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- Farmakis, D., et al.
(författare)
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Levosimendan beyond inotropy and acute heart failure: Evidence of pleiotropic effects on the heart and other organs: An expert panel position paper
- 2016
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 222, s. 303-312
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Tidskriftsartikel (refereegranskat)abstract
- Levosimendan is a positive inotrope with vasodilating properties (inodilator) indicated for decompensated heart failure (HF) patients with low cardiac output. Accumulated evidence supports several pleiotropic effects of levosimendan beyond inotropy, the heart and decompensated HF. Those effects are not readily explained by cardiac function enhancement and seem to be related to additional properties of the drug such as anti-inflammatory, anti-oxidative and anti-apoptotic ones. Mechanistic and proof-of-concept studies are still required to clarify the underlying mechanisms involved, while properly designed clinical trials are warranted to translate preclinical or early-phase clinical data into more robust clinical evidence. The present position paper, derived by a panel of 35 experts in the field of cardiology, cardiac anesthesiology, intensive care medicine, cardiac physiology, and cardiovascular pharmacology from 22 European countries, compiles the existing evidence on the pleiotropic effects of levosimendan, identifies potential novel areas of clinical application and defines the corresponding gaps in evidence and the required research efforts to address those gaps. © 2016 The Authors
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- Mesal, D., et al.
(författare)
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Exploring the R CrA environment with SPHERE Discovery of a new stellar companion
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 624
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Tidskriftsartikel (refereegranskat)abstract
- Aims. R Coronae Australis (R CrA) is the brightest star of the Coronet nebula of the Corona Australis (CrA) star forming region. This star is very red in color, probably due to dust absorption, and is strongly variable. High-contrast instruments allow for an unprecedented direct exploration of the immediate circumstellar environment of this star. Methods. We observed R CrA with the near-infrared (NIR) channels (IFS and IRDIS) of SPHERE at the Very Large Telescope (VET). In this paper, we used four different epochs, three of which are from open time observations while one is from SPHERE guaranteed time. The data were reduced using the data reduction and handling pipeline and the SPHERE Data Center. We implemented custom IDL routines on the reduced data with the aim to subtract the speckle halo. We have also obtained pupil-tracking H-band (1.45-1.85 mu m) observations with the VLT/SINFONI NIR medium-resolution (R similar to 3000) spectrograph. Results. A companion was found at a separation of 0.156 '' from the star in the first epoch and increasing to 0.184 '' in the final epoch. Furthermore, several extended structures were found around the star, the most noteworthy of which is a very bright jet-like structure northeast from the star. The astrometric measurements of the companion in the four epochs confirm that it is gravitationally bound to the star. The SPHERE photometry and SINFONI spectrum, once corrected for extinction, point toward a spectral type object that is early M with a mass between 0.3 and 0.55 M-circle dot. The astrometric analyis provides constraints on the orbit paramenters: e similar to 0.4, semimajor axis at 27-28 au, inclination of similar to 70 degrees, and a period larger than 30 yr. We were also able to put constraints of few M (jup) on the mass of possible other companions down to separations of few tens of au.
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- Pohl, A., et al.
(författare)
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The Circumstellar Disk HD 169142 : Gas, Dust, and Planets Acting in Concert?
- 2017
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 850:1
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Tidskriftsartikel (refereegranskat)abstract
- HD 169142 is an excellent target for investigating signs of planet-disk interaction due to previous evidence of gap structures. We perform J-band (similar to 1.2 mu m) polarized intensity imaging of HD 169142 with VLT/SPHERE. We observe polarized scattered light down to 0 ''.16 (similar to 19 au) and find an inner gap with a significantly reduced scattered-light flux. We confirm the previously detected double-ring structure peaking at 0 ''.18 (similar to 21 au) and 0 ''.56 (similar to 66 au) and marginally detect a faint third gap at 0 ''.70-0 ''.73 (similar to 82-85 au). We explore dust evolution models in a disk perturbed by two giant planets, as well as models with a parameterized dust size distribution. The dust evolution model is able to reproduce the ring locations and gap widths in polarized intensity but fails to reproduce their depths. However, it gives a good match with the ALMA dust continuum image at 1.3 mm. Models with a parameterized dust size distribution better reproduce the gap depth in scattered light, suggesting that dust filtration at the outer edges of the gaps is less effective. The pileup of millimeter grains in a dust trap and the continuous distribution of small grains throughout the gap likely require more efficient dust fragmentation and dust diffusion in the dust trap. Alternatively, turbulence or charging effects might lead to a reservoir of small grains at the surface layer that is not affected by the dust growth and fragmentation cycle dominating the dense disk midplane. The exploration of models shows that extracting planet properties such as mass from observed gap profiles is highly degenerate.
