sodium hyaluronate + 1,4-butanediol diglycidyl ether (BDDE) and group B with sodium hyaluronate + sodium carboxymethylcellulose (CMC). Visual analogue scale (VAS) of back and leg pain and the Oswestry disability index (ODI) and scar score ratings were assessed after surgery. RESULTS: Mean scar grade was 2.37+/-1.13 in group A and 2.75+/-0.97 in group B, a statistically significant difference (p=0.012). VAS of back and leg pain and ODI scores decreased significantly from baseline to 3 and 6 weeks postoperatively in both groups (p<0.001). However, VAS and ODI scores were not statistically different between groups A and B at baseline or at 3 and 6 weeks after operation (p>0.3). The number of adverse reactions related to the anti-adhesion gels was not statistically different (p=0.569), but subsequent analysis of nervous adverse reactions showed group B was superior with a statistically difference (p=0.027). CONCLUSION: Sodium hyaluronate with BDDE demonstrated similar anti-adhesion properties to sodium hyaluronate with CMC. But, care should be used to nervous adverse reactions by using sodium hyaluronate with BDDE.
Carboxymethylcellulose Sodium* ; Cicatrix ; Diskectomy* ; Ether* ; Gels ; Hyaluronic Acid* ; Hyaluronoglucosaminidase ; Injections, Epidural ; Leg ; Spine

BACKGROUND/AIMS: Combination single-pill therapy can improve cost-effectiveness in a typical medical therapy. However, there is a little evidence about the efficacy and tolerability of combination single-pill antiplatelet therapy after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). METHODS: From June to November 2012, in total, 142 patients who met the following criteria were enrolled: at least 18 years old; successful PCI with DES at least 3 months earlier; and regular medication of aspirin and clopidogrel with no side effects. After VerifyNow P2Y12 and aspirin assays, the combination single pill of aspirin and clopidogrel was given and laboratory tests were repeated 6 weeks later. RESULTS: At baseline, the incidence of aspirin resistance, defined as aspirin reaction unit (ARU) > or = 550, was 9.2%, that of clopidogrel resistance, defined as P2Y12 reaction unit (PRU) > or = 230, was 46.5%, and that of percent inhibition of PRU < 20% was 32.4%. At follow-up, the incidence of resistance by ARU value was 7.0%, 50.0% by PRU value, and 35.9% by percentage inhibition of PRU, respectively. The mean values of ARU (431.5 +/- 63.6 vs. 439.8 +/- 55.2; p = 0.216) and PRU (227.5 +/- 71.4 vs. 223.3 +/- 76.0; p = 0.350) were not significantly different before versus after antiplatelet-combination single-pill therapy. Five adverse events (3.5%) were observed during the study period. CONCLUSIONS: Combination single-pill antiplatelet therapy, which may reduce daily pill burden for patients after PCI with DES, demonstrated similar efficacy to separate dual-pill antiplatelet therapy.
Aged ; Antiplatyhelmintic Agents/*administration & dosage/adverse effects ; Aspirin/*administration & dosage/adverse effects ; Drug Combinations ; Drug Resistance ; *Drug-Eluting Stents ; Female ; Humans ; Intention to Treat Analysis ; Male ; Middle Aged ; Myocardial Ischemia/blood/diagnosis/*therapy ; Percutaneous Coronary Intervention/adverse effects/*instrumentation ; Platelet Function Tests ; Prospective Studies ; Tablets ; Ticlopidine/administration & dosage/adverse effects/*analogs & derivatives ; Time Factors ; Treatment Outcome