| 1. |
- Heidbuchel, Hein, et al.
(författare)
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Author reply : To PMID 23625942
- 2014
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 16:1, s. 151-152
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Tidskriftsartikel (refereegranskat)
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| 2. |
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| 3. |
- Heidbuchel, Hein, et al.
(författare)
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EHRA Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation : executive summary
- 2013
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 34:27, s. 2094-2106
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Tidskriftsartikel (refereegranskat)abstract
- New oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with non-valvular atrial fibrillation (AF). Both physicians and patients will have to learn how to use these drugs effectively and safely in specific clinical situations. This text is an executive summary of a practical guide that the European Heart Rhythm Association (EHRA) has assembled to help physicians in the use of the different NOACs. The full text is being published in EP Europace. Practical answers have been formulated for 15 concrete clinical scenarios: (i) practical start-up and follow-up scheme for patients on NOACs; (ii) how to measure the anticoagulant effect of NOACs; (iii) drug-drug interactions and pharmacokinetics of NOACs; (iv) switching between anticoagulant regimens; (v) ensuring compliance of NOAC intake; (vi) how to deal with dosing errors; (vii) patients with chronic kidney disease; (viii) what to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a risk of bleeding?; (ix) management of bleeding complications; (x) patients undergoing a planned surgical intervention or ablation; (xi) patients undergoing an urgent surgical intervention; (xii) patients with AF and coronary artery disease; (xiii) cardioversion in a NOAC-treated patient; (xiv) patients presenting with acute stroke while on NOACs; (xv) NOACs vs. VKAs in AF patients with a malignancy. Since new information is becoming available at a rapid pace, an EHRA web site with the latest updated information accompanies the guide (www.NOACforAF.eu). It also contains links to the ESC AF Guidelines, a key message pocket booklet, print-ready files for a proposed universal NOAC anticoagulation card, and feedback possibilities.
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| 4. |
- Heidbuchel, Hein, et al.
(författare)
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European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation
- 2013
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 15:5, s. 625-651
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Tidskriftsartikel (refereegranskat)abstract
- New oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with non-valvular atrial fibrillation (AF). Both physicians and patients will have to learn how to use these drugs effectively and safely in clinical practice. Many unresolved questions on how to optimally use these drugs in specific clinical situations remain. The European Heart Rhythm Association set out to coordinate a unified way of informing physicians on the use of the different NOACs. A writing group listed 15 topics of concrete clinical scenarios and formulated as practical answers as possible based on available evidence. The 15 topics are: (1) Practical start-up and follow-up scheme for patients on NOACs; (2) How to measure the anticoagulant effect of NOACs; (3) Drugdrug interactions and pharmacokinetics of NOACs; (4) Switching between anticoagulant regimens; (5) Ensuring compliance of NOAC intake; (6) How to deal with dosing errors; (7) Patients with chronic kidney disease; (8) What to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a risk of bleeding? (9) Management of bleeding complications; (10) Patients undergoing a planned surgical intervention or ablation; (11) Patients undergoing an urgent surgical intervention; (12) Patients with AF and coronary artery disease; (13) Cardioversion in a NOAC-treated patient; (14) Patients presenting with acute stroke while on NOACs; (15) NOACs vs. VKAs in AF patients with a malignancy. Since new information is becoming available at a rapid pace, an EHRA Web site with the latest updated information accompanies this text (www.NOACforAF.eu).
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| 5. |
- Heidbuchel, Hein, et al.
(författare)
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Updated European Heart Rhythm Association practical guide on the use of non-vitamin-K antagonist anticoagulants in patients with non-valvular atrial fibrillation : Executive summary
- 2017
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 38:27, s. 2137-2149
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Tidskriftsartikel (refereegranskat)abstract
- In 2013, the European Heart Rhythm Association (EHRA) published a Practical Guide on the use of non-VKA oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) (Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P, European Heart Rhythm A. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15:625-651; Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P. EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J 2013;34:2094-2106). The document received widespread interest, not only from cardiologists but also from neurologists, geriatricians, and general practitioners, as became evident from the distribution of >350 000 copies of its pocket version (the EHRA Key Message Booklet) world-wide. Since 2013, numerous new studies have appeared on different aspects of NOAC therapy in AF patients. Therefore, EHRA updated the Practical Guide, including new information but also providing balanced guiding in the many areas where prospective data are still lacking. The outline of the original guide that addressed 15 clinical scenarios has been preserved, but all chapters have been rewritten. Main changes in the Update comprise a discussion on the definition of 'non-valvular AF' and eligibility for NOAC therapy, inclusion of finalized information on the recently approved edoxaban, tailored dosing information dependent on concomitant drugs, and/or clinical characteristics, an expanded chapter on neurologic scenarios (ischaemic stroke or intracranial haemorrhage under NOAC), an updated anticoagulation card and more specifics on start-up and follow-up issues. There are also many new flow charts, like on appropriate switching between anticoagulants (VKA to NOAC or vice versa), default scenarios for acute management of coronary interventions, step-down schemes for long-term combined antiplatelet-anticoagulant management in coronary heart disease, management of bleeding, and cardioversion under NOAC therapy. The Updated Guide is available in full in EP Europace (Heidbuchel H, Verhamme P, Alings M, Antz M, Diener HC, HackeW, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P, Advisors. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 2015;17:1467-1507), while additional resources can be found at the related ESC/EHRA website (www.NOACforAF.eu).
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| 6. |
- Heidbuchel, Hein, et al.
(författare)
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Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation
- 2015
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 17:10, s. 1467-1507
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Tidskriftsartikel (refereegranskat)abstract
- The current manuscript is an update of the original Practical Guide, published in June 2013[Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with nonvalvular atrial fibrillation. Europace 2013; 15: 625-51; Heidbuchel H, Verhamme P, Alings M, Antz M, HackeW, Oldgren J, et al. EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J 2013; 34: 2094-106]. Non-vitamin K antagonist oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with non-valvular atrial fibrillation (AF). Both physicians and patients have to learn how to use these drugs effectively and safely in clinical practice. Many unresolved questions on how to optimally use these drugs in specific clinical situations remain. The European Heart Rhythm Association set out to coordinate a unified way of informing physicians on the use of the different NOACs. A writing group defined what needs to be considered as 'non-valvular AF' and listed 15 topics of concrete clinical scenarios for which practical answers were formulated, based on available evidence. The 15 topics are (i) practical start-up and follow-up scheme for patients on NOACs; (ii) how to measure the anticoagulant effect of NOACs; (iii) drug-drug interactions and pharmacokinetics of NOACs; (iv) switching between anticoagulant regimens; (v) ensuring adherence of NOAC intake; (vi) how to deal with dosing errors; (vii) patients with chronic kidney disease; (viii) what to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a risk of bleeding?; (xi) management of bleeding complications; (x) patients undergoing a planned surgical intervention or ablation; (xi) patients undergoing an urgent surgical intervention; (xii) patients with AF and coronary artery disease; (xiii) cardioversion in a NOAC-treated patient; (xiv) patients presenting with acute stroke while onNOACs; and (xv) NOACs vs. VKAs in AF patients with a malignancy. Additional information and downloads of the text and anticoagulation cards in >16 languages can be found on an European Heart Rhythm Association web site (www.NOACforAF.eu).
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| 7. |
- Steffel, Jan, et al.
