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1.
  • Nilton, Anna, et al. (författare)
  • Targeting Zfp148 activates p53 and reduces tumor initiation in the gut
  • 2016
  • Ingår i: OncoTarget. - : Impact Journals, LLC. - 1949-2553. ; 7:35, s. 56183-56192
  • Tidskriftsartikel (refereegranskat)abstract
    • The transcription factor Zinc finger protein 148 (Zfp148, ZBP-89, BFCOL, BERF1, htβ) interacts physically with the tumor suppressor p53, but the significance of this interaction is not known. We recently showed that knockout of Zfp148 in mice leads to ectopic activation of p53 in some tissues and cultured fibroblasts, suggesting that Zfp148 represses p53 activity. Here we hypothesize that targeting Zfp148 would unleash p53 activity and protect against cancer development, and test this idea in the APCMin/+ mouse model of intestinal adenomas. Loss of one copy of Zfp148 markedly reduced tumor numbers and tumor-associated intestinal bleedings, and improved survival. Furthermore, after activation of β-catenin-the initiating event in colorectal cancer-Zfp148 deficiency activated p53 and induced apoptosis in intestinal explants of APCMin/+ mice. The anti-tumor effect of targeting Zfp148 depended on p53, as Zfp148 deficiency did not affect tumor numbers in APCMin/+ mice lacking one or both copies of Trp53. The results suggest that Zfp148 controls the fate of newly transformed intestinal tumor cells by repressing p53 and that targeting Zfp148 might be useful in the treatment of colorectal cancer.
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2.
  • Näslund, Ulf, et al. (författare)
  • Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention (VIPVIZA) : a pragmatic, open-label, randomised controlled trial
  • 2019
  • Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 393:10167, s. 133-142
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Primary prevention of cardiovascular disease often fails because of poor adherence among practitioners and individuals to prevention guidelines. We aimed to investigate whether ultrasound-based pictorial information about subclinical carotid atherosclerosis, targeting both primary care physicians and individuals, improves prevention.METHODS: Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention (VIPVIZA) is a pragmatic, open-label, randomised controlled trial that was integrated within the Västerbotten Intervention Programme, an ongoing population-based cardiovascular disease prevention programme in northern Sweden. Individuals aged 40, 50, or 60 years with one or more conventional risk factors were eligible to participate. Participants underwent clinical examination, blood sampling, and ultrasound assessment of carotid intima media wall thickness and plaque formation. Participants were randomly assigned 1:1 with a computer-generated randomisation list to an intervention group (pictorial representation of carotid ultrasound plus a nurse phone call to confirm understanding) or a control group (not informed). The primary outcomes, Framingham risk score (FRS) and European systematic coronary risk evaluation (SCORE), were assessed after 1 year among participants who were followed up. This study is registered with ClinicalTrials.gov, number NCT01849575.FINDINGS: 3532 individuals were enrolled between April 29, 2013, and June 7, 2016, of which 1783 were randomly assigned to the control group and 1749 were assigned to the intervention group. 3175 participants completed the 1-year follow-up. At the 1-year follow-up, FRS and SCORE differed significantly between groups (FRS 1·07 [95% CI 0·11 to 2·03, p=0·0017] and SCORE 0·16 [0·02 to 0·30, p=0·0010]). FRS decreased from baseline to the 1-year follow-up in the intervention group and increased in the control group (-0·58 [95% CI -0·86 to -0·30] vs 0·35 [0·08 to 0·63]). SCORE increased in both groups (0·13 [95% CI 0·09 to 0·18] vs 0·27 [0·23 to 0·30]).INTERPRETATION: This study provides evidence of the contributory role of pictorial presentation of silent atherosclerosis for prevention of cardiovascular disease. It supports further development of methods to reduce the major problem of low adherence to medication and lifestyle modification.
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3.
  • Rohin Rajan, Meenu, et al. (författare)
  • Comparative analysis of obesity-related cardiometabolic and renal biomarkers in human plasma and serum.
  • 2019
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The search for biomarkers associated with obesity-related diseases is ongoing, but it is not clear whether plasma and serum can be used interchangeably in this process. Here we used high-throughput screening to analyze 358 proteins and 76 lipids, selected because of their relevance to obesity-associated diseases, in plasma and serum from age- and sex-matched lean and obese humans. Most of the proteins/lipids had similar concentrations in plasma and serum, but a subset showed significant differences. Notably, a key marker of cardiovascular disease PAI-1 showed a difference in concentration between the obese and lean groups only in plasma. Furthermore, some biomarkers showed poor correlations between plasma and serum, including PCSK9, an important regulator of cholesterol homeostasis. Collectively, our results show that the choice of biofluid may impact study outcome when screening for obesity-related biomarkers and we identify several markers where this will be the case.
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4.
  • Wilhelmson, Anna S K, et al. (författare)
  • Increased Intimal Hyperplasia After Vascular Injury in Male Androgen Receptor-Deficient Mice
  • 2016
  • Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 157:10, s. 3915-3923
  • Tidskriftsartikel (refereegranskat)abstract
    • Intimal hyperplasia is a vascular pathological process involved in the pathogenesis of atherosclerosis. Data suggest that T, the most important sex steroid hormone in males, protects men from atherosclerotic cardiovascular disease. T mainly acts via the androgen receptor (AR), and in this study we evaluated formation of intimal hyperplasia in male AR knockout (ARKO) mice using a vascular injury model. Two weeks after ligation of the carotid artery, male ARKO mice showed increased intimal area and intimal thickness compared with controls. After endothelial denudation by an in vivo scraping injury, there was no difference in the reendothelialization in ARKO compared with control mice. Ex vivo, we observed increased outgrowth of vascular smooth muscle cells from ARKO compared with control aortic tissue explants; the number of outgrown cells was almost doubled in ARKO. In vitro, stimulation of human aortic vascular smooth muscle cells with a physiological T concentration inhibited both migration and proliferation of the cells. Analyzing the expression of central regulators of cell proliferation and migration, we found that mRNA and protein levels of p27 were lower in uninjured arteries from ARKO mice and that T replacement to castrated male mice increased p27 mRNA in an AR-dependent manner. In conclusion, AR deficiency in male mice increases intimal hyperplasia in response to vascular injury, potentially related to the effects of androgens/AR to inhibit proliferation and migration of smooth muscle cells.
