Impact of Anesthesia Strategy and Valve Type on Clinical Outcomes After Transcatheter Aortic Valve Replacement

BackgroundThe randomized SOLVE-TAVI (compariSon of secOnd-generation seLf-expandable vs. balloon-expandable Valves and gEneral vs. local anesthesia in Transcatheter Aortic Valve Implantation) trial compared newer-generation self-expanding valves (SEV) and balloon-expandable valves (BEV) as well as local anesthesia with conscious sedation (CS) and general anesthesia (GA) in patients undergoing transfemoral transcatheter aortic valve replacement (TAVR). Both strategies showed similar outcomes at 30 days.ObjectivesThe purpose of this study was to compare clinical outcomes during 1-year follow-up in the randomized SOLVE-TAVI trial.MethodsUsing a 2 × 2 factorial design 447 intermediate- to high-risk patients with severe, symptomatic aortic stenosis were randomly assigned to transfemoral TAVR using either the SEV (Evolut R, Medtronic Inc., Minneapolis, Minnesota) or the BEV (Sapien 3, Edwards Lifesciences, Irvine, California) as well as CS or GA at 7 sites.ResultsIn the valve-comparison strategy, rates of the combined endpoint of all-cause mortality, stroke, moderate or severe paravalvular leakage, and permanent pacemaker implantation were similar between the BEV and SEV group (n = 84, 38.3% vs. n = 87, 40.4%; hazard ratio: 0.94; 95% confidence interval: 0.70 to 1.26; p = 0.66) at 1 year. Regarding the anesthesia comparison, the combined endpoint of all-cause mortality, stroke, myocardial infarction, and acute kidney injury occurred with similar rates in the GA and CS groups (n = 61, 25.7% vs. n = 54, 23.8%; hazard ratio: 1.09; 95% confidence interval: 0.76 to 1.57; p = 0.63).ConclusionsIn intermediate- to high-risk patients undergoing transfemoral TAVR, newer-generation SEV and BEV as well as CS and GA showed similar clinical outcomes at 1 year using a combined clinical endpoint. (SecOnd-generation seLf-expandable Versus Balloon-expandable Valves and gEneral Versus Local Anesthesia in TAVI [SOLVE-TAVI]; NCT02737150)     

The prediction of coronary atherosclerosis employing artificial neural networks

BACKGROUND: Atherosclerosis is a complex histopathologic process that is analogous to chronic inflammatory conditions. Several factors have been shown to correlate with the extent of atherosclerosis. Whereas hypertension, obesity, hyperlipidemia, diabetes, smoking, and family history are all well documented, recent literature points to additional associated factors. Thus, antibodies to oxidized low-density lipoprotein (oxLDL), cytomegalovirus (CMV), Chlamydia pneumonia, Helicobacter pylori, as well as homocysteine and C-reactive protein (CRP) levels have all been implicated as independent markers of accelerated atherosclerosis. HYPOTHESIS: In the current study we attempted to formulate a system by which to predict the extent of coronary atherosclerosis as assessed by angiographic vessel occlusion. METHODS: The 81 patients were categorized as having single-, double-, triple-, or no vessel involvement. The clinical data concerning the "classic" risk factors were obtained from clinical records, and sera were drawn from the patients for determination of the various parameters that are thought to be associated with atherosclerosis. RESULTS: Using four artificial neural networks, we have found the most effective parameters predictive of coronary vessel involvement were (in decreasing order of importance) antibodies to oxLDL, to cardiolipin, to CMV, to Chlamydia pneumonia, and to beta 2-glycoprotein I (beta 2GPI). Although important in the prediction of vessel occlusion, hyperlipidemia, hypertension, CRP levels, and diabetes were less accurate. CONCLUSION: The results of the current study, if reproduced in a larger population, may establish an integrated system based on the creation of artificial neural networks by which to predict the extent of atherosclerosis in a given subject fairly and noninvasively.     

