Efficacy and safety of rivaroxaban versus placebo after lower extremity bypass surgery: A post hoc analysis of a "CASPAR like" outcome from VOYAGER PAD.

BACKGROUND: The Clopidogrel and Acetylsalicylic Acid in Bypass Surgery for Peripheral Arterial Disease (CASPAR) trial is the only large, double-blind, placebo-controlled trial of dual antiplatelet therapy (DAPT) versus aspirin in patients with peripheral artery disease (PAD) after lower extremity revascularization (LER). The trial was neutral for index-graft occlusion/revascularization, amputation or death (hazard ratio [HR] 0.98, 95% confidence interval [CI] 0.78-1.23, p = .87) with an excess of global utilization of streptokinase and tissue plasminogen activator for occluded coronary arteries moderate or severe bleeding (HR 2.84, 95% CI 1.32-6.08, p = .007). HYPOTHESIS AND METHODS: VOYAGER-PAD demonstrated that rivaroxaban significantly reduces acute limb ischemia (ALI), major amputation, myocardial infarction (MI), stroke and CV death but increased bleeding. The relative efficacy and safety of rivaroxaban in a CASPAR like population and for similar outcomes is unknown. The current analysis is a post-hoc exploratory analysis of a "CASPAR like" composite of ALI, unplanned index limb revascularization (UILR), amputation or CV death in surgical patients. RESULTS: In the 2185 who underwent surgical LER, rivaroxaban reduced the CASPAR endpoint at 1 (HR 0.76, 95% CI 0.62-0.95, p = .0133) and 3 years (HR 0.84, 95% CI 0.71-1.00, p = .0461, Figure). There were similar reductions in composites of ALI, amputation or CV death (HR 0.79, p = .0228) and ALI, UILR, amputation, MI, IS or CV death (HR 0.85, p = .0410). CONCLUSIONS: The combination of rivaroxaban and aspirin significantly reduces ischemic outcomes in patients with PAD after LER. Although no formal head-to-head comparison exists, in a similar population and for similar outcomes, this regimen demonstrated benefit where trials of DAPT were neutral. These data suggest that factor Xa inhibition may provide specific benefits in this population and that DAPT should not be considered a proven substitution.

Revascularisation for Symptomatic Peripheral Artery Disease: External Applicability of the VOYAGER PAD Trial.

OBJECTIVE: In the VOYAGER PAD trial, rivaroxaban 2.5 mg plus aspirin significantly reduced the primary composite efficacy outcome of acute limb ischaemia, major amputation, myocardial infarction, ischaemic stroke, or cardiovascular death compared with aspirin alone. However, patients enrolled in the trial may not reflect patients encountered in daily clinical practice. This study described the proportion of patients eligible for VOYAGER PAD within the nationwide Danish Vascular Registry (DVR), reasons for ineligibility, and outcomes according to eligibility. METHODS: In total, 32 911 patients who underwent lower extremity revascularisation for symptomatic peripheral arterial disease (PAD) in the DVR (2000-2016) were identified. Trial inclusion and exclusion criteria were applied, and the three year cumulative incidence of primary and secondary trial outcomes was estimated. RESULTS: Altogether, 27.1% of patients with PAD in the DVR were "VOYAGER eligible". Of those not included, 30.7% had at least one exclusion criterion ("VOYAGER excluded"), and an additional 42.3% did not fulfil the inclusion criteria ("VOYAGER not included"). The main reasons for exclusion were atrial fibrillation (32.3%), poorly regulated hypertension (20.6%), requirement for long term dual antiplatelet therapy (10.9%), cytochrome P450 inhibitors or inducers (9.7%), and renal failure (9.3%). The three year rate of the primary efficacy outcome was 10.08 per 100 person years among the "VOYAGER eligible", 16.32 among "VOYAGER excluded", and 6.98 among the "VOYAGER not included". For the primary safety outcome of thrombolysis in myocardial infarction (TIMI) major bleeding, rates were 2.24, 3.76, and 1.17, respectively. Rates of secondary endpoints were also consistently lower for patients who did not meet the inclusion criteria (predominantly due to central aorto-iliac procedures) and highest for "VOYAGER excluded" patients. "VOYAGER eligible" patients experienced a higher cumulative incidence of most endpoints than patients enrolled in the control arm of the VOYAGER PAD trial. CONCLUSION: Among patients in routine clinical practice, 27.1% were eligible for the VOYAGER PAD trial. These patients were older, had more severe vascular symptoms, higher bleeding risk, and worse prognosis than trial participants.

Improving the Usability of Galileo and Voyager Images of Jupiter's Moon Europa.

