| 1. |
- Adler, Anneli, et al.
(författare)
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Variation of growth and phenology traits in poplars planted in clonal trials in Northern Europe-implications for breeding
- 2021
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Ingår i: BioEnergy Research. - : Springer Science and Business Media LLC. - 1939-1234 .- 1939-1242. ; 14, s. 426-444
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Tidskriftsartikel (refereegranskat)abstract
- The increased demand for wood to replace oil-based products with renewable products has lifted focus to the Baltic Sea region where the environment is favorable for woody biomass growth. The aim of this study was to estimate broad-sense heritabilities and genotype-by-environment (GxE) interactions in growth and phenology traits in six climatically different regions in Sweden and the Baltics. We tested the hypothesis that both bud burst and bud set have a significant effect on the early growth of selected poplar clones in Northern Europe. Provenance hybrids of Populus trichocarpa adapted to the Northern European climate were compared to reference clones with adaptation to the Central European climate. The volume index of stemwood was under low to medium genetic control with heritabilities from 0.22 to 0.75. Heritabilities for phenology traits varied between 0.31 and 0.91. Locally chosen elite clones were identified. GxE interactions were analyzed using pairwise comparisons of the trials. Three different breeding zones for poplars between the latitudes of 55 degrees N and 60 degrees N in the Baltic Sea Region were outlined. The studied provenance hybrids with origin from North America offer a great possibility to broaden the area with commercial poplar plantations in Northern Europe and further improve the collection of commercial clones to match local climates. We conclude that phenology is an important selection criterion after growth.
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| 2. |
- Cabrita, Rita, et al.
(författare)
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Tertiary lymphoid structures improve immunotherapy and survival in melanoma
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 577:7791, s. 561-565
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Tidskriftsartikel (refereegranskat)abstract
- Checkpoint blockade therapies that reactivate tumour-associated T cells can induce durable tumour control and result in the long-term survival of patients with advanced cancers1. Current predictive biomarkers for therapy response include high levels of intratumour immunological activity, a high tumour mutational burden and specific characteristics of the gut microbiota2,3. Although the role of T cells in antitumour responses has thoroughly been studied, other immune cells remain insufficiently explored. Here we use clinical samples of metastatic melanomas to investigate the role of B cells in antitumour responses, and find that the co-occurrence of tumour-associated CD8+ T cells and CD20+ B cells is associated with improved survival, independently of other clinical variables. Immunofluorescence staining of CXCR5 and CXCL13 in combination with CD20 reveals the formation of tertiary lymphoid structures in these CD8+CD20+ tumours. We derived a gene signature associated with tertiary lymphoid structures, which predicted clinical outcomes in cohorts of patients treated with immune checkpoint blockade. Furthermore, B-cell-rich tumours were accompanied by increased levels of TCF7+ naive and/or memory T cells. This was corroborated by digital spatial-profiling data, in which T cells in tumours without tertiary lymphoid structures had a dysfunctional molecular phenotype. Our results indicate that tertiary lymphoid structures have a key role in the immune microenvironment in melanoma, by conferring distinct T cell phenotypes. Therapeutic strategies to induce the formation of tertiary lymphoid structures should be explored to improve responses to cancer immunotherapy.
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| 3. |
- Cabrita, Rita, et al.
(författare)
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Tertiary lymphoid structures improve immunotherapy and survival in melanoma.
- 2020
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Ingår i: Nature. - : Nature Publishing Group. - 1476-4687 .- 0028-0836. ; 577:7791, s. 561-565
-
Tidskriftsartikel (refereegranskat)abstract
- Checkpoint blockade therapies that reactivate tumour-associated T cells can induce durable tumour control and result in the long-term survival of patients with advanced cancers1. Current predictive biomarkers for therapy response include high levels of intratumour immunological activity, a high tumour mutational burden and specific characteristics of the gut microbiota2,3. Although the role of T cells in antitumour responses has thoroughly been studied, other immune cells remain insufficiently explored. Here we use clinical samples of metastatic melanomas to investigate the role of B cells in antitumour responses, and find that the co-occurrence of tumour-associated CD8+ T cells and CD20+ B cells is associated with improved survival, independently of other clinical variables. Immunofluorescence staining of CXCR5 and CXCL13 in combination with CD20 reveals the formation of tertiary lymphoid structures in these CD8+CD20+ tumours. We derived a gene signature associated with tertiary lymphoid structures, which predicted clinical outcomes in cohorts of patients treated with immune checkpoint blockade. Furthermore, B-cell-rich tumours were accompanied by increased levels of TCF7+ naive and/or memory T cells. This was corroborated by digital spatial-profiling data, in which T cells in tumours without tertiary lymphoid structures had a dysfunctional molecular phenotype. Our results indicate that tertiary lymphoid structures have a key role in the immune microenvironment in melanoma, by conferring distinct T cell phenotypes. Therapeutic strategies to induce the formation of tertiary lymphoid structures should be explored to improve responses to cancer immunotherapy.
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| 4. |
- Christersson, Albert, et al.
(författare)
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Comparison of 2D radiography and a semi-automatic CT-based 3D method for measuring change in dorsal angulation over time in distal radius fractures
- 2016
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Ingår i: Skeletal Radiology. - : Springer Science and Business Media LLC. - 0364-2348 .- 1432-2161. ; 45:6, s. 763-769
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Tidskriftsartikel (refereegranskat)abstract
- Objective The aim of the present study was to compare the reliability and agreement between a computer tomography-based method (CT) and digitalised 2D radiographs (XR) when measuring change in dorsal angulation over time in distal radius fractures. Materials and methods Radiographs from 33 distal radius fractures treated with external fixation were retrospectively analysed. All fractures had been examined using both XR and CT at six times over 6 months postoperatively. The changes in dorsal angulation between the first reference images and the following examinations in every patient were calculated from 133 follow-up measurements by two assessors and repeated at two different time points. The measurements were analysed using Bland-Altman plots, comparing intra- and inter-observer agreement within and between XR and CT. Results The mean differences in intra- and inter-observer measurements for XR, CT, and between XR and CT were close to zero, implying equal validity. The average intra- and inter-observer limits of agreement for XR, CT, and between XR and CT were +/- 4.4 degrees, +/- 1.9 degrees and +/- 6.8 degrees respectively. Conclusions For scientific purpose, the reliability of XR seems unacceptably low when measuring changes in dorsal angulation in distal radius fractures, whereas the reliability for the semi-automatic CT-based method was higher and is therefore preferable when a more precise method is requested.
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| 5. |
- Christersson, Christina, et al.