What works? Interventions for maternal and child undernutrition and survival

We reviewed interventions that affect maternal and child undernutrition and nutrition-related outcomes. These interventions included promotion of breastfeeding; strategies to promote complementary feeding, with or without provision of food supplements; micronutrient interventions; general supportive strategies to improve family and community nutrition; and reduction of disease burden (promotion of handwashing and strategies to reduce the burden of malaria in pregnancy). We showed that although strategies for breastfeeding promotion have a large effect on survival, their effect on stunting is small. In populations with sufficient food, education about complementary feeding increased height-for-age Z score by 0.25 (95% CI 0.01-0.49), whereas provision of food supplements (with or without education) in populations with insufficient food increased the height-for-age Z score by 0.41 (0.05-0.76). Management of severe acute malnutrition according to WHO guidelines reduced the case-fatality rate by 55% (risk ratio 0.45, 0.32-0.62), and recent studies suggest that newer commodities, such as ready-to-use therapeutic foods, can be used to manage severe acute malnutrition in community settings. Effective micronutrient interventions for pregnant women included supplementation with iron folate (which increased haemoglobin at term by 12 g/L, 2.93-21.07) and micronutrients (which reduced the risk of low birthweight at term by 16% (relative risk 0.84, 0.74-0.95). Recommended micronutrient interventions for children included strategies for supplementation of vitamin A (in the neonatal period and late infancy), preventive zinc supplements, iron supplements for children in areas where malaria is not endemic, and universal promotion of iodised salt. We used a cohort model to assess the potential effect of these interventions on mothers and children in the 36 countries that have 90% of children with stunted linear growth. The model showed that existing interventions that were designed to improve nutrition and prevent related disease could reduce stunting at 36 months by 36%; mortality between birth and 36 months by about 25%; and disability-adjusted life-years associated with stunting, severe wasting, intrauterine growth restriction, and micronutrient deficiencies by about 25%. To eliminate stunting in the longer term, these interventions should be supplemented by improvements in the underlying determinants of undernutrition, such as poverty, poor education, disease burden, and lack of women's empowerment.     

Physiological Stress Elicits Impaired Left Ventricular Function in Preterm-Born Adults

Background

Experimental and clinical studies show that prematurity leads to altered left ventricular (LV) structure and function with preserved resting LV ejection fraction (EF). Large-scale epidemiological data now links prematurity to increased early heart failure risk.

Optimizing therapy in inflammatory arthritis: prediction of relapse after tapering or stopping treatment for rheumatoid arthritis patients achieving clinical and radiological remission

This study aims to assess clinical, lab/immunological or imaging (joint ultrasonography) markers able to predict disease relapse in RA patients in sustained remission when tapering or stopping their treatment. One hundred fifty-seven RA patients in clinical remission (DAS-28 <2.6 for >6 months), receiving treatment with sDMARDs and bDMARD therapy, were randomly allocated into any of five groups: Group 1: continue full dose DMARDs and taper biologic therapy by 50 % (31 patients); Group 2: taper both DMARDs and biologic therapy dose by 50 % (32 patients); Group 3: taper DMARDs by 50 % and stop biologic therapy (31 patients); Group 4: stop both DMARDs and biologic therapy (31 patients); Group 5: continue medications without change (31 patients). Forty joints were assessed ultrasonographically (DAS-28 joints + ankles + metatarsophalangeal joints) and prospectively monitored for 12 months. The primary endpoint was sustained remission for 12 months. Patients were considered as having a relapse when the DAS-28 score was >3.2 and anti-rheumatic treatment was escalated. The frequency of relapse was 41.9 % in Group 1, 59.3 % in Group 2, 67.7 % in Group 3, 77.4 % in Group 4 and 6.5 % in Group 5. Relapse rates were significantly higher in patients whose ultrasound scores raised within 3 months of stopping their medications (P < 0.001 for both GS and PD scores). Cox regression identified ACPA positivity (at baseline) and progression of functional disability (at 2 months) as predictors for relapse. Tapering therapy is feasible in RA patients. Tailored dynamic approach is advised. Joint ultrasonographic assessment, ACPA positivity and worsening functional disability predicted relapse within a short term after discontinuation of the treatment. RA patients whose DAS-28 score was <2 were more likely to remain in remission.     

On the dynamical nature of the active center in a single-site photocatalyst visualized by 4D ultrafast electron microscopy

