Short-term outcomes of atrial flutter ablation.

BACKGROUND: Understanding the factors associated with early readmissions following atrial flutter (AFL) ablation is critical to reduce the cost and improving the quality of life in AFL patients. METHOD: The study cohort was derived from the national readmission database 2013-2014. International Classification of Diseases, 9th Revision (ICD-9-CM) diagnosis code 427.32 and procedure code 37.34 were used to identify AFL and catheter ablation, respectively. The primary and secondary outcomes were 90-day readmission and complications including in-hospital mortality. Cox proportional regression and hierarchical logistic regression were used to generate the predictors of primary and secondary outcomes respectively. Readmission causes were identified by ICD-9-CM code in primary diagnosis field of readmissions. RESULT: Readmission rate of 18.19% (n = 1,010 with 1,396 readmissions) was noted among AFL patients (n = 5552). Common etiologies for readmission were heart failure (12.23%), atrial fibrillation (11.13%), atrial flutter (8.93%), respiratory complications (9.42%), infections (7.4%), bleeding (7.39%, including GI bleed-4.09% and intracranial bleed-0.79%) and stroke/TIA (1.89%). Multivariate predictors of 90-day readmission (hazard ratio, 95% confidence interval, P value) were preexisting heart failure (1.30, 1.13-1.49, P < 0.001), chronic pulmonary disease (1.37, 1.18-1.58, P < 0.001), anemia (1.23, 1.02-1.49, P = 0.035), malignancy (1.87, 1.40-2.49, P < 0.001), weekend admission compared to weekday admission (1.23, 1.02-1.47, P = 0.029), and length of stay (LOS) ≥5 days (1.39, 1.16-1.65, P < 0.001). Note that 50% of readmissions happened within 30 days of discharge. CONCLUSION: Cardiac etiologies remain the most common reason for the readmission after AFL ablation. Identifying high risk patients, careful discharge planning, and close follow-up postdischarge can potentially reduce readmission rates in AFL ablation patients.

Design, synthesis and identification of a new class of triarylmethyl amine compounds as inhibitors of apolipoprotein E production.

We have identified a new class of triarylmethyl amine compounds that can inhibit apolipoprotein E (apoE) production. ApoE is a cholesterol- and lipid-carrier protein implicated in aging, atherosclerosis, Alzheimer's Disease (AD), and other neurological and lipid-related disorders. Attenuation of apoE production is generally considered to be of therapeutic value. A majority of the apoE in the brain is produced by astrocytes. Here, we describe the design, synthesis, and biological screening of a small library of compounds that led to the identification of four triarylmethyl amines as potent inhibitors of apoE production in CCF-STTG1 astrocytoma cells.

Eosinophilic Myocarditis Demonstrated Using Cardiac Magnetic Resonance Imaging in a Patient with Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Disease).

Eosinophilic granulomatosis with polyangiitis (EGPA), historically known as the Churg-Strauss disease, is a small- to medium-sized vessel multi-organ vasculitis with a propensity to involve the heart. EGPA is a rare condition with an estimated annual incidence of one to 4.2 people per million. The cardiac involvement causes significant morbidity and mortality in EGPA patients. Approximately 50% of the deaths in EGPA are related to cardiac disease and occur within the first few months since diagnosis. The current recommendations support evaluation of cardiac involvement by using history, physical exam and multimodality imaging including echocardiogram and cardiac magnetic resonance imaging (CMR). Here, we report a rare case of eosinophilic myocarditis in a 19-year-old patient with EGPA seen on CMR. Pertinent literature is also reviewed. We highlighted the importance of CMR in diagnosing and follow up of EGPA patients.

Causes and Predictors of Readmission in Patients With Atrial Fibrillation Undergoing Catheter Ablation: A National Population-Based Cohort Study.

BACKGROUND: Reducing readmission after catheter ablation (CA) in atrial fibrillation (AF) is important. METHODS AND RESULTS: We utilized National Readmission Data (NRD) 2010-2014. AF was identified by International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) diagnostic code 427.31 in the primary field, while first CA of AF was identified via ICD-9-procedure code 37.34. Any admission within 30 or 90 days of index admission was considered a readmission. Cox proportional hazard regression was used to adjust for confounders. The primary outcomes were 30- and 90-day readmissions and the secondary outcome was AF recurrence. In total, 1 128 372 patients with AF were identified from January 1, 2010 to September 30, 2014. Of which 37 360 (3.3%) underwent CA. Patients aged ≥65 years and female sex were less likely to receive CA for AF. Overall, 10.9% and 16.5% of CA patients were readmitted within 30 and 90 days post-CA, respectively. Most common causes of readmissions were arrhythmia (AF, atrial flutter), heart failure, pulmonary causes (pneumonia, chronic obstructive pulmonary disease) and bleeding complications (gastrointestinal bleed, intracranial hemorrhage). Patients with diabetes mellitus, heart failure, coronary artery disease (CAD), chronic pulmonary and kidney disease, prior stroke/transient ischemic attack (TIA), female sex, length of stay ≥2 and disposition to the facility were prone to higher 30- and 90-day readmissions post-CA. Predictors of increase in AF recurrence post-CA were female sex, diabetes mellitus, chronic pulmonary disease, and length of stay ≥2. Trends of 90-day readmission and AF recurrence were found to improve over the study period. CONCLUSIONS: We identified several demographic and clinical factors associated with the use of CA in AF, and short-term outcomes of the same, which could potentially help in the patient selection and improve outcomes.

