Relationship between device acceptance and patient-reported outcomes in left ventricular assist device (LVAD) recipients

The number of Left Ventricular Assist Devices (LVADs) implanted each year is rising. Nevertheless, there are minimal data on device acceptance after LVAD implant, and on its relationship with patient-reported outcomes. We designed a cross-sectional study to address this knowledge gap and test the hypothesis that low device acceptance is associated with poorer quality of life, depression and anxiety. Self-report questionnaires were administered to assess quality of life (12-item Kansas City Cardiomyopathy Questionnaire quality of life subscale), level of anxiety (7-item Generalized Anxiety Disorder; GAD-7), level of depression (9-item Patient Health Questionnaire; PHQ-9) and device acceptance (Florida Patient Acceptance Survey; FPAS) to 101 consecutive patients presenting to LVAD clinic. Regression analysis showed a strong correlation between device acceptance and both psychological distress (p\u2009<\u20090.001) and quality of life (p\u2009<\u20090.001). Analysis of the sub-scales of the FPAS showed that patients had significant body image concerns, but return to function and device-related distress were the main drivers of the observed correlation between device acceptance and patient well-being. Younger age was associated with lower device acceptance (r\u2009=\u20090.36, p\u2009<\u20090.001) and lower quality of life (r\u2009=\u20090.54, p\u2009<\u20090.001). These findings suggest that interventions targeting device acceptance should be explored to improve outcomes in LVAD recipients

Association of early versus delayed normalisation of left ventricular ejection fraction with mortality in ischemic cardiomyopathy

OBJECTIVE: In patients with non-ischaemic cardiomyopathy and reduced left ventricular ejection fraction (LVEF), normalisation of LVEF is associated with improved outcomes. However, data on patients with ischaemic cardiomyopathy and recovered LVEF are lacking. The goal of this study was to assess the prognostic significance of normalisation of the LVEF in patients with ischaemic cardiomyopathy. METHODS/RESULTS: We performed a non-prespecified post hoc analysis of the Surgical Treatment for Ischaemic Heart Failure (STICH) trial to determine the association between normalisation of LVEF (\u3e50%) and mortality during follow-up. Of the 1212 patients with LVEF \u3c35% enroled in the STICH trial, 932 underwent assessment of LVEF at 4 months and/or 2 years after enrolment. Among them, 18 patients experienced normalisation in LVEF at 4-month follow-up and 35 patients experienced recovery in LVEF at 2 years. Recovery of LVEF at 4 months and recovery of LVEF at 2 years were not correlated. Recovery of LVEF at 4 months was not associated with reduced all-cause mortality in unadjusted analysis (log-rank test p=0.54) or in Cox proportional hazards analysis (HR: 0.93; 95% CI: 0.48 to 1.80; p=0.82). Ejection fraction recovery at 2 years was associated with a reduction in all-cause mortality, both in unadjusted analysis (log-rank test p=0.004) and in the Cox proportional hazard model (HR: 0.41; 95% CI: 0.21 to 0.80; p=0.009). CONCLUSIONS: In patients with ischaemic cardiomyopathy, delayed normalisation of LVEF is associated with reduced mortality, whereas early recovery of LVEF is not. Further studies are needed to confirm these findings

Developmental changes in myocardial B cells mirror changes in B cells associated with different organs

The naive heart harbors a population of intravascular B cells that make close contact with the cardiac microvasculature. However, the timing of their appearance and their organ specificity remain unknown. To address this knowledge gap, we performed a systematic analysis of B cells isolated from the myocardium and other organs, from embryonic life to adulthood. We found that the phenotype of myocardial B cells changed dynamically during development. While neonatal heart B cells were mostly CD11b+ and CD11b- CD21-CD23-, adult B cells were predominantly CD11b-CD21+CD23+. Histological analysis and intravital microscopy of lung and liver showed that organ-associated B cells in contact with the microvascular endothelium were not specific to the heart. Flow cytometric analysis of perfused hearts, livers, lungs, and spleen showed that the dynamic changes in B cell subpopulations observed in the heart during development mirrored changes observed in the other organs. Single cell RNA sequencing (scRNAseq) analysis of B cells showed that myocardial B cells were part of a larger population of organ-associated B cells that had a distinct transcriptional profile. These findings broaden our understanding of the biology of myocardial-associated B cells and suggest that current models of the dynamics of naive B cells during development are incomplete

Sentinel-2 Remote Sensed Image Classification with Patchwise Trained ConvNets for Grassland Habitat Discrimination

The present study focuses on the use of Convolutional Neural Networks (CNN or ConvNet) to classify a multi-seasonal dataset of Sentinel-2 images to discriminate four grassland habitats in the “Murgia Alta” protected site. To this end, we compared two approaches differing only by the first layer machinery, which, in one case, is instantiated as a fully-connected layer and, in the other case, results in a ConvNet equipped with kernels covering the whole input (wide-kernel ConvNet). A patchwise approach, tessellating training reference data in square patches, was adopted. Besides assessing the effectiveness of ConvNets with patched multispectral data, we analyzed how the information needed for classification spreads to patterns over convex sets of pixels. Our results show that: (a) with an F1-score of around 97% (5 x 5 patch size), ConvNets provides an excellent tool for patch-based pattern recognition with multispectral input data without requiring special feature extraction; (b) the information spreads over the limit of a single pixel: the performance of the network increases until 5 x 5 patch sizes are used and then ConvNet performance starts decreasing