(författare)
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Comparison of warfarin versus antiplatelet therapy after surgical bioprosthetic aortic valve replacement
- 2020
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 106:11, s. 838-844
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To compare effectiveness of warfarin and antiplatelet exposure regarding both thrombotic and bleeding events, following surgical aortic valve replacement with a biological prosthesis(bioSAVR).METHODS: The study included all patients in Sweden undergoing a bioSAVR during 2008-2014 who were alive at discharge from the index hospital stay. Exposure was analysed and defined as postdischarge dispension of any antithrombotic pharmaceutical, updated at each following dispensions and categorised as single antiplatelet (SAPT), warfarin, warfarin combined with SAPT, dual antiplatelet (DAPT) or no antithrombotic treatment. Exposure to SAPT was used as comparator. Outcome events were all-cause mortality, ischaemic stroke, haemorrhagic stroke, any thromboembolism and major bleedings. We continuously updated adjustments for comorbidities with any indication for antithrombotic treatment by Cox regression analysis.RESULTS: We identified 9539 patients with bioSAVR (36.8% women) at median age of 73 years with a mean follow-up of 3.13 years. As compared with SAPT, warfarin alone was associated with a lower incidence of ischaemic stroke (HR 0.49, 95% CI 0.35 to 0.70) and any thromboembolism (HR 0.75, 95% CI 0.60 to 0.94) but with no difference in mortality (HR 0.94, 95% CI 0.78 to 1.13). The incidence of haemorrhagic stroke (HR 1.94, 95% CI 1.07 to 3.51) and major bleeding (HR 1.67, 95% CI 1.30 to 2.15) was higher during warfarin exposure. As compared with SAPT, DAPT was not associated with any difference in ischaemic stroke or any thromboembolism. Risk-benefit analyses demonstrated that 2.7 (95% CI 1.0 to 11.9) of the ischaemic stroke cases could potentially be avoided per every haemorrhagic stroke caused by warfarin exposure instead of SAPT during the first year.CONCLUSION: In patients discharged after bioSAVR, warfarin exposure as compared with SAPT exposure was associated with lower long-term risk of ischaemic stroke and thromboembolic events, and with a higher incidence of bleeding events but with similar mortality.
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| 6. |
- Christersson, Christina, et al.
(författare)
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D-dimer and risk of thromboembolic and bleeding events in patients with atrial fibrillation : observations from the ARISTOTLE trial
- 2014
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 12:9, s. 1401-1412
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundD-dimer is related to adverse outcomes in arterial and venous thromboembolic diseases. ObjectivesTo evaluate the predictive value of D-dimer level for stroke, other cardiovascular events, and bleeds, in patients with atrial fibrillation (AF) treated with oral anticoagulation with apixaban or warfarin; and to evaluate the relationship between the D-dimer levels at baseline and the treatment effect of apixaban vs. warfarin. MethodsIn the ARISTOTLE trial, 18201 patients with AF were randomized to apixaban or warfarin. D-dimer was analyzed in 14878 patients at randomization. The cohort was separated into two groups; not receiving vitaminK antagonist (VKA) treatment and receiving VKA treatment at randomization. ResultsHigher D-dimer levels were associated with increased frequencies of stroke or systemic embolism (hazard ratio [HR][Q4 vs. Q1]1.72, 95% confidence interval [CI]1.14-2.59, P=0.003), death (HR[Q4 vs. Q1]4.04, 95%CI3.06-5.33) and major bleeding (HR[Q4 vs. Q1]2.47, 95%CI1.77-3.45, P<0.0001) in the no-VKA group. Similar results were obtained in the on-VKA group. Adding D-dimer level to the CHADS(2) score improved the C-index from 0.646 to 0.655 for stroke or systemic embolism, and from 0.598 to 0.662 for death, in the no-VKA group. D-dimer level improved the HAS-BLED score for prediction of major bleeds, with an increase in the C-index from 0.610 to 0.641. There were no significant interactions between efficacy and safety of study treatment and D-dimer level. ConclusionIn anticoagulated patients with AF, the level of D-dimer is related to the risk of stroke, death, and bleeding, and adds to the predictive value of clinical risk scores. The benefits of apixaban were consistent, regardless of the baseline D-dimer level.
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| 7. |
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| 8. |
- Christersson, Christina, et al.
(författare)
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Early decrease in coagulation activity after myocardial infarction is associated with lower risk of new ischemic events : Observations from the ESTEEM trial
- 2007
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 28:6, s. 692-698
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Patients with a recent myocardial infarction have an increased risk of recurrent ischaemic events. In the ESTEEM trial, the oral direct thrombin inhibitor ximelagatran reduced the risk of new ischaemic events when compared with placebo in aspirin treated post myocardial infarction patients. Ximelagatran persistently reduced markers of coagulation activity, i.e. prothrombin fragment 1 + 2 (F1 + 2) and D-dimer levels. The aim of this substudy was to evaluate the levels of these markers and activated thromboplastin time (APTT) in relation to new ischaemic events or bleeding. METHODS AND RESULTS: In the substudy, 518 out of 1883 patients were included and within 14 days after a myocardial infarction randomized to ximelagatran or placebo for 6 months. The clinical endpoints death, myocardial infarction, severe recurrent ischaemia, ischaemic stroke, and bleeding were evaluated. The levels of F1 + 2, D-dimer, and APTT were analysed at randomization and in serial samples during the study. Ximelagatran treatment appeared to have a larger treatment effect in patients with F1 + 2 and D-dimer levels above the median at randomization with a reduction of ischaemic events from 18 to 9% (P = 0.03) for F1 + 2 and from 20 to 9% for D-dimer (P = 0.009). A reduction of D-dimer levels was found in 60% of the patients 1 week after randomization and these patients had less ischaemic events when compared with patients with unchanged or increased levels (P = 0.03) regardless of treatment. F1 + 2 and D-dimer levels were unrelated to bleeding risk. In the ximelagatran group, increased APTT was not related to ischaemic events but associated with a raised risk of bleeding. CONCLUSION: A reduction of initially high coagulation activity, as measured by the D-dimer level, in patients with recent myocardial infarction identifies patients with a decreased risk of new ischaemic events, regardless whether the reduction occurs spontaneously or is induced by pharmacological means. Patients with higher initial coagulation activity seemed to benefit most from long-term treatment with ximelagatran.
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| 9. |
- Christersson, Christina, et al.
(författare)
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Effect of apixaban compared with warfarin on coagulation markers in atrial fibrillation.
- 2019
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 105:3, s. 235-242
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Compare the effect of apixaban and warfarin on coagulation and primary haemostasis biomarkers in atrial fibrillation (AF).METHODS: The biomarker substudy from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial included 4850 patients with AF randomised to treatment with apixaban or warfarin. Sixty per cent of patients used vitamin K antagonist (VKA) within 7 days before randomisation. Prothrombin fragment 1+2 (F1+2), D-dimer, soluble CD40 ligand (sCD40L) and von Willebrand factor (vWF) antigen were analysed at randomisation and after 2 months of study treatment.RESULTS: In patients not on VKA treatment at randomisation, F1+2 and D-dimer levels were decreased by 25% and 23%, respectively, with apixaban, and by 59% and 38%, respectively, with warfarin (p<0.0001 for treatment differences for both). In patients on VKA at randomisation, F1+2 and D-dimer levels increased by 41% and 10%, respectively, with apixaban and decreased by 37% and 11%, respectively, with warfarin (p<0.0001 for treatment differences for both). sCD40L levels were slightly increased at 2 months, regardless of VKA or randomised treatment. Apixaban and warfarin also both reduced vWF antigen regardless of VKA treatment. The efficacy (stroke) and safety (bleeding) of apixaban compared with warfarin was similar irrespectively of biomarker levels at 2 months.CONCLUSIONS: Treatment with apixaban compared with warfarin for stroke prevention in patients with AF was associated with less reduction in thrombin generation and fibrin turnover. This effect of apixaban could contribute to the clinical results where apixaban was superior to warfarin both in stroke prevention and in reducing bleeding risk.TRIAL REGISTRATION NUMBER: NCT00412984.
