Clinical and angiographic outcomes with drug-coated balloons for de novo coronary lesions: A meta-analysis of randomized clinical trials

Background The role of drug-coated balloons (DCBs) in the treatment of de novo coronary lesions is not well established. Methods and Results Electronic databases and major conference proceedings were searched for randomized controlled trials that compared DCBs with stents or angioplasty for de novo coronary lesions. The primary outcome was target lesion revascularization. Summary estimates were conducted using random-effects analysis complemented by several subgroup and sensitivity analyses. A total of 14 randomized controlled trials with 2483 patients were included. At a mean follow up of 12 months, DCBs were associated with no difference in the incidence of target lesion revascularization as compared with alternative strategies (risk ratio [RR], 0.79; 95% CI, 0.35-1.76). There was no difference in treatment effect based on the indication (ie, small-vessel disease, myocardial infarction, bifurcation, or high bleeding risk) (Pinteraction=0.22). DCBs were associated with lower target lesion revascularization compared with bare metal stents and similar target lesion revascularization compared with drug-eluting stents (Pinteraction=0.03). There was no difference between DCBs and control in terms of major adverse cardiac events, vessel thrombosis, or cardiovascular mortality. However, DCBs were associated with a lower incidence of myocardial infarction (RR, 0.48; 95% CI, 0.25-0.90) and all-cause mortality (RR, 0.45; 95% CI, 0.22-0.94). Conclusions In patients with de novo coronary lesions, use of DCBs was associated with comparable clinical outcomes irrespective of the indication or comparator device. DCBs had a similar rate of target lesion revascularization compared with drug-eluting stents. A randomized trial powered for clinical outcomes and evaluating the role of DCBs for all-comers is warranted

Data Analytics for the Cryptocurrencies Behavior

The cryptocurrencies are a new paradigm of transferring money be-tween users. Their anonymous and non-centralized is a subject of debate around the globe that paired with the massive spikes and declines in value that are in-herit to an unregistered asset. These facts make difficult for the common daily use of the cryptocurrencies as an exchange currency as instead they are being used as a new way to invest. What we propose in this article is a system for the better understanding of the cryptocurrencies economical behavior against the global market. For that we are using Data Analytics techniques to build a pre-dictor that uses as inputs said external financial variable. These forecasts would help determine if a coin is safe to trade with, if those forecasts can be precise by only using this external data. The results obtained indicates us that there is a certain degree of influence of the global market to the cryptocurrencies, but that is it not enough to correctly predict the fluctuations in price of the coins and that they care more about others factors and that they have their own bubbles, like the crypto collapse in late 2017.Instituto de Investigación en Informátic

Improvement of Subjective Well-Being by Ranolazine in Patients with Chronic Angina and Known Myocardial Ischemia (IMWELL Study)

Introduction: We aimed to assess if ranolazine would improve angina symptoms among patients with documented myocardial ischemia. Methods: Eligible subjects had chronic stable angina and at least one coronary stenosis with fractional flow reserve (FFR) ≤0.80 or at least one chronic total occlusion (CTO) without attempted revascularization. Subjects were randomized to oral ranolazine 500 mg twice daily for 1 week, then ranolazine 1000 mg twice daily for 15 weeks versus matching placebo. The primary end point was change in angina at 16 weeks as assessed by the Seattle Angina Questionnaire (SAQ). Results: Between September 2014 and January 2016, 25 subjects were randomized to ranolazine versus 25 to placebo. The most common reason for eligibility was CTO (72%), while the remainder had myocardial ischemia documented by low FFR. The mean FFR was 0.57 ± 0.12. Sixty-eight percent of subjects were on two or more anti-angina medications at baseline. Study medication was discontinued in 32% (eight of 25) of the ranolazine group versus 36% (nine of 25) of the placebo group. By intention-to-treat, 46 subjects had baseline and follow-up SAQ data completed. Ranolazine was not associated with an improvement in angina compared with placebo at 16 weeks. The results were similar among 33 subjects that completed study medication. The incidence of ischemia-driven hospitalization or catheterization was 12% (three of 25) of the ranolazine group versus 20% (five of 25) in the placebo group (p \u3e 0.05). Conclusions: In subjects with chronic stable angina and documented myocardial ischemia, ranolazine did not improve angina symptoms at 16 weeks

Early Invasive Strategy and In‐Hospital Survival Among Diabetics With Non‐ST‐Elevation Acute Coronary Syndromes: A Contemporary National Insight

