Comparison of Baseline Characteristics and Outcomes in Men Versus Women With Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation

Female gender has been linked to increased risk of adverse events after surgical aortic valve replacement; however, the evidence regarding the role of gender differences on clinical outcomes in patients who underwent transcatheter aortic valve implantation (TAVI) is still debated. This retrospective study included 910 consecutive patients with severe, symptomatic aortic stenosis who underwent TAVI in 2 institutions from January 2012 to July 2016. The primary end point was all-cause mortality at 1 year after TAVI in women versus men. Women had a higher incidence of in-hospital vascular complications (7.8% vs 4.1%) and major or life-threatening bleeding (4.0% vs 1.6%) than men. At 1 year, women showed a lower mortality rate than men (7.0% vs 12.7%, adjusted hazard ratio [HR] 0.42, 95% confidence interval [CI] [0.23 to 0.76], p = 0.004). When stratifying by specific subgroups of interest, the survival benefit in women persisted in (1) patients with a Society of Thoracic Surgery risk score ≤ 8 (adjusted HR 0.35, 95% CI [0.14 to 0.88], p = 0.026); (2) patients treated with first-generation devices (adjusted HR 0.46, 95% CI [0.24 to 0.86], p = 0.016); and (3) patients treated with balloon-expandable valves (adjusted HR 0.40, 95% CI [0.19 to 0.86], p = 0.019). In conclusion, in this large patient cohort, women had lower 1-year mortality after TAVI than men, particularly with an STS score ≤ 8, or treated with first-generation and balloon-expandable devices

Biophysical and biochemical characterization of a liposarcoma-derived recombinant MnSOD protein acting as an anticancer agent

A recombinant MnSOD (rMnSOD) synthesized by specific cDNA clones derived from a liposarcoma cell line was shown to have the same sequence as the wild-type MnSOD expressed in the human myeloid leukaemia cell line U937, except for the presence of the leader peptide at the N-terminus. These results were fully confirmed by the molecular mass of rMnSOD as evaluated by ES/MS analysis (26662.7 Da) and the nucleotide sequence of the MnSOD cDNA. The role of the leader peptide in rMnSOD was investigated using a fluorescent and/or 68Gallium-labelled synthetic peptide. The labelled peptide permeated MCF-7 cells and uptake could be inhibited in the presence of an excess of oestrogen. In vivo it was taken up by the tumour, suggesting that the molecule can be used for both therapy and diagnosis. The in vitro and in vivo pharmacology tests confirmed that rMnSOD is only oncotoxic for tumour cells expressing oestrogen receptors. Pharmacokinetic studies in animals performed with 125I- and 131I-labelled proteins confirmed that, when administered systemically, rMnSOD selectively reached the tumour, where its presence was unambiguously demonstrated by scintigraphic and PET scans. PCR analysis revealed that Bax gene expression was increased and the Bcl2 gene was down regulated in MCF7 cells treated with rMnSOD, which suggests that the protein induces a pro-apoptotic mechanism

Fuzzy logic on quantum annealers

Quantum computation is going to revolutionize the world of computing by enabling the design of massive parallel algorithms that solve hard problems in an efficient way, thanks to the exploitation of quantum mechanics effects, such as superposition, entanglement and interference. These computational improvements could strongly influence the way how fuzzy systems are designed and used in contexts, such as big data, where computational efficiency represents a non-negligible constraint to be taken into account. In order to pave the way towards this innovative scenario, this paper introduces a novel representation of fuzzy sets and operators based on Quadratic Unconstrained Binary Optimization (QUBO) problems, so as to enable the implementation of fuzzy inference engines on a type of quantum computers known as quantum annealers

Heart failure with preserved ejection fraction in humans and mice:Embracing clinical complexity in mouse models

Heart failure (HF) with preserved ejection fraction (HFpEF) is a multifactorial disease accounting for a large and increasing proportion of all clinical HF presentations. As a clinical syndrome, HFpEF is characterized by typical signs and symptoms of HF, a distinct cardiac phenotype and raised natriuretic peptides. Non-cardiac comorbidities frequently co-exist and contribute to the pathophysiology of HFpEF. To date, no therapy has proven to improve outcomes in HFpEF, with drug development hampered, at least partly, by lack of consensus on appropriate standards for pre-clinical HFpEF models. Recently, two clinical algorithms (HFA-PEFF and H(2)FPEF scores) have been developed to improve and standardize the diagnosis of HFpEF. In this review, we evaluate the translational utility of HFpEF mouse models in the context of these HFpEF scores. We systematically recorded evidence of symptoms and signs of HF or clinical HFpEF features and included several cardiac and extra-cardiac parameters as well as age and sex for each HFpEF mouse model. We found that most of the pre-clinical HFpEF models do not meet the HFpEF clinical criteria, although some multifactorial models resemble human HFpEF to a reasonable extent. We therefore conclude that to optimize the translational value of mouse models to human HFpEF, a novel approach for the development of pre-clinical HFpEF models is needed, taking into account the complex HFpEF pathophysiology in humans

