| 1. |
- Aulin, Christian, et al.
(författare)
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Aerogels from nanofibrillated cellulose with tunable oleophobicity
- 2010
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Ingår i: SOFT MATTER. - : Royal Society of Chemistry (RSC). - 1744-683X .- 1744-6848. ; 6:14, s. 3298-3305
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Tidskriftsartikel (refereegranskat)abstract
- The formation of structured porous aerogels of nanofibrillated cellulose (NFC) by freeze-drying has been demonstrated. The aerogels have a high porosity, as shown by FE-SEM and nitrogen adsorption/desorption measurements, and a very low density ( < 0.03 g cm(-3)). The density and surface texture of the aerogels can be tuned by selecting the concentration of the NFC dispersions before freeze-drying. Chemical vapor deposition (CVD) of 1H, 1H, 2H, 2H-perfluorodecyltrichlorosilane (PFOTS) was used to uniformly coat the aerogel to tune their wetting properties towards non-polar liquids. An XPS analysis of the chemical composition of the PFOTS-modified aerogels demonstrated the reproducibility of the PFOTS-coating and the high atomic fluorine concentration (ca. 51%) in the surfaces. The modified aerogels formed a robust composite interface with high apparent contact angles (theta* >> 90 degrees) for castor oil (gamma(1v) = 35.8 mN m(-1)) and hexadecane (gamma(1v) = 27.5 mN m(-1)).
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| 2. |
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| 3. |
- Aulin, Julia, et al.
(författare)
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Biomarkers and heart failure events in patients with atrial fibrillation in the ARISTOTLE trial evaluated by a multi-state model
- 2022
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Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 251, s. 13-24
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAtrial fibrillation (AF) and heart failure (HF) often coexist. We investigated the prognostic impact of biomarkers on the development of HF and death in patients with AF and different left ventricular systolic function considering the influence of competing events.MethodsThe study included 11,818 patients with AF from the ARISTOTLE trial who at entry had information on history of HF, an estimate of left ventricular function and plasma samples for determination of biomarkers representing cardiorenal dysfunction (NT-proBNP, troponin T, cystatin C) and inflammation (GDF-15, IL-6, CRP). Patients were categorized into: (I) HF with reduced ejection fraction (HFrEF, n = 2,048), (II) HF with preserved ejection fraction (HFpEF, n = 2,520), and (III) No HF (n = 7,250). Biomarker associations with HF hospitalization and death were analyzed using a multi-state model accounting also for repeated events.ResultsBaseline levels of NT-proBNP, troponin T, cystatin C, GDF-15, IL-6, and CRP were highest in HFrEF and lowest in No HF. During median 1.9 years follow-up, 546 patients were hospitalized at least once for HF and 819 died. Higher levels of all investigated biomarkers were associated with both outcomes (all P < .0001), with highest event rates in HFrEF and lowest in No HF. The associations remained after adjustments and were more pronounced for first than for recurrent events.ConclusionsIn anticoagulated patients with AF, biomarkers indicating cardiorenal dysfunction and inflammation improve the identification of patients at risk of developing HF or worsening of already existing HF. These biomarkers might be useful for targeting novel HF therapies in patients with AF.
