Impact of perioperative blood transfusions on oncologic outcomes after radical cystectomy: A systematic review and meta-analysis of comparative studies.

This study aimed at systematically analyzing and evaluating the impact of perioperative blood transfusions (PBT) on oncologic outcomes of patients undergoing radical cystectomy for bladder cancer. This systematic review follows the recommendations of the Cochrane Handbook for Systematic Reviews and Interventions and was conducted in line with the PRISMA statement and the AMSTAR II criteria. A comprehensive database search was performed based on the PICO criteria. Two independent reviewers performed all screening steps and quality assessment. Risk of bias and certainty in evidence were assessed with the Newcastle Ottawa Scale for non-randomized trials and the GRADE approach. Of 1123 identified studies 20 were eligible for qualitative analysis and 15 for quantitative analysis reporting on 21,915 patients. Receiving a PBT was associated with an increased risk of all-cause mortality (hazard ratio (HR) [95% confidence interval (CI)]: 1.29 [1.18, 1.40]; p < 0.001), cancer-specific mortality (HR [CI]: 1.27 [1.15; 1.41]; p < 0.001) and disease recurrence (HR [CI]: 1.22 [1.12; 1.34]; p < 0.001). Subgroup analysis of transfusion timing revealed a significantly increased risk of mortality with intraoperative or combined intra- and postoperative transfusions compared to postoperative transfusion only for all three outcomes (p < 0.001). Leukocyte-depletion was associated with increased all-cause mortality, but not cancer-specific mortality. The administration of PBT negatively impacts oncological outcomes after radical cystectomy. Therefore, careful treatment indication and strict adherence to transfusion guidelines is encouraged in order to avoid adverse effects during the perioperative course.

Exercise-based cardiac rehabilitation in patients with reduced left ventricular ejection fraction: The Cardiac Rehabilitation Outcome Study in Heart Failure (CROS-HF): A systematic review and meta-analysis.

BACKGROUND: In heart failure with reduced left ventricular ejection fraction (HFrEF) patients the effects of exercise-based cardiac rehabilitation on top of state-of-the-art pharmacological and device therapy on mortality, hospitalization, exercise capacity and quality-of-life are not well established. DESIGN: The design of this study involved a structured review and meta-analysis. METHODS: Evaluation of randomised controlled trials of exercise-based cardiac rehabilitation in HFrEF-patients with left ventricular ejection fraction ≤40% of any aetiology with a follow-up of ≥6 months published in 1999 or later. RESULTS: Out of 12,229 abstracts, 25 randomised controlled trials including 4481 HFrEF-patients were included in the final evaluation. Heterogeneity in study population, study design and exercise-based cardiac rehabilitation-intervention was evident. No significant difference in the effect of exercise-based cardiac rehabilitation on mortality compared to control-group was found (hazard ratio 0.75, 95% confidence interval 0.39-1.41, four studies; 12-months follow-up: relative risk 1.29, 95% confidence interval 0.66-2.49, eight studies; six-months follow-up: relative risk 0.91, 95% confidence interval 0.26-3.16, seven studies). In addition there was no significant difference between the groups with respect to 'hospitalization-for-any-reason' (12-months follow-up: relative risk 0.79, 95% confidence interval 0.41-1.53, four studies), or 'hospitalization-due-to-heart-failure' (12-months follow-up: relative risk 0.59, 95% confidence interval 0.12-2.91, four studies; six-months follow-up: relative risk 0.84, 95% confidence interval 0.07-9.71, three studies). All studies show improvement of exercise capacity. Participation in exercise-based cardiac rehabilitation significantly improved quality-of-life as evaluated with the Kansas City Cardiomyopathy Questionnaire: (six-months follow-up: mean difference 1.94, 95% confidence interval 0.35-3.56, two studies), but no significant results emerged for quality-of-life measured by the Minnesota Living with Heart Failure Questionnaire (nine-months or more follow-up: mean difference -4.19, 95% confidence interval -10.51-2.12, seven studies; six-months follow-up: mean difference -5.97, 95% confidence interval -16.17-4.23, four studies). CONCLUSION: No association between exercise-based cardiac rehabilitation and mortality or hospitalisation could be observed in HFrEF patients but exercise-based cardiac rehabilitation is likely to improve exercise capacity and quality of life.