Fuzzy inference on quantum annealers

Quantum computers can potentially perform certain types of optimisation problems much more efficiently than classical computers, making them a promising tool for solving complex fuzzy logic problems. In two recent developments, based on solving Quadratic Unconstrained Binary Optimization (QUBO) problems on a type of quantum computers known as quantum annealers, we have introduced novel representations of a) fuzzy sets; b) implementations of some basic fuzzy logic operators (union, intersection, alpha-cut and maximum) and; c) the centroid defuzzification. In this paper, the previous works are further extended by presenting an implementation of Mamdani inference on the quantum annealer machines. We first present how the fuzzy rules can be formulated for such an implementation, then we present how to cascade different quantum-fuzzy operators in order to implement the quantum-fuzzy inference, and finally, a sample implementation of the inference on a real quantum computer is demonstrated. Having the main components of a rule-based fuzzy logic system implemented on quantum computers, this paper provides an integrated solution for implementing a whole fuzzy rule-based system on quantum computers

Hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer recurrence: systematic review and meta-analysis.

Background: Ovarian cancer is the first cause of death among gynecological malignancies with a high incidence of recurrence. Different treatment options are suitable to prolong the survival rate of these patients. Over the last years, one of the most intriguing methods, adopted in different oncologic centers worldwide, is the hyperthermic intraperitoneal chemotherapy (HIPEC). Methods: A meta-analysis was performed to value the role of HIPEC for ovarian cancer recurrence. Search strategy was conducted with a combination of the following keywords: "ovarian recurrence, ovarian cancer recurrence, peritoneal cancer recurrence, ovarian recurrence AND HIPEC, secondary cytoreduction HIPEC". Seven studies were selected for analysis. Results: In women with recurrent ovarian cancer (ROC), the use of HIPEC in addition to cytoreductive surgery and chemotherapy significantly improved 1-year overall survival (OS) when compared to protocols without HIPEC (OR 2.42; 95% CI, 1.06-5.56; P=0.04; I2=4%). The improvement in OS was maintained significant also after 2, 3 and 5 years respectively (OR 3.33; 95% CI, 1.81-6.10; P<0.01; I2=0%), (OR 4.22; 95% CI, 2.07-8.60; P<0.01; I2=52%), (OR 5.17; 95% CI, 1.40-19.09; P=0.01; I2=82%). Conclusions: HIPEC seems to have an effective role to prolong survival in patients affected by ROC

Cerebral embolic lesions detected with diffusion-weighted magnetic resonance imaging following carotid artery stenting: a meta-analysis of 8 studies comparing filter cerebral protection and proximal balloon occlusion.

OBJECTIVES: The aim of this meta-analysis was to evaluate and compare the efficacy of the 2 different neuroprotection systems in preventing embolization during carotid artery stenting (CAS), as detected by diffusion-weighted magnetic resonance imaging (DW-MRI). BACKGROUND: Data from randomized and nonrandomized studies comparing both types of embolic protection devices revealed contrasting evidence about their efficacy in neuroprotection, as assessed by the incidence of new ischemic lesions detected by DW-MRI. METHODS: Eight studies, enrolling 357 patients, were included in the meta-analysis. Our study analyzed the incidence of new ischemic lesions/patient, comparing filter cerebral protection and proximal balloon occlusion. RESULTS: Following CAS, the incidence of new ischemic lesions/patient detected by DW-MRI was significantly lower in the proximal balloon occlusion group (effect size [ES]: -0.43; 95% confidence interval [CI]: -0.84 to -0.02, I(2) = 70.08, Q = 23.40). Furthermore, following CAS, the incidence of lesions at the contralateral site was significantly lower in the proximal protection group (ES: -0.50; 95% CI: -0.72 to -0.27, I(2) = 0.00, Q = 3.80). CONCLUSIONS: Our meta-analysis supports the concept that the use of proximal balloon occlusion compared with filter cerebral protection is associated with a reduction of the amount of CAS-related brain embolization. The data should be confirmed by a randomized clinical tria