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5.
  • Adam, Abderisak, 1988, et al. (författare)
  • Aggregation of factors causing cost overruns and time delays in large public construction projects: Trends and implications
  • 2017
  • Ingår i: Engineering, Construction and Architectural Management. - 1365-232X .- 0969-9988. ; 24:3, s. 393-406
  • Tidskriftsartikel (refereegranskat)abstract
    • PurposeThe purpose of this paper is to explore the impact that cost overruns and time delays exert on large public construction projects to clarify how past and current research regard factors causing cost overruns and time delays in large public construction projects.Design/methodology/approachThis paper, which is based on an analysis of a literature selection consisting of 40 journal articles, investigates and ranks the occurrence of and the explanations for cost overruns and time delays in large public construction projects. The study makes use of a kiviat diagram/radar chart in order to visualize multivariate data.FindingsAggregated rankings of important causes of cost overruns and time delays are reported. These show a strong emphasis on the management aspect as a primary cause of cost overruns and delays. Additionally, there seems to be a trend toward deemphasizing the role of financial considerations in explaining cost overruns and delays. It is argued that there needs to be a more rigorous assessment of the impact that each factor has on cost increases and delays based on factual observed data as opposed to retrospective accounts from questionnaire respondents.Research limitations/implicationsOnly public construction projects have been considered. The results will not be directly applicable to privately funded construction projects and/or projects of a smaller size.Originality/valueThe use of trend data, as illustrated in a kiviat diagram, showing how different ranking factors causing cost overruns and time delays has changed in importance over time.
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6.
  • Adam, Abderisak, 1988, et al. (författare)
  • Developing Capabilities for Public Construction Clients
  • 2014
  • Ingår i: Proceedings of the 19th International Symposium on the Advancement of Construction Management and Real Estate, 7-9 Nov 2014, Chongqing.
  • Konferensbidrag (refereegranskat)abstract
    • Clients in the public sector face a large number of challenges in designing, procur-ing and managing major construction projects in a manner that is conducive to the organization’s overall goals. The role of the client in bringing about successful project completion has more recently been emphasized with a growing number of studies focusing on developing dynamic client capabilities that facilitate the han-dling of a project through all of its different phases. Though the capabilities of the client carries immense importance in all con-struction projects, the importance is further exacerbated by the sheer scale of the projects involved in major construction projects, a development which has prompted governmental agencies to inquire into ways to improve processes in the client organization. To address such inquiries, this paper which is based on a literature review, ex-plores the types of dynamic capabilities that emerge with respect to public con-struction clients and in particular, if and how a specific client capability influences a specific project outcome. The mapping of capabilities constitutes a theoretical foundation for a forthcoming empirical study on the same topic.
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7.
  • Adam, Abderisak, 1988, et al. (författare)
  • Implications of cost overruns and time delays on major public construction projects
  • 2014
  • Ingår i: Proceedings of the 19th International Symposium on the Advancement of Construction Management and Real Estate, 7-9 Nov 2014, Chongqing.
  • Konferensbidrag (refereegranskat)abstract
    • For decades, the construction industry has been characterized by costs exceeding budgetary limits and completion times reaching further than what was set out ini-tially. This has been particularly noticeable for large public construction projects where cost overruns and time delays have long been regarded a common occur-rence. Due to the magnitude and frequency of these overruns, they have come to pose a significant financial risk to both clients and contractors, in addition to the impact exerted on the sustainability of the project. In dealing with this, researchers, auditors and practitioners have suggested a broad range of solutions, ranging from technical and economical to psychological and political approaches. In doing so, the contractor’s role has been emphasized whereas the role of the client organization has often been overlooked. This paper which is based on a literature review investigates the occurrence of and the expla-nations for cost overruns and time delays in major construction projects from the public client’s perspective. It also explores the implications of cost overruns and time delays; the purpose of which is to offer an extended understanding of the re-lationship between the client’s actions and effects on cost, time and sustainability parameters.
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8.
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9.
  • Angelov, Nikolay, et al. (författare)
  • Parenthood and the Gender Gap in Pay
  • 2016
  • Ingår i: Journal of Labor Economics. - 0734-306X .- 1537-5307. ; 34:3, s. 545-579
  • Tidskriftsartikel (refereegranskat)abstract
    • We compare the income and wage trajectories of women to those of their male partners before and after parenthood. Focusing on the within-couple gap allows us to control for both observed and unobserved attributes of the spouse and to estimate both short-and long-term effects of entering parenthood. We find that 15 years after the first child has been born, the male-female gender gaps in income and wages have increased by 32 and 10 percentage points, respectively. In line with a collective labor supply model, the magnitude of these effects depends on counterfactual relative incomes or wages within the family.
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10.
  • Avdic, Daniel, et al. (författare)
  • Sex differences in sickness absence and the morbidity-mortality paradox : a longitudinal study using Swedish administrative registers
  • 2019
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To analyse whether gender-specific health behaviour can be an explanation for why women outlive men, while having worse morbidity outcomes, known as the morbidity-mortality or gender paradox. Setting The working population in Sweden. Participants Thirty per cent random sample of Swedish women and men aged 40-59 with a hospital admission in the 1993-2004 period were included. The sample for analysis consists of 233274 individuals (115430 men and 117844 women) and in total 1 867013 observations on sickness absence. Intervention Hospital admission across 18 disease categories. Main outcome measures The main outcome measures were sickness absence (morbidity) and mortality. Longitudinal data at the individual level allow us to study how sickness absence changed after a hospital admission in men and women using a difference-in-differences regression analysis. Cox regression models are used to study differences in mortality after the admission. Results Women increased their sickness absence after a hospital admission by around five more days per year than men (95% CI 5.25 to 6.22). At the same time, men had higher mortality in the 18 diagnosis categories analysed. The pattern of more sickness absence in women was the same across 17 different diagnosis categories. For neoplasm, with a 57% higher risk of death for men (54.18%-59.89%), the results depended on the imputation method of sickness for those deceased. By using the premortality means of sickness absence, men had an additional 14.47 (-16.30- -12.64) days of absence, but with zero imputation women had an additional 1.6 days of absence (0.05-3.20). Analyses with or without covariates revealed a coherent picture. Conclusions The pattern of increased sickness absence (morbidity) and lower mortality in women provides evidence on the more proactive and preventive behaviour of women than of men, which could thus explain the morbidity-mortality paradox.