Dynamical charge density fluctuations pervading the phase diagram of a Cu-based high-T c superconductor.

Charge density modulations have been observed in all families of high-critical temperature (T c) superconducting cuprates. Although they are consistently found in the underdoped region of the phase diagram and at relatively low temperatures, it is still unclear to what extent they influence the unusual properties of these systems. Using resonant x-ray scattering, we carefully determined the temperature dependence of charge density modulations in YBa2Cu3O7-δ and Nd1+ x Ba2- x Cu3O7-δ for several doping levels. We isolated short-range dynamical charge density fluctuations in addition to the previously known quasi-critical charge density waves. They persist up to well above the pseudogap temperature T*, are characterized by energies of a few milli-electron volts, and pervade a large area of the phase diagram.

Gap suppression at a Lifshitz transition in a multi-condensate superconductor.

In multi-orbital materials, superconductivity can exhibit several coupled condensates. In this context, quantum confinement in two-dimensional superconducting oxide interfaces offers new degrees of freedom to engineer the band structure and selectively control the occupancy of 3d orbitals by electrostatic doping. Here, we use resonant microwave transport to extract the superfluid stiffness of the (110)-oriented LaAlO3/SrTiO3 interface in the entire phase diagram. We provide evidence of a transition from single-condensate to two-condensate superconductivity driven by continuous and reversible electrostatic doping, which we relate to the Lifshitz transition between 3d bands based on numerical simulations of the quantum well. We find that the superconducting gap is suppressed while the second band is populated, challenging Bardeen-Cooper-Schrieffer theory. We ascribe this behaviour to the existence of superconducting order parameters with opposite signs in the two condensates due to repulsive coupling. Our findings offer an innovative perspective on the possibility to tune and control multiple-orbital physics in superconducting interfaces.

Paradoxical embolism with thrombus stuck in a patent foramen ovale: a review of treatment strategies.

OBJECTIVE: Paradoxical embolism represents a rare condition occurring when a thrombus originating from venous system produces pulmonary embolism and systemic embolization through an intracardiac or pulmonary shunt. The evidence of a thrombus entrapped in a patent foramen ovale (PFO) is an even more rare condition. There is uncertainty about the optimal treatment strategy. PATIENTS AND METHODS: A 58-year-old male patient was admitted to our Internal Medicine Unit with the diagnosis of bilateral bronchopneumonia. During hospitalization, the co-occurrence of chest pain and amaurosis led us to hypothesize a paradoxical embolism. RESULTS: Transthoracic echocardiography showed the presence of a thrombus stuck over the interatrial septum. A contrast-enhanced chest CT scan showed multiple pulmonary embolisms and brain CT scan documented a hypodense area, of ischemic significance, in the left occipital lobe near tentorium. In order to prevent further embolization, emergency cardiac surgery (right atriotomy, removal of thrombus and closure of the PFO, pulmonary thrombectomy) was performed without complications. CONCLUSIONS: Although rare, the evidence of a thrombus stuck in a patent foramen ovale represents a clinical emergency. The optimal therapeutic approach is still debated. The surgical correction seems to be a safe and effective option for these patients.

Re-entrant charge order in overdoped (Bi,Pb)2.12Sr1.88CuO6+δ outside the pseudogap regime.

In the underdoped regime, the cuprate high-temperature superconductors exhibit a host of unusual collective phenomena, including unconventional spin and charge density modulations, Fermi surface reconstructions, and a pseudogap in various physical observables. Conversely, overdoped cuprates are generally regarded as conventional Fermi liquids possessing no collective electronic order. In partial contradiction to this widely held picture, we report resonant X-ray scattering measurements revealing incommensurate charge order reflections for overdoped (Bi,Pb)2.12Sr1.88CuO6+δ (Bi2201), with correlation lengths of 40-60 lattice units, that persist up to temperatures of at least 250 K. The value of the charge order wavevector decreases with doping, in line with the extrapolation of the trend previously observed in underdoped Bi2201. In overdoped materials, however, charge order coexists with a single, unreconstructed Fermi surface without nesting or pseudogap features. The discovery of re-entrant charge order in Bi2201 thus calls for investigations in other cuprate families and for a reconsideration of theories that posit an essential relationship between these phenomena.

