Commissural Alignment After Balloon-Expandable Transcatheter Aortic Valve Replacement Is Associated With Improved Hemodynamic Outcomes.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is generally performed without control over the alignment of the bioprosthesis to the native aortic valve (AV) commissures. Data on the impact of commissural misalignment (CMA) on the clinical and hemodynamic outcome after TAVR are scarce. OBJECTIVES: The aim of this study was to investigate the impact of commissural misalignment (CMA) on the clinical and hemodynamic outcome in patients with severe tricuspid aortic stenosis undergoing TAVR using the balloon-expandable (BE) SAPIEN 3 valve (Edwards LifeSciences). METHODS: Clinical data of consecutive patients who underwent BE TAVR at Cedars-Sinai Medical Center (Los Angeles, California, USA) enrolled in the RESOLVE (Assessment of TRanscathetER and Surgical Aortic BiOprosthetic Valve Thrombosis and Its TrEatment With Anticoagulation) registry were retrospectively analyzed to evaluate CMA, which was defined as a neocommissure position >30° compared with native commissures on computed tomography. RESULTS: A total of 324 patients (36.6% female, median Society of Thoracic Surgeons score of 3.9%) were included in the analysis. CMA was present in 171 individuals (52.8%). At 30 days, rates of aortic regurgitation greater than mild (5.6%) and a residual AV gradient ≥20 mm Hg (7.4%) were not different between CMA and non-CMA patients. Commissural orientation was independently associated with a relative AV mean gradient increase >50% from discharge to 30 days (per increase of 10° misalignment; OR: 1.3; 95% CI: 1.0-1.4; P = 0.01). The long-term composite outcome of death or stroke was not different between groups (log-rank P = 0.29). CONCLUSIONS: In patients with severe tricuspid aortic stenosis who undergo SAPIEN 3 TAVR, the neocommissures align randomly. Our data demonstrate that commissural alignment may impact device performance and clinical outcomes in patients undergoing BE TAVR. (Assessment of TRanscathetEr and Surgical Aortic BiOprosthetic VaLVve Dysfunction with Multimodality Imaging and Its TrEatment with Anticoagulation [RESOLVE]; NCT02318342).

Multiple Sclerosis and Serotonin: Potential Therapeutic Applications.

Multiple sclerosis (MS) is a neurodegenerative disease with a complex autoimmune component, and it has a high prevalence among middle-aged females. The manifestations of the disease range from episodic somatosensory dysfunction to progressive and permanent central nervous system (CNS) damage. Due to a high prevalence of psychiatric comorbidities and proven abnormalities in serotonin (5-HT) levels among MS patients, they are usually on drugs that modify the serotonergic system. Through a comprehensive literature review of studies published in the last 10 years related to 5-HT in MS and its therapeutic applications, we aimed to elucidate the mechanism behind the neurotransmitter (NT) levels' abnormalities. Most importantly, we endeavored to gather the most up-to-date information about the full therapeutic potential of agents acting on this system. We discovered that multiple processes cause low levels of 5-HT in MS patients. The varying levels of the availability of the 5-HT transporter (SERT) in the CNS decreasing overall tryptophan (TRP) levels, and diversion of the amino acid away from its synthetic pathway constitute some of those. Studies in animals have shown that 5-HT levels' elevations could cause immune-modulating effects and could probably slow down the disease progression rate. Human studies have shown a more diverse and complex response. Promising results have been obtained in the last 10 years regarding 5-HT's immune-modulatory role in MS patients and its therapeutic applications. Human studies with a larger population and feasible designs are still needed to fully ascertain the effects of serotonin on the immune system and disease progression in patients with MS.

Statins Versus Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors- Are We Doing Better? A Systematic Review on Treatment Disparity.

Coronary artery disease (CAD) is a significant contributor to mortality in America. A common risk factor of CAD is hyperlipidemia. Treatment guidelines of hyperlipidemia are well established. Statins are the cornerstone of treating hyperlipidemia. New medications such as proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9 inhibitors) have also illustrated significant results in treating hyperlipidemia. While multiple studies exemplify the disparities in statin and PCSK9 inhibitors utilization to reduce CAD mortality and risk factors, there are no systematic reviews to validate these disparities. We conducted a search on PubMed, including Medline and PubMed Central, and Google Scholar. For this analysis, we selected articles published between 2000 and 2020 and those that fit the inclusion and exclusion criteria. Based on the type of study, we performed appropriate quality assessments and deleted studies with a score of less than seven or with a high risk of biases. The search strategy resulted in 322 studies. After inclusion and exclusion criteria were applied, we included 20 articles in the analysis of this review. This systematic review demonstrates that non-white races and women were less likely to receive the correct, clinically indicated, therapy for hyperlipidemia. A multi-faceted approach is required to solve this inequality in healthcare.

Valve-in-Valve for Degenerated Transcatheter Aortic Valve Replacement Versus Valve-in-Valve for Degenerated Surgical Aortic Bioprostheses: A 3-Center Comparison of Hemodynamic and 1-Year Outcome.