(författare)
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The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation : executive summary
- 2018
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Ingår i: Europace. - : OXFORD UNIV PRESS. - 1099-5129 .- 1532-2092. ; 20:8, s. 1231-1242
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Tidskriftsartikel (refereegranskat)abstract
- The current manuscript is the Executive Summary of the second update to the original Practical Guide, published in 2013. Non-vitamin K antagonist oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with atrial fibrillation (AF), and have emerged as the preferred choice, particularly in patients newly started on anticoagulation. Both physicians and patients are becoming more accustomed to the use of these drugs in clinical practice. However, many unresolved questions on how to optimally use these agents in specific clinical situations remain. The European Heart Rhythm Association (EHRA) set out to co-ordinate a unified way of informing physicians on the use of the different NOACs. A writing group identified 20 topics of concrete clinical scenarios for which practical answers were formulated, based on available evidence. The 20 topics are (i) eligibility for NOACs; (ii) practical start-up and follow-up scheme for patients on NOACs; (iii) ensuring adherence to prescribed oral anticoagulant intake; (iv) switching between anticoagulant regimens; (v) pharmacokinetics and drug drug interactions of NOACs; (vi) NOACs in patients with chronic kidney or advanced liver disease; (vii) how to measure the anticoagulant effect of NOACs; (viii) NOAC plasma level measurement rare indications, precautions, and potential pitfalls; (ix) how to deal with dosing errors; (x) what to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a potential risk of bleeding (xi) management of bleeding under NOAC therapy; (xii) patients undergoing a planned invasive procedure, surgery or ablation; (xiii) patients requiring an urgent surgical intervention; (xiv) patients with AF and coronary artery disease; (xv) avoiding confusion with NOAC dosing across indications; (xvi) cardioversion in a NOAC-treated patient; (xvii) AF patients presenting with acute stroke while on NOACs; (xviii) NOACs in special situations; (xix) anticoagulation in AF patients with a malignancy, and (xx) optimizing dose adjustments of VKA. Additional information and downloads of the text and anticoagulation cards in different languages can be found on an EHRA web site (www.NOACforAF.eu)
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| 8. |
- Steffel, Jan, et al.
(författare)
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The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation : executive summary
- 2018
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Ingår i: Kardiologia polska. - : VIA MEDICA. - 0022-9032 .- 1897-4279. ; 76:9, s. 1283-1298
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Tidskriftsartikel (refereegranskat)abstract
- Poniższy tekst jest streszczeniem drugiej aktualizacji oryginalnego praktycznego przewodnika opublikowanego w 2013 roku. Leki przeciwkrzepliwe niebędące antagonistami witaminy K (NOAC) stanowią cenną alternatywę dla antagonistów witaminy K (VKA) w zapobieganiu udarom u pacjentów z migotaniem przedsionków (AF) i uznano je za leki preferowane, szczególnie dla osób rozpoczynających leczenie przeciwkrzepliwe. Zarówno lekarze, jak i pacjenci przyzwyczajają się do ich stosowania w praktyce klinicznej, istnieje jednak wiele nierozwiązanych kwestii dotyczących optymalnego stosowania tych leków w określonych sytuacjach klinicznych. Europejskie Stowarzyszenie Zaburzeń Rytmu Serca (EHRA, European Heart Rhythm Association) podjęło się koordynacji opracowania jednolitego sposobu komunikowania się z lekarzami na temat stosowania różnych preparatów NOAC. Grupa określiła 20 tematów zawierających konkretne scenariusze kliniczne, w odniesieniu do których sformułowano praktyczne wskazówki na podstawie dostępnych dowodów. Do problemów klinicznych należą: 1) odpowiednia kwalifikacja pacjentów do leczenia; 2) praktyczne schematy rozpoczynania oraz monitorowania terapii za pomocą NOAC; 3) zagwarantowanie przestrzegania zaleceń przyjmowania doustnych leków przeciwkrzepliwych; 4) zmiana schematów leczenia przeciwkrzepliwego; 5) farmakokinetyka oraz interakcje lekowe; 6) stosowanie NOAC u osób z przewlekłą chorobą nerek i zaawansowaną chorobą wątroby; 7) sposoby pomiaru efektu przeciwkrzepliwego NOAC; 8) pomiar stężenia NOAC w surowicy: rzadkie wskazania, środki ostrożności, potencjalne „pułapki”; 9) postępowanie w przypadku pomyłki w dawkowaniu; 10) postępowanie w przypadku (podejrzenia) przedawkowania bez krwawienia lub badania krzepnięcia wskazujące na potencjalne ryzyko krwawienia; 11) postępowanie w przypadku krwawienia w trakcie terapii za pomocą NOAC; 12) postępowanie u pacjentów poddanych planowym zabiegom chirurgicznym, procedurom inwazyjnym czy ablacji; 13) postępowanie u pacjentów wymagających pilnej interwencji chirurgicznej; 14) pacjenci z AF oraz chorobą wieńcową; 15) unikanie pomyłek w dawkowaniu NOAC w różnych wskazaniach; 16) kardiowersja u pacjenta leczonego NOAC; 17) AF u pacjentów z ostrym udarem mózgu leczonych NOAC; 18) NOAC w sytuacjach szczególnych; 19) leczenie przeciwkrzepliwe w przypadku AF u pacjentów z nowotworami złośliwymi; 20) optymalizacja leczenia za pomocą VKA. Dodatkowe informacje oraz materiały do pobrania, jak również karty leczenia przeciwkrzepliwego w kilku językach można znaleźć na stronie internetowej EHRA (www.NOACforAF.eu).
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| 9. |
- Steffel, Jan, et al.
(författare)
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The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation
- 2018
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 39:16, s. 1330-1393
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Tidskriftsartikel (refereegranskat)abstract
- The current manuscript is the second update of the original Practical Guide, published in 2013 [Heidbuchel et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15:625-651; Heidbuchel et at Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 2015;17:1467-1507]. Non-vitamin K antagonist oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with atrial fibrillation (AF) and have emerged as the preferred choice, particularly in patients newly started on anticoagulation. Both physicians and patients are becoming more accustomed to the use of these drugs in clinical practice. However, many unresolved questions on how to optimally use these agents in specific clinical situations remain. The European Heart Rhythm Association (EHRA) set out to coordinate a unified way of informing physicians on the use of the different NOACs. A writing group identified 20 topics of concrete clinical scenarios for which practical answers were formulated, based on available evidence. The 20 topics are as follows i.e., (1) Eligibility for NOACs; (2) Practical start-up and follow-up scheme for patients on NOACs; (3) Ensuring adherence to prescribed oral anticoagulant intake; (4) Switching between anticoagulant regimens; (5) Pharmacokinetics and drug-drug interactions of NOACs; (6) NOACs in patients with chronic kidney or advanced liver disease; (7) How to measure the anticoagulant effect of NOACs; (8) NOAC plasma level measurement rare indications, precautions, and potential pitfalls; (9) How to deal with dosing errors; (10) What to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a potential risk of bleeding; (11) Management of bleeding under NOAC therapy; (12) Patients undergoing a planned invasive procedure, surgery or ablation; (13) Patients requiring an urgent surgical intervention; (14) Patients with AF and coronary artery disease; (15) Avoiding confusion with NOAC dosing across indications; (16) Cardioversion in a NOAC-treated patient; (17) AF patients presenting with acute stroke while on NOACs; (18) NOACs in special situations; (19) Anticoagulation in AF patients with a malignancy; and (20) Optimizing dose adjustments of VKA. Additional information and downloads of the text and anticoagulation cards in different languages can be found on an EHRA website (www.NOACforAF.eu).
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| 10. |
- Ageno, Walter, et al.
