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- Arias, M., et al.
(författare)
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Low-frequency radio absorption in Cassiopeia A
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
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Tidskriftsartikel (refereegranskat)abstract
- Context. Cassiopeia A is one of the best-studied supernova remnants. Its bright radio and X-ray emission is due to shocked ejecta. Cas A is rather unique in that the unshocked ejecta can also be studied: through emission in the infrared, the radio-active decay of Ti-44, and the low-frequency free-free absorption caused by cold ionised gas, which is the topic of this paper. Aims. Free-free absorption processes are affected by the mass, geometry, temperature, and ionisation conditions in the absorbing gas. Observations at the lowest radio frequencies can constrain a combination of these properties. Methods. We used Low Frequency Array (LOFAR) Low Band Antenna observations at 30-77 MHz and Very Large Array (VLA) L-band observations at 1-2 GHz to fit for internal absorption as parametrised by the emission measure. We simultaneously fit multiple UV-matched images with a common resolution of 17 '' (this corresponds to 0.25 pc for a source at the distance of Cas A). The ample frequency coverage allows us separate the relative contributions from the absorbing gas, the unabsorbed front of the shell, and the absorbed back of the shell to the emission spectrum. We explored the effects that a temperature lower than the similar to 100-500 K proposed from infrared observations and a high degree of clumping can have on the derived physical properties of the unshocked material, such as its mass and density. We also compiled integrated radio flux density measurements, fit for the absorption processes that occur in the radio band, and considered their effect on the secular decline of the source. Results. We find a mass in the unshocked ejecta of M = 2.95 +/- 0.48 M-circle dot for an assumed gas temperature of T = 100 K. This estimate is reduced for colder gas temperatures and, most significantly, if the ejecta are clumped. We measure the reverse shock to have a radius of 114 '' +/- 6 '' and be centred at 23:23:26, +58:48:54 (J2000). We also find that a decrease in the amount of mass in the unshocked ejecta (as more and more material meets the reverse shock and heats up) cannot account for the observed low-frequency behaviour of the secular decline rate. Conclusions. To reconcile our low-frequency absorption measurements with models that reproduce much of the observed behaviour in Cas A and predict little mass in the unshocked ejecta, the ejecta need to be very clumped or the temperature in the cold gas needs to be low (similar to 10 K). Both of these options are plausible and can together contribute to the high absorption value that we find.
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- Saliba-Gustafsson, P., et al.
(författare)
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Subclinical atherosclerosis and its progression are modulated by PLIN2 through a feed-forward loop between LXR and autophagy
- 2019
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 660-675
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Tidskriftsartikel (refereegranskat)abstract
- Background Hyperlipidaemia is a major risk factor for cardiovascular disease, and atherosclerosis is the underlying cause of both myocardial infarction and stroke. We have previously shown that the Pro251 variant of perilipin-2 reduces plasma triglycerides and may therefore be beneficial to reduce atherosclerosis development. Objective We sought to delineate putative beneficial effects of the Pro251 variant of perlipin-2 on subclinical atherosclerosis and the mechanism by which it acts. Methods A pan-European cohort of high-risk individuals where carotid intima-media thickness has been assessed was adopted. Human primary monocyte-derived macrophages were prepared from whole blood from individuals recruited by perilipin-2 genotype or from buffy coats from the Karolinska University hospital blood central. Results The Pro251 variant of perilipin-2 is associated with decreased intima-media thickness at baseline and over 30 months of follow-up. Using human primary monocyte-derived macrophages from carriers of the beneficial Pro251 variant, we show that this variant increases autophagy activity, cholesterol efflux and a controlled inflammatory response. Through extensive mechanistic studies, we demonstrate that increase in autophagy activity is accompanied with an increase in liver-X-receptor (LXR) activity and that LXR and autophagy reciprocally activate each other in a feed-forward loop, regulated by CYP27A1 and 27OH-cholesterol. Conclusions For the first time, we show that perilipin-2 affects susceptibility to human atherosclerosis through activation of autophagy and stimulation of cholesterol efflux. We demonstrate that perilipin-2 modulates levels of the LXR ligand 27OH-cholesterol and initiates a feed-forward loop where LXR and autophagy reciprocally activate each other; the mechanism by which perilipin-2 exerts its beneficial effects on subclinical atherosclerosis.
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- Zucca, P., et al.