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11.
  • Ben Amor, Mehdi, et al. (författare)
  • Revisiting Industrial Organization : Product Service Systems Insight
  • 2018
  • Ingår i: Journal of Cleaner Production. - : Elsevier. - 0959-6526 .- 1879-1786. ; 96, s. 1459-1477
  • Forskningsöversikt (refereegranskat)abstract
    • This literature review puts forward a comparison between the traditional seller, usually represented by classic Industrial Organization (IO) models, and system providers, which are illustrated by Product Service System (PSS) models. A multidisciplinary systematic literature review, that compares PSS and IO models, is conducted, and ends up in to define PSS as a technology. It highlights the differences and similarities between classic IO and classic PSS and evaluate the weakness and strengths of different models. In total, 148 articles from different disciplines have been investigated, and a different understanding of PSS is provided. A new IO framework, that considers classic sellers and PSSs providers, is established to preserve PSS specificities and stress the role of policy maker and competition for PSSs expansion.
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12.
  • Bingisser, Roland, et al. (författare)
  • Cardiac troponin : a critical review of the case for point-of-care testing in the ED
  • 2012
  • Ingår i: American Journal of Emergency Medicine. - : Elsevier BV. - 0735-6757 .- 1532-8171. ; 30:8, s. 1639-1649
  • Forskningsöversikt (refereegranskat)abstract
    • The measurement of cardiac troponin concentrations in the blood is a key element in the evaluation of patients with suspected acute coronary syndromes, according to current guidelines, and contributes importantly to the ruling in or ruling out of acute myocardial infarction. The introduction of point-of-care testing for cardiac troponin has the potential to reduce turnaround time for assay results, compared with central laboratory testing, optimizing resource use. Although, in general, many point-of-care cardiac troponin tests are less sensitive than cardiac troponin tests developed for central laboratory-automated analyzers, point-of-care systems have been used successfully within accelerated protocols for the reliable ruling out of acute coronary syndromes, without increasing subsequent readmission rates for this condition. The impact of shortened assay turnaround times with point-of-care technology on length of stay in the emergency department has been limited to date, with most randomized evaluations of this technology having demonstrated little or no reduction in this outcome parameter. Accordingly, the point-of-care approach has not been shown to be cost-effective relative to central laboratory testing. Modeling studies suggest, however, that reengineering overall procedures within the emergency department setting, to take full advantage of reduced therapeutic turnaround time, has the potential to improve the flow of patients through the emergency department, to shorten discharge times, and to reduce cost. To properly evaluate the potential contribution of point-of-care technology in the emergency department, including its costeffectiveness, future evaluations of point-of-care platforms will need to be embedded completely within a local decision-making structure designed for its use.
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13.
  • Bingisser, Roland, et al. (författare)
  • Measurement of natriuretic peptides at the point of care in the emergency and ambulatory setting : Current status and future perspectives
  • 2013
  • Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 166:4, s. 614-
  • Tidskriftsartikel (refereegranskat)abstract
    • The measurement of natriuretic peptides (NPs), B-type NP or N-terminal pro-B-type NP, can be an important tool in the diagnosis of acute heart failure in patients presenting to an Emergency Department (ED) with acute dyspnea, according to international guidelines. Studies and subsequent meta-analyses are mixed on the absolute value of routine NP assessment of ED patients. However, levels of NPs are likely to be used also to guide treatment and to assess risk of adverse outcomes in other patients at risk of developing heart failure, including those with pulmonary embolism or diabetes, or receiving chemotherapy. Natriuretic peptide levels, like other biomarkers, can now be measured at the point of care (POC). We have reviewed the current status of NP measurement together with the potential contribution of POC measurement of NPs to clinical care delivery in the emergency and other settings. Several POC systems for measuring NP levels are now available: these produce test results within 15 minutes and appear sufficiently sensitive and robust to be used routinely in diagnostic evaluations. Point-of-care systems could be used to assess NP levels in the ED and community outpatient settings to monitor the risk of acute heart failure. Furthermore, the use of protocol-driven POC testing of NP within the time frame of a patient consultation in the ED may facilitate and accelerate the throughput and disposition of at-risk patients. Appropriately designed clinical trials will be needed to confirm these potential benefits. It is also important that processes of care delivery are redesigned to take full advantage of the faster turnaround times provided by POC technology.
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14.
  • Bjelkmar, Pär, 1980-, et al. (författare)
  • Implementation of the CHARMM Force Field in GROMACS : Analysis of Protein Stability Effects from Correction Maps, Virtual Interaction Sites, and Water Models
  • 2010
  • Ingår i: Journal of Chemical Theory and Computation. - Washington : American Chemical Society. - 1549-9618 .- 1549-9626. ; 6:2, s. 459-466
  • Tidskriftsartikel (refereegranskat)abstract
    • CHARMM27 is a widespread and popular force field for biomolecular simulation, and several recent algorithms such as implicit solvent models have been developed specifically for it. We have here implemented the CHARMM force field and all necessary extended functional forms in the GROMACS molecular simulation package, to make CHARMM-specific features available and to test them in combination with techniques for extended time steps, to make all major force fields available for comparison studies in GROMACS, and to test various solvent model optimizations, in particular the effect of Lennard-Jones interactions on hydrogens. The implementation has full support both for CHARMM-specific features such as multiple potentials over the same dihedral angle and the grid-based energy correction map on the , ψ protein backbone dihedrals, as well as all GROMACS features such as virtual hydrogen interaction sites that enable 5 fs time steps. The medium-to-long time effects of both the correction maps and virtual sites have been tested by performing a series of 100 ns simulations using different models for water representation, including comparisons between CHARMM and traditional TIP3P. Including the correction maps improves sampling of near native-state conformations in our systems, and to some extent it is even able to refine distorted protein conformations. Finally, we show that this accuracy is largely maintained with a new implicit solvent implementation that works with virtual interaction sites, which enables performance in excess of 250 ns/day for a 900-atom protein on a quad-core desktop computer.