NASA's Voyager 1, Voyager 2, and Galileo spacecraft acquired hundreds of images of Jupiter's moon Europa. These images provide the only moderate- to high-resolution views of the moon's surface and are therefore a critical resource for scientific analysis and future mission planning. Unfortunately, uncertain knowledge of the spacecraft's position and pointing during image acquisition resulted in significant errors in the location of the images on the surface. The result is that adjacent images are poorly aligned, with some images displaced by more than 100 km from their correct location. These errors severely degrade the usability of the Voyager and Galileo imaging data sets. To improve the usability of these data sets, we used the U.S. Geological Survey Integrated Software for Imagers and Spectrometers to build a nearly global image tie-point network with more than 50,000 tie points and 135,000 image measurements on 481 Galileo and 221 Voyager images. A global least-squares bundle adjustment of our final Europa tie-point network calculated latitude, longitude, and radius values for each point by minimizing residuals globally, and resulted in root mean square (RMS) uncertainties of 246.6 m, 307.0 m, and 70.5 m in latitude, longitude, and radius, respectively. The total RMS uncertainty was 0.32 pixels. This work enables direct use of nearly the entire Galileo and Voyager image data sets for Europa. We are providing the community with updated NASA Navigation and Ancillary Information Facility Spacecraft, Planet, Instrument, C-matrix (pointing), and Events kernels, mosaics of Galileo images acquired during each observation sequence, and individual processed and projected level 2 images.

[Modern strategy to improve remote results of surgical treatment of peripheral artery disease]. / Sovremennaia strategiia uluchsheniia otdalennykh rezul'tatov khirurgicheskogo lecheniia zabolevanii perifericheskikh arterii.

Treatment of patients presenting with peripheral artery disease requires a comprehensive approach: correction of risk factors, drug therapy and, if necessary, an endovascular/hybrid/open intervention. Reconstructive operation may effectively improve a patient's quality of life in intermittent claudication, save the limb and life in case of severe ischaemia. Discussed in the article are advantages and disadvantages of various types of surgical interventions for peripheral artery disease, the concept PLAN (Patient risk, Limb severity, and ANatomic complexity) and the new Global Anatomic Staging System (GLASS). Good remote results may be ensured by adequate medicamentous therapy. Variations of antithrombotic therapy are versatile and debatable. Long-term dual antithrombotic or systemic anticoagulant therapy with administration of vitamin K antagonists are not indicated for peripheral artery disease. In this connection, the findings of the COMPASS and VOYAGER PAD studies are analysed. The VOYAGER PAD trial showed that in patients with peripheral artery disease who underwent revascularization of lower limbs, the addition of rivaroxaban at a dose of 2.5 mg twice daily to aspirin decreased the risk of lower-extremity unfavourable ischaemic events and major adverse cardiovascular events by 15%. The obtained findings open new possibilities of conservative therapy having a significant role in decreasing the risk for development of limb-threatening conditions.

Lessons learned from (and since) the Voyager 2 flybys of Uranus and Neptune.

More than 30 years have passed since the Voyager 2 flybys of Uranus and Neptune. This paper outlines a range of lessons learned from Voyager, broadly grouped into 'process, planning and people.' In terms of process, we must be open to new concepts, whether new instrument technologies, new propulsion systems or operational modes. Examples from recent decades that could open new vistas in the exploration of the deep outer Solar System include the Cassini Resource Exchange and the 'sleep' mode from the New Horizons mission. Planning is crucial: mission gaps that last over three decades leave much scope for evolution both in mission development and in the targets themselves. The science is covered in other papers in this issue, but this paper addresses the structure of the US Planetary Decadal Surveys, with a specific urging to move from a 'destination-based' organization to a structure based on fundamental science. Coordination of distinct and divergent international planning timelines brings both challenges and opportunity. Complexity in the funding and political processes is amplified when multiple structures must be navigated; but the science is enriched by the diversity of international perspectives, as were represented at the Ice Giant discussion meeting that motivated this review. Finally, the paper turns to people: with generational-length gaps between missions, continuity in knowledge and skills requires careful attention to people. Lessons for the next generation of voyagers include: how to lead and inspire; how to develop the perspective to see their missions through decades-long development phases; and cultivation of strategic thinking, altruism and above all, patience. This article is part of a discussion meeting issue 'Future exploration of ice giant systems'.

Predictions of cognitive detriments from galactic cosmic ray exposures to astronauts on exploration missions.