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| 4. |
- Aulin, Julia
(författare)
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Biomarkers of inflammation in atrial fibrillation
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Atrial fibrillation (AF) is common and associated with increased risk of stroke, heart failure (HF) and mortality. Inflammation is linked to AF.The overall aim of this thesis was to investigate inflammatory activity and cardiovascular outcomes and mortality in patients with AF on effective oral anticoagulation. Levels of the inflammatory biomarkers interleukin 6 (IL-6), C-reactive protein (CRP) and fibrinogen at study entry and serial changes of IL-6 over time were investigated and related to stroke or systemic embolism, mortality and other cardiovascular events, including major bleeding. Associations between IL-6, CRP and biomarkers of cardiorenal dysfunction (NT-proBNP, troponin, GDF-15 and cystatin C) and HF hospitalisation, recurrent HF hospitalisations and mortality, were also investigated in patients with AF stratified for HF symptoms and reduced or preserved ejection fraction.The study populations consisted of patients with AF included in the biomarker substudies of the large multicentre randomised controlled trials RE-LY (n=6,187) and ARISTOTLE (n=14,954) with a median follow-up of 2.0 and 1.9 years, respectively. Repeated IL-6 measurements were available at study entry and at any postbaseline time point at 3, 6 and 12 months in RE-LY (n=2,559), and at study entry and at 2 months in ARISTOTLE (n=4,830). For HF stratification, patients in ARISTOTLE with information on HF symptoms and left ventricular function at study entry and with IL-6, CRP, NT-proBNP, troponin T, GDF-15 and cystatin C available at randomisation (n=11,818) were included.Higher level of IL-6, but not of CRP, was significantly associated with higher risk of mortality in Cox models adjusted for established clinical risk factors and other cardiovascular biomarkers. The level of any of the studied inflammatory biomarkers was not independently associated with any other cardiovascular outcome, including stroke or systemic embolism or major bleeding, in presence of other strong cardiovascular biomarkers. Levels of IL-6 were stable over time and persistent inflammatory activity was associated with increased risk of mortality, independent of clinical risk factors and other prognostic biomarkers. All biomarkers (IL-6, CRP, NT-proBNP, troponin T, GDF-15 and cystatin C) were associated with higher risk of HF hospitalisation and mortality regardless of HF symptoms and reduced or preserved ejection fraction.In conclusion, in anticoagulated patients with AF, higher level of IL-6, but not of CRP, was associated with higher risk of mortality, independent of clinical risk factors and other cardiovascular biomarkers. IL-6 levels were stable over time and provided incremental information on the risk of mortality irrespective of when measured. IL-6 may therefore serve as a risk marker for fatal outcomes. Biomarkers improved the identification of patients with AF at risk of HF in addition to clinical and echocardiography data.
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| 5. |
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| 6. |
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| 7. |
- Aulin, Julia, et al.
(författare)
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Interleukin-6 and C-reactive protein and risk for death and cardiovascular events in patients with atrial fibrillation
- 2015
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 170:6, s. 1151-1160
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Tidskriftsartikel (refereegranskat)abstract
- Background Inflammation has been associated with cardiovascular disease and the burden of atrial fibrillation (AF). In this study we evaluate inflammatory biomarkers and future cardiovascular events in AF patients in the RE-LY study. Methods Interleukin-6 (IL-6), C-reactive protein (CRP) (n = 6,187), and fibrinogen (n = 4,893) were analyzed at randomization; outcomes were evaluated by Cox models and C-statistics. Results Adjusted for clinical risk factors IL-6 was independently associated with stroke or systemic embolism (P =.0041), major bleedings (P =.0001), vascular death (P<.0001), and a composite thromboembolic outcome (ischemic stroke, systemic embolism, myocardial infarction, pulmonary embolism and vascular death) (P<.0001). CRP was independently related to myocardial infarction (P =.0047), vascular death (P =.0004), and the composite thromboembolic outcome (P =.0001). When further adjusted for cardiac (troponin andN-terminal fragment B-type natriuretic peptide [NT-proBNP]) and renal (cystatin-C) biomarkers on top of clinical risk factors IL-6 remained significantly related to vascular death (P<.0001), major bleeding (P<.0170) and the composite thromboembolic outcome (P<.0001), and CRP to myocardial infarction (.0104). Fibrinogen was not associated with any outcome. C-index for stroke or systemic embolism increased from 0.615 to 0.642 (P =.0017) when adding IL-6 to the clinically used CHA(2)DS(2)-VASc risk score with net reclassification improvement of 28%. Conclusion In patients with AF, IL-6 is related to higher risk of stroke and major bleeding, and both markers are related to higher risk of vascular death and the composite of thromboembolic events independent of clinical risk factors. Adjustment for cardiovascular biomarkers attenuated the prognostic value, although IL-6 remained related to mortality, the composite of thromboembolic events, and major bleeding, and CRP to myocardial infarction.