Competition between electron pairing and phase coherence in superconducting interfaces.

In LaAlO3/SrTiO3 heterostructures, a gate tunable superconducting electron gas is confined in a quantum well at the interface between two insulating oxides. Remarkably, the gas coexists with both magnetism and strong Rashba spin-orbit coupling. However, both the origin of superconductivity and the nature of the transition to the normal state over the whole doping range remain elusive. Here we use resonant microwave transport to extract the superfluid stiffness and the superconducting gap energy of the LaAlO3/SrTiO3 interface as a function of carrier density. We show that the superconducting phase diagram of this system is controlled by the competition between electron pairing and phase coherence. The analysis of the superfluid density reveals that only a very small fraction of the electrons condenses into the superconducting state. We propose that this corresponds to the weak filling of high-energy dxz/dyz bands in the quantum well, more apt to host superconductivity.

Diatom frustules decorated with zinc oxide nanoparticles for enhanced optical properties.

Zinc oxide (ZnO) nanoparticles were synthesized on diatomite (DE) surface by a low temperature sol gel technique, starting from zinc acetate dihydrate (Zn(CH3COO)2 · 2H2O) solution in water/ethyl alcohol, in presence of triethanolamine (TEA) with functions of Zn2+ chelating agent, catalyst and mediator of nanoparticle growth on DE surface. Microstructural features were investigated by field emission scanning electron microscopy and x-ray diffraction. ZnO crystalline nanoparticles, well distributed both on the surface and into the porous architecture of diatomite, were obtained just after the synthesis carried out at 80 °C without the need of calcination treatments. The optical properties of ZnO/DE hybrid powders were measured for the first time by means of photoacoustic spectroscopy (PAS). A new method to retrieve both the optical absorption and scattering coefficients from PAS is here discussed for powder aggregates. The fingerprint of the zinc oxide nanoparticles has been highlighted in the Mie scattering resonance in the UV-Vis range, and in the enhancement of the optical absorption with respect to diatomite.

Glue function of optimally and overdoped cuprates from inversion of the Raman spectra.

We address the issue of identifying the mediators of effective interactions in cuprates superconductors. Specifically, we use inversion theory to analyze Raman spectra of optimally and over-doped La2-x Sr x CuO4 samples. This allows us to extract the so-called glue function without making any a priori assumption based on any specific model. We use instead two different techniques, namely the singular value decomposition and a multi-rectangle decomposition. With both techniques we find consistent results showing that: (i) two distinct excitations are responsible for the glue function, which have completely different doping dependence. One excitation becomes weak above optimal doping, where on the contrary the other keeps (or even slightly increases) its strength; (ii) there is a marked temperature dependence on the weight and spectral distribution of these excitations, which therefore must have a somewhat critical character. It is quite natural to identify and characterize these two distinct excitations as damped antiferromagnetic spin waves and damped charge density waves, respectively. This sets the stage for a scenario in which superconductivity is concomitant and competing with a charge ordering instability.

Phase Separation from Electron Confinement at Oxide Interfaces.

Oxide heterostructures are of great interest for both fundamental and applicative reasons. In particular, the two-dimensional electron gas at the LaAlO_{3}/SrTiO_{3} or LaTiO_{3}/SrTiO_{3} interfaces displays many different properties and functionalities. However, there are clear experimental indications that the interface electronic state is strongly inhomogeneous and therefore it is crucial to investigate possible intrinsic mechanisms underlying this inhomogeneity. Here, the electrostatic potential confining the electron gas at the interface is calculated self-consistently, finding that such confinement may induce phase separation, to avoid a thermodynamically unstable state with a negative compressibility. This provides a robust mechanism for the inhomogeneous character of these interfaces.