(författare)
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Managing reversal of direct oral anticoagulants in emergency situations Anticoagulation Education Task Force White Paper
- 2016
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Ingår i: Thrombosis and Haemostasis. - : SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN. - 0340-6245 .- 2567-689X. ; 116:6, s. 1003-1010
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Tidskriftsartikel (refereegranskat)abstract
- Anticoagulation is the cornerstone of prevention and treatment of venous thromboembolism (VTE) and stroke prevention in patients with atrial fibrillation (AF). However, the mechanisms by which anticoagulants confer therapeutic benefit also increase the risk of bleeding. As such, reversal strategies are critical. Until recently, the direct oral anticoagulants (DOACs) dabigatran, rivaroxaban, apixaban, and edoxaban lacked a specific reversal agent. This report is based on findings from the Anticoagulation Education Task Force, which brought together patient groups and professionals representing different medical specialties with an interest in patient safety and expertise in AF, VTE, stroke, anticoagulation, and reversal agents, to discuss the current status of anticoagulation reversal and fundamental changes in management of bleeding associated with DOACs occasioned by the approval of idarucizumab, a specific reversal agent for dabigatran, as well as recent clinical data on specific reversal agents for factor Xa inhibitors. Recommendations are given for when there is a definite need for a reversal agent (e.g. in cases of life-threatening bleeding, bleeding into a closed space or organ, persistent bleeding despite local haemostatic measures, and need for urgent interventions and/or interventions that carry a high risk for bleeding), when reversal agents may be helpful, and when a reversal agent is generally not needed. Key stakeholders who require 24-7/around-the-clock access to these agents vary among hospitals; however, from a practical perspective the emergency department is recommended as an appropriate location for these agents. Clearly, the advent of new agents requires standardised protocols for treating bleeding on an institutional level.
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| 11. |
- Bauersachs, Rupert, et al.
(författare)
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Oral rivaroxaban for symptomatic venous thromboembolism.
- 2010
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Ingår i: The New England journal of medicine. - 1533-4406. ; 363:26, s. 2499-510
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Tidskriftsartikel (refereegranskat)abstract
- Rivaroxaban, an oral factor Xa inhibitor, may provide a simple, fixed-dose regimen for treating acute deep-vein thrombosis (DVT) and for continued treatment, without the need for laboratory monitoring.
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| 12. |
- Caolo, Vincenza, et al.
(författare)
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Shear Stress and VE-Cadherin : The Molecular Mechanism of Vascular Fusion
- 2018
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : LIPPINCOTT WILLIAMS & WILKINS. - 1079-5642 .- 1524-4636. ; 38:9, s. 2174-2183
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Vascular fusion represents an important mechanism of vessel enlargement during development; however, its significance in postnatal vessel enlargement is still unknown. During fusion, 2 adjoining vessels merge to share 1 larger lumen. The aim of this research was to identify the molecular mechanism responsible for vascular fusion.Approach and Results: We previously showed that both low shear stress and DAPT (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester) treatment in the embryo result in a hyperfused vascular plexus and that increasing shear stress levels could prevent DAPT-induced fusion. We, therefore, investigated vascular endothelial-cadherin (VEC) phosphorylation because this is a common downstream target of low shear stress and DAPT treatment. VEC phosphorylation increases after DAPT treatment and decreased shear stress. The increased phosphorylation occurred independent of the cleavage of the Notch intracellular domain. Increasing shear stress rescues hyperfusion by DAPT treatment by causing the association of the phosphatase vascular endothelial-protein tyrosine phosphatase with VEC, counteracting VEC phosphorylation. Finally, Src (proto-oncogene tyrosine-protein kinase Src) inhibition prevents VEC phosphorylation in endothelial cells and can rescue hyperfusion induced by low shear stress and DAPT treatment. Moesin, a VEC target that was previously reported to mediate endothelial cell rearrangement during lumenization, relocalizes to cell membranes in vascular beds undergoing hyperfusion.Conclusions: This study provides the first evidence that VEC phosphorylation, induced by DAPT treatment and low shear stress, is involved in the process of fusion during vascular remodeling.
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| 13. |
- Connolly, Stuart J., et al.
(författare)
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Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage
- 2024
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 390:19, s. 1745-1755
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with acute intracerebral hemorrhage who are receiving factor Xa inhibitors have a risk of hematoma expansion. The effect of andexanet alfa, an agent that reverses the effects of factor Xa inhibitors, on hematoma volume expansion has not been well studied. Methods We randomly assigned, in a 1:1 ratio, patients who had taken factor Xa inhibitors within 15 hours before having an acute intracerebral hemorrhage to receive andexanet or usual care. The primary end point was hemostatic efficacy, defined by expansion of the hematoma volume by 35% or less at 12 hours after baseline, an increase in the score on the National Institutes of Health Stroke Scale of less than 7 points (scores range from 0 to 42, with higher scores indicating worse neurologic deficit) at 12 hours, and no receipt of rescue therapy between 3 hours and 12 hours. Safety end points were thrombotic events and death. Results A total of 263 patients were assigned to receive andexanet, and 267 to receive usual care. Efficacy was assessed in an interim analysis that included 452 patients, and safety was analyzed in all 530 enrolled patients. Atrial fibrillation was the most common indication for factor Xa inhibitors. Of the patients receiving usual care, 85.5% received prothrombin complex concentrate. Hemostatic efficacy was achieved in 150 of 224 patients (67.0%) receiving andexanet and in 121 of 228 (53.1%) receiving usual care (adjusted difference, 13.4 percentage points; 95% confidence interval [CI], 4.6 to 22.2; P=0.003). The median reduction from baseline to the 1-to-2-hour nadir in anti-factor Xa activity was 94.5% with andexanet and 26.9% with usual care (P<0.001). Thrombotic events occurred in 27 of 263 patients (10.3%) receiving andexanet and in 15 of 267 (5.6%) receiving usual care (difference, 4.6 percentage points; 95% CI, 0.1 to 9.2; P=0.048); ischemic stroke occurred in 17 patients (6.5%) and 4 patients (1.5%), respectively. There were no appreciable differences between the groups in the score on the modified Rankin scale or in death within 30 days. Conclusions Among patients with intracerebral hemorrhage who were receiving factor Xa inhibitors, andexanet resulted in better control of hematoma expansion than usual care but was associated with thrombotic events, including ischemic stroke. (Funded by Alexion AstraZeneca Rare Disease and others; ANNEXA-I ClinicalTrials.gov number, NCT03661528.).
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| 14. |
- Duval, Florent, et al.
(författare)
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The Lyman alpha reference sample VI. Lyman alpha escape from the edge-on disk galaxy Mrk 1486
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 587
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Tidskriftsartikel (refereegranskat)abstract
- Context. Recent numerical simulations suggest that the strength of the Lyman alpha (Ly alpha) line of star-forming disk galaxies strongly depends on the inclination at which they are observed: from edge-on to face-on, we expect to see a change from a strongly attenuated Ly alpha line to a strong Ly alpha emission line.Aims. We aim to understand how a strong Ly alpha emission line is able to escape from the low-redshift highly inclined (edge-on) disk galaxy Mrk 1486 (z similar to 0.0338). To our knowledge, this work is the first observational study of Ly alpha transport inside an edge-on disk galaxy.Methods. Using a large set of HST imaging and spectroscopic data, we investigated the interstellar medium (ISM) structure and the dominant source of Ly alpha radiation inside Mrk 1486. Moreover, using a 3D Monte Carlo Ly alpha radiation transfer code, we studied the radiative transfer of Ly alpha and UV continuum photons inside a 3D geometry of neutral hydrogen (HI) and dust that models the ISM structure at the galaxy center. Our numerical simulations predicted the Ly alpha line profile that we then compared to the one observed in the HST/COS spectrum of Mrk 1486.Results. While a pronounced Ly alpha absorption line emerges from the disk of Mrk 1486, very extended Ly alpha structures are observed at large radii from the galaxy center: a large Ly alpha-halo and two very bright Ly alpha regions located slightly above and below the disk plane. The analysis of IFU H alpha spectroscopic data of Mrk 1486 indicates the presence of two bipolar outflowing halos of HI gas at the same location as these two bright Ly alpha regions. Comparing different diagnostic diagrams (such as [OIII](5007)/H beta versus [OI](6300)/H alpha) to photo-and shock-ionization models, we find that the Ly alpha production of Mrk 1486 is dominated by photoionization inside the galaxy disk. From this perspective, our numerical simulations succeed in reproducing the strength and shape of the observed Ly alpha emission line of Mrk 1486 by assuming a scenario in which the Ly alpha photons are produced inside the galaxy disk, travel along the outflowing halos, and scatter on cool HI materials toward the observer.Conclusions. Extended bipolar galactic winds are frequently observed from star-forming disk galaxies. Given the advantage Ly alpha photons take of such outflowing HI materials to easily escape from Mrk 1486, this mechanism may explain the origin of strong Ly alpha emission lines frequently observed from highly inclined galaxies at high-redshift. This therefore challenges the robustness of the expected viewing-angle effect on the Ly alpha properties of star-forming disk galaxies.