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| 10. |
- Christersson, Christina, et al.
(författare)
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Haemorrhagic stroke and major bleeding after intervention with biological aortic valve prosthesis : risk factors and antithrombotic treatment
- 2020
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Ingår i: European Heart Journal, Supplement. - : OXFORD UNIV PRESS. - 1520-765X .- 1554-2815. ; 22:C, s. C26-C33
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Tidskriftsartikel (refereegranskat)abstract
- The majority of patients with severe aortic stenosis are recommended intervention with a surgical biological prosthesis (bioSAVR) or a transcatheter aortic valve intervention (TAVI). The antithrombotic strategies after aortic valve intervention vary and include drugs targeting both platelets and the coagulation cascade. Long-term exposure and changes of antithrombotic treatment influence the risk of both bleeding and thromboembolic events. The aim was to describe an unselected sample of patients who have experienced haemorrhagic stroke and other major bleeding events after biological aortic prosthesis, their antithrombotic treatment and changes of treatments in relation to the bleeding event. All patients performing an bioSAVR or a TAVI 2008-2014 were identified in the SWEDEHEART registry and included in the study (n =10 711). The outcome events were haemorrhagic stroke and other major bleeding event. Information of drug exposure was collected from the dispensed drug registry. The incidence rate of any bleeding event was 2.85/100 patient-years the first year after aortic valve intervention. Heart failure and atrial fibrillation were present more often in patients with a first haemorrhagic stroke or other major bleeding event compared to without. The proportion of exposure to warfarin was 28.7% vs. 21.3% in patients with and without a haemorrhagic stroke. Comparable figures were 31.2% vs. 19.0% in patients with and without other major bleeding event. During 1 month prior a haemorrhagic stroke or other major bleeding event 39.4% and 38.0%, respectively, of the patients not previously exposed to antithrombotic treatment started warfarin or single antiplatelet therapy. Major bleeding events are not uncommon after aortic valve intervention with a biological prosthesis. Evaluation of comorbidities and previous bleeding might improve risk stratification for bleeding in these elderly patients. The pattern of change of antithrombotic treatment was similar in the groups with and without a bleeding event and in most patients the antithrombotic regime was unchanged the month before an event.
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| 11. |
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| 12. |
- Christersson, Christina, et al.
(författare)
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Long-term treatment with ximelagatran, an oral direct thrombin inhibitor, persistently reduces the coagulation activity after a myocardial infarction
- 2005
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 3:10, s. 2245-53
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In the ESTEEM study, patients with a recent myocardial infarction were treated with aspirin and randomized to one of four doses (24-60 mg b.i.d) of the oral direct thrombin inhibitor ximelagatran or placebo for 6 months. Ximelagatran and aspirin reduced the risk of recurrent ischemic events compared with aspirin alone. In the present substudy we evaluated the different doses of ximelagatran on pharmacokinetics as measured by plasma concentration of the active compound melagatran and activated partial thromboplastin time (APTT) and pharmacodynamics as related by markers for coagulation activity, prothrombin fragment 1 + 2 (F1 + 2) and D-dimer. METHODS AND RESULTS: Plasma samples from 518 patients were collected before, during and after the treatment period. There was a linear dose-concentration relation at peak and trough and a linear relation between concentration and APTT (P < 0.001). F1 + 2 and D-dimer were decreased by 25% and 52% at 1 week (P < 0.001) in the ximelagatran groups compared with the placebo group and the reductions were maintained during the 6 months treatment. There were no differences detected in F1 + 2 or D-dimer levels between the different ximelagatran dosages. There was no correlation between the melagatran concentration and the change in F1 + 2 and D-dimer levels. After cessation of ximelagatran F1 + 2 and D-dimer levels returned to the initial levels. CONCLUSION: The dose of ximelagatran and APTT are linearly related to the plasma concentration of melagatran. Ximelagatran induces a sustained and stable reduction of thrombin generation and fibrin turnover without any relation to dose above 24 mg b.i.d. These properties indicate that long-term treatment with a low dose of ximelagatran may provide valuable depression of coagulation activity in aspirin treated post myocardial infarction patients.
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| 13. |
- Christersson, Christina, 1966-
(författare)
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Regulation of Tissue Factor and Coagulation Activity : Translation Studies with Focus on Platelet-Monocyte Aggregates and Patients with Acute Coronary Syndrome
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Myocardial infarction (MI) is often caused by a disruption of an atherosclerotic plaque with activation of coagulation, platelets and inflammation. The aims were; to investigate whether the oral direct thrombin inhibitor, ximelagatran affected markers for coagulation, platelet and inflammation in a patient cohort with recent MI and if the coagulation markers could identify patients with increased risk of new ischemic events; to evaluate some of the mechanisms involved in formation of platelet-monocyte aggregates (PMAs). In a biomarker substudy patients with recent MI were randomized to 24-60 mg of ximelagatran or placebo for six months. There was a persistent dose-independent reduction of coagulation markers (F1+2, D-dimer) by ximelagatran treatment. 60 % reduced their D-dimer levels after one week and that group had less ischemic events during treatment. There was an early increase of the platelet activation marker and ximelagatran in higher doses attenuated these increased levels. Both in vivo and in vitro the direct thrombin inhibitor diminished procoagulant activity and tissue factor (TF) presenting microparticles. In contrast, the inflammatory markers increased after six months of ximelagatran treatment. The PMA-levels were elevated for long-term after MI. In vitro thrombin inhibition diminished formation of PMAs. Formation of PMAs in stimulated whole blood was P-selectin dependent and induced TF expression through phosphorylation of the Src-family member Lyn in monocytes. Addition of an oral direct thrombin inhibitor reduces coagulation and platelet activation markers for long-term after a MI together with reduced procoagulant activity which may contribute to the clinical benefit of the drug. Early reduction of D-dimer levels seems to be suitable to identify patients with reduced risk of new ischemic events independent of antithrombotic treatment. Circulating PMAs persist after a MI connecting coagulation to inflammation. Within these aggregates P-selectin induces TF, the main initiator of coagulation, partly through phosphorylation of Lyn.
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| 14. |
- Christersson, Christina, et al.