Understanding the dynamical nature of the catalytic active site embedded in complex systems at the atomic level is critical to developing efficient photocatalytic materials. Here, we report, using 4D ultrafast electron microscopy, the spatiotemporal behaviors of titanium and oxygen in a titanosilicate catalytic material. The observed changes in Bragg diffraction intensity with time at the specific lattice planes, and with a tilted geometry, provide the relaxation pathway: the Ti⁴⁺=O²⁻ double bond transformation to a Ti³⁺−O¹⁻ single bond via the individual atomic displacements of the titanium and the apical oxygen. The dilation of the double bond is up to 0.8 Å and occurs on the femtosecond time scale. These findings suggest the direct catalytic involvement of the Ti³⁺−O¹⁻ local structure, the significance of nonthermal processes at the reactive site, and the efficient photo-induced electron transfer that plays a pivotal role in many photocatalytic reactions.Single-site catalysts of both the thermally and photoactivated kind now occupy a prominent place in industrial- and laboratory-scale heterogeneous catalysis (1–8). Among the most versatile of these are the ones consisting of coordinatively unsaturated transition metal ions (Ti, Cr, Fe, Mn…) that occupy substitutional sites in well-defined, three-dimensionally extended, open-structure silicates of the zeolite type. The well-known and most widely used are the 4- or 5-coordinated Ti(IV) ions accommodated within the crystalline phase of silica, silicalite (9–14).Titanosilicates, especially, are used extensively both industrially and in the laboratory for a wide range of chemo-, regio-, and shape-selective oxidations of organic compounds (15–18). These single-site heterogeneous photocatalysts are quite distinct from those typified by TiO₂, SrTiO₃, and other titaniferous photocatalysts where the Ti(IV) ions are in 6-coordination; and where, in interpreting the processes involved in harnessing solar radiation, electronic band structure considerations hold sway in preference to the localized states (see, e.g., refs. 19, 20). It has been demonstrated (16–18, 21, 22) that single-site, coordinatively unsaturated Ti(IV)-centered photocatalysts are especially useful in the aerial oxidation of environmental pollutants in the photodegradation of NO (to N₂ and O₂), of H₂O (to H₂ and O₂), and in the photocatalytic reduction of CO₂ to yield methanol. There is an exigent need to explore the precise nature of the electronic, temporal, and spatial changes accompanying the initial act of photoabsorption that sets in train the ensuing elementary chemical processes that are of vital environmental significance in, for example, the utilization of anthropogenic CO₂ as a chemical feedstock (23).Here, we report the use of 4D ultrafast electron microscopy (UEM) (24–26) to trace the spatiotemporal behavior of the Ti(IV) and O²⁻ ions at the photocatalytic active center in the structurally well-characterized titanosilicate Na₄Ti₂Si₈O₂₂·4H₂O, known as JDF-L1 (27–29). JDF stands for Jilin–Davy–Faraday, as the crystalline solid described here was discovered and characterized in joint work involving Jilin University (P. R. China) and the Davy–Faraday Laboratory at the Royal Institution of Great Britain. L1 stands for the first layered catalyst formed during that collaboration; 5-coordinated solids containing Ti(IV) ions are rare among the hundred or so titaniferous minerals, the prime example being fresnoite, Ba₂Ti₂Si₂O₈. We choose this photocatalyst with 5-coordinated Ti because of its unique bonding structure. Our approach entails monitoring, at femtosecond resolution, the changes in intensities and anisotropies of Bragg (electron) diffraction reflections in such a manner as to retrieve the change in valency and the time scales involved in both the formation of Ti³⁺−O¹⁻ bond and the relaxation of the energy back to the local structure of the Ti = O bond in JDF-L1. Through these diffraction studies, and the associated Debye–Waller effect and structural factors anisotropies, it is found that a Ti³⁺−O¹⁻ bond is formed on the femtosecond time scale; whereas, the back relaxation from the site to the structure occurs on a much longer time scale, permitting ample time for reactivity involving Ti³⁺−O¹⁻, and indicating the potential significance of nonthermal processes in the photocatalytic activity at the reactive site.     

Development of Gendine-Coated Cannula for Continuous Subcutaneous Insulin Infusion for Extended Use

Continuous subcutaneous insulin infusion (CSII) using pumps is a widely used method for insulin therapy in patients with diabetes mellitus. Among the major factors that usually lead to the discontinuation of CSII are CSII set-related issues, including infection at the infusion site. The American Diabetic Association currently recommends rotating sites every 2 to 3 days. This recommendation adds cost and creates inconvenience. Therefore, in order to prevent infections and extend the duration between insertion site changes, we developed a Teflon cannula coated with a combination of gentian violet and chlorhexidine (gendine) and tested its antimicrobial efficacy against different pathogens. The cannulas were coated with gendine on the exterior surface and dried. The efficacy and durability of gendine-coated cannulas were determined against methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, methicillin-susceptible S. aureus, Streptococcus pyogenes, vancomycin-resistant enterococci, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, and Candida glabrata using a biofilm colonization method. The cytotoxicity of gendine was assessed against mouse fibroblast cell lines. The gendine-coated cannulas showed complete prevention of biofilm colonization of all organisms tested for up to 2 weeks (P < 0.0001) compared to that with the uncoated control. A gendine-coated catheter against mouse fibroblast cells was shown to be noncytotoxic. Our in vitro results show that a novel gendine cannula is highly effective in completely inhibiting the biofilm of multidrug-resistant pathogens for up to 2 weeks and may have potential clinical applications, such as prolonged use, cost reduction, and lower infection rate.