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| 15. |
- Gu, Yu-Mei, et al.
(författare)
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Outcome-Driven Thresholds for Ambulatory Pulse Pressure in 9938 Participants Recruited From 11 Populations
- 2014
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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 63:2, s. 229-237
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Tidskriftsartikel (refereegranskat)abstract
- Evidence-based thresholds for risk stratification based on pulse pressure (PP) are currently unavailable. To derive outcome-driven thresholds for the 24-hour ambulatory PP, we analyzed 9938 participants randomly recruited from 11 populations (47.3% women). After age stratification (<60 versus >= 60 years) and using average risk as reference, we computed multivariable-adjusted hazard ratios (IIRs) to assess risk by tenths of the PP distribution or risk associated with stepwise increasing (+1 mm Hg) PP levels. All adjustments included mean arterial pressure. Among 6028 younger participants (68 853 person-years), the risk of cardiovascular (HR, 1.58; P=0.011) or cardiac (HR, 1.52; P=0.056) events increased only in the top PP tenth (mean, 60.6 mm Hg). Using stepwise increasing PP levels, the lower boundary of the 95% confidence interval of the successive thresholds did not cross unity. Among 3910 older participants (39 923 person-years), risk increased (P <= 0.028) in the top PP tenth (mean, 76.1 mm Hg). HRs were 1.30 and 1.62 for total and cardiovascular mortality, and 1.52, 1.69, and 1.40 for all cardiovascular, cardiac, and cerebrovascular events. The lower boundary of the 95% confidence interval of the HRs associated with stepwise increasing PP levels crossed unity at 64 mm Hg. While accounting for all covariables, the top tenth of PP contributed less than 0.3% (generalized R-2 statistic) to the overall risk among the elderly. Thus, in randomly recruited people, ambulatory PP does not add to risk stratification below age 60; in the elderly, PP is a weak risk factor with levels below 64 mm Hg probably being innocuous.
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| 16. |
- Hayes, Matthew, et al.
(författare)
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THE LYMAN ALPHA REFERENCE SAMPLE : EXTENDED LYMAN ALPHA HALOS PRODUCED AT LOW DUST CONTENT
- 2013
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Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 765:2, s. L27-
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Tidskriftsartikel (refereegranskat)abstract
- We report on new imaging observations of the Lyman alpha emission line (Ly alpha), performed with the Hubble Space Telescope, that comprise the backbone of the Lyman alpha Reference Sample. We present images of 14 starburst galaxies at redshifts 0.028 < z < 0.18 in continuum-subtracted Ly alpha, H alpha, and the far ultraviolet continuum. We show that Ly alpha is emitted on scales that systematically exceed those of the massive stellar population and recombination nebulae: as measured by the Petrosian 20% radius, RP20, Ly alpha radii are larger than those of H alpha by factors ranging from 1 to 3.6, with an average of 2.4. The average ratio of Ly alpha-to-FUV radii is 2.9. This suggests that much of the Ly alpha light is pushed to large radii by resonance scattering. Defining the Relative Petrosian Extension of Ly alpha compared to H alpha, xi(Ly alpha) = R-P20(Ly alpha)/R-P20(H alpha), we find xi(Ly alpha) to be uncorrelated with total Ly alpha luminosity. However, xi(Ly alpha) is strongly correlated with quantities that scale with dust content, in the sense that a low dust abundance is a necessary requirement (although not the only one) in order to spread Ly alpha photons throughout the interstellar medium and drive a large extended Ly alpha halo.
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| 17. |
- Hayes, Matthew, et al.
(författare)
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THE LYMAN ALPHA REFERENCE SAMPLE. II. HUBBLE SPACE TELESCOPE IMAGING RESULTS, INTEGRATED PROPERTIES, AND TRENDS
- 2014
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 782:1
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Tidskriftsartikel (refereegranskat)abstract
- We report new results regarding the Ly alpha output of galaxies, derived from the Lyman Alpha Reference Sample, and focused on Hubble Space Telescope imaging. For 14 galaxies we present intensity images in Ly alpha, H alpha, and UV, and maps of H alpha/H beta, Ly alpha equivalent width (EW), and Ly alpha/H alpha. We present Ly alpha and UV radial light profiles and show they are well-fitted by Sersic profiles, but Ly alpha profiles show indices systematically lower than those of the UV (n approximate to 1-2 instead of greater than or similar to 4). This reveals a general lack of the central concentration in Ly alpha that is ubiquitous in the UV. Photometric growth curves increase more slowly for Ly alpha than the far ultraviolet, showing that small apertures may underestimate the EW. For most galaxies, however, flux and EW curves flatten by radii approximate to 10 kpc, suggesting that if placed at high-z only a few of our galaxies would suffer from large flux losses. We compute global properties of the sample in large apertures, and show total Ly alpha luminosities to be independent of all other quantities. Normalized Ly alpha throughput, however, shows significant correlations: escape is found to be higher in galaxies of lower star formation rate, dust content, mass, and nebular quantities that suggest harder ionizing continuum and lower metallicity. Six galaxies would be selected as high-z Ly alpha emitters, based upon their luminosity and EW. We discuss the results in the context of high-z Ly alpha and UV samples. A few galaxies have EWs above 50 angstrom, and one shows f(esc)(Ly alpha) of 80%; such objects have not previously been reported at low-z.
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| 18. |
- Herenz, Edmund Christian, et al.
(författare)
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The Lyman alpha reference sample VII. Spatially resolved H alpha kinematics
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 587
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Tidskriftsartikel (refereegranskat)abstract
- We present integral field spectroscopic observations with the Potsdam Multi-Aperture Spectrophotometer of all 14 galaxies in the z similar to 0.1 Lyman Alpha Reference Sample (LARS). We produce 2D line-of-sight velocity maps and velocity dispersion maps from the Balmer alpha (H alpha) emission in our data cubes. These maps trace the spectral and spatial properties of the LARS galaxies' intrinsic Ly alpha radiation field. We show our kinematic maps that are spatially registered onto the Hubble Space Telescope H alpha and Lyman alpha (Ly alpha) images. We can conjecture a causal connection between spatially resolved H alpha kinematics and Ly alpha photometry for individual galaxies, however, no general trend can be established for the whole sample. Furthermore, we compute the intrinsic velocity dispersion sigma(0), the shearing velocity v(shear), and the v(shear)/sigma(0) ratio from our kinematic maps. In general LARS galaxies are characterised by high intrinsic velocity dispersions (54 km s(-1) median) and low shearing velocities (65 km s(-1) median). The v(shear/sigma 0) values range from 0.5 to 3.2 with an average of 1.5. It is noteworthy that five galaxies of the sample are dispersion-dominated systems with v(shear)/sigma(0) < 1, and are thus kinematically similar to turbulent star-forming galaxies seen at high redshift. When linking our kinematical statistics to the global LARS Ly alpha properties, we find that dispersion-dominated systems show higher Ly alpha equivalent widths and higher Ly alpha escape fractions than systems with v(shear)/sigma(0) > 1. Our result indicates that turbulence in actively star-forming systems is causally connected to interstellar medium conditions that favour an escape of Ly alpha radiation.