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- Fung, P. P. L., et al.
(författare)
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Time to onset of bisphosphonate-related osteonecrosis of the jaws : a multicentre retrospective cohort study
- 2017
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Ingår i: Oral Diseases. - : WILEY. - 1354-523X .- 1601-0825. ; 23:4, s. 477-483
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of bisphosphonates (BP). Although the risk of ONJ increases with increasing duration of BP treatment, there are currently no reliable estimates of the ONJ time to onset (TTO). The objective of this study was to estimate the TTO and associated risk factors in BP-treated patients.Subjects and Methods: Retrospective analysis of data from 22 secondary care centres in seven countries relevant to 349 patients who developed BP-related ONJ between 2004 and 2012.Results: The median (95%CI) TTO was 6.0 years in patients treated with alendronate (n=88) and 2.2years in those treated with zoledronate (n=218). Multivariable Cox regression showed that dentoalveolar surgery was inversely associated, and the use of antiangiogenics directly associated, with the TTO in patients with cancer treated with zoledronate.Conclusions: The incidence of ONJ increases with the duration of BP therapy, with notable differences observed with respect to BP type and potency, route of administration and underlying disease. When data are stratified by BP type, a time of 6.0 and 2.2years of oral alendronate and intravenous zoledronate therapy, respectively, is required for 50% of patients to develop ONJ. After stratification by disease, a time of 5.3 and 2.2years of BP therapy is required for 50% of patients with osteoporosis and cancer, respectively, to develop ONJ. These findings have significant implications for the design of future clinical studies and the development of risk-reduction strategies aimed at either assessing or modulating the risk of ONJ associated with BP.
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- S, Bouchez, et al.
(författare)
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Levosimendan in Acute and Advanced Heart Failure: an Expert Perspective on Posology and Therapeutic Application.
- 2018
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Ingår i: Cardiovascular drugs and therapy. - : Springer Science and Business Media LLC. - 1573-7241 .- 0920-3206. ; 32:6, s. 617-624
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Tidskriftsartikel (refereegranskat)abstract
- Levosimendan, a calcium sensitizer and potassium channel-opener, is widely appreciated by many specialist heart failure practitioners for its effects on systemic and pulmonary hemodynamics and for the relief of symptoms of acute heart failure. The drug's impact on mortality in large randomized controlled trials has been inconsistent or inconclusive but, in contrast to conventional inotropes, there have been no indications of worsened survival and some signals of improved heart failure-related quality of life. For this reason, levosimendan has been proposed as a safer inodilator option than traditional agents in settings, such as advanced heart failure. Positive effects of levosimendan on renal function have also been described. At the HEART FAILURE 2018 congress of the Heart Failure Association of the European Society of Cardiology, safe and effective use levosimendan in acute and advanced heart failure was examined in a series of expert tutorials. The proceedings of those tutorials are summarized in this review, with special reference to advanced heart failure and heart failure with concomitant renal dysfunction. Meta-analysis of clinical trials data is supportive of a renal-protective effect of levosimendan, while physiological observations suggest that this effect is exerted at least in part via organ-specific effects that may include selective vasodilation of glomerular afferent arterioles and increased renal blood flow, with no compromise of renal oxygenation. These lines of evidence require further investigation and their clinical significance needs to be evaluated in specifically designed prospective trials.
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