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- van Bragt, JJMH, et al.
(författare)
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Characteristics and treatment regimens across ERS SHARP severe asthma registries
- 2020
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:1
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m−2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day−1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day−1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.
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| 3. |
- Dagnegård, H.H., et al.
(författare)
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Survival after aortic root replacement with a stentless xenograft is determined by patient characteristics
- 2022
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Ingår i: Journal of Thoracic and Cardiovascular Surgery. - : Mosby Inc.; Elsevier Inc.. - 0022-5223 .- 1097-685X. ; 164:6, s. 1712-1724
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Our objective was to examine intermediate-term survival and reinterventions in unselected patients, stratified according to indication, who received a Freestyle (Medtronic Inc, Minneapolis, Minn) bioprosthesis as a full aortic root replacement. Methods: Data from medical records were retrospectively collected for patients who had aortic root replacement using Freestyle bioprostheses between 1999 and 2018 at 6 North-Atlantic centers. Survival status was extracted from national registries and results stratified according to indication for surgery. Results: We included 1030 implantations in 1008 patients with elective indications for surgery: aneurysm (39.8%), small root (8.3%), and other (13.8%), and urgent/emergent indications: endocarditis (26.7%) and Stanford type A aortic dissection (11.4%). Across indications, 46.3% were nonelective cases and 34.0% were reoperations. Median age was 66.0 (interquartile range, 58.0-71.8) years and median follow-up was 5.0 (interquartile range, 2.6-7.9) years. Thirty-day mortality varied from 2.9% to 27.4% depending on indication. Intermediate survival for 90-day survivors with elective indications were not different from the general population standardized for age and sex (P = .95, 83, and .16 for aneurysms, small roots, and other, respectively). In contrast, patients with endocarditis and type A dissection had excess mortality (P < .001). Freedom from valve reinterventions was 95.0% and 94.4% at 5 and 8 years, respectively. In all, 52 patients (5.2%) underwent reinterventions, most because of endocarditis. Conclusions: At intermediate term follow-up this retrospective study provides further support for the use of the Freestyle bioprosthesis in the real-world setting of diverse, complex, and often high-risk aortic root replacement and suggests that outcome is determined by patient and disease, rather than by prosthesis, characteristics. © 2021 The Authors
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- Edfors, R., et al.
(författare)
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Use of proteomics to identify biomarkers associated with chronic kidney disease and long-term outcomes in patients with myocardial infarction
- 2020
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 288:5, s. 581-592
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with chronic kidney disease (CKD) have poor outcomes following myocardial infarction (MI). We performed an untargeted examination of 175 biomarkers to identify those with the strongest association with CKD and to examine the association of those biomarkers with long-term outcomes. Methods A total of 175 different biomarkers from MI patients enrolled in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry were analysed either by a multiple reaction monitoring mass spectrometry assay or by a multiplex assay (proximity extension assay). Random forests statistical models were used to assess the predictor importance of biomarkers, CKD and outcomes. Results A total of 1098 MI patients with a median estimated glomerular filtration rate of 85 mL min(-1)/1.73 m(2)were followed for a median of 3.2 years. The random forests analyses, without and with adjustment for differences in demography, comorbidities and severity of disease, identified six biomarkers (adrenomedullin, TNF receptor-1, adipocyte fatty acid-binding protein-4, TNF-related apoptosis-inducing ligand receptor 2, growth differentiation factor-15 and TNF receptor-2) to be strongly associated with CKD. All six biomarkers were also amongst the 15 strongest predictors for death, and four of them were amongst the strongest predictors of subsequent MI and heart failure hospitalization. Conclusion In patients with MI, a proteomic approach could identify six biomarkers that best predicted CKD. These biomarkers were also amongst the most important predictors of long-term outcomes. Thus, these biomarkers indicate underlying mechanisms that may contribute to the poor prognosis seen in patients with MI and CKD.
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- Radnahad, N, et al.
(författare)
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Is the association of QTc with atrial fibrillation and stroke in cohort studies a matter of time?