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| 19. |
- Kwiecinski, Jakub, 1985, et al.
(författare)
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Staphylokinase controls Staphylococcus aureus biofilm formation and detachment through host plasminogen activation.
- 2016
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 213:1, s. 139-148
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus biofilms, a leading cause of persistent infections, are highly resistant to immune defenses and antimicrobial therapies. In this study, we investigated the contribution of fibrin and staphylokinase to biofilm formation. Both in clinical S. aureus isolates and in laboratory strains, high staphylokinase-producing strains formed less biofilm than strains that lacked staphylokinase, suggesting that staphylokinase prevents biofilm formation. Additionally, staphylokinase induced detachment of mature biofilms. This effect depended on plasminogen activation by staphylokinase. Host-derived fibrin, the main substrate cleaved by staphylokinase-activated plasminogen, was a major component of biofilm matrix and dissolution of this fibrin scaffold greatly increased susceptibility of biofilms to antibiotics and neutrophil phagocytosis. Staphylokinase also attenuated biofilm-associated catheter infections in mouse models. In conclusion, our results reveal a novel role for staphylokinase-induced plasminogen activation that prevents S. aureus biofilm formation and induces detachment of existing biofilms through proteolytic cleavage of biofilm matrix components.
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| 20. |
- Leclercq, Floriane, et al.
(författare)
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The MUSE &ITHubble&IT Ultra Deep Field Survey VIII. Extended Lyman-alpha haloes around high-&ITz&IT star-forming galaxies
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 608
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Tidskriftsartikel (refereegranskat)abstract
- We report the detection of extended Ly alpha haloes around 145 individual star-forming galaxies at redshifts 3 <= z <= 6 in the Hubble Ultra Deep Field observed with the Multi-Unit Spectroscopic Explorer (MUSE) at ESO-VLT. Our sample consists of continuum-faint (-15 >= M-UV >= -22) Ly alpha emitters (LAEs). Using a 2D, two-component (continuum-like and halo) decomposition of Ly alpha emission assuming circular exponential distributions, we measure scale lengths and luminosities of Ly alpha haloes. We find that 80% of our objects having reliable Ly alpha halo measurements show Ly alpha emission that is significantly more extended than the UV continuum detected by HST (by a factor approximate to 4 to >20). The median exponential scale length of the Ly alpha haloes in our sample is approximate to 4.5 kpc with a few haloes exceeding 10 kpc. By comparing the maximal detected extent of the Ly alpha emission with the predicted dark matter halo virial radii of simulated galaxies, we show that the detected Ly alpha emission of our selected sample of Ly alpha emitters probes a significant portion of the cold circum-galactic medium of these galaxies (>50% in average). This result therefore shows that there must be significant HI reservoirs in the circum-galactic medium and reinforces the idea that Ly alpha haloes are ubiquitous around high-redshift Ly alpha emitting galaxies. Our characterization of the Ly alpha haloes indicates that the majority of the Ly alpha flux comes from the halo (approximate to 65%) and that their scale lengths seem to be linked to the UV properties of the galaxies (sizes and magnitudes). We do not observe a significant Ly alpha halo size evolution with redshift, although our sample for z > 5 is very small. We also explore the diversity of the Ly alpha line profiles in our sample and we find that the Ly alpha lines cover a large range of full width at half maximum (FWHM) from 118 to 512 km s(-1). While the FWHM does not seem to be correlated to the Ly alpha scale length, most compact Ly alpha haloes and those that are not detected with high significance tend to have narrower Ly alpha profiles (<350 km s(-1)). Finally, we investigate the origin of the extended Ly alpha emission but we conclude that our data do not allow us to disentangle the possible processes, i.e. scattering from star-forming regions, fluorescence, cooling radiation from cold gas accretion, and emission from satellite galaxies.
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| 21. |
- Loth, Daan W, et al.
(författare)
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Genome-wide association analysis identifies six new loci associated with forced vital capacity
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46, s. 669-677
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Tidskriftsartikel (refereegranskat)abstract
- Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
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| 22. |
- Melgarejo, Jesus D., et al.
(författare)
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Association of Fatal and Nonfatal Cardiovascular Outcomes With 24-Hour Mean Arterial Pressure
- 2021
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Ingår i: Hypertension. - : Wolters Kluwer. - 0194-911X .- 1524-4563. ; 77:1, s. 39-48
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Tidskriftsartikel (refereegranskat)abstract
- Major adverse cardiovascular events are closely associated with 24-hour blood pressure (BP). We determined outcome-driven thresholds for 24-hour mean arterial pressure (MAP), a BP index estimated by oscillometric devices. We assessed the association of major adverse cardiovascular events with 24-hour MAP, systolic BP (SBP), and diastolic BP (DBP) in a population-based cohort (n=11 596). Statistics included multivariable Cox regression and the generalized R-2 statistic to test model fit. Baseline office and 24-hour MAP averaged 97.4 and 90.4 mm Hg. Over 13.6 years (median), 2034 major adverse cardiovascular events occurred. Twenty-four-hour MAP levels of <90 (normotension, n=6183), 90 to <92 (elevated MAP, n=909), 92 to <96 (stage-1 hypertension, n=1544), and >= 96 (stage-2 hypertension, n=2960) mm Hg yielded equivalent 10-year major adverse cardiovascular events risks as office MAP categorized using 2017 American thresholds for office SBP and DBP. Compared with 24-hour MAP normotension, hazard ratios were 0.96 (95% CI, 0.80-1.16), 1.32 (1.15-1.51), and 1.77 (1.59-1.97), for elevated and stage-1 and stage-2 hypertensive MAP. On top of 24-hour MAP, higher 24-hour SBP increased, whereas higher 24-hour DBP attenuated risk (P<0.001). Considering the 24-hour measurements, R-2 statistics were similar for SBP (1.34) and MAP (1.28), lower for DBP than for MAP (0.47), and reduced to null, if the base model included SBP and DBP; if the ambulatory BP indexes were dichotomized according to the 2017 American guideline and the proposed 92 mm Hg for MAP, the R-2 values were 0.71, 0.89, 0.32, and 0.10, respectively. In conclusion, the clinical application of 24-hour MAP thresholds in conjunction with SBP and DBP refines risk estimates.
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| 23. |
- Melgarejo, Jesus D., et al.
