Short- and Medium-Term Outcomes Comparison of Native- and Valve-in-Valve TAVI Procedures.

Background: In high-risk patients with degenerated aortic bioprostheses, valve-in-valve (ViV) transcatheter aortic valve implantation (TAVI) has emerged as a less invasive alternative to surgical valve replacement. To compare outcomes of ViV and native valve (NV) TAVI procedures. Methods: 34 aortic ViV-TAVI performed between 2012 and 2022 using self-expanding valves, were included in this retrospective analysis. Propensity score matching (1:2 ratio, 19 criteria) was used to select a comparison NV-TAVI group from a database of 1206 TAVI procedures. Clinical and echocardiographic endpoints, short- and long-term all-cause mortality (ACM) and cardiovascular mortality (CVM) data were obtained. Subgroup analyses were completed according to the true internal diameter, dividing patients into a small ( ≤ 19 mm) valve group (SVG) and a large ( > 19 mm) valve group (LVG). Results: Clinical outcomes of ViV- and NV-TAVI were comparable, including device success [88.2% vs. 91.1%, p = 0.727], major adverse cardiovascular and cerebrovascular events [5.8% vs. 5.8%, p = 1.000], hemodialysis need [5.8% vs. 2.9%, p = 0.599], pacemaker need [2.9% vs. 11.7%, p = 0.265], major vascular complications [2.9% vs. 1.4%, p = 1.000], life-threatening or major bleeding [2.9% vs. 1.4%, p = 1.000] and in-hospital mortality [8.8% vs. 5.9%, p = 0.556]. There was a significant difference in the immediate post-intervention mean residual aortic valve gradient (MAVG) [14.6 ± 8.5 mm Hg vs. 6.4 ± 4.5 mm Hg, p < 0.0001], which persisted at 1 year [p = 0.0002]. There were no differences in 12- or 30-month ACM [11.8% vs. 8.8%, p = 0.588; 23.5% vs. 27.9%, p = 0.948], and CVM [11.8% vs. 7.3%, p = 0.441; 23.5% vs. 16.2%, p = 0.239]. Lastly, there was no difference in CVM at 1 year and 30 months [11.1% vs. 12.5%, p = 0.889; 22.2% vs. 25.0%, p = 0.742]. Conclusions: Analyzing a limited group (n = 34) of ViV-TAVI procedures out of 1206 TAVIs done at a single institution, ViV-TAVI appeared to be an acceptable approach in patients not deemed appropriate candidates for redo valve replacement surgery. Clinical outcomes of ViV-TAVI were comparable to TAVI for native valve stenosis.

Development of gel-forming lyophilized formulation with recombinant human thrombin.

The objective of this work was development and evaluation of gel-forming lyophilized formulation with recombinant human thrombin for topical administration. The influence of pH, ionic strength and buffer type on protein stability was evaluated as part of the pre-formulation screening studies. Results indicated an optimal pH from 6.0 to 7.0 and increased stability with increasing content of sodium chloride. The tested buffer types had no significant effect on thrombin stability. For further development, thermosensitive Pluronic® F-127 was employed as a bulking and gelling agent. Physical and mechanical characterization and viscosity measurement confirmed the gel-forming properties of the formulation at the application temperature of 32 °C. Several techniques (addition of well-soluble polyols, different freezing protocols and reconstitution under vacuum) were tested to decrease the reconstitution time. The obtained results revealed that a vacuum in the vial headspace is crucial for acceptable reconstitution. The freeze drying process has no negative impact on recombinant thrombin stability, and this was confirmed by reverse-phase-HPLC, activity assay and optical density measurements.

2-(Adamantan-1-yl)-1,3-bis-(4-methyl-phen-yl)propan-2-ol.

The conformation of the title compound, C27H34O, is stabilized by a weak intra-molecular C-H⋯π inter-action. The dihedral angle between the benzene rings is 54.79 (4)°. The adamantane cage consists of three fused cyclo-hexane rings in classical chair conformations, with C-C-C angles in the range 107.75 (10)-111.35 (9)°. Although the mol-ecule contains a hy-droxy group as a conceivable hydrogen-bond donor, this group is sterically hindered by bulky substituents and no hydrogen bonds are observed in the crystal structure.