(författare)
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Shock location and CME 3D reconstruction of a solar type II radio burst with LOFAR
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 615
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Tidskriftsartikel (refereegranskat)abstract
- Context. Type II radio bursts are evidence of shocks in the solar atmosphere and inner heliosphere that emit radio waves ranging from sub-meter to kilometer lengths. These shocks may be associated with coronal mass ejections (CMEs) and reach speeds higher than the local magnetosonic speed. Radio imaging of decameter wavelengths (20-90 MHz) is now possible with the Low Frequency Array (LOFAR), opening a new radio window in which to study coronal shocks that leave the inner solar corona and enter the interplanetary medium and to understand their association with CMEs. Aims. To this end, we study a coronal shock associated with a CME and type II radio burst to determine the locations at which the radio emission is generated, and we investigate the origin of the band-splitting phenomenon. Methods. The type II shock source-positions and spectra were obtained using 91 simultaneous tied-array beams of LOFAR, and the CME was observed by the Large Angle and Spectrometric Coronagraph (LASCO) on board the Solar and Heliospheric Observatory (SOHO) and by the COR2A coronagraph of the SECCHI instruments on board the Solar Terrestrial Relation Observatory (STEREO). The 3D structure was inferred using triangulation of the coronographic observations. Coronal magnetic fields were obtained from a 3D magnetohydrodynamics (MHD) polytropic model using the photospheric fields measured by the Heliospheric Imager (HMI) on board the Solar Dynamic Observatory (SDO) as lower boundary. Results. The type II radio source of the coronal shock observed between 50 and 70 MHz was found to be located at the expanding flank of the CME, where the shock geometry is quasi-perpendicular with theta(Bn)similar to 70 degrees. The type II radio burst showed first and second harmonic emission; the second harmonic source was cospatial with the first harmonic source to within the observational uncertainty. This suggests that radio wave propagation does not alter the apparent location of the harmonic source. The sources of the two split bands were also found to be cospatial within the observational uncertainty, in agreement with the interpretation that split bands are simultaneous radio emission from upstream and downstream of the shock front. The fast magnetosonic Mach number derived from this interpretation was found to lie in the range 1.3-1.5. The fast magnetosonic Mach numbers derived from modelling the CME and the coronal magnetic field around the type II source were found to lie in the range 1.4-1.6.
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- Axelsson, Annika, et al.
(författare)
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Sox5 regulates beta-cell phenotype and is reduced in type 2 diabetes
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes (T2D) is characterized by insulin resistance and impaired insulin secretion, but the mechanisms underlying insulin secretion failure are not completely understood. Here, we show that a set of co-expressed genes, which is enriched for genes with islet-selective open chromatin, is associated with T2D. These genes are perturbed in T2D and have a similar expression pattern to that of dedifferentiated islets. We identify Sox5 as a regulator of the module. Sox5 knockdown induces gene expression changes similar to those observed in T2D and diabetic animals and has profound effects on insulin secretion, including reduced depolarization-evoked Ca 2+-influx and β-cell exocytosis. SOX5 overexpression reverses the expression perturbations observed in a mouse model of T2D, increases the expression of key β-cell genes and improves glucose-stimulated insulin secretion in human islets from donors with T2D. We suggest that human islets in T2D display changes reminiscent of dedifferentiation and highlight SOX5 as a regulator of β-cell phenotype and function.
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| 10. |
- de Leede, E. M., et al.
(författare)
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Common variables in European pancreatic cancer registries: The introduction of the EURECCA pancreatic cancer project
- 2016
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Ingår i: European Journal of Surgical Oncology. - : Elsevier. - 0748-7983 .- 1532-2157. ; 42:9, s. 1414-1419
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Tidskriftsartikel (refereegranskat)abstract
- Background: Quality assurance of cancer care is of utmost importance to detect and avoid under and over treatment. Most cancer data are collected by different procedures in different countries, and are poorly comparable at an international level. EURECCA, acronym for European Registration of Cancer Care, is a platform aiming to harmonize cancer data collection and improve cancer care by feedback. After the prior launch of the projects on colorectal, breast and upper GI cancer, EURECCAs newest project is collecting data on pancreatic cancer in several European countries. Methods: National cancer registries, as well as specific pancreatic cancer audits/registries, were invited to participate in EURECCA Pancreas. Participating countries were requested to share an overview of their collected data items. Of the received datasets, a shared items list was made which creates insight in similarities between different national registries and will enable data comparison on a larger scale. Additionally, first data was requested from the participating countries. Results: Over 24 countries have been approached and 11 confirmed participation: Austria, Belgium, Bulgaria, Denmark, Germany, The Netherlands, Slovenia, Spain, Sweden, Ukraine and United Kingdom. The number of collected data items varied between 16 and 285. This led to a shared items list of 25 variables divided into five categories: patient characteristics, preoperative diagnostics, treatment, staging and survival. Eight countries shared their first data. Conclusions: A list of 25 shared items on pancreatic cancer coming from eleven participating registries was created, providing a basis for future prospective data collection in pancreatic cancer treatment internationally.