(författare)
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Relative and Absolute Risk to Guide the Management of Pulse Pressure, an Age-Related Cardiovascular Risk Factor
- 2021
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Ingår i: American Journal of Hypertension. - : Oxford University Press. - 0895-7061 .- 1941-7225. ; 34:9, s. 929-938
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Pulse pressure (PP) reflects the age-related stiffening of the central arteries, but no study addressed the management of the PP-related risk over the human lifespan.METHODS In 4,663 young (18-49 years) and 7,185 older adults (>= 50 years), brachial PP was recorded over 24 hours. Total mortality and all major cardiovascular events (MACEs) combined were coprimary endpoints. Cardiovascular death, coronary events, and stroke were secondary endpoints.RESULTS In young adults (median follow-up, 14.1 years; mean PP, 45.1 mm Hg), greater PP was not associated with absolute risk; the endpoint rates were <= 2.01 per 1,000 person-years. The adjusted hazard ratios expressed per 10-mm Hg PP increments were less than unity (P <= 0.027) for MACE (0.67; 95% confidence interval [CI], 0.47-0.96) and cardiovascular death (0.33; 95% CI, 0.11-0.75). In older adults (median follow-up, 13.1 years; mean PP, 52.7 mm Hg), the endpoint rates, expressing absolute risk, ranged from 22.5 to 45.4 per 1,000 person-years and the adjusted hazard ratios, reflecting relative risk, from 1.09 to 1.54 (P < 0.0001). The PP-related relative risks of death, MACE, and stroke decreased >3-fold from age 55 to 75 years, whereas absolute risk rose by a factor 3.CONCLUSIONS From 50 years onwards, the PP-related relative risk decreases, whereas absolute risk increases. From a lifecourse perspective, young adulthood provides a window of opportunity to manage risk factors and prevent target organ damage as forerunner of premature death and MACE. In older adults, treatment should address absolute risk, thereby extending life in years and quality.
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| 24. |
- Melinder, Jens, et al.
(författare)
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Lyman alpha escape from 45 star forming galaxies– the Lyα Reference Sample XIV
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We present Lyα imaging of 45 low redshift star-forming galaxies observed with the Hubble space telescope. The galaxies have been selected to have moderate to high star formation rates using FUVluminosity and Hα equivalent width criteria, but no constraints on Lyα luminosity have been applied. We employ a pixel SED fitting code to obtain accurate continuum subtracted Lyα, Hα and Hβ maps. We find that Lyα is less concentrated than FUV and optical line emission in almost all galaxies with significant Lyα emission. We present global measurements of Lyα and other quantities measured in apertures designed to capture all of the Lyα emission. We then show how the escape fraction ofLyα relates to a number of other measured quantities (mass, metallicity, star formation, ionization parameter, and extinction). We find that the escape fraction is strongly anti-correlated with both nebular and stellar extinction, weakly anti-correlated with stellar mass, but no conclusive evidence for correlations to other quantities. We show that Lyα escape fractions are inconsistent with common dust extinction laws and discuss how a combination of radiative transfer effects and clumpy dust models can help resolve the discrepancies. We present a star formation rate calibration based on Lyαluminosity, where the equivalent width of Lyα is used to correct for non-unity escape fraction, and show that this relation provides a reasonably accurate calibration but with a large scatter. We also show stacked growth curves of Lyα for the galaxies that can be used to find aperture loss fractions at a given physical radius
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| 25. |
- Melinder, Jens, 1977-, et al.
(författare)
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The Lyα Reference Sample. XIV. Lyα Imaging of 45 Low-redshift Star-forming Galaxies and Inferences on Global Emission
- 2023
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Ingår i: Astrophysical Journal Supplement Series. - 0067-0049 .- 1538-4365. ; 266:1
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Tidskriftsartikel (refereegranskat)abstract
- We present Lyα imaging of 45 low-redshift star-forming galaxies observed with the Hubble Space Telescope. The galaxies have been selected to have moderate to high star formation rates (SFRs) using far-ultraviolet (FUV) luminosity and Hα equivalent width criteria, but no constraints on Lyα luminosity. We employ a pixel stellar continuum fitting code to obtain accurate continuum-subtracted Lyα, Hα, and Hβ maps. We find that Lyα is less concentrated than FUV and optical line emission in almost all galaxies with significant Lyα emission. We present global measurements of Lyα and other quantities measured in apertures designed to capture all of the Lyα emission. We then show how the escape fraction of Lyα relates to a number of other measured quantities (mass, metallicity, star formation, ionization parameter, and extinction). We find that the escape fraction is strongly anticorrelated with nebular and stellar extinction, weakly anticorrelated with stellar mass, but no conclusive evidence for correlations with other quantities. We show that Lyα escape fractions are inconsistent with common dust extinction laws, and discuss how a combination of radiative transfer effects and clumpy dust models can help resolve the discrepancies. We present an SFR calibration based on Lyα luminosity, where the equivalent width of Lyα is used to correct for nonunity escape fraction, and show that this relation provides a reasonably accurate SFR estimate. We also show stacked growth curves of Lyα for the galaxies that can be used to find aperture loss fractions at a given physical radius.
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| 26. |
- Moreno-Martos, David, et al.
(författare)
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Characteristics and outcomes of COVID-19 patients with COPD from the United States, South Korea, and Europe
- 2023
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Ingår i: Wellcome Open Research. - : F1000 Research Ltd. - 2398-502X. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Characterization studies of COVID-19 patients with chronic obstructive pulmonary disease (COPD) are limited in size and scope. The aim of the study is to provide a large-scale characterization of COVID-19 patients with COPD. Methods: We included thirteen databases contributing data from January-June 2020 from North America (US), Europe and Asia. We defined two cohorts of patients with COVID-19 namely a ‘diagnosed’ and ‘hospitalized’ cohort. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes among COPD patients with COVID-19. Results: The study included 934,778 patients in the diagnosed COVID-19 cohort and 177,201 in the hospitalized COVID-19 cohort. Observed COPD prevalence in the diagnosed cohort ranged from 3.8% (95%CI 3.5-4.1%) in French data to 22.7% (95%CI 22.4-23.0) in US data, and from 1.9% (95%CI 1.6-2.2) in South Korean to 44.0% (95%CI 43.1-45.0) in US data, in the hospitalized cohorts. COPD patients in the hospitalized cohort had greater comorbidity than those in the diagnosed cohort, including hypertension, heart disease, diabetes and obesity. Mortality was higher in COPD patients in the hospitalized cohort and ranged from 7.6% (95%CI 6.9-8.4) to 32.2% (95%CI 28.0-36.7) across databases. ARDS, acute renal failure, cardiac arrhythmia and sepsis were the most common outcomes among hospitalized COPD patients. Conclusion: COPD patients with COVID-19 have high levels of COVID-19-associated comorbidities and poor COVID-19 outcomes. Further research is required to identify patients with COPD at high risk of worse outcomes.
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| 27. |
- Na, Manli, et al.
(författare)
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The Expression of von Willebrand Factor-Binding Protein Determines Joint-Invading Capacity of Staphylococcus aureus, a Core Mechanism of Septic Arthritis.
- 2020
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Ingår i: mBio. - 2150-7511. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- Septic arthritis, one of the most dangerous joint diseases, is predominantly caused by Staphylococcus aureus In contrast, coagulase-negative staphylococci are rarely found in septic arthritis. We hypothesize that coagulases released by S. aureus, including coagulase (Coa) and von Willebrand factor-binding protein (vWbp), play potent roles in the induction of septic arthritis. Four isogenic S. aureus strains differing in expression of coagulases (wild-type [WT] Newman, Δcoa, Δvwb, and Δcoa Δvwb) were used to induce septic arthritis in both wild-type and von Willebrand factor (vWF)-deficient mice. Septic arthritis severity was greatly reduced when wild-type mice were infected with the Δcoa Δvwb and Δvwb variants compared to WT or Δcoa strains, suggesting that vWbp rather than Coa is a major virulence factor in S. aureus septic arthritis. vWF-deficient mice were more susceptible to bone damage in septic arthritis, especially when the Δvwb strain was used. Importantly, no difference in arthritis severity between the Δvwb and WT strains was observed in vWF-deficient mice. Collectively, we conclude that vWbp production by S. aureus enhances staphylococcal septic arthritis.IMPORTANCE Septic arthritis remains one of the most dangerous joint diseases with a rapidly progressive disease character. Despite advances in the use of antibiotics, permanent reductions in joint function due to joint deformation and deleterious contractures occur in up to 50% of patients with septic arthritis. So far, it is still largely unknown how S. aureus initiates and establishes joint infection. Here, we demonstrate that von Willebrand factor-binding protein expressed by S. aureus facilitates the initiation of septic arthritis. Such effect might be mediated through its interaction with a host factor (von Willebrand factor). Our finding contributes significantly to the full understanding of septic arthritis etiology and will pave the way for new therapeutic modalities for this devastating disease.
