Mortality Prediction by Quantitative PET Perfusion Expressed as Coronary Flow Capacity With and Without Revascularization

ObjectivesThis study sought to determine the relationship between the severity of reduced quantitative perfusion parameters and mortality with and without revascularization.BackgroundThe physiological mechanisms for differential mortality risk of coronary flow reserve (CFR) and coronary flow capacity (CFC) before and after revascularization are unknown.MethodsGlobal and regional rest-stress (ml/min/g), CFR, their regional per-pixel combination as CFC, and relative stress in ml/min/g were measured as percent of LV in all serial routine 5,274 diagnostic PET scans with systematic follow-up over 10 years (mean 4.2 ± 2.5 years) for all-cause mortality with and without revascularization.ResultsSeverely reduced CFR of 1.0 to 1.5 and stress perfusion ≤1.0 cc/min/g incurred increasing size-dependent risks that were additive because regional severely reduced CFC (CFCsevere) was associated with the highest major adverse cardiac event rate of 80% (p < 0.0001 vs. either alone) and a mortality risk of 14% (vs. 2.3% for no CFCsevere; p = 0.001). Small regions of CFCsevere ≤0.5% predicted high risk (p < 0.0001 vs. no CFCsevere) related to a wave front of border zones at risk around the small most severe center. By receiver-operating characteristic analysis, relative stress topogram maps of stress (ml/min/g) as a fraction of LV defined these border zones at risk or for mildly reduced CFC (area under the curve [AUC]: 0.69) with a reduced relative tomographic subendocardial-to-subepicardial ratio. CFCsevere incurred the highest mortality risk that was reduced by revascularization (p = 0.005 vs. no revascularization) for artery-specific stenosis not defined by global CFR or stress perfusion alone.ConclusionsCFC is associated with the size-dependent highest mortality risk resulting from the additive risk of CFR and stress (ml/min/g) that is significantly reduced after revascularization, a finding not seen for global CFR. Small regions of CFCsevere ≤0.5% of LV also carry a high risk because of the surrounding border zones at risk defined by relative stress perfusion and a reduced relative subendocardial-to-subepicardial ratio.     

Physical activity affects plasma coenzyme Q10 levels differently in young and old humans

Coenzyme Q (Q) is a key lipidic compound for cell bioenergetics and membrane antioxidant activities. It has been shown that also has a central role in the prevention of oxidation of plasma lipoproteins. Q has been associated with the prevention of cholesterol oxidation and several aging-related diseases. However, to date no clear data on the levels of plasma Q during aging are available. We have measured the levels of plasmatic Q₁₀ and cholesterol in young and old individuals showing different degrees of physical activity. Our results indicate that plasma Q₁₀ levels in old people are higher that the levels found in young people. Our analysis also indicates that there is no a relationship between the degree of physical activity and Q₁₀ levels when the general population is studied. However, very interestingly, we have found a different tendency between Q₁₀ levels and physical activity depending on the age of individuals. In young people, higher activity correlates with lower Q₁₀ levels in plasma whereas in older adults this ratio changes and higher activity is related to higher plasma Q₁₀ levels and higher Q₁₀/Chol ratios. Higher Q₁₀ levels in plasma are related to lower lipoperoxidation and oxidized LDL levels in elderly people. Our results highlight the importance of life habits in the analysis of Q₁₀ in plasma and indicate that the practice of physical activity at old age can improve antioxidant capacity in plasma and help to prevent cardiovascular diseases.     

Reentrant para‐Hisian ventricular tachycardia eliminated from the noncoronary cusp: Importance of regional anatomy for vantage‐point ablation

We present a rare case of reentrant ventricular tachycardia proven by entrainment maneuvers that was successfully ablated from the noncoronary cusp. The case highlights regional anatomy, pacing maneuvers with multi‐modality images from fluoroscopy, intracardiac echo, and electroanatomical mapping.     

Glecaprevir/pibrentasvir for patients with chronic hepatitis C virus infection and severe renal impairment

Data are limited regarding the real‐world effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) in patients with chronic hepatitis C virus (HCV) infection and severe renal impairment (RI). We aimed to evaluate the performance of GLE/PIB in patients with chronic kidney disease (CKD) stage 4 or 5 in Taiwan. 108 chronic HCV patients with CKD stage 4 (n = 32) or 5 (n = 76) receiving GLE/PIB for 8‐12 weeks were retrospectively recruited at 4 academic centres in Taiwan. The effectiveness was determined by sustained virologic response at off‐therapy week 12 (SVR₁₂) for evaluable (EP) and per‐protocol populations (PP). The safety profiles were also assessed. By EP and PP analyses, the SVR₁₂ rate was 99.1% (107 of 108 patients; 95% confidence interval (CI): 94.9%‐99.8%) and 100% (107 of 107 patients; 95% CI: 96.5%‐100%). The SVR₁₂ rates were 100% (95% CI: 89.3%‐100%) and 98.7% (95% CI: 92.9%‐99.8%) in patients with CKD stage 4 and 5, respectively. One patient, who declined off‐therapy follow‐up after permanently discontinuing GLE/PIB at on‐treatment week 9 due to scheduled cardiac surgery, had nonvirologic failure. Sixteen (14.8%) patients had serious adverse events (AEs), which were judged not related to GLE/PIB. The three most common AEs were pruritus (19.4%), fatigue (15.7%) and nausea (13.9%). None had ≥3‐fold upper limit of normal for total bilirubin and alanine aminotransferase levels. None of the 9 patients with hepatitis B virus (HBV) coinfection developed HBV‐associated hepatitis. In conclusion, GLE/PIB for 8‐12 weeks is effective and well‐tolerated in HCV patients with severe RI.     