(författare)
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Screening for Biomarkers Associated with Left Ventricular Function During Follow-up After Acute Coronary Syndrome
- 2023
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Ingår i: Journal of Cardiovascular Translational Research. - : Springer Nature. - 1937-5387 .- 1937-5395. ; 16:1, s. 244-254
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Tidskriftsartikel (refereegranskat)abstract
- A proportion of patients with the acute coronary syndrome (ACS) will suffer progressive remodeling of the left ventricular (LV). The aim was to screen for important biomarkers from a large-scale protein profiling in 420 ACS patients and define biomarkers associated with reduced LV function early and 1 year after the ACS. Transferrin receptor protein 1 and NT-proBNP were associated with LV function early and after 1 year, whereas osteopontin and soluble ST2 were associated with LV function in the early phase and, tissue-type plasminogen activator after 1 year. Fatty-acid-binding protein and galectin 3 were related to worse GLS but not to LVEF 1 year after the ACS. Proteins involved in remodeling and iron transport in cardiomyocytes were related to worse LV function after ACS. Biomarkers for energy metabolism and fibrosis were exclusively related to worse LV function by GLS. Studies on the functions of these proteins might add knowledge to the biological processes involved in heart failure in long term after ACS.
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| 15. |
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| 16. |
- Christersson, Christina, et al.
(författare)
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The utility of coagulation activity for prediction of risk of mortality and cardiovascular events in guideline-treated myocardial infarction patients
- 2017
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Ingår i: Upsala Journal of Medical Sciences. - : Taylor & Francis. - 0300-9734 .- 2000-1967. ; 122:4, s. 224-233
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Despite improved treatment of myocardial infarction (MI), real-world patients still suffer substantial risk for subsequent cardiovascular events. Little is known about coagulation activity shortly after MI and whether coagulation activity markers may identify patients at increased risk despite contemporary treatment.OBJECTIVE: To evaluate D-dimer concentration and thrombin generation potential shortly after discharge after MI and evaluate if these markers could predict the risk of future cardiovascular and bleeding events.METHODS: Unselected MI patients (n = 421) were included in the observational REBUS study (NCT01102933) and followed for two years. D-dimer concentrations, thrombin peak, and endogenous thrombin potential (ETP) were analyzed at inclusion (3-5 days after MI) and at early follow-up (after 2-3 weeks).RESULTS: Seventy-five patients (17.8%) experienced the composite endpoint (all-cause death, MI, congestive heart failure, or all-cause stroke), and 31 patients (7.4%) experienced a clinically relevant bleeding event. D-dimer concentrations at early follow-up were associated with the composite endpoint (HR [per SD increase] 1.51 [95% CI 1.22-1.87]) and with clinically relevant bleeding (HR [per SD increase] 1.80 [95% CI 1.32-2.44]). Thrombin generation potential was not significantly associated with either the composite endpoint or with clinically relevant bleeding. Higher thrombin peak and ETP at early follow-up were both inversely associated with stroke (HR [per SD increase] 0.50 [95% CI 0.30-0.81] and 0.43 [95% CI 0.22-0.83], respectively).CONCLUSION: In unselected MI patients treated according to contemporary guidelines, D-dimer measurements may identify patients at increased risk of new cardiovascular and bleeding events. The inverse association of thrombin generation potential and risk of stroke has to be further investigated.
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| 17. |
- Christersson, Christina, et al.
(författare)
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Treatment with an Oral Direct Thrombin Inhibitor Decreases Platelet Activity but Increases Markers of Inflammation in Patients with Myocardial Infarction.
- 2011
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 270:3, s. 215-223
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Tidskriftsartikel (refereegranskat)abstract
- Background: Thrombin has a role not only in the coagulation process but also in inflammatory responses. Oral direct thrombin inhibitors (DTIs) are currently being evaluated in patients with thromboembolic diseases. Objectives: To investigate whether an oral DTI affects markers for platelet and inflammatory activity after myocardial infarction (MI). Methods: A total of 518 patients with MI were randomly assigned to ximelagatran treatment (four different dose groups) in combination with aspirin, or aspirin alone for 6 months. The levels of soluble (s) P-selectin, soluble tissue factor, C-reactive protein (CRP), interleukin (IL)-10 and IL-18 were analysed in serial blood samples.Results: sP-selectin concentration increased after 1 week and persisted at an elevated level for 6 months in all study groups (p<0.001). In the two highest ximelagatran dose groups, there was a reduced increase in sP-selectin compared to treatment with lower doses of ximelagatran and aspirin alone (p=0.01 and p=0.002, respectively). IL-18 levels did not change in the aspirin alone treatment group. By contrast, there was an elevation in IL-18 level in the lower and higher ximelagatran dose groups after 6 months (p=0.006 and p<0.001, respectively). Ximelagatran increased IL-10 levels (p=0.002) and reduced the decrease in CRP levels after 6 months compared to treatment with aspirin alone (p=0.002).Conclusion: A persistent elevation of platelet activity is found in patients with a recent MI after the cessation of acute antithrombotic treatment, and the addition of an oral DTI at higher doses decreases the activity. By contrast, long-term treatment with a DTI increases the levels of several markers of inflammation. Further studies with prolonged exposure of oral DTIs are needed for evaluation of the effect on inflammatory processes and to determine whether these agents influence clinical outcomes.
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| 18. |
- Christersson, Lars
(författare)
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Ekonomiska och energirelaterade resultat från avverkade och ännu växande poppel- och hybridaspbestånd i södra Sverige
- 2016
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Ingår i: Fakta. Skog. - 1400-7789.
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Annan publikation (populärvet., debatt m.m.)abstract
- Skogens roll i Sveriges energiförsörjning och i det allmänna klimatarbetet accentuerades ytterligare under oljekrisernas 70-tal genom introduktionen av de nya verksamhetsområdena energiskog och skogsenergi. Olika salixarters produktionspotential varit kända sedan länge, nu börjar vi också få resultat av olika poppelkloners produktionskapacitet.har Vid avverkning av ett 0,8 ha stort 24-årigt poppelbestånd under bark plus flis av 29 m utbytet blev 4 200 kr/ha, år med 3 % ränta. Fortfarande växande, likåldriga poppelplanteringar visar likvärdiga resultat.erhölls en produktion av ved3/ha, år. Det ekonomiska I dag planteras nyframtagna poppelkloner med en ny planteringsmetod. hypotesen är, att det med 3,5–4 m långa sticklingar av nyförädlat poppelmaterial är möjligt att på 15 år och utan markberedning och skötselåtgärder producera 500 m första generation och 600 m Vattentillgången är oftast den begränsande faktorn.Den bakomliggande3/ha i en3/ha i en andra. 1 m 700 kWh el eller 280 liter metanol.3 aspved ger ca 2 000 kWh värme eller
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| 19. |
- Christersson, Lars
(författare)
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Här växer framtidens drivmedel
- 2018
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Ingår i: Forskning och framsteg. - 0015-7937. ; , s. 1-9
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- En ny typ av energiskog kan vara nyckeln till fossilfria bränslen i Sverige. Här skriver forskaren Lars Christersson om hur skördarna kan ökas dramatiskt.