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| 11. |
- Schvartz, D., et al.
(författare)
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The Human Diabetes Proteome Project (HDPP) : The 2014 update
- 2015
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Ingår i: Translational Proteomics. - : Elsevier BV. - 2212-9626. ; 8-9, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Diabetes is an increasing worldwide problem leading to major associated health issues and increased health care costs. In 2012, 9.3% of the American population was affected by diabetes, according to the American Diabetes Association, with 1.7 million of new cases since during the year (www.diabetes.org). Proteome initiatives can provide a deeper understanding of the biology of this disease and help develop more effective treatments. The collaborative effort of the Human Diabetes Proteome Project (HDPP) brings together a wide variety of complementary resources to increase the existing knowledge about both type 1 and type 2 diabetes and their related complications. The goals are to identify proteins and protein isoforms associated with the pathology and to characterize underlying disease-related pathways and mechanisms. Moreover, a considerable effort is being made on data integration and network biology. Sharing these data with the scientific community will be an important part of the consortium. Here we report on: the content of the HDPP session held at the 12th HUPO meeting in Yokohama; recent achievements of the consortium; discussions of several HDPP workshops; as well as future HDPP directions as discussed at the 13th HUPO congress in Madrid, with a special attention given to the lists of prioritized, diabetes-related proteins and the proteomic means to study them.
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- Linnarsson, D, et al.
(författare)
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Effects of an artificial gravity countermeasure on orthostatic tolerance, blood volumes and aerobic power after short-term bed rest (BR-AG1)
- 2015
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Ingår i: Journal of applied physiology (Bethesda, Md. : 1985). - : American Physiological Society. - 1522-1601 .- 8750-7587. ; 118:1, s. 29-35
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to artificial gravity (AG) in a short-arm centrifuge has potential benefits for maintaining human performance during long-term space missions. Eleven subjects were investigated during three campaigns of 5 days head-down bed rest: 1) bed rest without countermeasures (control), 2) bed rest and 30 min of AG (AG1) daily, and 3) bed rest and six periods of 5 min AG (AG2) daily. During centrifugation, the supine subjects were exposed to AG in the head-to-feet direction with 1 G at the center of mass. Subjects participated in the three campaigns in random order. The cardiovascular effects of bed rest and countermeasures were determined from changes in tolerance to a head-up tilt test with superimposed lower body negative pressure (HUT), from changes in plasma volume (PV) and from changes in maximum aerobic power (V̇o2peak) during upright work on a cycle ergometer. Complete data sets were obtained in eight subjects. After bed rest, HUT tolerance times were 36, 64, and 78% of pre-bed rest baseline during control, AG1 and AG2, respectively, with a significant difference between AG2 and control. PV and V̇o2peakdecreased to 85 and 95% of pre-bed rest baseline, respectively, with no differences between the treatments. It was concluded that the AG2 countermeasure should be further investigated during future long-term bed rest studies, especially as it was better tolerated than AG1. The superior effect of AG2 on orthostatic tolerance could not be related to concomitant changes in PV or aerobic power.
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| 18. |
- Martinsen, V., et al.