Photoinduced transformations of stiff-stilbene-based discrete metallacycles to metallosupramolecular polymers

Control over structural transformations in supramolecular entities by external stimuli is critical for the development of adaptable and functional soft materials. Herein, we have designed and synthesized a dipyridyl donor containing a central Z-configured stiff-stilbene unit that self-assembles in the presence of two 180° di-Pt(II) acceptors to produce size-controllable discrete organoplatinum(II) metallacycles with high efficiency by means of the directional-bonding approach. These discrete metallacycles undergo transformation into extended metallosupramolecular polymers upon the conformational switching of the dipyridyl ligand from Z-configured (0°) to E-configured (180°) when photoirradiated. This transformation is accompanied by interesting morphological changes at nanoscopic length scales. The discrete metallacycles aggregate to spherical nanoparticles that evolve into long nanofibers upon polymer formation. These fibers can be reversibly converted to cyclic oligomers by changing the wavelength of irradiation, which reintroduces Z-configured building blocks owing to the reversible nature of stiff-stilbene photoisomerization. The design strategy defined here represents a novel self-assembly pathway to deliver advanced supramolecular assemblies by means of photocontrol.Natural systems provide many examples of self-assembled biosupramolecules that respond to external stimuli through conformational changes that ultimately play a role in carrying out their various biological functions. Mimicking this stimuli-responsive behavior in artificial systems is a promising route toward obtaining sophisticated molecular-based architectures with functional and structural tunability (1–3). Using the absorption of photons as a trigger is particularly attractive in that light-induced transformations maintain high spatial and temporal resolution without producing waste products even during multiple reversible switching sequences (4). In materials science, one of the most appealing characteristics of photochromic molecules is the direct conversion of light into mechanical energy based on their photo-reversible structural transformations (5). Among such chromophores, a stiff-stilbene moiety (1,1′-biindane) is useful owing to its unique characteristics (6). First, stiff stilbene can adopt either a cis or trans configuration with respect to its central double bond. Second, the high activation barrier between the two isomers (∼43 kcal⋅mol⁻¹, corresponding to a half-life of ∼10⁹ y at 300 K) makes thermal E/Z isomerization negligible at temperatures of 420 K and lower. Third, the quantum yield for the photoisomerization of either isomer is high (50%). Fourth, the stiff-stilbene core is readily substituted using well-established synthetic methods. Owing to these promising characteristics, Boulatov and coworkers (7) constructed a molecular force probe by integrating the moiety into a stretched polymer to mimic the strain generated in diverse functional groups. Yang and coworkers (8) reported hydrogen-bonded supramolecular polymers and studied their polymerization mechanisms and physical properties based on the photoisomerization of the stiff-stilbene units. Nevertheless, stiff-stilbene-based supramolecular entities are underexplored despite exhibiting properties that make the functionality potentially useful in the construction of photoresponsive supramolecular materials.Coordination-driven self-assembly is a powerful method of constructing supramolecular coordination complexes (SCCs) by the spontaneous formation of metal–ligand bonds that draws inspiration from the design principles of natural systems (9–20). This approach organizes metal acceptors and organic donors to prepare well-defined cavity-cored 2D metallacycles and 3D metallacages, which can be functionalized on their interior or exterior vertices for applications in host–guest chemistry (21, 22), catalysis (23), molecular flasks (24), bioengineering (25), amphiphilic self-assembly (26), and so on. The versatility of coordination-driven self-assembly can be enhanced by designs that allow for post-self-assembly modifications that in some cases result in complete structural transformations. For example, the Stang group previously demonstrated the transformation of self-assembled polygons by changing the angle between the bonding sites of a ligand from 180° to 120° upon treatment of Co₂(CO)₆ with an acetylene moiety (27). Yang and coworkers (28) reported the construction of multibisthienylethene hexagons capable of reversible supramolecule-to-supramolecule conversions induced by ring-open and ring-closed conformational changes of the bisthienylethene units. Herein we expand upon the transformations established by the systems described above designing SCCs capable of evolving from discrete metallacycles into infinite constructs using external stimuli.Supramolecular polymers can be defined as dynamically reversible polymeric arrays (29–37) that form from the explicit manipulation of noncovalent forces between monomeric units (38–43). Supramolecular polymer chemistry can readily complement coordination-driven self-assembly, as exemplified by our efforts to design hierarchical supramolecular polymerizations of discrete organoplatinum(II) metallacycles, thus accessing novel supramolecular polymeric materials, such as macroscopic hexagonal supramolecular polymer fibers (44), dendronized organoplatinum(II) metallacyclic polymers (45), and a responsive, cavity-cored supramolecular polymer network metallogel (46). Herein, we report photoresponsive supramolecular transformations between discrete organoplatinum(II) metallacycles and infinite metallosupramolecular polymers induced by a cis/trans conformational transition of a stiff-stilbene-based dipyridyl ligand. The self-assembly behaviors, physical properties, topologies, and morphologies of these SCCs can be regulated by photoisomerization, demonstrating this powerful approach to prepare advanced supramolecular coordination complexes.     

Nonsurgical and nonprosthetic camouflage treatment of skeletal Class II open bite with bilaterally missing lower first molars

This report illustrates the successful nonsurgical and nonprosthetic camouflage treatment of a skeletal Class II open bite malocclusion combined with missing mandibular first molars bilaterally. In the mandible, the second and third molars were uprighted and protracted, substituting for the missing first molars. In the maxilla, anterior bodily retraction and full-arch intrusion were achieved following premolar and second molar extraction, which also induced autorotation of the mandible. The treatment outcome and prognosis were confirmed with three-dimensional superimposition techniques, along with long-term stability.