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| 20. |
- Christersson, Lars
(författare)
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Remarkable Economic and Energy-Based Income from a Harvested Poplar Plantation in the South of Sweden
- 2017
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Ingår i: Annals of Experimental Biology. - 2348-1935. ; 5, s. 7-8
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Search for alternative energy sources has been going on in Sweden since the middle of the 70 ties. Energy plantations of different Salix clones are well established and now even poplar plantations start to become of interest. A poplar plantation in the south of Sweden has been harvested with the following results: a woody production above ground of 29 m3 /ha, year. This production gives an economic outcome of 510 US$/ha, year. Efficient Light Absorption Factor (ELAF) for woody biomass production above ground and under bark was 0.6% in this plantation.
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| 21. |
- Christersson, Lars, et al.
(författare)
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Vombsjösänkans pil- och poppelpark
- 2018
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- En ny, liten försökspark, speciellt avsedd för tester av pil- och poppelodlingar, har etablerats i södra Sverige, strax öster om Vombsjön i Skåne. Den har döpts till VOMBSJÖSÄNKANS PIL- OCH POPPELPARK (VPP). Syftet är att testa nyframkorsade pil- och poppelkloners fenologi och produktionspotential med avseende på vedbiomassa för energiändamål, pappersmassa- och textiltillverkning samt som råvara för korslimmade byggnadsprodukter. Nya planteringsmetoder för piloch poppelplanteringar har utarbetats. De äldsta planteringarna är i dag (2018) 29 år gamla och vid en jämförelse med tidigare resultat antyder genomförda mätningar kraftigt förbättrade produktionsresultat, speciellt för de yngsta planteringarna. Parken är delvis förlagd till ett mycket sandigt område och delvis till ett bördigt, organogent men mycket sommarfrostlänt område med en stark population av kronhjort. Vissa år är även populationer av både åker- och vattensork synnerligen besvärande. Både biotiska och abiotiska skaderisker är således förekommande på parken och stora ansträngningar görs för att undvika dess effekter. Parken är öppen för exkursioner. Guidade visningar kan arrangeras, tel. 0760 16 80 28.
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| 22. |
- Christersson, Lars
(författare)
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Wood production potential in poplar plantations in Sweden
- 2010
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Ingår i: Biomass and Bioenergy. - : Elsevier BV. - 0961-9534 .- 1873-2909. ; 34, s. 1289-1299
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Tidskriftsartikel (refereegranskat)abstract
- Shortage of oil, large variations in exports from Russia of wood to Europe, plenty of abandoned agriculture land, new ideas about a more intensive silviculture; these circumstances are driving forces in Sweden for planting fast-growing poplar and hybrid aspen clones on suitable land. The advantage of such trees is that the wood can be used for both energy (heat, biofuels, electricity), paper and for construction. Poplar clones bred in the USA and Belgium, and older hybrid aspen clones from Sweden, together with new poplar clones collected and selected for Swedish conditions from British Columbia, Canada, were planted during the 1990s in south and central Sweden. The stem diameters and heights of the trees have been measured during the last 10 years and the woody biomass production above ground has been calculated. MAI for all the plantations is 10-31 m(3) or 3-10 ton DM per hectare with the highest annual woody production of 45 m(3) or 15 ton DM per hectare in some years in a very dense plantation in the most southern part of Sweden. All the plantations have been fenced for at least the first ten years. The damage has been caused by stem canker, insects, leaf rust and by moose after removal of the fences. The possibilities for the use of poplar plantations as energy forest and vegetation filters are discussed. (C) 2010 Elsevier Ltd. All rights reserved.
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| 23. |
- Erlinge, David, et al.
(författare)
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Identification of vulnerable plaques and patients by intracoronary near-infrared spectroscopy and ultrasound (PROSPECT II) : a prospective natural history study
- 2021
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 397:10278, s. 985-995
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Tidskriftsartikel (refereegranskat)abstract
- Background: Near-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs).Methods: PROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065.Findings: Between June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17%] women, 745 [83%] men; median age 63 [IQR 55-70] years). Median follow-up was 3.7 (IQR 3.0-4.4) years. Adverse events within 4 years occurred in 112 (13.2%, 95% CI 11.0-15.6) of 898 patients, with 66 (8.0%, 95% CI 6.2-10.0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46.9% [SD 15.9]). Highly lipidic lesions (851 [24%] of 3500 lesions, present in 520 [59%] of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adjusted odds ratio 2.27, 95% CI 1.25-4.13) and nonculprit lesion-specific MACEs (7.83, 4.12-14.89). Large plaque burden (787 [22%] of 3629 lesions, present in 530 [59%] of 898 patients) was also an independent predictor of non-culprit lesion-related MACEs. Lesions with both large plaque burden by intravascular ultrasound and large lipid-rich cores by NIRS had a 4-year non-culprit lesion-related MACE rate of 7.0% (95% CI 4.0-10.0). Patients in whom one or more such lesions were identified had a 4-year non-culprit lesion-related MACE rate of 13.2% (95% CI 9.4-17.6).Interpretation: Combined NIRS and intravascular ultrasound detects angiographically non-obstructive lesions with a high lipid content and large plaque burden that are at increased risk for future adverse cardiac outcomes.
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| 24. |
- Hijazi, Ziad, et al.
(författare)
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N-Terminal Pro-B-Type Natriuretic Peptide for Risk Assessment in Patients With Atrial Fibrillation : Insights from the ARISTOTLE trial
- 2013
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 61:22, s. 2274-2284
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:This study sought to assess the prognostic value of N-terminal pro–B-type natriuretic peptide (NT-proBNP) in patients with atrial fibrillation (AF) enrolled in the ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) trial, and the treatment effect of apixaban according to NT-proBNP levels.BACKGROUND:Natriuretic peptides are associated with mortality and cardiovascular events in several cardiac diseases.METHODS:In the ARISTOTLE trial, 18,201 patients with AF were randomized to apixaban or warfarin. Plasma samples at randomization were available from 14,892 patients. The association between NT-proBNP concentrations and clinical outcomes was evaluated using Cox proportional hazard models, after adjusting for established cardiovascular risk factors.RESULTS:Quartiles of NT-proBNP were Q1:≤363, Q2:364-713, Q3:714-1250 and Q4:>1250 ng/L. During 1.8 years the annual rates of stroke or systemic embolism ranged from 0.74% in the bottom NT-proBNP quartile to 2.21% in the top quartile, adjusted hazard ratio (HR) 2.35 (95% CI 1.62-3.40, p<0.0001. Annual rates of cardiac death ranged from 0.86% in Q1 to 4.14% in Q4, adjusted HR 2.50 (1.81-3.45), p<0.0001. Adding NT-proBNP levels to the CHA2DS2VASc score improved C-statistics from 0.62 to 0.65 (p=0.0009) for stroke or systemic embolism and from 0.59 to 0.69 for cardiac death (p<0.0001). Apixaban reduced stroke, mortality, and bleeding regardless of the NT-proBNP level.CONCLUSIONS:NT-proBNP levels are often elevated in AF and independently associated with an increased risk of stroke and mortality. NT-proBNP improves risk stratification beyond the CHA2DS2VASc score and might be a novel tool for improved stroke prediction in AF. The efficacy of apixaban compared with warfarin is independent of the NT-proBNP level. (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation [ARISTOTLE].
