Catheter ablation of atrial fibrillation in elderly population

Background Although elderly patients have been included in published series of catheter ablation for atrial fibrillation (AF), clinical benefit and safety remain still less defined in this population. A retrospective analysis of the results of catheter ablation for AF in a large volume center focused on comparison of elderly patients with the rest of the patient cohort was conducted in this study. Methods Consecutive patients who underwent catheter ablation for AF between January 2001 and December 2016 were analysed. A total population of 3197 patients was dichotomized by the age of 70 years (394 elderly vs. 2803 younger subjects). Patients were followed in terms of arrhythmia status and sur?vival for a median period of 18 vs. 21 and 35 vs. 57 months, respectively. Results Elderly patients were more frequently females (49% vs. 29%, P < 0.0001), had a history of hypertension (79% vs. 57%, P < 0.0001), diabetes (16% vs. 11%, P < 0.01), stroke (9% vs. 6%, P < 0.01), coronary/peripheral artery disease (14% vs. 8%, P < 0.0001), and CHA2DS2-VASc score (3.1 ± 1.3 vs. 1.5 ± 1.2 s, P < 0.0001). Major complications were more frequent in elderly (5.3% vs. 3.2%, P = 0.03); however, this difference was driven by vascular complications (3.6% vs. 1.9%, P = 0.04). There were comparable rates of cerebrovascular (0.3 vs. 0.3%) or nonvascular complications (1.8 vs. 1.2%). Good arrhythmia control was inferior in elderly patients as compared with the rest of the cohort, both without and with antiarrhythmic drugs: 44.2% vs. 58.2% (P < 0.0001) and 78.2 vs. 83.2% (P < 0.01), respectively. Poor arrhythmia control was associated with relative risk of all-cause mortality of 2.7 (95% CI: 1.1–6.4) in elderly patients and 1.4 (95% CI: 0.9–2.0) in younger subjects. Conclusions Catheter abla?tion for AF in elderly patients is safe although somewhat less effective. Good arrhythmia control is associated with better survival, especially in elderly patients.     

Comparison of in-hospital outcomes between octogenarians and nonagenarians undergoing transcatheter aortic valve replacement: a propensity matched analysis

Background Aortic valve stenosis (AS) is very common in the elderly patients above 80 years. Transcatheter aortic valve replacement (TAVR) in such patients is being increasingly performed. This study sought to assess in-hospital outcome differences between octogenarians and nonagenarians and predictors of mortality in nonagenarians undergoing TAVR with severe AS. Method The study population was derived from the National Inpatient Sample (NIS) for the years 2012–2014 using ICD-9 CM procedure codes 35.05 and 35.06 for TAVR. Hospitalizations below 80 years of age were excluded. After performing propensity score matching (1: 2), in-hospital outcomes were compared in matched cohorts. Then, multivariate model was developed to analyze predictors of in-hospital mortality in nonagenarians. Results There were 11,630 hospitalizations in the octogenarian and 5815 hospitalizations in the nonagenarian group. Primary outcome of in-hospital mortality (6% vs. 4.1%, P ≤ 0.001) was higher in nonagenarians compared to octogenarians. Secondary outcomes including stroke (3.4% vs. 2.8%, P ≤ 0.001), renal failure (18.9% vs. 17.3%, P ≤ 0.001), blood transfusion (35% vs. 32.6%, P ≤ 0.001), vascular complications (4.5% vs. 3.5%, P ≤ 0.001), and pacemaker implantation (27.8% vs. 24.8%, P ≤ 0.001) were higher in nonagenarians. There was no difference in their length of stay. Median cost (70,374$ vs. 65,381$, P ≤ 0.001) was slightly higher with nonagenarian. Conclusions Although in-hospital mortality is slightly higher in nonagenarians, it is acceptable. This difference in mortality is at least partly explained by higher complications in nonagenarians. Efforts should be made to decrease the complications which can further narrow the difference in in-hospital mortality between the groups.     

我国山丘疫区和平原疫区利什曼原虫分离株基因组DNA基因型分析

目的：分析我国山丘和平原疫区利什曼原虫分离株基因组DNA（nDNA）的多态性。方法：对基因组DNA进行内切酶酶切、Southern杂交、染色体定位。探针采用地高辛标记。结果：采用gp63探针，显示杜氏利什曼原虫（Leishmaniadonovani，L．d．）江苏人株和L．d．Jeddah nDNA之间有相似的染色体杂交带，L．d．四川人株和L．infantum nDNA之间有相似的染色体杂交带；采用β－tubulin探针，显示L．d．江苏人株与L．d．Jeddah nDNA之间有两条相似的染色体杂交带，L．d．四川犬株与L．d．甘肃犬株nDNA之间有三条相似的染色体杂交带、与L．d．汶川人株nDNA之间有两条相似的染色体杂交带。结论：提示平原疫区的江苏人株与L. d. J eddah 之间存在同源性, 山丘疫区的L. d. 四川人株与L. infantum 之间存在同源性, L. d. 四川犬株与L. d. 甘肃犬株之间存在同源性、与L. d. 汶川人株之间既存在同源性又存在差异, 山丘疫区与平原疫区分离株之间存在异源性。     