Interplay between density and superconducting quantum critical fluctuations.

We consider the case of a density-driven metal-superconductor transition in the proximity of an electronic phase separation. In particular, we investigate the interplay between superconducting fluctuations and density fluctuations, which become quantum critical when the electronic phase separation vanishes at zero temperature into a quantum critical point. In this situation, the critical dynamical density fluctuations strongly affect the dynamics of the Cooper-pair fluctuations, which acquire a more singular character with a z = 3 dynamical critical index. This gives rise to a scenario that possibly rules the disappearance of superconductivity when the electron density is reduced by electrostatic gating at the LaAlO3/SrTiO3 interface.

Field-effect control of superconductivity and Rashba spin-orbit coupling in top-gated LaAlO3/SrTiO3 devices.

The recent development in the fabrication of artificial oxide heterostructures opens new avenues in the field of quantum materials by enabling the manipulation of the charge, spin and orbital degrees of freedom. In this context, the discovery of two-dimensional electron gases (2-DEGs) at LaAlO3/SrTiO3 interfaces, which exhibit both superconductivity and strong Rashba spin-orbit coupling (SOC), represents a major breakthrough. Here, we report on the realisation of a field-effect LaAlO3/SrTiO3 device, whose physical properties, including superconductivity and SOC, can be tuned over a wide range by a top-gate voltage. We derive a phase diagram, which emphasises a field-effect-induced superconductor-to-insulator quantum phase transition. Magneto-transport measurements show that the Rashba coupling constant increases linearly with the interfacial electric field. Our results pave the way for the realisation of mesoscopic devices, where these two properties can be manipulated on a local scale by means of top-gates.

Electronic polymers and soft-matter-like broken symmetries in underdoped cuprates.

Empirical evidence in heavy fermion, pnictide and other systems suggests that unconventional superconductivity appears associated to some form of real-space electronic order. For the cuprates, despite several proposals, the emergence of order in the phase diagram between the commensurate antiferromagnetic state and the superconducting state is not well understood. Here we show that in this regime doped holes assemble in 'electronic polymers'. Within a Monte Carlo study, we find that in clean systems by lowering the temperature the polymer melt condenses first in a smectic state and then in a Wigner crystal both with the addition of inversion symmetry breaking. Disorder blurs the positional order leaving a robust inversion symmetry breaking and a nematic order, accompanied by vector chiral spin order and with the persistence of a thermodynamic transition. Such electronic phases, whose properties are reminiscent of soft-matter physics, produce charge and spin responses in good accord with experiments.

Spin excitations of ferronematic order in underdoped cuprate superconductors.

High-temperature superconductors exhibit a characteristic hourglass-shaped spectrum of magnetic fluctuations which most likely contribute to the pairing glue in the cuprates. Recent neutron scattering experiments in strongly underdoped compounds have revealed a significant low energy anisotropy of these fluctuations which we explain by a model in which topological defects of the antiferromagnet clump to producing domain wall segments with ferronematic order. This state does not invoke global charge order but breaks C4 rotational and inversion symmetry. The incommensurability of the low doping charge-disordered state is in good agreement with experiment and interpolates smoothly with the incommensurability of the stripe phase at higher doping. Within linear spin-wave theory the dynamic structure factor is in very good agreement with inelastic neutron scattering data and can account for the observed energy dependent anisotropy.

Multiple quantum criticality in a two-dimensional superconductor.

The diverse phenomena associated with the two-dimensional electron gas (2DEG) that occurs at oxide interfaces include, among others, exceptional carrier mobilities, magnetism and superconductivity. Although these have mostly been the focus of interest for potential future applications, they also offer an opportunity for studying more fundamental quantum many-body effects. Here, we examine the magnetic-field-driven quantum phase transition that occurs in electrostatically gated superconducting LaTiO3/SrTiO3 interfaces. Through a finite-size scaling analysis, we show that it belongs to the (2+1)D XY model universality class. The system can be described as a disordered array of superconducting puddles coupled by a 2DEG and, depending on its conductance, the observed critical behaviour is single (corresponding to the long-range phase coherence in the whole array) or double (one related to local phase coherence, the other one to the array). A phase diagram illustrating the dependence of the critical field on the 2DEG conductance is constructed, and shown to agree with theoretical proposals. Moreover, by retrieving the coherence-length critical exponent ν, we show that the quantum critical behaviour can be clean or dirty according to the Harris criterion, depending on whether the phase-coherence length is smaller or larger than the size of the puddles.

