The aim of this study was to report the 2-year results of the SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) trial and confirm the interim Bayesian analysis.
Transcatheter ...aortic valve replacement (TAVR) with a self-expanding valve was noninferior to surgery in patients with severe aortic stenosis and intermediate operative risk using Bayesian statistical methods. Novel Bayesian designs have been used to shorten the time to primary endpoint analysis in randomized clinical trials, although the predictive value of Bayesian analysis compared with frequentist approaches remains debated.
The SURTAVI trial randomized 1,660 patients. An interim analysis was performed 1 year after the 1,400th patient was treated to estimate the primary 2-year endpoint of all-cause mortality or disabling strokes for all patients.
The Kaplan-Meier rate for the complete 2-year primary endpoint was 12.7% in the TAVR group and 12.6% in the surgery group (0.0% difference; 95% confidence interval: −3.4% to 3.5%), compared with 12.6% with TAVR and 14.0% with surgery (−1.4% difference; Bayesian credible interval: −5.2% to 2.3%) in the interim Bayesian analysis. A comparison of individual clinical, hemodynamic, and quality-of-life endpoints using Bayesian and frequentist methods found no significant differences.
The complete analysis of all patients with aortic stenosis at intermediate risk for surgery in the SURTAVI trial confirmed the noninferiority, with respect to the frequency of all-cause mortality or disabling stroke, of TAVR to surgery, as determined in the interim Bayesian analysis. Follow-up will extend out to 10 years.
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The genome sequence of Leifsonia xyli subsp. xyli, which causes ratoon stunting disease and affects sugarcane worldwide, was determined. The single circular chromosome of Leifsonia xyli subsp. xyli ...CTCB07 was 2.6 Mb in length with a GC content of 68% and 2,044 predicted open reading frames. The analysis also revealed 307 predicted pseudogenes, which is more than any bacterial plant pathogen sequenced to date. Many of these pseudogenes, if functional, would likely be involved in the degradation of plant heteropolysaccharides, uptake of free sugars, and synthesis of amino acids. Although L. xyli subsp. xyli has only been identified colonizing the xylem vessels of sugarcane, the numbers of predicted regulatory genes and sugar transporters are similar to those in free-living organisms. Some of the predicted pathogenicity genes appear to have been acquired by lateral transfer and include genes for cellulase, pectinase, wilt-inducing protein, lysozyme, and desaturase. The presence of the latter may contribute to stunting, since it is likely involved in the synthesis of abscisic acid, a hormone that arrests growth. Our findings are consistent with the nutritionally fastidious behavior exhibited by L. xyli subsp. xyli and suggest an ongoing adaptation to the restricted ecological niche it inhabits.
Objectives. The aim of our study is to examine the role of some factors (sociodemographic patterns, social relationship support, and trust in healthcare actors) on structure of quality of life among ...the Italian elderly population, by stratifying according to presence or absence of disability. Methods. Using data of the Italian National Institute of Statistics (ISTAT) survey, we obtained a sample of 25,183 Italian people aged 65+ years. Multiple Correspondence Analysis (MCA) was used to test such a relationship. Results. By applying the MCA between disabled and nondisabled elderly population, we identified three dimensions: “demographic structure and social contacts,” “social relationships,” “trust in the Italian National Health Services (INHS).” Furthermore, the difference in trust on the INHS and its actors was seen among disabled and non-disabled elderly population. Conclusions. Knowledge on the concept of quality of life and its application to the elderly population either with or without disability should make a difference in both people’s life and policies and practices affecting life. New domains, such as information and trusting relationships both within and towards the care network’s nodes, are likely to play an important role in this relationship.
LEOPARD syndrome (LS) is an autosomal dominant syndrome characterized by multiple lentigines and café-au-lait spots, electrocardiographic-conduction abnormalities, ocular hypertelorism/obstructive ...cardiomyopathy, pulmonary stenosis, abnormalities of the genitalia in males, retardation of growth, and deafness. LS shares many features with Noonan syndrome (NS), in which lentigines and deafness are usually not present. Molecular studies have shown that LS and NS are allelic disorders, caused by different missense mutations in PTPN11, a gene encoding the protein tyrosine phosphatase SHP-2 located at chromosome 12q22-qter. The clinical diagnosis of LS is generally difficult in the first months of life because the distinctive lentigines are generally not present at birth and develop during childhood. From January 2002 to December 2004, we suspected LS clinically in 10 patients admitted to our genetic counseling services in the first 12 months of life. A PTPN11 gene mutation was detected in 8/10 (80%) patients. In one patient without a PTPN11 mutation a subsequent clinical diagnosis of neurofibromatosis type 1 (NF1) was made, following the evaluation of the mother, who had previously undiagnosed classic NF1. The age of LS patients with PTPN11 mutation ranged between 1 and 11 months (mean age +/- SD 7.5 +/- 3.96 months). Review of the clinical characteristics of patients with LS confirmed by molecular study during the first year of life demonstrates that the diagnosis of LS in the first months of age can be clinically suspected in patients presenting with three main features, that is, characteristic facial features (100%), hypertrophic cardiomyopathy (HCM) (87%), and cafe-au-lait spots (75%). Characteristic facial features can be mild or severe, and consist of hypertelorism, downslanting palpebral fissures, ptosis, and dysmorphic ears. The clinical suspicion of LS may be confirmed by molecular screening for PTPN11 mutations. An early diagnosis of the disease is useful for the prospective care of associated medical problems and for precise genetic counseling.