细胞因子体外扩增脐血CD^＋34细胞移植SCID鼠人类免疫功能的 …

ObjectiveTo explore the hematopoietic function of cytokine-expanding CD⁺₃₄ cells from umbilical cord blood in vitro.MethodCord blood cells expanded with FLT3(FMS-like tyrosine kinase 3)-ligand and thrombopoietin were transplanted in SCID(severe combined immune-deficient)mice. Human mature cell surface markers were detected with flow cytometry and used as indicator of succeeding transplantation.ResultAfter 2 and 3 weeks culture,the number of CD⁺₃₄ cells increased approximately 10 and 37 folds. After transplantation with 6.6×10⁴ to 6.9×10⁵ CD⁺₃₄ cells,respectively the percentage of human CD⁺₄₅ cells in the bone marrow of all 10 SCID mice is 0.2%～4.0%. The percentage of human CD⁺₃ cells in the peripheral blood and spleen of 6 SCID mice is 0.1%～2.3%. The percentage of human CD⁺₁₉ cells in the peripheral blood and spleen of 3 SCID mice are 0.3%～1.3%.ConclusionCD⁺₃₄ cells expanded with FLT3-ligand and thrombopoietin are potential engraft used for reconstitution of both hematopoietic and immunologic function of SCID mice.     

Formoterol,a new long-acting selectiveβ 2-agonist,decreases airway responsiveness in children with asthma

We compared the protective effect and duration of action of inhaled formoterol with salbutamol and placebo in 16 asthmatic children in a double-blind, cross-over study. All had an FEV₁ ≥ 70% predicted normal and a provocative concentration of methacholine (MCh) required to decrease their FEV₁ by 20% (PC₂₀) ≤ 4 mg/ml. On each study day, FEV₁ was within 10% and PC₂₀ within one doubling-dose of the initial visit. Patients received either placebo, salbutamol 200μg, formoterol 12μg, or formoterol 24μg by metered-dose inhaler. FEV₁ and PC₂₀ were measured repeatedly over 12 h. After salbutamol, peak FEV₁ was 120% of baseline at 30 min and returned to baseline in 3 h. After formoterol (12 or 24μg) peak FEV₁ was 118% at 3 h and remained above baseline for at least 12 h. Protection from MCh by both doses of formoterol was significantly better than by salbutamol. Protection from formoterol 12 and 24μg at 12 h was equivalent to that from salbutamol at 3 h. The PC₂₀ of four children 48 h after formoterol 24μg was more than twice their baseline PC₂₀. Formoterol by inhalation is potent and long-acting and provides significantly better antiasthma protection than salbutamol.     

Growth hormone-releasing hormone and gonadotropin-releasing hormone stimulate nitric oxide production in 17beta-estradiol-primed rat anterior pituitary cells

It was reported that neuronal nitric oxide synthase (nNOS) was expressed only in gonadotrophs and folliculo-stellate cells in the anterior lobe of the pituitary gland. However, recent studies have demonstrated the occurrence of nNOS in the somatotrophs and lactotrophs. In the present study, we investigated effects of growth hormone-releasing hormone (GHRH), gonadotropin-releasing hormone (GnRH), and 17β-estradiol on nitric oxide (NO) release in cultured rat anterior pituitary cells in vitro. The NO ₂ ⁻ level in the incubation medium of the rat anterior pituitary cells was dependent on the cell density. Pretreatment with 10 μM 17β-estradiol resulted in an increase in medium NO ₂ ⁻ level. GHRH and GnRH failed to change medium NO ₂ ⁻ levels, but they elicited increases in medium NO ₂ ⁻ levels in estrogen-treated cells. The GHRH-induced increase in NO ₂ ⁻ level was inhibited by Nχ-nitro-l-arginine methyl ester, a NOS inhibitor. These findings suggest that GnRH and GHRH could activate nNOS in the gonadotrophs and the somatotrophs, respectively.     

Real-world comparison of non-vitamin K antagonist oral anticoagulants and warfarin in Asian octogenarian patients with atrial fibrillation

Background The efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in Asian octogenarian atrial fibrillation (AF) patients have not been established in a real-world setting. We aimed to evaluate the efficacy and safety of NOACs and warfarin in Korean octogenarian patients. Methods A total of 293 consecutive patients aged ≥ 80 years with non-valvular AF who had taken either NOACs (148 cases, 50.5%) or warfarin (145 cases, 49.5%) were retrospectively reviewed. The efficacy outcome was the composite of stroke or systemic embolism. The safety outcome was major bleeding. Results The follow-up duration was 375 patient-years (172 patient-years with NOACs and 203 patient-years with warfarin). Patients on NOACs were slightly older (P = 0.006) and had slightly higher HAS-BLED scores (P = 0.034). The efficacy of both anticoagulants was high (1.16% for NOACs vs. 2.98% for warfarin per 100 patient-years, P = 0.46). The safety outcome was relatively high in both NOACs and warfarin groups (8.96% vs. 12.46%, P = 0.29). The efficacy and safety outcomes tended to decrease non-significantly in low dose NOACs than in common dose NOACs or warfarin (0.85% vs. 1.84% vs. 2.98% in efficacy outcome, P = 0.69; and 6.97% vs. 13.29% vs. 12.46% in safety outcome, P = 0.34). Conclusions NOACs were highly effective for prevention of stroke or systemic embolism in Asian octogenarian AF patients. However, major bleeding occurred excessively high in both anticoagulant groups. Further study is required on the optimal anticoagulant regimen in octogenarian population.     