- 2022
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Ingår i: Open heart. - : BMJ. - 2053-3624. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the association of the heart rate-corrected QT interval (QTc) with the risk of atrial fibrillation (AF) and ischaemic stroke.MethodsWe estimated the risk of AF and ischaemic stroke associated with QTc duration (ms) by Cox regression in study participants from the cohort of 60-year-old men and women from Stockholm (60YO) (n=4232). Univariate and multivariate adjusted risk estimates were expressed as HR and 95% CI. Main results were validated in elderly patients with AF, included in the Carebbean-e study, where an ECG in sinus rhythm (SR) (ECG-SR) recorded before the ECG diagnostic for (ECG-AF) was available (n=803). We estimated the correlation between the time interval (years) between the ECG-SR and ECG-AF with the QTc duration, by the Spearman correlation coefficient (rho).ResultsIn the 60YO, the highest QTc duration quartile (>427 ms) associated with the AF risk (n=435) with a multivariable adjusted HR of 1.68 and 95% CI (1.26 to 2.24). No association was observed with ischaemic stroke. In the Carebbean-e study, no significant association was observed between the QTc duration measured on the ECG-SR and risk of ischaemic stroke during follow-up. QTc duration showed an inverse correlation (rho: −0.26, p<0.0001) with the time interval intercurred between ECG-SR and ECG-AF.ConclusionsThe association of QTc duration with AF risk might depend on the time interval between the QTc measurement and the clinical diagnosis of AF. No association was observed between QTc duration and ischaemic stroke.
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- Berendse, F, et al.
(författare)
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Raised atmospheric CO2 levels and increased N deposition cause shifts in plant species composition and production in Sphagnum bogs
- 2001
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 7:5, s. 591-598
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Tidskriftsartikel (refereegranskat)abstract
- Part of the missing sink in the global CO2 budget has been attributed to the positive effects of CO2 fertilization and N deposition on carbon sequestration in Northern Hemisphere terrestrial ecosystems. The genus Sphagnum is one of the most important groups of plant species sequestrating carbon in temperate and northern bog ecosystems, because of the low decomposability of the dead material it produces. The effects of raised CO2 and increased atmospheric N deposition on growth of Sphagnum and other plants were studied in bogs at four sites across Western Europe. Contrary to expectations, elevated CO2 did not significantly affect Sphagnum biomass growth. Increased N deposition reduced Sphagnum mass growth, because it increased the cover of vascular plants and the tall moss Polytrichum strictum. Such changes in plant species composition may decrease carbon sequestration in Sphagnum-dominated bog ecosystems.
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| 30. |
- Mörtberg, Josefin, et al.
(författare)
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Prognostic importance of biomarkers associated with haemostatic, vascular and endothelial disturbances in acute coronary syndrome patients in relation to kidney function
- 2023
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 373, s. 64-71
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with kidney failure have a high risk for cardiovascular events. We aimed to evaluate the prognostic importance of selected biomarkers related to haemostasis, endothelial function, and vascular regulation in patients with acute coronary syndrome (ACS), and to study whether this association differed in patients with renal dysfunction.METHODS: Plasma was collected in 1370 ACS patients included between 2008 and 2015. Biomarkers were analysed using a Proximity Extension Assay and a Multiple Reaction Monitoring mass spectrometry assay. To reduce multiplicity, biomarkers correlating with eGFR were selected a priori among 36 plasma biomarkers reflecting endothelial and vascular function, and haemostasis. Adjusted Cox regression were used to study their association with the composite outcome of myocardial infarction, ischemic stroke, heart failure or death. Interaction with eGFR strata above or below 60 ml/min/1.73 m 2 was tested. RESULTS: Tissue factor, proteinase-activated receptor, soluble urokinase plasminogen activator surface receptor (suPAR), thrombomodulin, adrenomedullin, renin, and angiotensinogen correlated inversely with eGFR and were selected for the Cox regression. Mean follow-up was 5.2 years during which 428 events occurred. Adrenomedullin, suPAR, and renin were independently associated with the composite outcome. Adrenomedullin showed interaction with eGFR strata (p = 0.010) and was associated with increased risk (HR 1.88; CI 1.44-2.45) only in patients with eGFR ≥60 ml/min/ 1.73 m 2. CONCLUSIONS: Adrenomedullin, suPAR, and renin were associated with the composite outcome in all. Adrenomedullin, involved in endothelial protection, showed a significant interaction with renal function and outcome, and was associated with the composite outcome only in patients with preserved kidney function.