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15.
  • Bjurman, Christian, 1983, et al. (författare)
  • Decreased admissions and hospital costs with a neutral effect on mortality following lowering of the troponin T cutoff point to the 99th percentile
  • 2017
  • Ingår i: Cardiology journal. - 1897-5593 .- 1898-018X. ; 24:6, s. 612-622
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The implementation of high-sensitivity cardiac troponin T (hs-cTnT) assays and a cutoff based on the 99th cTnT percentile in the evaluation of patients with suspected acute coronary syndrome has not been uniform due to uncertain effects on health benefits and utilization of limited resources.Methods:Clinical and laboratory data from patients with chest pain or dyspnea at the emergency department (ED) were evaluated before (n = 20516) and after (n = 18485) the lowering of the hs-cTnT cutoff point from 40 ng/L to the 99th hs-cTnT percentile of 14 ng/L in February 2012. Myocardial infarction (MI) was diagnosed at the discretion of the attending clinicians responsible for the patient.Results:Following lowering of the hs-cTnT cutoff point fewer ED patients with chest pain or dyspnea as the principal complaint were analyzed with an hs-cTnT sample (81% vs. 72%, p < 0.001). Overall 30-day mortality was unaffected but increased among patients not analyzed with an hs-cTnT sample (5.3% vs. 7.6%, p < 0.001). The MI frequency was unchanged (4.0% vs. 3.9%, p = 0.72) whereas admission rates decreased (51% vs. 45%, p < 0.001) as well as hospital costs. Coronary angiographies were used more frequently (2.8% vs. 3.3%, p = 0.004) but with no corresponding change in coronary interventions.Conclusions:At the participating hospital, lowering of the hs-cTnT cutoff point to the 99th percentile decreased admissions and hospital costs but did not result in any apparent prognostic or treatment benefits for the patients.
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16.
  • Bjurman, Christian, 1983, et al. (författare)
  • Small changes in Troponin T levels are common in patients with non-ST-elevation myocardial infarction and are linked to higher mortality
  • 2013
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 62:14, s. 1231-1238
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE:To examine the extent of change in Troponin T levels in patients with non-ST-elevation myocardial infarction (NSTEMI).BACKGROUND:Changes in cardiac troponin levels are required for the diagnosis of NSTEMI, according to the new universal definition of acute myocardial infarction. A relative change of 20-230 % and an absolute change of 7- 9 ng/L have been suggested as cut-off points.METHOD:In a clinical setting, where a change in cTnT was not mandatory for the diagnosis of NSTEMI, serial samples of cTnT were measured with a high-sensitive cTnT (hs-cTnT) assay, and 37 clinical parameters were evaluated in 1178 patients with a final diagnosis of NSTEMI presenting <24h after symptom onset.RESULTS:After six hours of observation, the relative change in the hs-cTnT level remained <20 % in 26 % and the absolute change <9 ng/L in 12 % of the NSTEMI patients. A relative hs-cTnT change <20% was linked to higher long-term mortality across quartiles (p=0.002) and in multivariate analyses (HR 1.61 (1.17-2.21) p=0.004), whereas 30-day mortality was similar across quartiles of relative hs-cTnT changeCONCLUSION:Because stable hs-TnT levels are common in patients with a clinical diagnosis of NSTEMI in our hospital, a small hs-cTnT change may not be useful to exclude NSTEMI, particularly as these patients show both short-term and long-term mortality at least as high as patients with large changes in hs-cTnT.
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17.
  • Carlsson, Lena M S, 1957, et al. (författare)
  • Long-term incidence of serious fall-related injuries after bariatric surgery in Swedish obese subjects.
  • 2019
  • Ingår i: International journal of obesity (2005). - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 43:4, s. 933-937
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity increases risk of falling, but the effect of bariatric surgery on fall-related injuries is unknown. The aim of this study was therefore to study the association between bariatric surgery and long-term incidence of fall-related injuries in the prospective, controlled Swedish Obese Subjects study. At inclusion, body mass index was≥34kg/m2 in men and ≥38kg/m2 in women. The surgery per-protocol group (n=2007) underwent gastric bypass (n=266), banding (n=376), or vertical banded gastroplasty (n=1365), and controls (n=2040) received usual care. At the time of analysis (31 December 2013), median follow-up was 19 years (maximal 26 years). Fall-related injuries requiring hospital treatment were captured using data from the Swedish National Patient Register. During follow-up, there were 617 first-time fall-related injuries in the surgery group and 513 in the control group (adjusted hazard ratio 1.21, 95% CI, 1.07-1.36; P=0.002). The incidence differed between treatment groups (P<0.001, log-rank test) and was higher after gastric bypass than after usual care, banding and vertical banded gastroplasty (adjusted hazard ratio 0.50-0.52, P<0.001 for all three comparisons). In conclusion, gastric bypass surgery was associated with increased risk of serious fall-related injury requiring hospital treatment.
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18.