Association of non-synonymous variants in WIPF3 and LIPA genes with ab-dominal aortic aneurysm: an autopsy study

Background Abdominal aortic aneurysm (AAA) is a multifactorial disease with strong genetic components. Various genetic loci have been associated with clinical AAA, but few studies have investigated pathological AAA, an intermediate phenotype of the disease. Methods We examined 2263 consecutive autopsies of older Japanese subjects from a study on geriatric diseases in Japanese individuals (The JG-SNP study). The presence of AAA was determined with a pathological diagnosis during autopsy. Single nucleotide variants (SNVs) associated with AAA were determined with an Illumina HumanExome Beadchip array. Logistic regression analyses were performed to determine genetic associations. Age, gender, and other risk factors of AAA were analyzed as covariates. Results 118 subjects with AAA and 2145 subjects without AAA were analyzed in a case-control setting. No variants reached significance after applying the Bonferroni correction (P < 2.05×10^?6). The strongest associations were found with rs3750092 (p.E321G, OR: 0.36, 95% CI: 0.24–0.56, P = 6.09 ? 10^?6), a variant in the WAS/WASL interacting protein family 3 (WIPF3), and with rs1051338 (p.T16P, OR: 2.50, 95% CI: 1.70–3.66, P = 2.79 ? 10^?6) and rs2246942 (intronic, OR: 2.32, 95% CI: 1.58–3.41, P = 1.61 ? 10^?5), variants in the lysosomal acid lipase A (LIPA). LIPA is essential for macrophage cholesterol metabolism. Immunohistological analyses of WIPF3 protein in AAA samples from three subjects revealed that WIPF3 was expressed in macrophages of atheromatous plaques. Conclusions This study suggests that WIPF3 and LIPA, both of which are expressed in the macrophages are involved in pathological AAA. These results should be regarded as hypothesis-generating; thus, replication study is warranted.     

Is cardiac resynchronisation therapy (CRT) safe, feasible and beneficial in the very elderly?

Objective To evaluate whether cardiac resynchronisation therapy (CRT) implantation was feasible and safe in octogenarians and the association with symptoms. Methods Consecutive patients undergoing CRT implantation were recruited from two UK centers. Patients grouped according to age: < 80 & ≥ 80 years. Baseline demographics, complications and outcomes were compared between those groups. Results A total of 439 patients were included in this study, of whom 26% were aged ≥ 80 years. Octogenarians more often received cardiac resynchronization therapy pacemaker in comparison to cardiac resynchronisation therapy-defibrillator. Upgrade from pacemaker was common in both groups (16% < 80 years vs. 22% ≥ 80 years, P = NS). Co-morbidities were similarly common in both groups (overall diabetes: 25%, atrial fibrillation: 23%, hypertension: 45%). More patient age ≥ 80 years had significant chronic kidney disease (CKD, estimated glomerular filtration rate < 45 mL/min per 1.73m2, 44% vs. 22%, P < 0.01). Overall complication rates (any) were similar in both groups (16% vs. 17%, P = NS). Both groups demonstrated symptomatic benefit. One-year mortality rates were almost four fold greater in octogenarians as compared with the younger cohort (13.9% vs. 3.7%, P < 0.01). Conclusions CRT appears to be safe in the very elderly despite extensive co-morbidity, and in particular frequent severe CKD. Symptomatic improvement appears to be meaningful. Strategies to increase the appropriate identification of elderly patients with CHF who are potential candidates for CRT are required.     

Prolonged treatment with oral and inhaled tulobuterol does not induce airways tachyphlaxis

β ₂-agonists have been shown to induceβ ₂-adrenoceptor down-regulation in vivo and in vitro. Whether this has any functional relevance remains unclear. Tulobuterol is a new syntheticβ ₂-agonist with potent and prolonged bronchodilator activity when given by oral and inhaled routes. The effect of tulobuterol aerosol (400μg q.i.d.) and tulobuterol tablets (2 mg b.i.d.) was studied in patients with chronic asthma and reversible airways obstruction in two separate trials. Tulobuterol produced significant bronchodilatation after the first and final dose over a 6-h period and the effects were comparable. The bronchodilator activity of tulobuterol given by inhalation and oral routes was not attenuated after 6 months of continuous treatment. There was significant improvement in symptom score and lung function measurements. Side effects, predominantly tremors, were observed at the start of treatment with tablet formulation but the incidence and severity of tremors decreased after 6 months. The changes in BP and pulse rate were not clinically significant. These results confirm the potent bronchodilator activity of tulobuterol and the lack of tachyphylaxis after prolonged treatment.