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| 28. |
- Pardy, Stephen A., et al.
(författare)
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THE LYMAN ALPHA REFERENCE SAMPLE. III. PROPERTIES OF THE NEUTRAL ISM FROM GBT AND VLA OBSERVATIONS
- 2014
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 794:2
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Tidskriftsartikel (refereegranskat)abstract
- We present new Hi imaging and spectroscopy of the 14 UV-selected star-forming galaxies in the Lyman Alpha Reference Sample (LARS), aimed for a detailed study of the processes governing the production, propagation, and escape of Ly alpha photons. New Hi spectroscopy, obtained with the 100 m Green Bank Telescope (GBT), robustly detects the Hi spectral line in 11 of the 14 observed LARS galaxies (although the profiles of two of the galaxies are likely confused by other sources within the GBT beam); the three highest redshift galaxies are not detected at our current sensitivity limits. The GBT profiles are used to derive fundamental Hi line properties of the LARS galaxies. We also present new pilot Hi spectral line imaging of five of the LARS galaxies obtained with the Karl G. Jansky Very Large Array (VLA). This imaging localizes the Hi gas and provides a measurement of the total Hi mass in each galaxy. In one system, LARS 03 (UGC 8335 or Arp 238), VLA observations reveal an enormous tidal structure that extends over 160 kpc from the main interacting systems and that contains >10(9) M-circle dot of Hi. We compare various Hi properties with global Ly alpha quantities derived from Hubble Space Telescope measurements. The measurements of the Ly alpha escape fraction are coupled with the new direct measurements of Hi mass and significantly disturbed Hi velocities. Our robustly detected sample reveals tentative correlations between the total Hi mass and linewidth, and key Ly alpha tracers. Further, on global scales, these data support a complex coupling between Ly alpha propagation and the Hi properties of the surrounding medium.
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| 29. |
- Peetermans, Marijke, et al.
(författare)
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Plasminogen activation by staphylokinase enhances local spreading of S. aureus in skin infections.
- 2014
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Ingår i: BMC microbiology. - : Springer Science and Business Media LLC. - 1471-2180. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Staphylococcus aureus (S. aureus) is a frequent cause of skin and soft tissue infections. A unique feature of S. aureus is the combined presence of coagulases that trigger fibrin formation and of the plasminogen activator staphylokinase (SAK). Whereas the importance of fibrin generation for S. aureus virulence has been established, the role of SAK remains unclear.We studied the role of plasminogen activation by SAK in a skin infection model in mice and evaluated the impact of alpha-2-antiplasmin (¿2AP) deficiency on the spreading and proteolytic activity of S. aureus skin infections. The species-selectivity of SAK was overcome by adenoviral expression of human plasminogen. Bacterial spread and density was assessed non-invasively by imaging the bioluminescence of S. aureus Xen36.ResultsSAK-mediated plasmin activity increased the local invasiveness of S. aureus, leading to larger lesions with skin disruption as well as decreased bacterial clearance by the host. Even though fibrin and bacterial surfaces protected SAK-mediated plasmin activity from inhibition by ¿2AP, the deficiency of ¿2AP resulted in increased bacterial spreading. SAK-mediated plasmin also induced secondary activation of gelatinases, shown both in vitro and in lesions from the in vivo model.ConclusionSAK contributes to the phenotype of S. aureus skin infections by enhancing bacterial spreading as a result of fibrinolytic and proteolytic activation.
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| 30. |
- Rivera-Thorsen, Thöger E., et al.
(författare)
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THE LYMAN ALPHA REFERENCE SAMPLE. V. THE IMPACT OF NEUTRAL ISM KINEMATICS ANDGEOMETRY ON Lyα ESCAPE
- 2015
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 805:14
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Tidskriftsartikel (refereegranskat)abstract
- We present high-resolution far-UV spectroscopy of the 14 galaxies of the Lyα Reference Sample; a sample of strongly star-forming galaxies at low redshifts (0.028 < z < 0.18). We compare the derived properties to global properties derived from multi-band imaging and 21 cm H i interferometry and single-dish observations, as well as archival optical SDSS spectra. Besides the Lyα line, the spectra contain a number of metal absorption features allowing us to probe the kinematics of the neutral ISM and evaluate the optical depth and and covering fraction of the neutral medium as a function of line of sight velocity. Furthermore, we show how this, in combination with the precise determination of systemic velocity and good Lyα spectra, can be used to distinguish a model in which separate clumps together fully cover the background source, from the "picket fence" model named by Heckman et al. We find that no one single effect dominates in governing Lyα radiative transfer and escape. Lyα escape in our sample coincides with a maximum velocity-binned covering fraction of 0.9 and bulk outflow velocities of 50 km s−1, although a number of galaxies show these characteristics and yet little or no Lyα escape. We find that Lyα peak velocities, where available, are not consistent with a strong backscattered component, but rather with a simpler model of an intrinsic emission line overlaid by a blueshifted absorption profile from the outflowing wind. Finally, we find a strong anticorrelation between Hα equivalent width and maximum velocity-binned covering factor, and propose a heuristic explanatory model.
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| 31. |
- Sacco, Clara, et al.
(författare)
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Lemierre Syndrome : Clinical Update and Protocol for a Systematic Review and Individual Patient Data Meta-analysis
- 2019
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Ingår i: Hämostaseologie. - : Georg Thieme Verlag KG. - 0720-9355 .- 2567-5761. ; 39:1, s. 76-86
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Forskningsöversikt (refereegranskat)abstract
- Lemierre syndrome usually affects otherwise healthy adolescents or young adults and occurs at an overall rate of 1 to 10 cases per million person-years with an estimated fatality rate of 4 to 9%. Diagnostic criteria remain debated and include acute neck/head bacterial infection (often tonsillitis caused by anaerobes at high potential for sepsis and vascular invasion, notably Fusobacterium necrophorum) complicated by local vein thrombosis, usually involving the internal jugular vein, and systemic septic embolism. Medical treatment is based on antibiotic therapy with anaerobic coverage, anticoagulant drugs and supportive care in case of sepsis. Surgical procedures can be required, including drainage of the abscesses, tissue debridement and jugular vein ligation. Evidence for clinical management is extremely poor in the absence of any adequately sized study with clinical outcomes. In this article, we illustrate two cases of Lemierre syndrome not caused by Fusobacterium necrophorum and provide a clinically oriented discussion on the main issues on epidemiology, pathophysiology and management strategies of this disorder. Finally, we summarize the study protocol of a proposed systematic review and individual patient data meta-analysis of the literature. Our ongoing work aims to investigate the risk of new thromboembolic events, major bleeding or death in patients diagnosed with Lemierre syndrome, and to better elucidate the role of anticoagulant therapy in this setting. This effort represents the starting point for an evidence-based treatment of Lemierre syndrome built on multinational interdisciplinary collaborative studies.
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| 32. |
- Valerio, Luca, et al.