  • Chaireti, Roza, 1979- (författare)
  • Thrombin generation in different cohorts : Evaluation of the haemostatic potential
  • 2013
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The aim of this thesis is to evaluate thrombin generation in patients with thrombophilia (Paper I), in patients with venous thromboembolism (Paper II), in healthy women during the menstrual cycle (Paper III), in patients with liver disease (Paper IV) and in patients with mild deficiency of factor VII (Paper V).For this purpose, thrombin generation was measured in platelet poor plasma by the calibrated automated thrombogram (CAT®) assay. Thrombin generation expresses the overall haemostatic potential, in contrast to the more traditional coagulation tests, which concentrate on individual factors or coagulation pathways. The thrombin generation markers that were measured and studied were: lagtime (clotting time), endogenous thrombin potential (ETP, total thrombin concentration), peak (maximum thrombin concentration) and time to peak (ttpeak).The cohorts for Papers I and II are part of a larger cohort (The LInköping Study on Thrombosis, LIST), which included 516 consecutive patients who presented at the Emergency Department of Linköping University Hospital, Sweden with the clinical suspicion of venous thrombosis. In Paper I thrombin generation was measured in the absence of thrombomodulin in patients with thrombophilia (factor V Leiden, n=98 and prothrombin G20210A mutation, n=15) and in an equal number of age- and gendermatched controls. The results were associated with the presence of thrombosis, as well as gender and age. It was shown that thrombin generation did not differ significantly among patients and controls. Patients with and patients without thrombophilia who had suffered a thrombosis upon inclusion had longer lagtime compared with their counterparts without thrombosis. Neither age nor gender had any effect on the results.In Paper II, thrombin generation at the time of an acute thromboembolic episode was studied as a potential early marker for recurrence during a 7-year follow-up in 115 patients with venous thrombosis upon inclusion. It was shown that patients with recurrences during follow-up had longer lagtime and ttpeak at the time of the acute thrombosis, whereas those without recurrences had higher ETP and peak. Those results were particularly evident in the group of patients with an unprovoked thrombosis upon inclusion.In Paper III, thrombin generation was measured in the follicular and luteal phase of a normal menstrual cycle in 102 healthy women not taking oral contraceptives. The results were associated with haemostatic parameters (fibrinogen, antithrombin, D-dimer, plasminogen activator inhibitor-1, factors VII, VIII, X and von Willebrand) as well as the physiological concentrations of oestradiol, progesterone, antimüllerian hormone and sex hormone-binding globulin and the number of pregnancies and deliveries for these women. ETP was significantly higher during the luteal phase. However, this could not be explained by the elevation of other procoagulant factors during the same phase. Progesterone was found to exert a more significant effect on haemostasis than oestradiol during both phases (multiple regression analysis).In Paper IV, thrombin generation was measured in the presence and absence of thrombomodulin in 47 patients with portal vein thrombosis, PVT (11 with cirrhotic PVT and 36 with non-cirrhotic PVT), 15 patients with Budd-Chiari syndrome and 24 patients with cirrhosis, as well as 21 healthy controls. Since 15 patients with PVT (2 with cirrhotic PVT and 13 with non-cirrhotic PVT) and 10 patients with Budd-Chiari syndrome were treated with warfarin at the time of the blood sampling, an equal number of patients matched for age, gender and prothrombin time-international normalized ratio with atrial fibrillation and no hepatic diseases were used as controls. It was shown that hypercoagulability, expressed as total and maximum concentration of generated thrombin as well as thrombomodulin resistance [thrombin generation markers measured in the presence]/[thrombin generation markers measured in the absence of thrombomodulin] was pronounced in the groups of patients with cirrhosis, regardless of the presence of splanchnic thrombosis.In Paper V, thrombin generation in the presence of human and different concentrations of rabbit thromboplastin was measured in 10 patients with mild deficiency of factor VII and in 12 controls. In these patients, the levels of factor VII varied slightly depending on the origin of the thromboplastin used in the reagent. Nine out of 10 patients had a mutation in common (Arg353Gln), which was, however, not associated with the diversity in the factor VII measurements due to the origin of thromboplastin. ETP in patients with mild factor VII deficiency was about 86% of the ETP in the control group. The expected thrombin generation patterns with increasing concentrations of thromboplastin did not differ depending on the origin of thromboplastin in the patient group.
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19.
  • Contreras, F.-Xabier, et al. (författare)
  • Molecular recognition of a single sphingolipid species by a protein's transmembrane domain
  • 2012
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 481:7382, s. 525-529
  • Tidskriftsartikel (refereegranskat)abstract
    • Functioning and processing of membrane proteins critically depend on the way their transmembrane segments are embedded in the membrane. Sphingolipids are structural components of membranes and can also act as intracellular second messengers. Not much is known of sphingolipids binding to transmembrane domains (TMDs) of proteins within the hydrophobic bilayer, and how this could affect protein function. Here we show a direct and highly specific interaction of exclusively one sphingomyelin species, SM 18, with the TMD of the COPI machinery protein p24 (ref. 2). Strikingly, the interaction depends on both the headgroup and the backbone of the sphingolipid, and on a signature sequence (VXXTLXXIY) within the TMD. Molecular dynamics simulations show a close interaction of SM 18 with the TMD. We suggest a role of SM 18 in regulating the equilibrium between an inactive monomeric and an active oligomeric state of the p24 protein, which in turn regulates COPI-dependent transport. Bioinformatic analyses predict that the signature sequence represents a conserved sphingolipid-binding cavity in a variety of mammalian membrane proteins. Thus, in addition to a function as second messengers, sphingolipids can act as cofactors to regulate the function of transmembrane proteins. Our discovery of an unprecedented specificity of interaction of a TMD with an individual sphingolipid species adds to our understanding of why biological membranes are assembled from such a large variety of different lipids.
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20.
  • Damman, Peter, et al. (författare)
  • Invasive strategies and outcomes for non-ST-segment elevation acute coronary syndromes : a twelve-year experience from SWEDEHEART.
  • 2016
  • Ingår i: EuroIntervention. - 1774-024X .- 1969-6213. ; 12:9, s. 1108-1116
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: Despite recommendations in recent guidelines for a routine invasive strategy for non-ST-segment elevation acute coronary syndrome (NSTE-ACS), long-term data on the implementation of treatment strategies in clinical practice are not available. Our aim was to provide long-term data on the implementation of a routine invasive strategy in NSTE-ACS in clinical practice.METHODS AND RESULTS: In the SWEDEHEART registry, data from 204,092 consecutive NSTE-ACS patients admitted between 1996 and 2007 were recorded. The use of the routine invasive strategy, retrospectively defined as coronary angiography (and subsequent revascularisation) within three days after admission, increased from 3.8% in the period 1996-1998 to 37.4% in the period 2005-2007. The largest absolute increase in the use of this strategy was observed in low-risk patients, while a similar relative increase was observed in all risk categories. The use of the selective invasive strategy, defined as coronary angiography later than three days after admission or none at all, decreased from 96.2% in the period 1996-1998 to 62.5% in the period 2005-2007. In the total population, there was a gradual decrease in three-year all-cause mortality, from 29.1% in the period 1996-1998 to 23.9% in the period 2005-2007.CONCLUSIONS: There has been an increase in the use of a routine invasive strategy in NSTE-ACS patients over the course of 12 years in Sweden. There was a decrease in three-year mortality over the same time course.