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| 25. |
- Jönelid, Birgitta, et al.
(författare)
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Ankle brachial index most important to identify polyvascular disease in patients with non-ST elevation or ST-elevation myocardial infarction
- 2016
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Ingår i: European journal of internal medicine. - : Elsevier BV. - 0953-6205 .- 1879-0828. ; 30, s. 55-60
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Atherosclerosis is a systemic disease. In patients with acute myocardial infarction (MI) the extent of polyvascular disease (PvD) is largely unknown. In this study we investigate the prevalence and clinical characteristics predictive of PvD in patients with non-ST-elevation (NSTEMI) and ST-elevation (STEMI) MI.METHOD: 375 patients with acute MI included in the REBUS (Relevance of Biomarkers for Future Risk of Thromboembolic Events in Unselected Post-myocardial Infarction Patients) study were examined. Atherosclerotic changes were assessed in three arterial beds by coronary angiography, carotid ultrasound and ankle brachial index (ABI). Results compared findings of atherosclerosis in three arterial beds to fewer than 3 beds. PvD was defined as atherosclerosis in all three arterial beds.RESULTS: A medical history of MI, peripheral artery disease (PAD) or stroke was reported at admission in 17.9%, 2.1% and 3.7% of the patients, respectively. After evaluation, abnormal ABI was found in 20.3% and carotid artery atherosclerosis in 54.9% of the patients. In the total population, PvD was found in 13.8% of patients with no significant differences observed between NSTEMI and STEMI patients. Age (p<0.001), diabetes (p=0.039), previous PAD (p=0.009) and female gender (p=0.016) were associated with PvD. ABI was the most important predictor of PvD with a positive predictive value of 68.4% (95% CI 57.7-79.2%) and specificity of 92.4% (95% CI 89.5-95.4%).CONCLUSIONS: PvD is underdiagnosed in patients suffering from MI, both NSTEMI and STEMI. ABI is a useful and simple measurement that appears predictive of widespread atherosclerosis in these patients.
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| 26. |
- Jönelid, Birgitta, et al.
(författare)
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Biochemical biomarkers associated with peripheral artery disease contribute to prediction of outcome during long-term follow up after myocardial infarction
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- AbstractBackground: Few studies have investigated biomarkers and their association to cardiovascular (CV) outcomes in patients with myocardial infarction (MI) and peripheral artery disease (PAD). Tumor necrosis factor receptor 1(TNFR-1), tumor necrosis factor receptor 2(TNFR-2) and growth differentiation factor 15 (GDF-15) are inflammatory biomarkers found to predict PAD.Aim: To evaluate whether pathological ankle brachial index (ABI) and the group of biomarkers TNFR-1, TNFR-2 and GDF-15 analyzed early after a MI, were associated with all-cause mortality and the risk of new cardiovascular events during long-term follow up. Method: 388 patients with MI included in the REBUS (Relevance of Biomarkers for future risk of Thromboembolic Events in Unselected Post-myocardial Infarction Patients) study were examined with ABI to diagnose PAD (defined as an ABI score <0.9 or > 1.4 on at least one side). TNFR-1, -2 and GDF-15 was measured using the Proseek Multiplex CVD III ⁹⁶˟⁹⁶ proximity extension assay (www.olink.com/products/cvd-i and iii-panel). The composite results for these 3 biomarkers were dichotomized into two groups (i.e high and low values) We evaluated pathological ABI and the group with higher biomarkers values with the association to long-term outcome, and if the group of biomarkers for inflammation could further improve prediction of recurrence of cardiovascular events (mortality, new acute coronary syndrome (ACS) and the composite of mortality, new ACS, stroke/TIA and PAD) after an MI. Results: The mean follow-up time was 5.5 years. After adjustment for established CV risk factors, pathological ABI was associated with a higher risk of new ACS, HR 1.97, 95 % CI 1.12-3.49, p = 0.019, and the composite endpoint; HR 1.97, 95 % CI 1.29-3.01, p=0.002, compared to patients with normal ABI. The group with the higher biomarker value was associated with a higher risk for all-cause mortality; HR 1.84, 95 % CI 1.00-3.38, p=0.049 and the composite endpoint; HR 1.62, 95 % CI 1.03-2.53, p=0.035. In the ROC analyses pathological ABI added to established CV risk factors improved the AUC for a new ACS from 0.753 (95% C.I. 0.684-0.822, p<0.001) to 0.763 (95% C.I. 0.697-0.830, p<0.001). When the group with higher biomarker values was added to established CV risk factors AUC for all-cause mortality increased from 0.789 (95% C-I. 0.729-0.849, p<0.001) to 0.805 (95% C.I. 0.746-0.863, p<0.001).Conclusion: Despite a high proportion of revascularization and guideline-recommended secondary medical treatment, both pathological ABI and the group with higher values of the inflammatory biomarkers (TNFR-1, TNFR-2, GDF-15) predictive for PAD were associated with the risk of new CV events and mortality in patients with a recent MI. The group of inflammatory biomarkers provide additional information to established risk factors in prediction of CV outcome in this cohort with recent MI.
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| 27. |
- Jönelid, Birgitta, et al.
(författare)
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Biomarkers in addition to clinical characteristics for prediction of peripheral artery disease in patients with recent myocardial infarction
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- AbstractBackground Few studies have examined biomarkers in CAD and peripheral artery disease (PAD), their association and the ability to predict PAD.Methods: Two prospectively observational studies including unselected patients with recent myocardial infarction were used for the analyses. PAD was defined as an abnormal ankle brachial index (ABI) score (<0.9 or > 1.4) on at least one side. The proximity extension assay (PEA) technique was used to simultaneously analyze 92 biomarkers with association to cardiovascular disease in samples early after an acute MI. Random forest was used to identify the biomarkers with a higher association to PAD. The additional discriminatory accuracy of adding biomarkers to clinical characteristics were analyzed by the c-statistics.Results: Six biomarkers were identified associated with prediction of PAD in the REBUS cohort. Three of these could be validated in the VaMIS cohort; Tumor necrosis factor receptor (TNFR-1), Tumor necrosis factor receptor 2 (TNFR-2) and Growth Differentiation Factor 15 (GDF-15) with an increase in c-statistics; Tnfr1:0.709 (95% CI 0.640, 0.779) and 0.746 (95% CI 0.706,0.787), Tnfr2: 0.703 (95% CI 0.633, 0.773) and 0.745 (95% CI 0.704, 0.785), GDF-15: 0.710 (95% CI 0.640, 0.781) and 0.752 (95% CI 0.711, 0.792) in the REBUS and VaMIS cohort respectively. Adding a group of biomarkers to clinical characteristics further increased the c-statistics compared to a single biomarker.Conclusions: Three biomarkers out of a panel of 92; TNFR-1, TNFR-2 and GDF-15 were identified associated with PAD in MI patients and could improve prediction of PAD in addition to clinical characteristics.