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| 8. |
- Aulin, Julia, et al.
(författare)
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Neurofilament Light Chain and Risk of Stroke in Patients With Atrial Fibrillation.
- 2024
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Ingår i: Circulation. - 0009-7322 .- 1524-4539.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Biomarkers reflecting brain injury are not routinely used in risk assessment of stroke in atrial fibrillation (AF). Neurofilament light chain (NFL) is a novel biomarker released into blood after cerebral insults. We investigated the association between plasma concentrations of NFL, other biomarkers, and risk of stroke and death in patients with AF not receiving oral anticoagulation.METHODS: For this observational study, baseline plasma samples were available from 3077 patients with AF randomized to aspirin in ACTIVE A (Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events; 2003 to 2008) and AVERROES (Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment; 2007 to 2009). Median follow-up was 1.5 years. NFL was analyzed with a Single Molecule Array (Simoa). Associations with outcomes (total stroke or systemic embolism, ischemic stroke, cardiovascular death, and all-cause death) were explored with Cox regression models.RESULTS: In the combined cohort, the median NFL level was 16.9 ng/L (interquartile range, 11.1-26.5 ng/L), the median age was 71 years, 58% were men, and 13% had a history of previous stroke. NFL was associated with older age, higher creatinine, lower body mass index, previous stroke, female sex, and diabetes but not cardiac rhythm. Higher NFL was associated with a higher risk of stroke or systemic embolism (n=206) independently of clinical characteristics (hazard ratio, 1.27 [95% CI, 1.10-1.46] per doubling of NFL) and other biomarkers (hazard ratio, 1.18 [95% CI, 1.01-1.37]) and including in patients without previous stroke (hazard ratio, 1.23 [95% CI, 1.02-1.48]). NFL was also independently associated with cardiovascular (n=219) and all-cause (n=311) death. The C index for stroke using only NFL was 0.642, on par with the currently used clinical risk scores. Addition of information on NFL improved discrimination in a model also including clinical information, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and high-sensitivity cardiac troponin T, yielding a C index of 0.727.CONCLUSIONS: NFL reflects overt and covert episodes of cerebral ischemia and improves risk assessment of stroke and death in patients with AF without oral anticoagulation, including in patients without previous stroke. The combination of NFL with information on age, history of stroke, and other biomarkers should be explored as a future avenue for stroke risk assessments in patients with AF.
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| 9. |
- Aulin, Julia, et al.
(författare)
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Serial measurement of interleukin-6 and risk of mortality in anticoagulated patients with atrial fibrillation : Insights from ARISTOTLE and RE-LY trials.
- 2020
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 18:9, s. 2287-2295
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The inflammatory biomarker interleukin-6 (IL-6) is associated with mortality in atrial fibrillation (AF).OBJECTIVE: To investigate if repeated IL-6 measurements improve the prognostication for stroke or systemic embolism, major bleeding, and mortality in anticoagulated patients with AF.METHODS: IL-6 levels by ELISA were measured at study entry and at 2 months in 4830 patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial with 1.8 years median follow-up. In the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial, IL-6 was measured at study entry, 3, 6, and 12 months in 2559 patients with 2.0 years median follow-up. Associations between a second IL-6 measurement and outcomes, adjusted for baseline IL-6, clinical variables, and other cardiovascular biomarkers, were analyzed by Cox regression.RESULTS: Median IL-6 levels were 2.0 ng/L (interquartile range [IQR] 1.30-3.20) and 2.10 ng/L (IQR 1.40-3.40) at the two time-points in ARISTOTLE, and, in RE-LY, 2.5 ng/L (IQR 1.6-4.3), 2.5 ng/L (IQR 1.6-4.2), 2.4 ng/L (IQR 1.6, 3.9), and 2.4 ng/L (IQR 1.5, 3.9), respectively. IL-6 was associated with mortality; hazard ratios per 50% higher IL-6 at 2 or 3 months, respectively, were 1.32 (95% confidence interval, 1.23-1.41; P < .0001) in ARISTOTLE, and 1.11 (1.01-1.22, P = .0290) in RE-LY; with improved C index from 0.74 to 0.76 in ARISTOTLE, but not in the smaller RE-LY cohort. There were no consistent associations with second IL-6 and stroke or systemic embolism, or major bleeding.CONCLUSIONS: Persistent systemic inflammatory activity, assessed by repeated IL-6 measurements, is associated with mortality independent of established clinical risk factors and other strong cardiovascular biomarkers in anticoagulated patients with AF.