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21.
  • Ebeling Barbier, Charlotte, et al. (författare)
  • Cardiac Troponin I Associated with the Development of Unrecognized Myocardial Infarctions Detected with MRI
  • 2014
  • Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 60:10, s. 1327-1335
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Late enhancement MRI (LE-MRI) and cardiac troponin I (cTnI) are sensitive methods to detect subclinical myocardial injury. We sought to investigate the relation between plasma concentrations of cTnI measured with a high-sensitivity assay (hs-cTnI) and the development of unrecognized myocardial infarctions (UMIs) detected with LE-MRI.METHODS:After approval from the ethics committee and written informed consent were obtained, LE-MRI was performed on 248 randomly selected community-living 70-year-old volunteers and hs-cTnI was determined with a highly sensitive premarket assay. Five years later these individuals were invited to a second LE-MRI, and 176 of them (82 women, 94 men), who did not have a hospital diagnosis of MI, constitute the present study population. LE-MR images were analyzed by 2 radiologists independently and in a consensus reading, blinded to any information on previous disease or assessments.RESULTS:New or larger UMIs were detected in 37 participants during follow-up. Plasma concentrations of hs-cTnI at 70 years of age, which were mainly within what is considered to be the reference interval, were related to new or larger UMIs at 75 years of age with an odds ratio of 1.98 per 1 unit increase in ln-transformed cTnI (95% CI, 1.17-3.35; P = 0.010). Plasma concentrations of hs-cTnI at 70 years of age were associated with the volumes of the UMIs detected at 75 years of age (P = 0.028).CONCLUSIONS:hs-cTnI in 70-year-old community-living women and men was associated with the development of MRI-detected UMIs within 5 years.
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22.
  • Eggers, Kai M, et al. (författare)
  • Associations of mid-regional pro-adrenomedullin levels to cardiovascular and metabolic abnormalities, and mortality in an elderly population from the community
  • 2013
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 168:4, s. 3537-3542
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:The mid-regional part of the prohormone of adrenomedullin (MR-proADM) is emerging as a novel risk indicator in patients with cardiac disease. We investigated MR-proADM levels and their changes over 5years in elderly community-dwellers, together with the underlying cardiovascular and metabolic conditions, and the prognostic implications of these measurements.METHODS AND RESULTS:MR-proADM was analyzed using a sandwich immunoassay (Thermo Fisher Scientific) in participants from the PIVUS study. Measurements were performed at 70 (n=1002) and 75years of age (n=795) together with various measurements of other markers of cardiovascular function. In cross-sectional analyses, MR-proADM was independently related to current smoking, renal dysfunction, obesity, lower left-ventricular ejection fraction, and higher levels of N-terminal pro-B-type natriuretic peptide and C-reactive protein. There were no independent associations to other cardiovascular risk factors or vascular pathologies. MR-proADM levels predicted all-cause mortality during 8.0years of follow-up independent of cardiovascular risk indicators (adjusted HR 5.1 [95% CI 2.8-9.5]; p<0.001) using results obtained at 70 and 75years as updated covariates. Baseline MR-proADM levels improved prognostic discrimination (IDI=0.018 [p=0.001]). Also the change in MR-proADM levels over time independently predicted all-cause mortality occurring after 75years (adjusted HR 13.4 [95% CI 3.5-50.5]; p<0.001).CONCLUSIONS:MR-proADM levels in the elderly integrate information on several relevant aspects in cardiovascular disease, namely cardiovascular risk factors including obesity, low-grade inflammation, renal dysfunction and left-ventricular abnormalities. Furthermore, MR-proADM and its changes over time predicted mortality, and might provide utility as an indicator of the overall cardiovascular risk burden.
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23.
  • Eggers, Kai M., et al. (författare)
  • Cardiac troponin I levels in an elderly population from the community - The implications of sex
  • 2015
  • Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 48:12, s. 751-756
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The importance of sex on cardiac troponin levels is increasingly recognized. We investigated whether the entities associated with troponin leakage and the prognostic consequences thereof would differ between elderly men and women from the community. Design and methods: Cardiac troponin I (cTnI) levels were measured using a high-sensitivity assay (Abbott Laboratories) in 70-year old men (n = 502) and women (n = 502) from the PIVUS study. All study participants were followed up for 10 years regarding all-cause mortality and incident cardiovascular (CV) disease. Results: Median cTnI levels were 4.1 and 3.0 ng/L in men and women, respectively (p < 0.001). By multiple linear regression, the relative contribution of lower left-ventricular ejection fraction and ischemic ECG changes to cTnI levels was greater in men compared to women. For other clinical and echocardiographic variables, similar associations were found. cTnI independently predicted all-cause mortality in men (n = 93 [18.5%]; hazard ratio [HR] 1.38 [1.12-1.70]) and women (n = 62 [12.4%]; HR 1.59 [1.11-2.28]) but not incident CV disease in subjects being CV healthy at baseline (n = 163/857). The interaction terms of sex on the associations of cTnI with both outcomes were non-significant. Sex-specific cut-offs did not improve prognostication. Variations in the pattern of entities associated with cTnI leakage had no impact on event rates. Conclusions: We found some differences in the entities associated with higher cTnI levels in elderly community-dwelling men and women. However, this did not translate into differences in the associations of cTnI with adverse outcome.
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24.
