Neuroautonomic evaluation of patients with unexplained syncope: Incidence of complex neurally mediated diagnoses in the elderly

BACKGROUND: The incidence of syncope increases in individuals over the age of 70 years, but data about this condition in the elderly are limited. Little is known about tilt testing (TT), carotid sinus massage (CSM), or supine and upright blood pressure measurement related to age or about patients with complex diagnoses, for example, those with a double diagnosis, ie, positivity in two of these three tests. METHODS: A total of 873 consecutive patients of mean age 66.5±18 years underwent TT, CSM, and blood pressure measurement in the supine and upright positions according to the European Society of Cardiology guidelines on syncope.1 Neuroautonomic evaluation was performed if the first-line evaluation (clinical history, physical examination, electrocardiogram) was suggestive of neurally mediated syncope, or if the first-line evaluation was suggestive of cardiac syncope but this diagnosis was excluded after specific diagnostic tests according to European Society of Cardiology guidelines on syncope, or if certain or suspected diagnostic criteria were not present after the first-line evaluation. RESULTS: A diagnosis was reached in 64.3% of cases. TT was diagnostic in 50.4% of cases, CSM was diagnostic in 11.8% of cases, and orthostatic hypotension was present in 19.9% of cases. Predictors of a positive tilt test were prodromal symptoms and typical situational syncope. Increased age and a pathologic electrocardiogram were predictors of carotid sinus syndrome. Varicose veins and alpha-receptor blockers, nitrates, and benzodiazepines were associated with orthostatic hypotension. Twenty-three percent of the patients had a complex diagnosis. The most frequent association was between vasovagal syncope and orthostatic hypotension (15.8%); 42.9% of patients aged 80 years or older had a complex diagnosis, for which age was the strongest predictor. CONCLUSION: Neuroautonomic evaluation is useful in older patients with unexplained syncope after the initial evaluation. A complex neurally mediated diagnosis is frequent in older people. Our results suggest that complete neuroautonomic evaluation should be done particularly in older patients

Pyridazinones and structurally related derivatives with anti-inflammatory activity

Persistent inflammation contributes to a number of diseases; therefore, control of the inflammatory response is an important therapeutic goal. In an effort to identify novel anti-inflammatory compounds, we screened a library of pyridazinones and structurally related derivatives that were used previously to identify N-formyl peptide receptor (FPR) agonists. Screening of the compounds for their ability to inhibit lipopolysaccharide (LPS)-induced nuclear factor κB (NF-κB) transcriptional activity in human THP1-Blue monocytic cells identified 48 compounds with anti-inflammatory activity. Interestingly, 34 compounds were FPR agonists, whereas 14 inhibitors of LPS-induced NF-κB activity were not FPR agonists, indicating that they inhibited different signaling pathways. Further analysis of the most potent inhibitors showed that they also inhibited LPS-induced production of interleukin 6 (IL-6) by human MonoMac-6 monocytic cells, again verifying their anti-inflammatory properties. Structure–activity relationship (SAR) classification models based on atom pair descriptors and physicochemical ADME parameters were developed to achieve better insight into the relationships between chemical structures of the compounds and their biological activities, and we found that there was little correlation between FPR agonist activity and inhibition of LPS-induced NF-κB activity. Indeed, Cmpd43, a well-known pyrazolone-based FPR agonist, as well as FPR1 and FPR2 peptide agonists had no effect on the LPS-induced NF-κB activity in THP1-Blue cells. Thus, some FPR agonists reported to have anti-inflammatory activity may actually mediate their effects through FPR-independent pathways, as it is suggested by our results with this series of compounds. This could explain how treatment with some agonists known to be inflammatory (i.e., FPR1 agonists) could result in anti-inflammatory effects. Further research is clearly needed to define the molecular targets of pyridazinones and structurally related compounds with anti-inflammatory activity and to define their relationships (if any) to FPR signaling events

Childhood-onset Chorea caused by a recurrent de novo DRD2 variant

[No abstract available

Management and prognosis of atrial fibrillation in diabetic patients: An EORP-AF General Pilot Registry report

Aims Diabetes mellitus (DM) is one of the most important cardiovascular risk factors. The aim of this study was to evaluate clinical correlates of DM, including management and outcomes, in the EURObservational Research Programme (EORP)-Atrial Fibrillation (AF) General Pilot (EORP-AF) Registry of the European Society of Cardiology. Methods and results We studied consecutive patients (N= 3101) enrolled in 70 centres of nine European countries between February 2012 and March 2013, and compared diabetics with non-diabetics during a 1-year follow-up. In the overall cohort, the prevalence of DM was 20.6%. Diabetics were older (71 \ub1 9 vs. 68 \ub1 12 years, P < 0.0001) and had more comorbidities, higher CHA2DS2-VASc score (4.6 \ub1 1.6 vs. 2.9 \ub1 1.7, P < 0.0001) and higher prevalence of permanent AF (21.5 vs. 16.0%, P = 0.0022). Quality of life amongst DM patients was significantly worse [atrial fibrillation quality of life questionnaire (AF-QoL) score 45.2 \ub1 19.2 vs. 49.3 \ub1 20.1, P < 0.0001]. Amongst diabetics, the use of electrical cardioversion (16.2 vs. 24.6%, P < 0.0001) and catheter ablation (3.3 vs. 8.6%, P < 0.0001) was lower, whilst oral anticoagulants were more often prescribed (84.3 vs. 78.9%, P = 0.0027). After one year, diabetic patients had significantly higher all-cause (11.9 vs. 4.9%, P < 0.0001), cardiovascular (6.2 vs. 1.9%, P < 0.0001), and non-cardiovascular mortality (2.3 vs. 1.1%, P = 0.0356). Conclusion In AF patients, DM is associated with a higher prevalence of comorbidities and a worse quality of life. After one year, all-cause, cardiovascular, and non-cardiovascular mortality were significantly higher in diabetic subjects