4-(Adamantan-1-yl)-2-(4-fluoro-phen-yl)quinoline.

In the mol-ecule of the title compound, C25H24FN, the dihedral angle between the best planes of the quinoline fragment (rings A and B) and the benzene ring (C) is 9.51 (4)°. In the crystal, mol-ecules are linked into centrosymmetric dimers via pairs of weak C-H⋯F inter-actions. The mol-ecules are stacked into chains along the a axis by weak off-set π-π inter-actions between the A and C rings of translation-related mol-ecules with a centroid-centroid distance of 3.6440 (2) Å.

N-Benzyl-9-isopropyl-9H-purin-6-amine.

The asymmetric unit of the title compound, C15H17N5, consists of two mol-ecules in which the dihedral angles between the best planes of the purine ring system (r.m.s. deviations = 0.0060 and 0.0190 Å) and the benzene ring are 89.21 (3) and 82.14 (4)°. The mol-ecules within the asymmetric unit are linked into dimers by pairs of N-H⋯N hydrogen bonds. Weak C-H⋯π contacts and π-π inter-actions [centroid-centroid = 3.3071 (1) Å] further connect the mol-ecules into a three-dimensional network.

2-Chloro-N-ethyl-9-isopropyl-9H-purin-6-amine.

In the title compound, C(10)H(14)ClN(5), the purine ring system is essentially planar, with an r.m.s. deviation from the least-squares plane defined by the nine constituent atoms of 0.0063 (11) Å. In the crystal, mol-ecules are linked by weak N-H⋯N and C-H⋯π inter-actions.

Diphenyl (methyl-amido)-phosphate.

The N-H bond in the title compound, C(13)H(14)NO(3)P, is syn-oriented relative to the P=O bond. The N atom deviates somewhat from planarity, the sum of the bond angles being 353.3°. The P atom has a distorted tetra-hedral coordination; its bond angles are in the range 93.96 (5)-116.83 (6)°. In the crystal, mol-ecules form centrosymmetric dimers through P=O⋯H-N hydrogen bonds.

Characterization of a novel long-chain n-alkane-degrading strain, Dietzia sp. E1.

The newly isolated strain E1, identified as a Dietzia sp., proved to have an excellent ability to degrade n-C12 to n-C38 alkane components of crude oil. The preferred substrate was the very long-chain alkane n-eicosane at an optimal temperature of 37 degrees C and an optimal pH of 8 under aerobic conditions. The growth and substrate uptake kinetics were monitored during the n-alkane fermentation process, and Dietzia sp. E1 cells were found to possess three distinct levels of cell-surface hydrophobicity. Gas chromatographic/mass spectrometric analysis revealed that intracellular substrate mineralization occurred through the conversion of n-alkane to the corresponding n-alkanal. The monoterminal oxidation pathway was presumably initiated by AlkB and CYP153 terminal alkane hydroxylases, both of their partial coding sequences were successfully detected in the genome of strain E1, a novel member of the Dietzia genus.

Isolation and characterization of a novel n-alkane-degrading strain, Acinetobacter haemolyticus AR-46.

Strain AR-46, isolated and identified as Acinetobacter haemolyticus, evolutionally distant from the known hydrocarbon-degrading Acinetobacter spp., proved to have excellent long-chain n-alkane-degrading ability. This is the first detailed report on an n-alkane-utilizing strain belonging to this species. The preferred substrate is n-hexadecane, with an optimal temperature of 37 degrees C under aerobic conditions. Five complete and two partial open reading frames were sequenced and correlated with the early steps of monoterminal oxidation-initiated n-alkane mineralization. The encoded protein sequences and the arrangement of these genes displayed high similarity to those found in Acinetobacter sp. M-1, but AR-46 seemed to have only one alkane hydroxylase gene, with a completely different induction profile. Unique behaviour was also observed in n-alkane bioavailability. Substrate uptake occurred through the hydrophobic surface of n-alkane droplet-adhered cells possessing long, thick fimbriae, which were presumed to play a major role in n-alkane solubilization. A majority of the cells was in detached form, with thick, but short fimbriae. These free cells were permanently hydrophilic, unlike the cells of other Acinetobacter strains.