Assessment of Platelet REACtivity After Transcatheter Aortic Valve Replacement : The REAC-TAVI Trial

The REAC-TAVI (Assessment of platelet REACtivity after Transcatheter Aortic Valve Implantation) trial enrolled patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) pre-treated with aspirin + clopidogrel, aimed to compare the efficacy of clopidogrel and ticagrelor in suppressing high platelet reactivity (HPR) after TAVI. Current recommendations support short-term use of aspirin + clopidogrel for patients with severe AS undergoing TAVR despite the lack of compelling evidence. This was a prospective, randomized, multicenter investigation. Platelet reactivity was measured at 6 different time points with the VerifyNow assay (Accriva Diagnostics, San Diego, California). HPR was defined as (P2Y reaction units (PRU) ≥208. Patients with HPR before TAVR were randomized to either aspirin + ticagrelor or aspirin + clopidogrel for 3 months. Patients without HPR continued with aspirin + clopidogrel (registry cohort). The primary endpoint was non-HPR status (PRU <208) in ≥70% of patients treated with ticagrelor at 90 days post-TAVR. A total of 68 patients were included. Of these, 48 (71%) had HPR (PRU 273 ± 09) and were randomized to aspirin + ticagrelor (n = 24, PRU 277 ± 08) or continued with aspirin + clopidogrel (n = 24, PRU 269 ± 49). The remaining 20 patients (29%) without HPR (PRU 133 ± 12) were included in the registry. Overall, platelet reactivity across all the study time points after TAVR was lower in patients randomized to ticagrelor compared with those treated with clopidogrel, including those enrolled in the registry (p < 0.001). The primary endpoint was achieved in 100% of patients with ticagrelor compared with 21% with clopidogrel (p < 0.001). Interestingly, 33% of clopidogrel responder patients at baseline developed HPR status during the first month after TAVR. HPR to clopidogrel is present in a considerable number of patients with AS undergoing TAVR. Ticagrelor achieves a better and faster effect, providing sustained suppression of HPR to these patients. (Platelet Reactivity After TAVI: A Multicenter Pilot Study [REAC-TAVI]; NCT02224066

Carotid sinus syndrome is common in very elderly patients undergoing tilt table testing and carotid sinus massage because of syncope or unexplained falls

The role of matter circulation between the disk and halo in establishing the volume filling factors of the different ISM phases in the Galactic disk (|z| ≤ 250 pc) is investigated, using a modified version of the three-dimensional supernova-driven ISM model of Avillez (2000). We carried out adaptive mesh refinement simulations of the ISM with five supernova rates (in units of the Galactic value), σ/σGal = 1, 2, 4, 8 and 16 (corresponding to starburst conditions) using three finer level resolutions of 2.5, 1.25 and 0.625 pc, allowing us to understand how resolution would affect the volumes of gas phases in pressure equilibrium. We find that the volume filling factors of the different ISM phases depend sensitively on the existence of a duty cycle between the disk and halo acting as a pressure release valve for the hot (T > 10^5.5 K) phase in the disk. The amount of cold gas (defined as the gas with T < 10^3 K) picked up in the simulations varies from a value of 19% for σ/σGal = 1 to ∼5% for σ/σGal = 4 and ≤1% for higher SN rates. Background heating prevents the cold gas from immediate collapse and thus ensures the stability of the cold gas phase. The mean occupation fraction of the hot phase varies from about 17% for the Galactic SN rate to ∼28%, for σ/σ Gal = 4, and to 44% for σ/σGal = 16. Overall the filling factor of the hot gas does not increase much as we move towards higher SN rates, following a power law of fv, hot ∝ (σ/σGal)^0.363 . Such a modest dependence on the SN rate is a consequence of the evacuation of the hot phase into the halo through the duty cycle. This leads to volume filling factors of the hot phase considerably smaller than those predicted in the three-phase model of McKee & Ostriker (1977) even in the absence of magnetic fields

Comprehensive geriatric assessment and 2-year mortality in elderly patients hospitalized for heart failure

BACKGROUND: In older adults hospitalized for heart failure, a poor score on a comprehensive geriatric assessment (CGA) is associated with worse prognosis during hospitalization and at 1 month after discharge. However, the association between the CGA score and long-term mortality is uncertain. METHODS AND RESULTS: This is a prospective study of 487 patients aged ≥75 years admitted for decompensated heart failure. At discharge, a CGA score (range, 0-10) was calculated based on limitation in activities of daily living, mobility limitation, comorbidity, cognitive decline, and previous medication use. The analysis of the association between the CGA score and 2-year subsequent mortality was performed with Cox regression and adjusted for the main confounders. A 1-point increase in the CGA score was associated with a 19% higher mortality (hazard ratio, 1.19; 95% confidence interval, 1.11-1.27). Results were similar regardless of age, sex, left ventricular ejection fraction, and the coexistence of atrial fibrillation, ischemic heart disease, or hypertensive cardiopathy. All components of the CGA score showed a consistent association with higher death risk: the hazard ratio (95% confidence interval) of mortality was 1.78 (1.25-2.54) with ≥3 versus 0 limitations in activities of daily living, 1.36 (1.0-1.86) with moderate or severe versus no or mild limitation in mobility, 1.98 (1.29-3.03) with a ≥5 versus ≤1 score on the Charlson index, 2.48 (1.84-3.34) with previous cognitive decline, and 1.77 (0.99-3.18) in those using ≥8 versus ≤3 medications. CONCLUSIONS: The score on a simple CGA is associated with long-term mortality in older patients hospitalized for heart failure