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| 31. |
- Olausson, N, et al.
(författare)
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Changes in the plasma microvesicle proteome during the ovarian hyperstimulation phase of assisted reproductive technology
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 13645-
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of pulmonary and venous thromboembolism is increased during the first trimester of pregnancies after assisted reproductive technology (ART) compared to spontaneous conception. We previously found that haemostatic plasma variables changed but within normal limits during controlled ovarian hyperstimulation (COH) concomitant with a major increase in plasma microvesicles (MVs) and markers indicating cell activation. We now explored the proteome of these MVs. Thirty-one women undergoing ART were blood sampled at down-regulation (DR) of oestrogen and at high level stimulation (HLS) with its 10–100-fold increased oestrogen level. Samples were analysed by liquid chromatography and tandem mass spectrometry to identify and quantify the proteome. We identified 306 proteins in the MVs and 72 had changed significantly at HLS compared to DR and more than 20% of them were associated with haemostasis. Thus, proteins related to both haemostasis and complement activation altered in plasma MVs in parallel with MV activation during COH. This needs to be further explored in the clinical context.
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- Plüss, Catrine Edström, et al.
(författare)
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Effects of an expanded cardiac rehabilitation programme in patients treated for an acute myocardial infarction or a coronary artery by-pass graft operation
- 2008
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Ingår i: Clinical Rehabilitation. - : SAGE Publications. - 0269-2155 .- 1477-0873. ; 22:4, s. 306-318
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the effects of expanded cardiac rehabilitation with multifactorial interventions on metabolic and inflammatory markers, exercise performance and on established cardiovascular risk factors. Design: Single-centre prospective randomized controlled trial. Setting: A university hospital. Subjects: Two hundred and twenty-four patients with an acute myocardial infarction or patients undergoing coronary artery by-pass grafting. Intervention: Patients were randomized to expanded cardiac rehabilitation including stress management, increased physical training, staying at a 'patient hotel' and cooking sessions, or to usual cardiac rehabilitation Main measures: Biochemical risk markers and exercise performance; follow-up was one year. Results: There were no significant differences between the two treatment groups in the changes of biochemical risk markers or in exercise performance. Thus, low-density lipoprotein (LDL)-cholesterol levels decreased from 3.00 (0.97) to 2.54 (0.66) mmol/L in the intervention group and from 3.20 (0.85) to 2.54 (0,63) mmol/L in the control group, fibrinogen levels decreased from 5.30 (2.00) to 4.25 (1.01) g/L in the intervention group and from 5.29 (1.89) to 4.33 (0.83) g/L in the control group and C-reactive protein (CRP) levels decreased from 3.04 (2.79) to 2.09 (2.13) mg/L in the intervention group and from 4.01 (3.49) to 2.39 (2.49) mg/L in the control group. Total workload (W) improved from 118 (35) to 136 (34) in the intervention group and from 117 (36) to 133 (39) in the control group. Conclusion: There was no further significant benefit in biochemical risk markers or in exercise performance among patients undergoing the expanded rehabilitation as compared to the control group which received usual cardiac rehabilitation.
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| 38. |
- Rehnqvist, N., et al.
(författare)
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Effects of metoprolol vs verapamil in patients with stable angina pectoris : The Angina Prognosis Study in Stockholm (APSIS)
- 1996
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 17:1, s. 76-81
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Tidskriftsartikel (refereegranskat)abstract
- Objective To study long-term treatment effects of metoprolol or verapamil on combined cardiovascular end points and psychological variables in patients with stable angina pectoris. Design Randomized, double-blind, double-dummy trial. Patients The study included 809 patients under 70 years of age with stable angina pectoris. The mean age of the patients was 59 +/- 7 years and 31% were women. Exclusion criteria were myocardial infarction within the previous 3 years and contraindications to beta-blockers and calcium antagonists. The patients were followed between 6 and 75 months (median 3.4 years and a total of 2887 patient years). Intervention The patients were treated with either metoprolol (Seloken ZOC 200 mg o.d.) or verapamil (Isoptin Retard 240 b.i.d.). Acetylsalicylic acid, ACE inhibitors, lipid lowering drugs and long acting nitrates were allowed in the study. End points Death, non-fatal cardiovascular events including acute myocardial infarction, incapacitating or unstable angina, cerebrovascular or peripheral vascular events. Psychological variables reflecting quality of life i.e. psychosomatic symptoms, sleep disturbances and an evaluation of overall life satisfaction. Results Combined cardiovascular events did not differ and occurred in 30.8% and 29.3% of metoprolol and verapamil treated patients respectively. Total mortality in metoprolol and verapamil treated patients was 5.4 and 6.2%, respectively. Cardiovascular mortality was 4.7% in both groups. Non-fatal cardiovascular events occurred in 26.1 and 24.3% of metoprolol and verapamil-treated patients, respectively. Psychosomatic symptoms and sleep disturbances were significantly improved in both treatment groups. The magnitudes of change were small and did not differ between treatments. Life satisfaction did not change on either drug. Withdrawals due to side effects occurred in 11.1 and 14.6%, respectively. Conclusion This long term study indicates that both drugs are well tolerated and that no difference was shown on the effect on mortality, cardiovascular end points and measures of quality of life.
