Correlative study on impaired prostaglandin E2 regulation in EAT and maladaptive cardiac remodeling via EPAC2 and ST2 signaling in overweight CVD subjects

There is recent evidence that the dysfunctional responses of a peculiar visceral fat deposit known as epicardial adipose tissue (EAT) can directly promote cardiac enlargement in the case of obesity. Here, we observed a newer molecular pattern associated with LV dysfunction mediated by prostaglandin E2 (PGE(2)) deregulation in EAT in a cardiovascular disease (CVD) population. A series of 33 overweight CVD males were enrolled and their EAT thickness, LV mass, and volumes were measured by echocardiography. Blood, plasma, EAT, and SAT biopsies were collected for molecular and proteomic assays. Our data show that PGE(2) biosynthetic enzyme (PTGES-2) correlates with echocardiographic parameters of LV enlargement: LV diameters, LV end diastolic volume, and LV masses. Moreover, PTGES-2 is directly associated with EPAC2 gene (r = 0.70, p < 0.0001), known as a molecular inducer of ST2/IL-33 mediators involved in maladaptive heart remodelling. Furthermore, PGE(2) receptor 3 (PTEGER3) results are downregulated and its expression is inversely associated with ST2/IL-33 expression. Contrarily, PGE(2) receptor 4 (PTGER4) is upregulated in EAT and directly correlates with ST2 molecular expression. Our data suggest that excessive body fatness can shift the EAT transcriptome to a pro-tissue remodelling profile, may be driven by PGE(2) deregulation, with consequent promotion of EPAC2 and ST2 signalling

Genotype-Phenotype Correlation in a Family with Brugada Syndrome Harboring the Novel p.Gln371* Nonsense Variant in the SCN5A Gene

Brugada syndrome (BrS) is marked by coved ST-segment elevation and increased risk of sudden cardiac death. The genetics of this syndrome are elusive in over half of the cases. Variants in the SCN5A gene are the single most common known genetic unifier, accounting for about a third of cases. Research models, such as animal models and cell lines, are limited. In the present study, we report the novel NM_198056.2:c.1111C&gt;T (p.Gln371*) heterozygous variant in the SCN5A gene, as well as its segregation with BrS in a large family. The results herein suggest a pathogenic effect of this variant. Functional studies are certainly warranted to characterize the molecular effects of this variant

New electromechanical substrate abnormalities in high-risk patients with Brugada syndrome

Background: The relationship between the typical electrocardiographic pattern and electromechanical abnormalities has never been systematically explored in Brugada syndrome (BrS). Objectives: The aims of this study were to characterize the electromechanical substrate in patients with BrS and to evaluate the relationship between electrical and mechanical abnormalities. Methods: We enrolled 50 consecutive high-risk patients with BrS (mean age 42 ± 7.2 years), with implantable cardioverter-defibrillator implantation for primary or secondary prevention of ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF]), undergoing substrate mapping and ablation. Patients underwent 3-dimensional (3D) echocardiography with 3D wall motion/deformation quantification and electroanatomic mapping before and after ajmaline administration (1 mg/kg in 5 minutes); 3D mechanical changes were compared with 50 age- and sex-matched controls. The effect of substrate ablation on electromechanical abnormalities was also assessed. Results: In all patients, ajmaline administration induced Brugada type 1 pattern, with a significant increase in the electrical substrate (P &lt;.001), particularly in patients with previous spontaneous VT/VF (P =.007). Induction of Brugada pattern was associated with lowering of right ventricular (RV) ejection fraction (P &lt;.001) and worsening of 3D RV mechanical function (P &lt;.001), particularly in the anterior free wall of the RV outflow tract, without changes in controls. RV electrical and mechanical abnormalities were highly correlated (r = 0.728, P &lt;.001). By multivariate analysis, only the area of RV dysfunction was an independent predictor of spontaneous VT/VF (odds ratio 1.480; 95% confidence interval 1.159–1.889; P =.002). Substrate ablation abolished both BrS-electrocardiographic pattern and mechanical abnormalities, despite ajmaline rechallenge. Conclusion: BrS is an electromechanical disease affecting the RV. The typical BrS pattern reflects an extensive RV arrhythmic substrate, driving consistent RV mechanical abnormalities. Substrate ablation abolished both Brugada pattern and mechanical abnormalities

Accidental dural puncture rate using real-time pressure sensing technology: A prospective multicenter observational study

Milestone Scientific, Inc

Color-coding triage and allergic reactions in an Italian ED.

Emergency Department (ED) crowding is an international public health problem. Moreover, it is associated with prolonged stay and increased risk of adverse drug events (ADEs). Adverse drug reactions (ADRs) account for 3-6% of all hospital admissions, and occur in 10-15% of hospitalized patiens. An ADE should be differentiated from ADR, the latter including harm related to medication errors and drug/food medications. Only few studies have focused prevalence and incidence of drug allergy in hospital-based populations. We were interested to drug allergy, defined as an immunologically-mediated drug hypersensitivity reaction, characterized by either IgE or non-IgE mediated mechanism. In particular, we aimed to focus on drug allergies referring to the ED and requiring hospitalization, to evaluate type and prevalence, and relationships between initial triage assessment and hospital lenght of stay (LOS). This study was conducted, between January and December 2009, at the Emergency Department of St. Anna Hospital of Ferrara, a 863-bed tertiary care teaching hospital, with a yearly patient flow in the ED of approximately 76 000. Allergic reactions were defined as erythema, exanthema, urticaria and angioedema. Age, sex, triage assessment colour code, history, body temperature, drugs involved, LOS, and therapy were evaluated. Descriptive analysis and chi-square test were performed, and triage assessment represented the grouping variable. Multivariate analysis was not performed due to the limited sample size. Out of 75 966 patients arrived to the ED in the year 2009, 2842 (3.7%) were admitted to the ED ward. Of these, 58 (2%) presented a drug-related allergic reaction. Mean age was 58±5 years (range 18-88), 62% were female. Comorbilities included metabolic, heart, bone, infectious, gastric, vascular, neurologic, renal, and bowel diseases; 14% had a history of cancer. Allergic reactions were due to several kind of medications: anti-infective, anti-inflammatory, endocrine, cardiovascular, antineoplastic, and other. Triage assessment showed colour code green in 26% of cases, yellow in 55% and red in 19%. LOS was 6-12 hours in 19% of cases, between 12 hours and 3 days in 41%, and >3 days in 40%. Therapy at first evaluation included antihistaminics, steroids, non-steroidal-anti-inflammatory drugs, plasma expanders, and oxygen. Triage assessment colour code red was associated with history of heart disease, lung disease and vascular disease, whereas only allergic reactions defined as urticaria were related to the green code. The red code was significantly associated with longer LOS >3 days. Allergic reactions are very frequent among ED attenders: national data in the USA estimated incidence of ADRs as 2.4 visits x 1000 population. Of these, 33.5% were drug allergies, and 11.3% required hospitalization. Although triage represents a highly useful tool to prioritize patients’s care in EDs, very limited data relating triage assessment colour code for allergic reactions are available. The importance of a correct triage is important, since it has been shown that ED patients presenting with ADEs incurred great health services utilization and costs of hospital care. To the best of our knowledge, this is the first study evaluating the relationship between triage colour code, clinical features, and LOS in subjects with allergic reactions presenting to the ED. Patients’ age was younger compared with previous reports, and LOS exceeded 3 days in more than 40% of cases, with a good correspondence with the triage colour code assigned upon ED arrival. EDs could represent optimal settings for research, and support important translational knowledge