(författare)
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pH effects of the addition of three biochars to acidic Indonesian mineral soils
- 2015
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Ingår i: Soil science and plant nutrition (Tokyo). - : Informa UK Limited. - 0038-0768 .- 1747-0765. ; 61:5, s. 821-834
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Tidskriftsartikel (refereegranskat)abstract
- Soil acidity may severely reduce crop production. Biochar (BC) may increase soil pH and cation exchange capacity (CEC) but reported effects differ substantially. In a systematic approach, using a standardized protocol on a uniquely large number set of 31 acidic soils, we quantified the effect of increasing amounts (0-30%; weight:weight) of three types of field-produced BCs (from cacao (Theobroma cacao. L.) shell, oil palm (Elaeis guineensis. Jacq.) shell and rice (Oryza sativa. L.) husk) on soil pH and CEC. Soils were sampled from croplands at Java, Sumatra and Kalimantan, Indonesia. All BCs caused a significant increase in mean soil pH with a stronger response and a greater maximum increase for the cacao shell BC addition, due to a greater acid neutralizing capacity (ANC) and larger amounts of extractable base cations. At 1% BC addition, corresponding to about 30tonsha(-1), the estimated increase in soil pH from the initial mean pH of 4.7 was about 0.5 units for the cacao shell BC, whereas this was only 0.05 and 0.04 units for the oil palm shell and rice husk BC, respectively. Besides depending on BC type, the increase in soil pH upon the addition of each of the three BCs was mainly dependent on soil CEC (low CEC resulting in stronger pH increase), and to a lesser extent on initial soil pH (higher initial pH resulting in stronger pH increase). Addition of BC also increased the amount of exchangeable base cations (cacao shell >> oil palm and rice husk) and CEC. Through this systematic screening of the effect of BC on pH and CEC of acidic soils, we show that a small addition of BC, in particular if made of cacao shell, to acidic agricultural soils increases soil pH and CEC. However, the response is highly dependent on the type, quality and amount of the added BC as well as on intrinsic soil properties, mainly CEC.
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- Zhang, M. -D, et al.
(författare)
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Comparative anatomical distribution of neuronal calcium-binding protein (NECAB) 1 and -2 in rodent and human spinal cord
- 2016
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Ingår i: Brain Structure and Function. - : Springer. - 1863-2653 .- 1863-2661. ; , s. 1-21
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Tidskriftsartikel (refereegranskat)abstract
- Neuronal calcium-binding protein 1 and -2 (NECAB1/2) localize to multiple excitatory neuron populations in the mouse spinal cord. Here, we analyzed rat and human spinal cord, combining in situ hybridization and immunohistochemistry, complementing newly collated data on mouse spinal cord for direct comparisons. Necab1/2 mRNA transcripts showed complementary distribution in rodent’s spinal cord. Multiple-labeling fluorescence histochemistry with neuronal phenotypic markers localized NECAB1 to a dense fiber plexus in the dorsal horn, to neurons mainly in superficial layers and to commissural interneurons in both rodent species. NECAB1-positive (+) motor neurons were only found in mice. NECAB1 distribution in the human spinal cord was similar with the addition of NECAB1-like immunoreactivity surrounding myelinated axons. NECAB2 was mainly present in excitatory synaptic boutons in the dorsal horn of all three species, and often in calbindin-D28k+ neuronal somata. Rodent ependymal cells expressed calbindin-D28k. In humans, they instead were NECAB2+ and/or calretinin+. Our results reveal that the association of NECAB2 to excitatory neuronal circuits in the spinal cord is evolutionarily conserved across the mammalian species investigated so far. In contrast, NECAB1 expression is more heterogeneous. Thus, our study suggests that the phenotypic segregation of NECAB1 and -2 to respective excitatory and inhibitory spinal systems can underpin functional modalities in determining the fidelity of synaptic neurotransmission and neuronal responsiveness, and might bear translational relevance to humans.
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- Loeffen, Erik A. H., et al.
(författare)
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Reducing pain in children with cancer : Methodology for the development of a clinical practice guideline
- 2019
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 66:6
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Tidskriftsartikel (refereegranskat)abstract
- Although pain is one of the most prevalent and bothersome symptoms children with cancer experience, evidence-based guidance regarding assessment and management is lacking. With 44 international, multidisciplinary healthcare professionals and nine patient representatives, we aimed to develop a clinical practice guideline (following GRADE methodology), addressing assessment and pharmacological, psychological, and physical management of tumor-, treatment-, and procedure-related pain in children with cancer. In this paper, we present our thorough methodology for this development, including the challenges we faced and how we approached these. This lays the foundation for our clinical practice guideline, for which there is a high clinical demand.
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- Vinereanu, Dragos, et al.