Background: There are limited data on the merits of an early invasive strategy in diabetics with non‐ST‐elevation acute coronary syndrome, with unclear influence of this strategy on survival. The aim of this study was to evaluate the in‐hospital survival of diabetics with non‐ST‐elevation acute coronary syndrome treated with an early invasive strategy compared with an initial conservative strategy. Methods and Results: The National Inpatient Sample database, years 2012–2013, was queried for diabetics with a primary diagnosis of non‐ST‐elevation acute coronary syndrome defined as either non‐ST‐elevation myocardial infarction or unstable angina (unstable angina). An early invasive strategy was defined as coronary angiography±revascularization within 48 hours of admission. Propensity scores were used to assemble a cohort managed with either an early invasive or initial conservative strategy balanced on \u3e50 baseline characteristics and hospital presentations. Incidence of in‐hospital mortality was compared in both groups. In a cohort of 363 500 diabetics with non‐ST‐elevation acute coronary syndrome, 164 740 (45.3%) were treated with an early invasive strategy. Propensity scoring matched 21 681 diabetics in both arms. Incidence of in‐hospital mortality was lower with an early invasive strategy in both the unadjusted (2.0% vs 4.8%; odds ratio [OR], 0.41; 95% CI, 0.39–0.42; P\u3c0.0001) and propensity‐matched models (2.2% vs 3.8%; OR, 0.57; 95% CI, 0.50–0.63; P\u3c0.0001). The benefit was observed across various subgroups, except for patients with unstable angina (Pinteraction=0.02). Conclusions: An early invasive strategy may be associated with a lower incidence of in‐hospital mortality in patients with diabetes. The benefit of this strategy appears to be superior in patients presenting with non‐ST‐elevation myocardial infarction compared with unstable angina

Sex Differences in Transcatheter Structural Heart Disease Interventions: How Much Do We Know?

The number of structural heart disease interventions has greatly increased in the past decade. Moreover, interest in the sex-specific outcomes of various cardiovascular conditions and procedures has increased. In this review, we discuss the sex differences in the clinical profiles and outcomes of patients undergoing the most commonly performed structural procedures: transcatheter aortic valve replacement, transcatheter edge to edge repair of the mitral and tricuspid valve, transcatheter pulmonary valve replacement, patent foramen ovale closure and left atrial appendage occlusion. We shed light on potential reasons for these differences and emphasize the importance of increasing the representation of women in randomized clinical trials, to understand these differences and support the application of these cutting-edge technologies

The partially alternating ternary sum in an associative dialgebra

The alternating ternary sum in an associative algebra, $abc - acb - bac + bca + cab - cba$, gives rise to the partially alternating ternary sum in an associative dialgebra with products $\dashv$ and $\vdash$ by making the argument $a$ the center of each term: $a \dashv b \dashv c - a \dashv c \dashv b - b \vdash a \dashv c + c \vdash a \dashv b + b \vdash c \vdash a - c \vdash b \vdash a$. We use computer algebra to determine the polynomial identities in degree $\le 9$ satisfied by this new trilinear operation. In degrees 3 and 5 we obtain $[a,b,c] + [a,c,b] \equiv 0$ and $[a,[b,c,d],e] + [a,[c,b,d],e] \equiv 0$; these identities define a new variety of partially alternating ternary algebras. We show that there is a 49-dimensional space of multilinear identities in degree 7, and we find equivalent nonlinear identities. We use the representation theory of the symmetric group to show that there are no new identities in degree 9.Comment: 14 page

Mitochondrial pyruvate carrier inhibitors improve metabolic parameters in diet-induced obese mice

The mitochondrial pyruvate carrier (MPC) is an inner mitochondrial membrane complex that plays a critical role in intermediary metabolism. Inhibition of the MPC, especially in liver, may have efficacy for treating type 2 diabetes mellitus. Herein, we examined the antidiabetic effects of zaprinast and 7ACC2, small molecules which have been reported to act as MPC inhibitors. Both compounds activated a bioluminescence resonance energy transfer-based MPC reporter assay (reporter sensitive to pyruvate) and potently inhibited pyruvate-mediated respiration in isolated mitochondria. Furthermore, zaprinast and 7ACC2 acutely improved glucose tolerance in diet-induced obese mice in vivo. Although some findings were suggestive of improved insulin sensitivity, hyperinsulinemic-euglycemic clamp studies did not detect enhanced insulin action in response to 7ACC2 treatment. Rather, our data suggest acute glucose-lowering effects of MPC inhibition may be due to suppressed hepatic gluconeogenesis. Finally, we used reporter sensitive to pyruvate to screen a chemical library of drugs and identified 35 potentially novel MPC modulators. Using available evidence, we generated a pharmacophore model to prioritize which hits to pursue. Our analysis revealed carsalam and six quinolone antibiotics, as well as 7ACC1, share a common pharmacophore with 7ACC2. We validated that these compounds are novel inhibitors of the MPC and suppress hepatocyte glucose production and demonstrated that one quinolone (nalidixic acid) improved glucose tolerance in obese mice. In conclusion, these data demonstrate the feasibility of therapeutic targeting of the MPC for treating diabetes and provide scaffolds that can be used to develop potent and novel classes of MPC inhibitors

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death