Background As transcatheter aortic valve replacement (TAVR) is expected to progress into younger patient populations, valve-in-TAVR (ViTAVR) may become a frequent consideration. Data on ViTAVR, however, are limited. This study investigated the outcome of ViTAVR in comparison to valve in surgical aortic valve replacement (ViSAVR), because ViSAVR is an established procedure for higher-risk patients requiring repeated aortic valve intervention. Methods and Results Clinical and procedural data of patients who underwent ViTAVR at 3 sites in the United States and Germany were retrospectively compared with data of patients who underwent ViSAVR at Cedars-Sinai Medical Center, according to Valve Academic Research Consortium-2 criteria. A total of 99 consecutive patients, 52.5% women, with a median Society of Thoracic Surgeons score of 7.2 were identified. Seventy-four patients (74.7%) underwent ViSAVR, and 25 patients (25.3%) underwent ViTAVR. Balloon-expandable devices were used in 72.7%. ViSAVR patients presented with smaller index devices (21.0 versus 26.0 mm median true internal diameter; P<0.001). Significantly better postprocedural hemodynamics (median prosthesis mean gradient, 12.5 [interquartile range, 8.8-16.2] versus 16.0 [interquartile range, 13.0-20.5] mm Hg; P=0.045) were observed for ViTAVR compared with the ViSAVR. Device success, however, was not different (79.2% and 66.2% for ViTAVR and ViSAVR, respectively; P=0.35), as were rates of permanent pacemaker implantation (16.7% versus 5.4%; P=0.1). One-year-mortality was 9.4% and 13.4% for ViTAVR and ViSAVR, respectively (log-rank P=0.38). Conclusions Compared with ViSAVR, ViTAVR provides acceptable outcomes, with slightly better hemodynamics, similar device success rates, and similar 1-year mortality.

Striped nanowires and nanorods from mixed SAMS.

We investigate the use of mixed self-assembled monolayers (SAMs) for creating nanoscale striped patterns on nanowires and nanorods. Our simulations predict that SAMs comprised of an equal composition of length-mismatched, thermodynamically incompatible surfactants adsorbed on nanowire surfaces self-organize into equilibrium stripes of alternating composition always perpendicular, rather than parallel, to the nanowire axis. We support the simulation results with preliminary experimental investigations of gold nanorods coated with binary mixtures of ligand molecules, which show stripes roughly perpendicular to the rod axis in all cases.

Coarse-grained models of tethers for fast self-assembly simulations.

Long molecular ligands or "tethers" play an important role in the self-assembly of many nanoscale systems. These tethers, whose only interaction may be a hard-core repulsion, contribute significantly to the free energy of the system because of their large conformational entropy. Here, we investigate how simple approximate models can be developed and used to quickly determine the configurations into which tethers will self assemble in nanoscale systems. We derive criteria that determine when these models are expected to be accurate. Finally, we propose a generalized two-body approximation that can be used as a toy model for the self-assembly of tethers in systems of arbitrary geometry and apply this to the self-assembly of self-assembled monolayers on a planar surface. We compare our results to those in the literature obtained via atomistic and dissipative particle dynamics simulations.

Exploiting substrate stress to modify nanoscale SAM patterns.

We describe a simple method based on postadsorption substrate stress induction to modify and control nanoscale phase-separated patterns formed in self-assembled monolayers. We show using mesoscale computer simulations and experiments that this method helps quickly progress a kinetically arrested patchy pattern into the equilibrium striped pattern, which is otherwise difficult to access. This work also establishes the role of curvature in the formation of aligned stripes several molecules wide on spherical nanoparticles and nanocylinders.

The effect of nanometre-scale structure on interfacial energy.

Natural surfaces are often structured with nanometre-scale domains, yet a framework providing a quantitative understanding of how nanostructure affects interfacial energy, gamma(SL), is lacking. Conventional continuum thermodynamics treats gamma(SL) solely as a function of average composition, ignoring structure. Here we show that, when a surface has domains commensurate in size with solvent molecules, gamma(SL) is determined not only by its average composition but also by a structural component that causes gamma(SL) to deviate from the continuum prediction by a substantial amount, as much as 20% in our system. By contrasting surfaces coated with either molecular- (<2 nm) or larger-scale domains (>5 nm), we find that whereas the latter surfaces have the expected linear dependence of gamma(SL) on surface composition, the former show a markedly different non-monotonic trend. Molecular dynamics simulations show how the organization of the solvent molecules at the interface is controlled by the nanostructured surface, which in turn appreciably modifies gamma(SL).

Size limitations for the formation of ordered striped nanoparticles.

A combination of immiscible molecules in the ligand shell of a gold nanoparticle (NP) has been shown to phase separate into a rippled structure; this phase separation can be used to direct the assembly of the NPs into chains. Here we demonstrate that only NPs within a certain size range can form chains, and we conclude that the rippled morphology of the ligand shell also exists only within that given size range. We corroborate this result with simulations of the ligand arrangement on NPs of various sizes.

Entropy-mediated patterning of surfactant-coated nanoparticles and surfaces.

We perform atomistic and mesoscale simulations to explain the origin of experimentally observed stripelike patterns formed by immiscible ligands coadsorbed on the surfaces of gold and silver nanoparticles. We show that when the conformational entropy gained via this morphology is sufficient, microphase-separated stripelike patterns form. When the entropic gain is not sufficient, we instead predict bulk phase-separated Janus particles. We also show corroborating experimental results that confirm our simulational predictions that stripes form on flat surfaces as well as on curved nanoparticle surfaces.