  • Eggers, Kai M, 1962-, et al. (författare)
  • Cardiac troponin I levels in patients with non-ST-elevation acute coronary syndrome : the importance of gender
  • 2014
  • Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 168:3, s. 317-324.e1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Measurement of high-sensitivity cardiac troponin levels is increasingly used in non-ST-elevation acute coronary syndrome (NSTE-ACS). However, studies investigating the distribution and prognostic implications of high-sensitivity troponin levels in men and women separately are currently lacking.METHODS: Cardiac troponin I (cTnI) levels were determined using a high-sensitivity assay (Abbott Laboratories, Abbott Park, IL) in 1,677 male and 1,073 female NSTE-ACS patients participating in the GUSTO IV study. The prognostic associations of cTnI to outcome (30-day composite end point of recurrent myocardial infarction and 1-year mortality) were assessed in multivariable models, using cTnI both as a continuous variable and dichotomized at different sets of single and gender-specific 99th percentiles.RESULTS: Median cTnI levels were 947 and 175 ng/L in men and women, respectively (P < .001). The adjusted odds ratios for cTnI (ln) were similar in men and women. The adjusted odds ratios for cTnI above the tested 99th percentiles levels in contrast were twice as high in women compared with men. This was a consequence of differences in the cTnI distribution and risk gradients across cTnI levels, in particular due to lower event rates in women without cTnI elevation. Gender-specific cutoffs did not improve risk prediction.CONCLUSIONS: Despite overall lower levels, cTnI above the tested 99th percentiles exhibited stronger prognostic information in women with NSTE-ACS compared with men. This likely reflects differences in the pathophysiology and the clinical presentation in NSTE-ACS. Our data, thus, emphasize that women with symptoms of unstable coronary artery disease encompass a broader risk panorama than men.
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25.
  • Eggers, Kai M., et al. (författare)
  • Cardiac troponin I levels measured with a high-sensitive assay increase over time and are strong predictors of mortality in an elderly population
  • 2013
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 61:18, s. 1906-1913
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Cardiac troponin levels are often detectable in community-dwellers when sensitive assays are applied. However, information on the course of troponin levels over time is limited.OBJECTIVES:We assessed changes in troponin levels, underlying conditions and the prognostic implications thereof in elderly subjects from the community.METHODS: Cardiac troponin I (cTnI) was measured using a novel high-sensitive assay from Abbott Laboratories in community-dwellers aged 70 years (PIVUS study). Measurements were performed at baseline (n=1004) and after 5 years (n=814). Total follow-up was 8.0 years.RESULTS:cTnI levels were detectable in 968 (96.4%) subjects at baseline, and independently predicted all-cause mortality (adjusted HR 1.44 [95% CI 1.18-1.77]) and cardiovascular mortality (adjusted HR 1.66 [95% CI 1.20-2.29]) when levels from baseline and 5-year follow-up were used as updated covariates. The integrated discrimination improvement of cTnI regarding all-cause mortality was 0.014 (p=0.04) and the category-free net reclassification improvement was 0.231 (p=0.02). Median cTnI levels increased by 45% between both measurements. The change in cTnI levels was significantly related to male sex (p=0.02), body mass index (p=0.01), HDL-cholesterol (p=0.005), N-terminal pro B-type natriuretic peptide (p=0.004) and the left-ventricular ejection fraction (p=0.04), and independently predicted all-cause mortality occurring after 5-year follow-up (adjusted HR 1.97 [1.14-3.40]; p=0.02).CONCLUSIONS:Using a novel high-sensitive assay, cTnI levels could be determined in nearly all elderly subjects. cTnI levels increased over time and were a strong marker of mortality risk. Our data suggest that cTnI might offer utility for clinical assessment of subjects in the general population.
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26.
  • Eggers, Kai M., et al. (författare)
  • Clinical implications of the change of cardiac troponin I levels in patients with acute chest pain - An evaluation with respect to the Universal Definition of Myocardial Infarction
  • 2011
  • Ingår i: Clinica Chimica Acta. - : Elsevier BV. - 0009-8981 .- 1873-3492. ; 412:1-2, s. 91-97
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The Universal Definition of Myocardial Infarction incorporates elevated cardiac troponin levels (>99th percentile) together with a significant rise/fall of troponins as biochemical criterion. We sought to evaluate the clinical implications of the relative change of cardiac troponin I (cTnI) levels with respect to the Universal Definition in patients with acute chest pain. Methods: cTnI (Stratus CS) was measured serially in 454 patients within 24 h from admission. Acute myocardial infarction (AMI) was defined using the criteria adapted to the ESC/ACC consensus document, or corresponding to the Universal Definition together with prespecified cTnI changes of >= 20%, >= 50% and >= 100%. Follow-up was completed after 5.8 years. Results: A peak cTnI level above the 99th percentile together with a cTnI change of >= 20% was found in 160 patients of whom 25 did not have AMI according to the ESC/ACC criteria. These 160 patients had a significantly raised mortality (HR 2.5[95% CI 1.7-3.8]). Higher cTnI deltas were not associated with higher mortalities but identified smaller patient cohorts at risk. Conclusions: The Universal Definition of AMI together with a >= 20% cTnI change appears to improve the discrimination of acute from chronic causes of cTnI release, and allows a reliable identification of patients at risk.
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27.
  • Eggers, Kai M, et al. (författare)
  • Evaluation of Temporal Changes in Cardiovascular Biomarker Concentrations Improves Risk Prediction in an Elderly Population from the Community
  • 2016
  • Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 62:3, s. 485-493
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: There is increasing interest in measurements of cardiovascular (CV) biomarker concentrations for risk prediction in the general population. We investigated the prognostic utility of a panel of novel CV biomarkers and their changes over time.METHODS: We measured concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), midregional proadrenomedullin, high-sensitivity cardiac troponin I, growth-differentiation factor-15 (GDF-15), soluble ST2 (sST2), and galectin-3 at baseline and 5 years later in 1016 elderly individuals participating in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Assessed outcomes included all-cause mortality and fatal and nonfatal CV events (in participants without CV disease at baseline) during 10 years of follow-up.RESULTS: GDF-15 exhibited the strongest association with all-cause mortality (n = 158) with a hazard ratio (HR) per 1-SD increase in standardized ln GDF-15 of 1.68 (95% CI, 1.44-1.96). NT-proBNP was the only biomarker to predict CV events (n = 163; HR 1.54 [95% CI, 1.30-1.84]). GDF-15 and NT-proBNP also improved metrics of discrimination and reclassification of the respective outcomes. Changes in GDF-15 concentrations between 70 and 75 years predicted all-cause mortality whereas changes in NT-proBNP predicted both outcomes. The other biomarkers and their temporal changes provided only moderate prognostic value apart from sST2 which had a neutral relationship with adverse events.CONCLUSIONS: Evaluation of temporal changes in GDF-15 and NT-proBNP concentrations improves risk prediction in an elderly population. These findings are of considerable interest given the emphasis on biomarkers as tools to identify and monitor at-risk individuals with preclinical and potentially modifiable stages of CV disease.