Caloric restriction attenuates Abeta-deposition in Alzheimer transgenic models.

Dietary influences on Alzheimer disease (AD) are gaining recognition. Because many aging processes are attenuated in laboratory mammals by caloric restriction (CR), we examined the effects of short-term CR in two AD-transgenic mice, APP(swe/ind) (J20) and APP(swe) + PS1(M146L) (APP + PS1). CR substantially decreased the accumulation of Abeta-plaques in both lines: by 40% in APP(swe/ind) (CR, 6 weeks), and by 55% in APP + PS1 (CR, 14 weeks). CR also decreased astrocytic activation (GFAP immunoreactivity). These influences of CR on AD-transgenic mice are consistent with epidemiological reports that show that high caloric diets associate with the risk of AD, and suggest that dietary interventions in adult life might slow disease progression.

Macrosialin increases during normal brain aging are attenuated by caloric restriction.

During normal aging, microglia develop an activated phenotype characterized by morphologic changes and induction of CD11b, MHC II, and other inflammatory markers. We show that macrosialin (CD68), a macrophage-specific protein, is increased by aging in selected brain regions of male C57BL/6NNia mice. In corpus callosum and striatum, macrosialin mRNA and protein increased >or=50% (24 months versus 4 months); hippocampus and cerebellum were unchanged. Caloric restriction (CR) attenuated these age-related increases. Since CR attenuates age-related increases in oxidative damage and inflammation, we examined whether oxidized lipoproteins and inflammatory processes regulate macrosialin using murine BV-2 microglial cells as a model. Oxidized low-density lipoproteins (oxLDL) induced macrosialin protein by 50%. Moreover, macrosialin was induced in response to lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma) which activates inflammatory pathways in BV-2 cells. Thus, the previously documented increase in oxidized lipoproteins, inflammation, and microglial activation during normal aging may contribute to the age-related increase in macrosialin expression.

Progressive changes in regulation of apolipoproteins E and J in glial cultures during postnatal development and aging.

Apolipoprotein (Apo) E and ApoJ are lipid- and cholesterol-carriers in the central nervous system and are implicated in age-related neurodegenerative diseases. The primary source of secreted ApoE and ApoJ (clusterin) in the brain is glia. Regulation of these apolipoproteins in mixed glial cultures from rat cerebral cortex differed most strongly between neonatal- and adult-derived glia. Basal secretion of ApoJ was two-fold greater in neonatal than adult glia. Responses to cytokines also differed by donor age. In adult glia, IL-6 increased ApoE secretion, but slightly decreased ApoJ. Both IL-1 beta and TNFalpha treatments increased ApoJ secretion from adult glia, with little effect on ApoE. In contrast to adult glia, neonatal ApoJ secretion did not respond to IL-1 beta, IL-6, or TNFalpha, and ApoE secretion from neonatal glia was slightly increased by IL-6. These differences may contribute to age-related neuroinflammatory processes, and are pertinent to the general use of neonatal-derived primary glia in models for neurodegenerative disease.

Glycogen synthase kinase 3 (GSK3) inhibitor, SB-216763, promotes pluripotency in mouse embryonic stem cells.

Canonical Wnt/ß-catenin signaling has been suggested to promote self-renewal of pluripotent mouse and human embryonic stem cells. Here, we show that SB-216763, a glycogen synthase kinase-3 (GSK3) inhibitor, can maintain mouse embryonic stem cells (mESCs) in a pluripotent state in the absence of exogenous leukemia inhibitory factor (LIF) when cultured on mouse embryonic fibroblasts (MEFs). MESCs maintained with SB-216763 for one month were morphologically indistinguishable from LIF-treated mESCs and expressed pluripotent-specific genes Oct4, Sox2, and Nanog. Furthermore, Nanog immunostaining was more homogenous in SB-216763-treated colonies compared to LIF. Embryoid bodies (EBs) prepared from these mESCs expressed early-stage markers for all three germ layers, and could efficiently differentiate into cardiac-like cells and MAP2-immunoreactive neurons. To our knowledge, SB-216763 is the first GSK3 inhibitor that can promote self-renewal of mESC co-cultured with MEFs for more than two months.

Linking lipids, Alzheimer's and LXRs?

Deposition of the beta-amyloid (Abeta) peptide is thought to underlie development of Alzheimer's disease (AD). This pathological linkage has spurred considerable interest in therapeutic strategies to reduce Abeta production. It is becoming increasingly clear that altered cholesterol homeostasis can modulate Abeta production and/or accumulation. In this review, we discuss the molecular pathology of AD, the cholesterol connection and recent data suggesting that the oxysterol receptor, liver X receptor LXR (NR1H2 and NR1H3), may modulate these events.