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| 28. |
- Jönelid, Birgitta, et al.
(författare)
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Low Walking Impairment Questionnaire score after a recent myocardial infarction identifies patients with polyvascular disease
- 2019
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Ingår i: JRSM Cardiovascular Disease. - : SAGE Publications. - 2048-0040. ; 8, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate whether the Walking Impairment Questionnaire score could identify patients with polyvascular disease in a population with recent myocardial infarction and their association with cardiovascular events during two-year follow-up.Design: A prospective observational study.Setting: Patients admitted to the acute coronary care unit, the Department of Cardiology, Uppsala University Hospital.Participants: Patients admitted with acute Non-STEMI- or STEMI-elevation myocardial infarction.Main outcome measures: The Walking Impairment Questionnaire, developed as a self-administered instrument to assess walking distance, speed, and stair climbing in patients with peripheral artery disease, predicts future cardiovascular events and mortality. Two hundred and sixty-three patients with recent myocardial infarction answered Walking Impairment Questionnaire. Polyvascular disease was defined as abnormal findings in the coronary- and carotid arteries and an abnormal ankle-brachial index. The calculated score for each of all three categories were divided into quartiles with the lowest score in first quartile.Results: The lowest (worst) quartile in all three Walking Impairment Questionnaire categories was associated with polyvascular disease, fully adjusted; distance, odds ratio (OR) 5.4 (95% confidence interval (CI) 1.8-16.1); speed, OR 7.4 (95% CI 1.5-36.5); stair climbing, OR 8.4 (95% CI 1.0-73.6). In stair climbing score, patients with the lowest (worst) score had a higher risk for the composite cardiovascular endpoint compared to the highest (best) score; hazard ratio 5.3 (95% CI 1.5-19.0). The adherence to medical treatment was high (between 81.7% and 99.2%).Conclusions: The Walking Impairment Questionnaire is a simple tool to identify myocardial infarction patients with more widespread atherosclerotic disease and although well treated medically, stair climbing predicts cardiovascular events.
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| 29. |
- Jönelid, Birgitta, et al.
(författare)
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Screening of biomarkers for prediction of multisite artery disease in patients with recent myocardial infarction
- 2021
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 81:5, s. 353-360
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Tidskriftsartikel (refereegranskat)abstract
- A few studies have examined biomarkers in patients with myocardial infarction (MI) and peripheral artery disease (PAD), i.e. multisite artery disease (MSAD). The aim of the study was firstly, to associate biomarkers with the occurrence of PAD/MSAD and secondly, if those can, in addition to clinical characteristics, identify MI patients with MSAD.In two prospectively observational studies including unselected patients with recent MI, PAD was defined as an abnormal ankle-brachial index (ABI) score (1.4). The proximity extension assay (PEA) technique was used, simultaneously analyzing 92 biomarkers with association to cardiovascular disease. Biomarkers were tested for univariate associations with PAD. Random forest was used to identify biomarkers with a higher association to PAD. The additional discriminatory accuracy of adding biomarkers to clinical characteristics was analyzed by the c-statistics. Nine biomarkers were identified as significantly associated with MSAD/PAD in the primary patient cohort, analyzed early after the MI. In the prediction analysis, six biomarkers were identified associated with PAD. Three of these; Tumor necrosis factor receptor (TNFR-1), Tumor necrosis factor receptor 2 (TNFR-2) and Growth Differentiation Factor 15 (GDF-15) improved c-statistics when added to clinical characteristics from 0.683 (95% CI 0.610-0.756) to 0.715 (95% CI 0.645-0.784) in the primary patient cohort with a similar result, 0.729 (95% CI 0.687-0.770) to 0.752 (95% CI 0.771-0.792) in the secondary patient cohort. Biomarkers associated with inflammatory pathways are associated with MSAD in MI patients. Three biomarkers of 92; TNFR-1, TNFR-2 and GDF-15, in this exploratory added information in the prediction of MSAD and emphasis the importance of further studies.
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| 30. |
- Karacic, Almir, et al.
(författare)
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An Analysis of Poplar Growth and Quality Traits to Facilitate Identification of Climate-Adapted Plant Material for Sweden
- 2021
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Ingår i: BioEnergy Research. - : Springer Science and Business Media LLC. - 1939-1234 .- 1939-1242. ; 14, s. 409-425
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Tidskriftsartikel (refereegranskat)abstract
- Poplar plantations harbor large potential as a renewable source of biomass for bioenergy and other industrial applications. The overall aim of this study is to analyze growth, phenology, stem form, and branching characteristics of 32 poplar clones grown in a trial in southern Sweden for their suitability to be grown as industrial feedstock. In a linear mixed model, performed for diameter at breast height and stem volume, the precision was improved by the use of two competition indices. The significance of phenology and quality characteristics for growth performance and ranking of poplar clones was evaluated through genotypic correlations, and multivariate hierarchical cluster analysis used to group the material. All traits showed moderate to high broad sense heritability. In general, higher stem volume was positively correlated with later leaf senescence, and uncorrelated with spring phenology. Selection efficiency for stem diameter and height was greatly improved between age 3 and 6 years allowing a better precision in selecting a subset of clones to be further tested in production plots and pilot plantations. Two commercial Populus maximowiczii Henry x trichocarpa Torr. & Gray cultivars performed best, while some intraspecific hybrids of P. trichocarpa are considered useful to genetically diversify commercial plantations in Southern Sweden (Belgian clones) or establish plantations in north-central parts of Sweden (Swedish clones). The cluster analysis emphasized growth traits and the grouping of the clones corresponded to their origin (or parentage). The results will facilitate decisions on the use of studied material in breeding, further testing and commercial deployment of poplar plantations in Sweden.
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| 31. |
- Lindgren, Gustaf, et al.
(författare)
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Erythropoietin suppresses the activation of pro-apoptotic genes in head and neck squamous cell carcinoma xenografts exposed to surgical trauma.
- 2014
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Several studies on the use of erythropoietin (Epo) to treat anaemia in patients undergoing cancer treatment have shown adverse effects on tumour control and survival. Experimental studies indicate that this could be linked to an interaction with wound healing processes and not an effect on tumour cells per se. We have previously shown that erythropoietin in combination with surgical trauma stimulates tumour growth. In the present study, we investigated the effect of surgery and Epo on gene expression.
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| 32. |
- McMurray, John J V, et al.
(författare)
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A trial to evaluate the effect of the sodium-glucose co-transporter 2 inhibitor dapagliflozin on morbidity and mortality in patients with heart failure and reduced left ventricular ejection fraction (DAPA-HF).