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| 10. |
- Hijazi, Ziad, et al.
(författare)
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Biomarkers of inflammation and risk of cardiovascular events in anticoagulated patients with atrial fibrillation
- 2016
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 102:7, s. 508-517
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Atrial fibrillation (AF) is a risk factor for stroke and mortality and the prothrombotic state has been linked to inflammation. In this study we evaluated the relationship between inflammatory biomarkers at baseline and future risk of cardiovascular events in the Apixaban for Reduction In Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.Methods: The ARISTOTLE trial randomised 18 201 patients with AF to apixaban or warfarin. Interleukin 6 (IL-6) and C reactive protein (CRP) were analysed in plasma obtained at randomisation from 14 954 participants, and median follow-up was 1.9 years. Association between quartile groups of IL-6 and CRP and outcomes were analysed by Cox regression adjusted for clinical risk factors and other cardiovascular biomarkers (NT-proBNP, troponin, GDF-15, cystatin C).Results: The IL-6 median level was 2.3 ng/L (IQR 1.5-3.9), median CRP level was 2.2 mg/L (1.0-4.8). IL-6 and CRP were significantly associated with all-cause mortality independent of clinical risk factors and other biomarkers (HR (95% CI) 1.93 (1.57 to 2.37) and 1.49 (1.24 to 1.79), respectively, Q4 vs Q1). IL-6 was associated with myocardial infarction, cardiovascular mortality, and major bleeding beyond clinical risk factors but not in the presence of cardiovascular biomarkers (NT-proBNP, troponin, GDF-15, cystatin C). Neither inflammatory biomarker was associated with stroke/systemic embolism. Risk prediction for stroke, death and major bleeding was not improved by IL-6 or CRP when added to clinical risk factors and the other cardiovascular biomarkers (NT-proBNP, troponin, GDF-15, cystatin C).Conclusions: In patients with AF on anticoagulation, after accounting for clinical risk factors and other biomarkers, biomarkers of inflammation were significantly associated with an increased risk of mortality. However, there were no associations with the risk of stroke or major bleeding.
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| 11. |
- Sandhu, Roopinder K., et al.
(författare)
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Obesity paradox on outcome in atrial fibrillation maintained even considering the prognostic influence of biomarkers : insights from the ARISTOTLE trial
- 2018
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Ingår i: Open heart. - : BMJ. - 2053-3624. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveWe investigated the association between obesity and biomarkers indicating cardiac or renal dysfunction or inflammation and their interaction with obesity and outcomes.MethodsA total of 14 753 patients in the Apixaban for Reduction In STroke and Other ThromboemboLic Events in Atrial Fibrillation (ARISTOTLE) trial provided plasma samples at randomisation to apixaban or warfarin. Median follow-up was 1.9 years. Body Mass Index (BMI) was measured at baseline and categorised as normal, 18.5-25 kg/m(2); overweight, >25 to <30 kg/m(2); and obese, >= 30 kg/m(2). We analysed the biomarkers high-sensitivity C reactive protein (hs-CRP), interleukin 6 (IL-6), growth differentiation factor-15 (GDF-15), troponin T and N-terminal B-type natriuretic peptide (NT-pro-BNP). Outcomes included stroke/systemic embolism (SE), myocardial infarction (MI), composite (stroke/SE, MI, or all-cause mortality), all-cause and cardiac mortality, and major bleeding.ResultsCompared with normal BMI, obese patients had significantly higher levels of hs-CRP and IL-6 and lower levels of GDF-15, troponin T and NT-pro-BNP. In multivariable analyses, higher compared with normal BMI was associated with a lower risk of all-cause mortality (overweight: HR 0.73 (95% CI 0.63 to 0.86); obese: 0.67 (0.56 to 0.80), p<0.0001), cardiac death (overweight: HR 0.74 (95% CI 0.60 to 0.93); obese: 0.71 (0.56 to 0.92), p=0.01) and composite endpoint (overweight: 0.80 (0.70 to 0.92); obese: 0.72 (0.62 to 0.84), p<0.0001).ConclusionsRegardless of biomarkers indicating inflammation or cardiac or renal dysfunction, obesity was independently associated with an improved survival in anticoagulated patients with AF.