For the first-time we report on predictions on cognitive detriments from galactic cosmic ray (GCR) exposures on long-duration space missions outside the protection of the Earth's magnetosphere and solid body shielding. Estimates are based on a relative risk (RR) model of the fluence response for proton and heavy ion in rodent studies using the widely used novel object recognition (NOR) test, which estimates detriments in recognition or object memory. Our recent meta-analysis showed that linear and linear-quadratic dose response models were not accurate, while exponential increasing fluence response models based on particle track structure provided good descriptions of rodent data for doses up to 1 Gy. Using detailed models of the GCR environment and particle transport in shielding and tissue, we predict the excess relative risk (ERR) for NOR detriments for several long-term space mission scenarios. Predictions suggest ERR < 0.15 for most space mission scenarios with ERR<0.1 for 1-year lunar surface missions, and about ERR~0.1 for a 1000 day Mars mission for average solar cycle conditions. We discuss possible implications of these ERR levels of cognitive performance detriments relative to other neurological challenges such as rodent models of Alzheimer's disease (AD), Parkinson's disease (PD) and traumatic brain injury (TBI). Comparisons suggest a small but potentially clinically significant risk for possible space mission scenarios.

Lo mejor del Congreso Virtual ACC/WCC 2020 / The best of the 2020 ACC/WCC Virtual Congress / O melhor do Congresso Virtual ACC/WCC 2020

Resumen: La pandemia generada por el SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus) ha constituido un desafío mundial. En momentos de dificultad como los que se han presentado recientemente, es aún más necesaria la investigación para avanzar en el diagnóstico y tratamiento de las diferentes patologías. Utilizando el amplio desarrollo de los medios de comunicación, este año el Congreso del Colegio Americano de Cardiología (ACC por su sigla en inglés) se celebró del 28 al 30 de marzo en un formato virtual, permitiendo a profesionales de todo el mundo acceder a múltiples actividades científicas con el mismo nivel de excelencia que en las sesiones presenciales. Realizaremos un breve resumen de alguno de los principales trabajos científicos presentados: - Tailored Antiplatelet Initiation to Lessen Outcomes Due to Decreased Clopidogrel Response after Percutaneous Coronary Intervention: TAILOR-PCI. - Rivaroxaban in Peripheral Artery Disease after Revascularization: VOYAGER PAD trial. - Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction: VICTORIA Study Group. - The Evolut Low Risk Bicuspid Study. - PARTNER 3. Two-year clinical and echocardiographic outcomes. - Ticagrelor with and without Aspirin in Acute Coronary Syndrome After PCI: the TICO Trial - Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer: Caravaggio trial. - Ten-year Outcomes After Drug-eluting Stents Versus Coronary Artery Bypass Grafting for Left Main Coronary Disease: Extended Follow Up of the PRECOMBAT Trial. - Anticoagulation with or without Clopidogrel after Transcatheter Aortic-Valve Implantation: POPular TAVI.

Summary The SARS-CoV-2 pandemic has been a global challenge. In times of difficulty such as those that have recently arisen, research is even more necessary to advance in the diagnosis and treatment of different pathologies. Using the extensive development of the media, this year the American Congress of Cardiology was held from March 28 to 30 in a virtual format, allowing professionals from around the world to access multiple scientific activities with the same level of excellence as in face-to-face sessions. We will make a brief summary of some of the main scientific papers presented: - Tailored Antiplatelet Initiation to Lessen Outcomes Due to Decreased Clopidogrel Response after Percutaneous Coronary Intervention: TAILOR-PCI. - Rivaroxaban in Peripheral Artery Disease after Revascularization: VOYAGER PAD trial:. - Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction: VICTORIA Study Group. - The Evolut Low Risk Bicuspid Study. - PARTNER 3. Two-year clinical and echocardiographic outcomes. - Ticagrelor with and without Aspirin in Acute Coronary Syndrome After PCI: the TICO Trial. - Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer: Caravaggio trial. - Ten-year Outcomes After Drug-eluting Stents Versus Coronary Artery Bypass Grafting for Left Main Coronary Disease: Extended Follow Up of the PRECOMBAT Trial. - Anticoagulation with or without Clopidogrel after Transcatheter Aortic-Valve Implantation: POPular TAVI.

Resumo: A pandemia de SARS-CoV-2 tem sido um desafio global. Em tempos de dificuldade como os que surgiram recentemente, a pesquisa é ainda mais necessária para avançar no diagnóstico e tratamento de diferentes patologias. Utilizando o amplo desenvolvimento da mídia, este ano o Congresso Americano de Cardiologia foi realizado de 28 ao 30 de março em um formato virtual, permitindo que profissionais de todo o mundo acessassem diversas atividades científicas com o mesmo nível de excelência que nas sessões presenciais. Faremos um breve resumo de alguns dos principais trabalhos científicos apresentados: - Tailored Antiplatelet Initiation to Lessen Outcomes Due to Decreased Clopidogrel Response after Percutaneous Coronary Intervention: TAILOR - PCI. - Rivaroxaban in Peripheral Artery Disease after Revascularization: VOYAGER PAD trial. - Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction: VICTORIA Study Group. - The Evolut Low Risk Bicuspid Study. - PARTNER 3. Two-year clinical and echocardiographic outcomes. - Ticagrelor with and without Aspirin in Acute Coronary Syndrome After PCI: the TICO Trial. - Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer: Caravaggio trial. - Ten-year Outcomes After Drug-eluting Stents Versus Coronary Artery Bypass Grafting for Left Main Coronary Disease: Extended Follow Up of the PRECOMBAT Trial. - Anticoagulation with or without Clopidogrel after Transcatheter Aortic-Valve Implantation: POPular TAVI.