Intrinsic instability of electronic interfaces with strong Rashba coupling.

We consider a model for the two-dimensional electron gas formed at the interface of oxide heterostructures, which includes a Rashba spin-orbit coupling proportional to the electric field perpendicular to the interface. Based on the standard mechanism of polarity catastrophe, we assume that the electric field has a contribution proportional to the electron density. Under these simple and general assumptions, we show that a phase separation instability (signaled by a negative compressibility) occurs for realistic values of the spin-orbit coupling and of the electronic band-structure parameters. This provides an intrinsic mechanism for the inhomogeneous phases observed at the LaAlO(3)/SrTiO(3) or LaTiO(3)/SrTiO(3) interfaces.

Concomitant evaluation of flow-mediated vasodilation and epicardial fat thickness in idiopathic deep venous thrombosis.

Flow mediated vasodilation (FMD) evaluates the endothelium-dependent vasodilation, is a reliable marker of arterial endothelial dysfunction and is related to coronary artery disease. Visceral fat predicts an unfavorable cardiovascular and metabolic risk profile in humans and echocardiographic assessment of epicardial fat (EF) is a reliable marker of visceral adiposity. We measured the FMD and EF thickness in 77 subjects, 38 without idiopathic deep vein thrombosis (DVT) (mean age 65.95 ± 16.29 years) and 39 with idiopathic DVT (mean age 65.49 ± 17.22 years). The purpose of this work is to investigate the presence of statistical association between FMD and DVT and between EF thickness and DVT. Furthermore, to account for possible atherosclerosis risk factor unbalances, comparison between FMD and DVT (and between EF and DVT) was assessed using a multivariate logistic regression model which included the following covariates: FMD, EF, age, sex, smoking and the presence of obesity. Subjects without DVT showed significant lower values of EF thickness (9.07 ± 1.89 mm vs 12.32 ± 1.73 mm, p=0.005) and borderline-significant greater values of FMD (9.01 ± 2.77 percent vs 7.47 ± 5.37 percent, p=0.058) as compared to those with DVT. In conclusion, the data presented indicate that subjects affected by spontaneous deep vein thrombosis may have an impaired endothelium-dependent vasodilation, a marker of arterial endothelial dysfunction related to coronary artery disease, and an increased epicardial adipose tissue, a marker of cardiometabolic risk.

Arterial endothelial dysfunction and idiopathic deep venous thrombosis.

Recent epidemiological studies have highlighted higher risk of subsequent development of atherosclerotic disease in patients with deep venous thrombosis (DVT). We evaluated the Flow Mediated Dilation (FMD) looking for arterial endothelial dysfunction, predictive for future ischaemic cardiovascular events, in patients with idiopathic DVT. FMD was measured in the brachial artery in 60 subjects with idiopathic DVT (age 60.1±17.4) and in 60 subjects without idiopathic DVT (age 61.2±15.1), with a similar cardiovascular risk factor profile. DVT patients showed lower FMD (6.78%±5.53% vs 10.88±3.31%, p<0.001). Univariate linear models showed that obesity (p=0.010), dyslipidemia (p=0.004), arterial hypertension (p=0.046), use of platelet anti-aggregating agents (p=0.018) and DVT (p<0.001) were associated to lower levels of FMD. In multivariate linear model, only DVT (p<0.001) remained an independent predictor of lower levels of FMD. Furthermore, an 8.5% cut-off value of FMD was chosen in a ROC curve analysis. Values of FMD ≤ 8.5% were more frequent in DVT patients (71.67% vs 41.67%, p<0.001). Univariate logistic regression models showed that dyslipidemia (p=0.008), use of platelet anti-aggregating agents (p=0.004) and DVT (p<0.001) were associated to a higher risk of having FMD ≤ 8.5%. Multivariate logistic regression model showed that DVT was the unique independent predictor for FMD ≤ 8.5% (p<0.001). In conclusion, DVT patients more frequently have impaired FMD, recognized as an indicator of arterial endothelial dysfunction and a marker for increased cardiovascular risk.