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| 12. |
- Sjölin, Karl, 1979-, et al.
(författare)
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Plasma profiles of neuroglial injury biomarkers after ischemic stroke
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objective: To determine the temporal profiles of glial fibrillary acidic protein (GFAP), neurofilament light (NFL), total tau (t-tau), and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) in plasma the first week after acute ischemic stroke, and identify the optimal time points for assessing infarct volume by these biomarkers.Patients & Methods: In this cohort study, biomarker plasma concentrations were determined daily over the first week and at 90 days after symptom onset in patients with acute ischemic stroke. A brain MRI was performed on day three. Temporal variations in biomarker levels were analyzed using linear mixed-effects models, and optimal time points for infarct volume correlation were identified with continuous Pearson analysis.Results: 38 patients with a median age of 78 (IQR 72-86) and mean infarct volume of 5.5 (IQR 1.6-17) cm3 were included. We identified three distinct temporal patterns: (1) a parabolic trajectory of GFAP, reaching zenith after three days, (2) a consistent increase in NFL throughout the week, and (3) an initial surge in t-tau and UCHL1 levels, stabilizing by day three. The optimal time point for infarct volume correlation occurred at 119 h for GFAP (r=0.94, 95% CI: [0.84-0.98]), 144 h for NFL (r=0.78, [0.47, 0.92]), 122 h for t-tau (r=0.82, [0.56, 0.93]) and 113 h for UCHL1 (r=0.83, [0.60, 0.93]).Conclusion: This high-resolution serial sampling of plasma GFAP, NFL, t-tau, and UCHL1 the first week after acute ischemic stroke identified three distinct temporal profiles. These biomarkers provided the most accurate infarct volume assessment 4-6 days after symptom onset.
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| 13. |
- Sjölin, Karl, et al.
(författare)
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Serum Neurofilament Light Chain in Patients With Atrial Fibrillation
- 2022
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Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 11:14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Atrial fibrillation (AF) is associated with stroke and MRI features of cerebral tissue damage but its impact on levels of serum neurofilament light chain (sNFL), an established biochemical marker of neuroaxonal damage, is unknown.METHODS AND RESULTS: In this observational study, sNFL was analyzed in 280 patients with AF and 280 controls without AF matched for age, sex, and diabetes status within the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial. None of the patients had a history of previous stroke or transient ischemic attack. Patients with a diagnosis of AF were divided into two groups based on if they were in AF rhythm at the time of blood sampling (AF ECG+, n=74), or not (AF ECG-, n=206). Multiple linear regression analysis was performed to adjust for clinical risk factors. In patients with AF, the levels of sNFL were 15% (AF ECG+) and 10% (AF ECG-) higher than in the control group after adjustment for clinical risk factors, P=0.047 and 0.04, respectively. There was no association between anticoagulation treatment and sNFL levels.CONCLUSIONS: sNFL was elevated in patients with AF compared with matched controls without AF. Ongoing AF rhythm was associated with even higher levels of sNFL than in patients with a diagnosis of AF but currently not in AF rhythm. Anticoagulation treatment did not affect sNFL levels.
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