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| 43. |
- Rosell, A, et al.
(författare)
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Prognostic value of circulating markers of neutrophil activation, neutrophil extracellular traps, coagulation and fibrinolysis in patients with terminal cancer
- 2021
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 5074-
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Tidskriftsartikel (refereegranskat)abstract
- Predicting survival accurately in patients with advanced cancer is important in guiding interventions and planning future care. Objective tools are therefore needed. Blood biomarkers are appealing due to their rapid measurement and objective nature. Thrombosis is a common complication in cancer. Recent data indicate that tumor-induced neutrophil extracellular traps (NETs) are pro-thrombotic. We therefore performed a comprehensive investigation of circulating markers of neutrophil activation, NET formation, coagulation and fibrinolysis in 106 patients with terminal cancer. We found that neutrophil activation and NET markers were prognostic in terminal cancer patients. Interestingly, markers of coagulation and fibrinolysis did not have a prognostic value in this patient group, and there were weak or no correlations between these markers and markers of neutrophil activation and NETs. This suggest that NETs are linked to a poor prognosis through pathways independent of coagulation. Additional studies are needed to determine the utility of circulating neutrophil activation and NET markers, alone or in concert with established clinical parameters, as objective and reliable prognostic tools in advanced cancer.
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| 48. |
- Wallén, P, et al.
(författare)
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Purification and characterization of a melanoma cell plasminogen activator.
- 1983
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Ingår i: European Journal of Biochemistry. - 0014-2956 .- 1432-1033. ; 132:3, s. 681-6
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Tidskriftsartikel (refereegranskat)abstract
- The plasminogen activator from a human melanoma cell line was purified with immunoadsorption as a major step. The cells were cultured in the presence of aprotinin in order to avoid proteolysis. A three-step purification involved adsorption on antibodies to porcine tissue plasminogen activator before chromatographies on arginine-Sepharose and Sephadex G-150. All solvents contained Tween-80 (0.01%) and, except for the last step, aprotinin. The final product had a specific activity of about 220000 IU/mg measured against the WHO urokinase standard. The activator obtained has an apparent Mr of 72000 and consists of single-chain molecules. Evidence was obtained that four different types of activator variants occur. First and known previously, the one-chain form can be proteolytically cleaved into a two-chain form. Secondly, both the one-chain and two-chain molecules exhibit two forms with molecular weight differences of about 3000 (possibly due to carbohydrate differences). Thirdly, the one-chain preparations contain two variants, each constituting about 50% of the material and differing in length by three N-terminal amino acids. Finally, a possible positional microheterogeneity was detected. Digestion with plasmin yields the two-chain form with disulfide-bonded polypeptide chains, 'A' and 'B' (from the N-terminal and C-terminal parts, respectively). At the same time, the variability of the original N terminus is removed. The A chain keeps the two Mr variants (now about 40000 and 37000, respectively). The B chain (Mr about 33000) contains the active site of the molecule, as demonstrated by labelling with [3H]diisopropyl phosphofluoridate, and is homologous to the enzymatically active chains of thrombin, plasmin and other serine proteases. In contrast to these enzymes, the plasminogen activator is enzymatically active in the one-chain form. A speculative explanation for this activity may possibly be the presence of an epsilon-amino group of a lysine residue at a position close to the bond cleaved in the two-chain form.
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