(författare)
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Echocardiographic Risk Factors for Stroke and Outcomes in Patients With Atrial Fibrillation Anticoagulated With Apixaban or Warfarin
- 2017
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Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 48:12, s. 3266-3273
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Few data exist on the long-term outcomes of patients with spontaneous echo contrast (SEC), left atrial/left atrial appendage (LA/LAA) thrombus, and complex aortic plaque (CAP), in patients with atrial fibrillation receiving oral anticoagulation. We explored the relationship between these 3 echocardiographic findings and clinical outcomes, and the comparative efficacy and safety of apixaban and warfarin for each finding.METHODS: Patients from the ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) with SEC, LA/LAA thrombus, or CAP diagnosed by either transthoracic or transesophageal echocardiography were compared with patients with none of these findings on transesophageal echocardiography.RESULTS: A total of 1251 patients were included: 217 had SEC, 127 had LA/LAA thrombus, 241 had CAP, and 746 had none. The rates of stroke/systemic embolism were not significantly different among patients with and without these echocardiographic findings (hazard ratio, 0.96; 95% confidence interval, 0.25-3.60 for SEC; hazard ratio, 1.27; 95% confidence interval, 0.23-6.86 for LA/LAA thrombus; hazard ratio, 2.21; 95% confidence interval, 0.71-6.85 for CAP). Rates of ischemic stroke, myocardial infarction, cardiovascular death, and all-cause death were also not different between patients with and without these findings. For patients with either SEC or CAP, there was no evidence of a differential effect of apixaban over warfarin. For patients with LA/LAA thrombus, there was also no significant interaction, with the exception of all-cause death and any bleeding where there was a greater benefit of apixaban compared with warfarin among patients with no LA/LAA thrombus.CONCLUSIONS: In anticoagulated patients with atrial fibrillation and risk factors for stroke, echocardiographic findings do not seem to add to the risk of thromboembolic events.CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.
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| 24. |
- Vinereanu, Dragos, et al.
(författare)
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Outcomes in anticoagulated patients with atrial fibrillation and with mitral or aortic valve disease
- 2018
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Ingår i: Heart. - : BMJ PUBLISHING GROUP. - 1355-6037 .- 1468-201X. ; 104:15, s. 1292-1299
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess stroke/systemic embolism, major bleeding and other outcomes, and treatment effect of apixaban versus warfarin, in patients with atrial fibrillation (AF) and different types of valvular heart disease (VHD), using data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial.Methods: There were 14 793 patients with known VHD status, categorised as having moderate or severe mitral regurgitation (MR) (n=3382), aortic regurgitation (AR) (n=842) or aortic stenosis (AS) (n=324); patients with moderate or severe mitral stenosis were excluded from the trial. Baseline characteristics, efficacy and safety outcomes were compared between each type and no significant VHD. Treatment effect was assessed using an adjusted model.Results: Patients with MR or AR had similar rates of stroke/systemic embolism and bleeding compared with patients without MR or AR, respectively. Patients with AS had significantly higher event rates (presented as rate per 100 patient-years of follow-up) of stroke/systemic embolism (3.47 vs 1.36; adjusted HR (adjHR) 2.21, 95% CI 1.35 to 3.63), death (8.30 vs 3.53; adjHR 1.92, 95% CI 1.41 to 2.61), major bleeding (5.31 vs 2.53; adjHR 1.80, 95% CI 1.19 to 2.75) and intracranial bleeding (1.29 vs 0.51; adjHR 2.54, 95% CI 1.08 to 5.96) than patients without AS. The superiority of apixaban over warfarin on stroke/systemic embolism was similar in patients with versus without MR (HR 0.69, 95% CI 0.46 to 1.04 vs HR 0.79, 95% CI 0.63 to 1.00; interaction P value 0.52), with versus without AR (HR 0.57, 95% CI 0.27 to 1.20 vs HR 0.78, 95% CI 0.63 to 0.96; interaction P value 0.52), and with versus without AS (HR 0.44, 95% CI 0.17 to 1.13 vs HR 0.79, 95% CI 0.64 to 0.97; interaction P value 0.19). For each of the primary and secondary efficacy and safety outcomes, there was no evidence of a different effect of apixaban over warfarin in patients with any VHD subcategory.Conclusions; In anticoagulated patients with AF, AS is associated with a higher risk of stroke/systemic embolism, bleeding and death. The efficacy and safety benefits of apixaban compared with warfarin were consistent, regardless of presence of MR, AR or AS.
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