(författare)
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Patients with Lemierre syndrome have a high risk of new thromboembolic complications, clinical sequelae and death : an analysis of 712 cases
- 2021
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 289:3, s. 325-339
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lemierre syndrome is characterized by head/neck vein thrombosis and septic embolism usually complicating an acute oropharyngeal bacterial infection in adolescents and young adults. We described the course of Lemierre syndrome in the contemporary era. Methods: In our individual-level analysis of 712 patients (2000–2017), we included cases described as Lemierre syndrome if these criteria were met: (i) primary site of bacterial infection in the head/neck; (ii) objectively confirmed local thrombotic complications or septic embolism. The study outcomes were new or recurrent venous thromboembolism or peripheral septic lesions, major bleeding, all-cause death and clinical sequelae. Results: The median age was 21 (Q1–Q3: 17–33) years, and 295 (41%) were female. At diagnosis, acute thrombosis of head/neck veins was detected in 597 (84%) patients, septic embolism in 582 (82%) and both in 468 (80%). After diagnosis and during in-hospital follow-up, new venous thromboembolism occurred in 34 (5.2%, 95% CI 3.8–7.2%) patients, new peripheral septic lesions became evident in 76 (11.7%; 9.4–14.3%). The rate of either was lower in patients who received anticoagulation (OR: 0.59; 0.36–0.94), higher in those with initial intracranial involvement (OR: 2.35; 1.45–3.80). Major bleeding occurred in 19 patients (2.9%; 1.9–4.5%), and 26 died (4.0%; 2.7–5.8%). Clinical sequelae were reported in 65 (10.4%, 8.2–13.0%) individuals, often consisting of cranial nerve palsy (n = 24) and orthopaedic limitations (n = 19). Conclusions: Patients with Lemierre syndrome were characterized by a substantial risk of new thromboembolic complications and death. This risk was higher in the presence of initial intracranial involvement. One-tenth of survivors suffered major clinical sequelae.
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- Yang, Wen-Yi, et al.
(författare)
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Association of Office and Ambulatory Blood Pressure With Mortality and Cardiovascular Outcomes
- 2019
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Ingår i: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 322:5, s. 409-420
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Tidskriftsartikel (refereegranskat)abstract
- ImportanceBlood pressure (BP) is a known risk factor for overall mortality and cardiovascular (CV)-specific fatal and nonfatal outcomes. It is uncertain which BP index is most strongly associated with these outcomes. ObjectiveTo evaluate the association of BP indexes with death and a composite CV event. Design, Setting, and ParticipantsLongitudinal population-based cohort study of 11135 adults from Europe, Asia, and South America with baseline observations collected from May 1988 to May 2010 (last follow-ups, August 2006-October 2016). ExposuresBlood pressure measured by an observer or an automated office machine; measured for 24 hours, during the day or the night; and the dipping ratio (nighttime divided by daytime readings). Main Outcomes and MeasuresMultivariable-adjusted hazard ratios (HRs) expressed the risk of death or a CV event associated with BP increments of 20/10 mm Hg. Cardiovascular events included CV mortality combined with nonfatal coronary events, heart failure, and stroke. Improvement in model performance was assessed by the change in the area under the curve (AUC). ResultsAmong 11135 participants (median age, 54.7 years, 49.3% women), 2836 participants died (18.5 per 1000 person-years) and 2049 (13.4 per 1000 person-years) experienced a CV event over a median of 13.8 years of follow-up. Both end points were significantly associated with all single systolic BP indexes (P<.001). For nighttime systolic BP level, the HR for total mortality was 1.23 (95% CI, 1.17-1.28) and for CV events, 1.36 (95% CI, 1.30-1.43). For the 24-hour systolic BP level, the HR for total mortality was 1.22 (95% CI, 1.16-1.28) and for CV events, 1.45 (95% CI, 1.37-1.54). With adjustment for any of the other systolic BP indexes, the associations of nighttime and 24-hour systolic BP with the primary outcomes remained statistically significant (HRs ranging from 1.17 [95% CI, 1.10-1.25] to 1.87 [95% CI, 1.62-2.16]). Base models that included single systolic BP indexes yielded an AUC of 0.83 for mortality and 0.84 for the CV outcomes. Adding 24-hour or nighttime systolic BP to base models that included other BP indexes resulted in incremental improvements in the AUC of 0.0013 to 0.0027 for mortality and 0.0031 to 0.0075 for the composite CV outcome. Adding any systolic BP index to models already including nighttime or 24-hour systolic BP did not significantly improve model performance. These findings were consistent for diastolic BP. Conclusions and RelevanceIn this population-based cohort study, higher 24-hour and nighttime blood pressure measurements were significantly associated with greater risks of death and a composite CV outcome, even after adjusting for other office-based or ambulatory blood pressure measurements. Thus, 24-hour and nighttime blood pressure may be considered optimal measurements for estimating CV risk, although statistically, model improvement compared with other blood pressure indexes was small.
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| 35. |
- Östlin, Göran, et al.
(författare)
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THE Ly alpha REFERENCE SAMPLE. I. SURVEY OUTLINE AND FIRST RESULTS FOR MARKARIAN 259
- 2014
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 797:1
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Tidskriftsartikel (refereegranskat)abstract
- The Ly alpha Reference Sample (LARS) is a substantial program with the Hubble Space Telescope (HST) that provides a sample of local universe laboratory galaxies in which to study the detailed astrophysics of the visibility and strength of the Ly alpha line of neutral hydrogen. Ly alpha is the dominant spectral line in use for characterizing high-redshift (z) galaxies. This paper presents an overview of the survey, its selection function, and HST imaging observations. The sample was selected from the combined GALEX+Sloan Digital Sky Survey catalog at z = 0.028-0.19, in order to allow Ly alpha to be captured with combinations of long-pass filters in the Solar Blind Channel (SBC) of the Advanced Camera for Surveys (ACS) onboard HST. In addition, LARS utilizes H alpha and H beta narrowband and u, b, i broadband imaging with ACS and the Wide Field Camera 3 (WFC3). In order to study galaxies in which large numbers of Ly alpha photons are produced (whether or not they escape), we demanded an H alpha equivalent width W(H alpha) >= 100 angstrom. The final sample of 14 galaxies covers far-UV (FUV, lambda similar to 1500 angstrom) luminosities that overlap with those of high-z Ly alpha emitters (LAEs) and Lyman break galaxies (LBGs), making LARS a valid comparison sample. We present the reduction steps used to obtain the Ly alpha images, including our LARS eXtraction software (LaXs), which utilizes pixel-by-pixel spectral synthesis fitting of the energy distribution to determine and subtract the continuum at Ly alpha. We demonstrate that the use of SBC long-pass-filter combinations increase the signal-to-noise ratio by an order of magnitude compared to the nominal Ly alpha filter available in SBC. To exemplify the science potential of LARS, we also present some first results for a single galaxy, Mrk 259 (LARS #1). This irregular galaxy shows bright and extended (indicative of resonance scattering) but strongly asymmetric Ly alpha emission. Spectroscopy from the Cosmic Origins Spectrograph on board HST centered on the brightest UV knot shows a moderate outflow in the neutral interstellar medium (probed by low ionization stage absorption features) and Ly alpha emission with an asymmetric profile. Radiative transfer modeling is able to reproduce the essential features of the Ly alpha line profile and confirms the presence of an outflow. From the integrated photometry we measure an Ly alpha luminosity of L-Ly alpha= 1.3x10(42) erg s(-1) an equivalent width W(Ly alpha) = 45 angstrom and an FUV absolute magnitude M-FUV = -19.2 (AB). Mrk 259 would hence be detectable in high-z Ly alpha and LBG surveys. The total Ly alpha escape fraction is 12%. This number is higher than the low-z average, but similar to that at z > 4, demonstrating that LARS provides a valid comparison sample for high-z galaxy studies.
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