Objective
It was previously reported that docosahexanoic acid (DHA) reduces TNF-α-induced necrosis in L929 cells. However, the mechanisms underlying this reduction have not been investigated. The ...present study was designed to investigate cellular and biochemical mechanisms underlying the attenuation of TNF-α-induced necroptosis by DHA in L929 cells.
Methods
L929 cells were pre-treated with DHA prior to exposure to TNF-α, zVAD, or Necrostatin-1 (Nec-1). Cell death and survival were assessed by MTT and caspase activity assays, and microscopic visualization. Reactive oxygen species (ROS) were measured by flow cytometry. C16- and C18-ceramides were measured by mass spectrometry. Lysosomal membrane permeabilization (LMP) was evaluated by fluorescence microscopy and flow cytometry using Acridine Orange. Cathepsin L activation was evaluated by immunoblotting and fluorescence microscopy. Autophagy was assessed by immunoblotting of LC3-II and Beclin.
Results
Exposure of L929 cells to TNF-α alone for 24 h induced necroptosis, as evidenced by the inhibition of cell death by Nec-1, absence of caspase-3 activity and Lamin B cleavage, and morphological analysis. DHA attenuated multiple biochemical events associated with TNF-α-induced necroptosis, including ROS generation, ceramide production, lysosomal dysfunction, cathepsin L activation, and autophagic features. DHA also attenuated zVAD-induced necroptosis but did not attenuate the enhanced apoptosis and necrosis induced by the combination of TNF-α with Actinomycin D or zVAD, respectively, suggesting that its protective effects might be limited by the strength of the cell death insult induced by TNF-α.
Conclusions
DHA effectively attenuates TNF-α-induced necroptosis and autophagy, most likely via its ability to inhibit TNF-α-induced sphingolipid metabolism and oxidative stress. These results highlight the role of this Omega-3 fatty acid in antagonizing inflammatory cell death.
The aim of the current study was to investigate whether the combination between mean platelet volume (MPV) and platelet distribution width (PDW) may improve the prognostic information in the ...prediction of prevalence and extent of coronary artery disease (CAD). We measured MPV and PDW in 2330 consecutive patients undergoing coronary angiography. Significant CAD was defined as stenosis more than 50% in at least one coronary vessel. We additionally measured carotid intima-media thickness (IMT) in 359 patients. Patients were grouped according to the median value of MPV (10.8fl) and PDW (13fl): Group 1 (MPV and PDW < 50th percentile; n = 958); Group 2 (MPV or PDW ≥50th percentile; n = 288); Group 3 (MPW and PDW ≥ 50th percentile; n = 1055). Patients in Group 3 were older (P < 0.001) with larger prevalence of diabetes (P = 0.024). Combined MPV-PWD was significantly associated with baseline glycemia (P < 0.001) and red blood cell count (P < 0.0001), but inversely related to platelet count (P < 0.0001). Combined MPV-PDW was inversely associated with the presence of thrombus, but directly related to the prevalence of chronic occlusion and worse TIMI flow. However, combined MPV-MPV was not associated with the prevalence of CAD odds ratio (OR) (95% confidence interval (CI) = 0.99 (0.90-1.09), P = 0.87; adjusted OR (95%CI) = 0.95 (0.85-1.05), P = 0.3, or severe CAD OR (95%CI) = 1.05 (0.95-1.16), P = 0.3; adjusted OR (95% CI) = 0.97 (0.87-1.08), P = 0.63. No relationship was observed between IMT and the combination of PDW and MPW. This study showed that the combined information on MPV and PDW is not related to the extent of CAD and carotid IMT. Thus, both MPV and PDW can not be considered as a risk factor for CAD.
Context. Solar Orbiter, the new-generation mission dedicated to solar and heliospheric exploration, was successfully launched on February 10, 2020, 04:03 UTC from Cape Canaveral. During its first ...perihelion passage in June 2020, two successive interplanetary coronal mass ejections (ICMEs), propagating along the heliospheric current sheet (HCS), impacted the spacecraft. Aims. This paper addresses the investigation of the ICMEs encountered by Solar Orbiter on June 7−8, 2020, from both an observational and a modeling perspective. The aim is to provide a full description of those events, their mutual interaction, and their coupling with the ambient solar wind and the HCS. Methods. Data acquired by the MAG magnetometer, the Energetic Particle Detector suite, and the Radio and Plasma Waves instrument are used to provide information on the ICMEs’ magnetic topology configuration, their magnetic connectivity to the Sun, and insights into the heliospheric plasma environment where they travel, respectively. On the modeling side, the Heliospheric Upwind eXtrapolation model, the 3D COronal Rope Ejection technique, and the EUropean Heliospheric FORecasting Information Asset (EUHFORIA) tool are used to complement Solar Orbiter observations of the ambient solar wind and ICMEs, and to simulate the evolution and interaction of the ejecta in the inner heliosphere, respectively. Results. Both data analysis and numerical simulations indicate that the passage of two distinct, dynamically and magnetically interacting (via magnetic reconnection processes) ICMEs at Solar Orbiter is a possible scenario, supported by the numerous similarities between EUHFORIA time series at Solar Orbiter and Solar Orbiter data. Conclusions. The combination of in situ measurements and numerical simulations (together with remote sensing observations of the corona and inner heliosphere) will significantly lead to a deeper understanding of the physical processes occurring during the CME-CME interaction.
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