- 2019
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 21:5, s. 665-675
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce the risk of incident heart failure hospitalization in individuals with type 2 diabetes who have, or are at high risk of, cardiovascular disease. Most patients in these trials did not have heart failure at baseline and the effect of SGLT2 inhibitors on outcomes in individuals with established heart failure (with or without diabetes) is unknown.DESIGN AND METHODS: The Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF) is an international, multicentre, parallel group, randomized, double-blind, study in patients with chronic heart failure, evaluating the effect of dapagliflozin 10 mg, compared with placebo, given once daily, in addition to standard care, on the primary composite outcome of a worsening heart failure event (hospitalization or equivalent event, i.e. an urgent heart failure visit) or cardiovascular death. Patients with and without diabetes are eligible and must have a left ventricular ejection fraction ≤ 40%, a moderately elevated N-terminal pro B-type natriuretic peptide level, and an estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2 . The trial is event-driven, with a target of 844 primary outcomes. Secondary outcomes include the composite of total heart failure hospitalizations (including repeat episodes), and cardiovascular death and patient-reported outcomes. A total of 4744 patients have been randomized.CONCLUSIONS: DAPA-HF will determine the efficacy and safety of the SGLT2 inhibitor dapagliflozin, added to conventional therapy, in a broad spectrum of patients with heart failure and reduced ejection fraction.
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| 33. |
- Schophuus Jensen, Annette, et al.
(författare)
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Cause-Specific Mortality in Patients During Long-Term Follow-Up After Atrial Switch for Transposition of the Great Arteries
- 2022
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Ingår i: Journal of the American Heart Association. - : American Heart Association. - 2047-9980. ; 11:14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Little is known about the cause of death (CoD) in patients with transposition of the great arteries palliated with a Mustard or Senning procedure. The aim was to describe the CoD for patients with the Mustard and Senning procedure during short-(<10 years), mid-(10–20 years), and long-term (>20 years) follow-up after the operation.METHODS AND RESULTS: This is a retrospective, descriptive multicenter cohort study including all Nordic patients (Denmark, Finland, Norway, and Sweden) who underwent a Mustard or Senning procedure between 1967 and 2003. Patients who died within 30 days after the index operation were excluded. Among 968 patients with Mustard/Senning palliated transposition of the great arteries, 814 patients were eligible for the study, with a mean follow-up of 33.6 years. The estimated risk of all-cause mortality reached 36.0% after 43 years of follow-up, and the risk of death was highest among male patients as compared with female patients (P=0.004). The most common CoD was sudden cardiac death (SCD), followed by heart failure/heart transplantation accounting for 29% and 27%, respectively. During short-, mid-, and long-term follow-up, there was a change in CoD with SCD accounting for 23.7%, 46.6%, and 19.0% (P=0.002) and heart failure/heart transplantation 18.6%, 22.4%, and 46.6% (P=0.0005), respectively.CONCLUSIONS: Among patients corrected with Mustard or Senning transposition of the great arteries, the most common CoD is SCD followed by heart failure/heart transplantation. The CoD changes as the patients age, with SCD as the most common cause in adolescence and heart failure as the dominant cause in adulthood. Furthermore, the risk of all-cause mortality, SCD, and death attributable to heart failure or heart transplantation was increased in men >10 years after the Mustard/Senning operation.
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| 34. |
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| 35. |
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| 36. |
- Thilén, Maria, et al.
(författare)
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Preoperative heart failure worsens outcome after aortic valve replacement irrespective of left ventricular ejection fraction.
- 2021
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Ingår i: European Heart Journal - Quality of Care and Clinical Outcomes. - : Oxford University Press. - 2058-5225 .- 2058-1742. ; 8:2, s. 127-134
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Left ventricular ejection fraction (LVEF) affects outcome of valve replacement (AVR) in aortic stenosis (AS). The study aim was to investigate the prognostic importance of concomitant cardiovascular disease in relation to preoperative LVEF.METHODS AND RESULTS: All adult patients undergoing AVR due to AS 2008-2014 in a national register for heart diseases were included. All-cause mortality and hospitalization for heart failure during follow-up after AVR, stratified by preserved or reduced LVEF (=50%), was derived from national patient registers and analyzed by Cox regression.During the study period 10,406 patients, median age 73 years, a median follow-up of 35 months were identified. Preserved LVEF was present in 7,512 (72.2%). Among them 647 (8.6%) had a history of heart failure (HF) and 1,099 (14.6%) atrial fibrillation (AF) before intervention. Preoperative HF was associated with higher mortality irrespective of preserved or reduced LVEF: Hazard Ratio (HR) 1.64 (95% C.I. 1.35 -1.99) and 1.58 (95% C.I. 1.30 -1.92). Prior AF was associated with a higher risk of mortality in patients with preserved but not in those with reduced LVEF: HR 1.62 (95% C.I. 1.36 -1.92) and 1.05 (95% C.I. 0.86 -1.28). Irrespective of LVEF preoperative HF and AF were associated with an increased risk of postoperative heart failure hospitalization.CONCLUSION: In patients planned for AVR, a history of HF or AF, irrespective of LVEF, worsens the postoperative prognosis. HF and AF can be seen as markers of myocardial fibrosis not necessarily discovered by LVEF and the merely use of it, besides symptoms, for timing of AVR seems suboptimal.
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| 37. |
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| 38. |
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| 39. |
- Zeitouni, Michel, et al.
(författare)
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Clinical and Pharmacological Effects of Apixaban Dose Adjustment in the ARISTOTLE Trial
- 2020
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Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 75:10, s. 1145-1155
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial, patients with atrial fibrillation and >= 2 dose-adjustment criteria (age >= 80 years, weight <= 60 kg, or creatinine >= 1.5 mg/dl [133 mu mol/l]) were randomized to receive apixaban 2.5 mg twice daily or warfarin.OBJECTIVES: The purpose of this study was to describe the effects of apixaban dose adjustment on clinical and pharmacological outcomes.METHODS: Patients receiving the correct dose of study drug were included (n = 18,073). The effect of apixaban 2.5 mg twice daily versus warfarin on population pharmacokinetics, D-dimer, prothrombin fragment 1 + 2 (PF1+2), and clinical outcomes was compared with the standard dose (5 mg twice daily).RESULTS: Patients receiving apixaban 2.5 mg twice daily exhibited lower apixaban exposure (median area under the concentration time curve at a steady state 2,720 ng/ml vs. 3,599 ng/ml; p < 0.0001) than those receiving the standard dose. In patients with >= 2 dose-adjustment criteria, reductions in D-dimers (p interaction = 0.20) and PF1+2 (p interaction = 0.55) were consistent with those observed in the standard-dose population. Patients with >= 2 dose-adjustment criteria (n = 751) were at higher risk for stroke/systemic embolism, major bleeding, and all-cause death than the standard-dose population (0 or 1 dose-adjustment criterion, n = 17,322). The effect of apixaban 2.5 mg twice daily versus warfarin in the >= 2 dose-adjustment criteria population was consistent with the standard dose in the reductions in stroke or systemic embolism (p interaction = 0.26), major bleeding (p interaction = 0.25), and death (p interaction = 0.72).CONCLUSIONS: Apixaban drug concentrations were lower in patients receiving 2.5 mg twice daily compared with 5 mg twice daily. However, the effects of apixaban dose adjustment to 2.5 mg versus warfarin were consistent for coagulation biomarkers and clinical outcomes, providing reassuring data on efficacy and safety. (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation [ARISTOTLE]; NCT00412984)
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