Necrotic cardiac myocytes skew macrophage polarization towards a classically activated phenotype

Necrotic and dying cells release damage-associated molecular patterns (DAMPs) that can initiate sterile inflammatory responses in the heart. Although macrophages are essential for myocardial repair and regeneration, the effect of DAMPs on macrophage activation remains unclear. To address this gap in knowledge we studied the effect of necrotic cardiac myocyte extracts on primary peritoneal macrophage (PPM) cultures in vitro. We first performed unbiased transcriptomic profiling with RNA-sequencing of PPMs cultured for up to 72 hours in the presence and absence of: 1) necrotic cell extracts (NCEs) from necrotic cardiac myocytes in order to mimic the release of DAMPs; 2) lipopolysaccharide (LPS), which is known to polarize macrophages towards a classically activated phenotype and 3) Interleukin-4 (IL-4), which is known to promote polarization of macrophages towards an alternatively activated phenotype. NCEs provoke changes in differential gene expression (DEGs) that had considerable overlap with LPS-induced changes, suggesting that NCEs promote macrophage polarization towards a classically activated phenotype. Treating NCEs with proteinase-K abolished the effects of NCEs on macrophage activation, whereas NCE treatment with DNase and RNase did not affect macrophage activation. Stimulation of macrophage cultures with NCEs and LPS resulted in a significant increase in macrophage phagocytosis and interleukin-1β secretion, whereas treatment with IL-4 had no significant effect on phagocytosis and interleukin-1β. Taken together, our findings suggest that proteins released from necrotic cardiac myocytes are sufficient to skew the polarization of macrophages towards a classically activated phenotype

Regolith as Baseline to a Future Space Farm

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The programmed death-1 signaling axis modulates inflammation and LV structure/function in a stress-induced cardiomyopathy model

The role of immune checkpoints in the setting of tissue injury remains unknown. Using an experimental model of isoproterenol (ISO)-induced stress cardiomyopathy, we show that ISO-induced myocardial injury provokes tissue-autonomous up-regulation of the programmed death-1 (PD-1):programmed death ligand (PD-L) axis in cardiac resident innate immune cells and T cells. PD-1 signaling was responsible for modulating the acute inflammatory response, as well as normalization of impaired left ventricular structure and function after ISO injection. Necrotic cardiac extracts were sufficient to increase the expression of PD-1 in macrophages and T cells in vitro. Viewed together these studies suggest that the PD-1:PD-L signaling axis regulates immune responses to cardiac tissue injury and is important for restoring myocardial homeostasis

Biological and geochemical markers of the geographical origin and genetic identity of potatoes

There is a growing interest in agriculture productions combining safety and quality attributes with clear regional identity. In the last few years several methods have been employed for food authentication and traceability. In this study we tested geochemical data for elemental concentrations of Mn, Cu, Zn, Rb, Stand Cd and strontium isotope ratio in combination with biological data of 11 secondary metabolites and DNA as markers for the authentication of the origin of early potatoes at small geographical scale levels in Italy. DNA fingerprints through 12 SSR (simple sequence repeat) primer pairs allowed cultivar identification, confirming the discrimination power of molecular markers. Element concentrations, strontium isotope ratio and secondary metabolite data, through multivariate statistics (partial least squares discriminant analysis. PLS-DA), made it possible to clearly assign all the potato samples to the respective administrative regions of cultivation. The validation of the models was successful. It included external prediction tests on 20% of the data randomly selected from each administrative province and a study on the robustness of these multivariate data treatments to uncertainties on measurement results

Immunomodulatory role of non-neuronal cholinergic signaling in myocardial injury

Whereas prior studies have demonstrated an important immunomodulatory role for the neuronal cholinergic system in the heart, the role of the non-neuronal cholinergic system is not well understood. To address the immunomodulatory role of the non-neuronal cholinergic system in the heart we used a previously validated diphtheria toxin (DT)-induced cardiomyocyte ablation model (Rosa26-DTMlc2v-Cre mice). DT-injected Rosa26-DTMlc2v-Cre mice were treated with diluent or Pyridostigmine Bromide (PYR), a reversible cholinesterase inhibitor. PYR treatment resulted in increased survival and decreased numbers of MHC-IIlowCCR2+ macrophages in DT-injected Rosa26-DTMlc2v-Cre mice compared to diluent treated Rosa26-DTMlc2v-Cre mice. Importantly, the expression of CCL2/7 mRNA and protein was reduced in the hearts of PYR-treated mice. Backcrossing Rosa26-DTMlc2v-Cre mice with a transgenic mouse line (Chat-ChR2) that constitutively overexpresses the vesicular acetylcholine transporter (VAChT) resulted in decreased expression of Ccl2/7 mRNA and decreased numbers of CD68+ cells in DT-injured Rosa26-DTMlc2v-Cre/Chat-ChR2 mouse hearts, consistent with the pharmacologic studies with PYR. In vitro studies with cultures of LPS-stimulated peritoneal macrophages revealed a concentration-dependent reduction in CCL2 secretion following stimulation with ACh, nicotine and muscarine. Viewed together, these findings reveal a previously unappreciated immunomodulatory role for the non-neuronal cholinergic system in regulating homeostatic responses in the heart following tissue injury