Synthesis and characterization of new polyamides derived from alanine and valine derivatives

<p>Abstract</p> <p>Background</p> <p>Many efforts have been recently devoted to design, investigate and synthesize biocompatible, biodegradable polymers for applications in medicine for either the fabrication of biodegradable devices or as drug delivery systems. Many of them consist of condensation of polymers having incorporated peptide linkages susceptible to enzymatic cleavage. Polyamides (PAs) containing α-amino acid residues such as L-leucine, L-alanine and L-phenylalanine have been reported as biodegradable materials. Furthermore, polyamides (PAs) derived from C₁₀ and C₁₄ dicarboxylic acids and amide-diamines derived from 1,6-hexanediamine or 1,12-dodecanediamine and L-phenylalanine, L-valyl-L-phenylalanine or L-phenylalanyl-L-valine residues have been reported as biocompatible polymers. We have previously described the synthesis and thermal properties of a new type of polyamides-containing amino acids based on eight new symmetric <it>meta</it>-oriented protected diamines derived from coupling of amino acids namely; Fomc-glycine, Fmoc-alanine, Fomc-valine and Fomc-leucine with <it>m</it>-phenylene diamine or 2,6-diaminopyridine. Results revealed that incorporation of pyridine onto the polymeric backbone of all series decreases the thermal stability.</p> <p>Here we describe another family of polyamides based on benzene dicarboxylic acid, pyridine dicarboxylic acid, and α-amino acid linked to benzidine and 4,4^′-oxydianiline to study the effect of the dicarboxylic acid as well as the amino acids on the nature and thermal stability of the polymers.</p> <p>Results</p> <p>We report here the preparation of a new type of polyamides based on benzene dicarboxylic acid, pyridine dicarboxylic acid, and α-amino acid linked to benzidine and 4,4^′-oxydianiline to study the effect of the dicarboxylic acid as well as the amino acids on the nature and thermal stability of polymers. The thermal properties of the polymers were evaluated by different techniques. Results revealed that structure-thermal property correlation based on changing the dicarboxylic acid monomer or the diamine monomer demonstrated an interesting connection between a single change (changing the dicarboxylic acids in each series while the diamine is fixed) and thermal properties. The newly prepared polymers may possess biodegradability and thus may find some applications as novel biomaterials<b>.</b></p> <p>Conclusions</p> <p>The thermal properties of the new type of polyamides based on benzene dicarboxylic acid, pyridine dicarboxylic acid, and α-amino acid (alanine and valine) linked to benzidine and 4,4′-oxydianiline were evaluated by thermal gravimetric (TG), differential thermal gravimetric (DTG) and differential thermal analysis (DTA) techniques. Results revealed that the structure-thermal property correlation based on changing the dicarboxylic acid monomer or the diamine monomer demonstrated an interesting connection between a single change (changing the dicarboxylic acids in each series while the diamine is fixed) and thermal properties. In addition, pyridine-containing polymers exhibited semicrystalline characteristic with melting temperature, <it>T</it>_<it>m</it>. where none of the valine-containing polymers showed a melting and crystallization peak indicating that the polymers were amorphous. This is expected since L-valine side chain can inhibit close packing and eliminate crystallization. The newly prepared polymers may possess biodegradability and thus may find some applications as novel biomaterials.</p

Structure-property relationships for a series of poly(ester amide)s containing amino acids

Poly(ester amide)s (PEAs) composed of variable diols, dicarboxylic acids, and α-amino acids were synthesized and characterized to elucidate structure-property relationships. The PEAs were synthesized using both solution and interfacial approaches to obtain varying molecular weights (MWs) and polydispersities. Studies using differential scanning calorimetry and powder X-ray diffraction revealed a range of amorphous and semicrystalline behavior that was dependent on structure. The viscosities of the PEAs as a function of temperature were studied by rheology, and phase transitions were confirmed for some polymers. Mechanical properties were also investigated, and it was found that the PEAs could be tuned to exhibit elastomeric or brittle behavior by varying both the length of the diol and the amino acid moiety. This information provides new insights into the effects of PEA structure, MW, and MW distribution on PEA properties and will aid in the design and selection of PEAs with optimal properties for targeted applications. © 2013 American Chemical Society