Terraforming: synthetic biology's final frontier.

Synthetic biology, the design and synthesis of synthetic biological systems from DNA to whole cells, has provided us with the ultimate tools for space exploration and colonisation. Herein, we explore some of the most significant advances and future prospects in the field of synthetic biology, in the context of astrobiology and terraforming.

A feasibility study of the Nativis Voyager® device in patients with recurrent glioblastoma in Australia.

AIM: Evaluation of the Nativis Voyager®, an investigational medical device, as monotherapy for recurrent glioblastoma (rGBM). MATERIALS & METHODS: A total of 15 patients with rGBM were treated with one of two Voyager ultra-low radio frequency energy cognates: A1A or A2HU. Safety and clinical utility were assessed every 2-4 months. RESULTS: Median overall survival was 8.04 months in the A1A arm and 6.89 months in the A2HU arm. No serious adverse events associated with Voyager were reported. No clinically relevant trends were noted in clinical laboratory parameters or physical exams. CONCLUSION: The data suggest that the Voyager is safe and feasible for the treatment of rGBM.

Comparing a novel equation for calculating low-density lipoprotein cholesterol with the Friedewald equation: A VOYAGER analysis.

Treating elevated low-density lipoprotein cholesterol (LDL-C) to risk-stratified target levels is recommended in several guidelines. Thus, accurate estimation of LDL-C is required. LDL-C is typically calculated using the Friedewald equation: (total cholesterol) - (non-high-density lipoprotein cholesterol [non-HDL-C]) - (triglycerides [TGs]/5). As the equation uses a fixed value equal to 5 as a divisor for TGs, it does not account for inter-individual variability, often resulting in underestimation of risk and potentially undertreatment. It is specifically inapplicable in patients with fasting triglycerides ≥400 mg/dL. A novel method of LDL-C calculation was derived and validated by Martin et al.: (non-HDL-C) - (triglycerides/adjustable factor). This equation uses an adjustable factor, the median TG:very-low-density lipoprotein cholesterol ratio in strata defined by levels of TG and non-HDLC, as divisor for TGs, and the adjustable factor ranging from 3 to 12 has been shown to provide more accurate estimates of LDL-C compared with the Friedewald equation using a direct assay as the gold standard. We used 70,209 baseline and on-treatment lipid values from the VOYAGER meta-analysis database to determine the difference in calculated LDL-C values using the Friedewald and novel equations. In patients with TGs <400 mg/dL, LDL-C values calculated using the novel equation were plotted against those calculated using the Friedewald equation. The novel equation generally resulted in LDL-C values greater than the Friedewald calculation, with differences increasing with decreasing LDL-C levels; 23% of individuals who reached a LDL-C target of 70 mg/dL with the Friedewald equation did not achieve this target when the novel equation was used to calculate LDL-C; these figures were 8% and 2% for <100 mg/dL and < 130 mg/dL targets, respectively. In patients with triglycerides ≥400 mg/dL, in whom the Friedewald equation is not valid, lipid values calculated using the novel equation were compared with those obtained by ß-quantification. Values calculated with the novel equation did not appear to be closely related with those calculated by ß-quantification in these patients. In conclusion, the novel equation provides a higher estimation of exact LDL-C values than the Friedewald equation, particularly in patients with low LDL-C levels, which may result in undertreatment of some patients whose LDL-C was calculated using the Friedewald method. However, neither may be suitable for patients with TG ≥400 mg/dL.

Voyager observations of the interaction of the heliosphere with the interstellar medium.

This paper provides a brief review and update on the Voyager observations of the interaction of the heliosphere with the interstellar medium. Voyager has found many surprises: (1) a new energetic particle component which is accelerated at the termination shock (TS) and leaks into the outer heliosphere forming a foreshock region; (2) a termination shock which is modulated by energetic particles and which transfers most of the solar wind flow energy to the pickup ions (not the thermal ions); (3) the heliosphere is asymmetric; (4) the TS does not accelerate anomalous cosmic rays at the Voyager locations; and (5) the plasma flow in the Voyagers 1 (V1) and 2 (V2) directions are very different. At V1 the flow was small after the TS and has recently slowed to near zero, whereas at V2 the speed has remained constant while the flow direction has turned tailward. V1 may have entered an extended boundary region in front of the heliopause (HP) in 2010 in which the plasma flow speeds are near zero.