Pre-synaptic nicotinic receptors evoke endogenous glutamate and aspartate release from hippocampal synaptosomes by way of distinct coupling mechanisms.

BACKGROUND AND PURPOSE: The present work aimed to investigate whether and through which mechanisms selective α7 and α4ß2 nicotinic receptor (nAChR) agonists stimulate endogenous glutamate (GLU) and aspartate (ASP) release in rat hippocampus. EXPERIMENTAL APPROACH: Rat hippocampal synaptosomes were purified on Percoll gradients and superfused in vitro to study endogenous GLU and ASP release. The synaptosomes were superfused with selective α7 and α4ß2 nAChR agonists and antagonists. The excitatory amino acid (EAA) content of the samples of superfusate was determined by HPLC after pre-column derivatization and separation on a chromatographic column coupled with fluorimetric detection. KEY RESULTS: Choline (Ch), a selective α7 receptor agonist, elicited a significant release of both GLU and ASP which was blocked by the α7 receptor antagonist methyllycaconitine (MLA), but was unaltered by the α4ß2 receptor antagonist dihydro-ß-erythroidine (DHßE). The stimulant effect of Ch was strongly reduced in a Ca(2+) -free medium, was not inhibited by Cd(2+) and tetrodotoxin (TTX), but was antagonized by dantrolene, xestospongin C and thapsigargin. 5-Iodo-A-85380 dihydrochloride (5IA85380), a selective α4ß2 receptor agonist, elicited EAA release in a DHßE-sensitive, MLA-insensitive fashion. The 5IA85380-evoked release was dependent on extracellular Ca(2+) , blocked by Cd(2+) and TTX, but unaffected by dantrolene. CONCLUSIONS AND IMPLICATIONS: Our study shows for the first time that rat hippocampal synaptosomes possess α7 and α4ß2 nAChR subtypes, which can enhance the release of endogenous GLU and ASP via two distinct mechanisms of action. These results extend our knowledge of the nicotinic modulation of excitatory synaptic transmission in the hippocampus.

Specific inhibitory effect of amyloid-beta on presynaptic muscarinic receptor subtypes modulating neurotransmitter release in the rat nucleus accumbens.

In this study we investigate on the effect of amyloid-beta1-40 (A beta 1-40) on the oxotremorine (OXO)-induced release of [(3)H] dopamine (DA), [(3)H]GABA and [(3)H]acetylcholine (ACh) from synaptosomes in the rat nucleus accumbens (NAc). OXO in presence of himbacine (HIMBA) was able to increase the basal release of [(3)H]GABA. The OXO-elicited [(3)H]GABA overflow was significantly antagonized by atropine (A; 94%), by the M3 antagonists DAU5884 (96%) and 4-DAMP (70%), and by A beta 1-40 (65%). Exposure of NAc synaptosomes to OXO produced a dose-dependent increase of [(3)H]DA overflow which was antagonized by A, partially inhibited by A beta 1-40 (100 nM) but unaffected by DAU5884 and 4-DAMP. The K(+)-evoked [(3)H]ACh overflow was inhibited by OXO. This effect was counteracted by the M2 antagonist AFDX-116 but not by the selective M4 antagonist mamba toxin 3 (MT3). The K(+)-evoked [(3)H]GABA overflow was also inhibited by OXO but conversely, this effect was counteracted by MT3 and not by AFDX-116. A beta 1-40 (100 nM) did not modify the inhibitory effect of OXO both on the K(+)-evoked [(3)H]ACh and [(3)H]GABA overflow. The results show that in the rat NAc, A beta 1-40 selectively inhibits the function of the muscarinic subtypes which stimulate neurotransmitter release and not those which modulate negatively the stimulated release.