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28.
  • Eggers, Kai M, et al. (författare)
  • Factors Influencing the 99th Percentile of Cardiac Troponin I Evaluated in Community-Dwelling Individuals at 70 and 75 Years of Age
  • 2013
  • Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 59:7, s. 1068-1073
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: We aimed to investigate the effects of sex, prevalent cardiovascular disease (CVD), and ageing on the 99th percentile of cardiac troponin I (cTnI).METHODS:cTnI was measured using a high-sensitivity assay (Abbott Diagnostics) in 814 community-dwelling individuals at both 70 and 75 years of age. We determined the cTnI 99th percentiles separately using nonparametric methods in the total sample, in men and women, and in individuals with and without CVD.RESULTS:The cTnI 99th percentile at baseline was 55.2 ng/L for the total cohort. Higher 99th percentiles were noted in men (69.3 ng/L) and individuals with CVD (74.5 ng/L). The cTnI 99th percentile in individuals free from CVD at baseline (n = 498) increased by 51% from 38.4 to 58.0 ng/L during the 5-year observation period. Relative increases ranging from 44% to 83% were noted across all subgroups. Male sex [odds ratio, 5.3 (95% CI, 1.5-18.3)], log-transformed N-terminal pro-B-type natriuretic peptide [odds ratio, 1.9 (95% CI, 1.2-3.0)], and left-ventricular mass index [odds ratio, 1.3 (95% CI, 1.1-1.5)] predicted increases in cTnI concentrations from below the 99th percentile (i.e., 38.4 ng/L) at baseline to concentrations above the 99th percentile at the age of 75 years.CONCLUSIONS: cTnI concentration and its 99th percentile threshold depend strongly on the characteristics of the population being assessed. Among elderly community dwellers, higher concentrations were seen in men and individuals with prevalent CVD. Ageing contributes to increasing concentrations, given the pronounced changes seen with increasing age across all subgroups. These findings should be taken into consideration when applying cTnI decision thresholds in clinical settings.
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29.
  • Eggers, Kai M., 1962-, et al. (författare)
  • Growth-differentiation factor-15 for long-term risk prediction in patients stabilized after an episode of non-ST-segment-elevation acute coronary syndrome
  • 2010
  • Ingår i: Circulation: Cardiovascular Genetics. - 1942-3268. ; 3:1, s. 88-96
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Growth-differentiation factor-15 (GDF-15) has emerged as a prognostic biomarker in patients with non-ST-segment-elevation acute coronary syndrome. This study assessed the time course and the long-term prognostic relevance of GDF-15 levels measured repetitively in patients with non-ST-segment-elevation acute coronary syndrome during 6 months after the acute event. METHODS AND RESULTS: GDF-15 and other biomarkers were measured at randomization, after 6 weeks, and after 3 and 6 months in 950 patients with non-ST-segment-elevation acute coronary syndrome included in the FRagmin and Fast Revascularization during InStability in Coronary artery disease II study. Study end points were death, recurrent myocardial infarction, and their composite during 5-year follow-up. Median GDF-15 levels decreased slightly from 1357 ng/L at randomization to 1302 ng/L at 6 months (P<0.001). GDF-15 was consistently related to cardiovascular risk factors and biochemical markers of hemodynamic stress, renal dysfunction, and inflammation. Moreover, GDF-15 was independently related to the 5-year risk of the composite end point when measured at both 3 months (adjusted hazard ratio, 1.8 [1.0 to 3.0]) and 6 months (adjusted hazard ratio, 2.3 [1.3 to 4.1]). Serial measurements of GDF-15 at randomization and 6 months helped to identify patient cohorts at different levels of risk, with patients with persistently elevated GDF-15 levels >1800 ng/L having the highest rate of the composite end point. CONCLUSIONS: GDF-15 is independently related to adverse events in non-ST-segment-elevation acute coronary syndrome both in the acute setting and for at least 6 months after clinical stabilization. Therefore, continued research on GDF-15 should be focused on the usefulness of GDF-15 for support of clinical management in acute and chronic ischemic heart disease.
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30.
  • Eggers, Kai M., et al. (författare)
  • High-sensitive cardiac troponin T outperforms novel diagnostic biomarkers in patients with acute chest pain
  • 2012
  • Ingår i: Clinica Chimica Acta. - : Elsevier BV. - 0009-8981 .- 1873-3492. ; 413:13-14, s. 1135-1140
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Measurement of high-sensitive cardiac troponin (hs-cTn) has facilitated the early diagnostic assessment of chest pain patients. However, the information obtained from hs-cTnT levels might be improved when combined with results of other biomarkers of myocardial injury.Methods: We measured admission levels of hs-cTnT (Roche Diagnostics), heart-type fatty-acid binding protein (H-FABP; Randox Laboratories) and copeptin using a novel ultra-sensitive (us) assay (Thermo Fisher Scientific) in 360 chest pain patients with a non-diagnostic ECG. Non-STEMI was defined according to the Universal Definition using cardiac troponin I (Stratus CS; Siemens Healthcare Diagnostics) as biochemical gold standard.Results: Non-STEMI was diagnosed in 128 (36%) patients. Hs-cTnT had a greater diagnostic accuracy regarding non-STEMI (C-statistics 0.84) compared to H-FABP (C-statistics 0.80; p = 0.04) and us-copeptin C-statistics(0.62; p < 0.001). Compared to hs-cTnT alone, no increase in the C-statistics was noted for the combination of hs-cTnT with H-FABP (0.85; p = 0.43) or with us-copeptin (0.84; p = 0.88). Due to suboptimal sensitivities and/or specificities, neither H-FABP nor us-copeptin dichotomized at commonly applied diagnostic thresholds added information to hs-cTnT that would have facilitated early diagnostic assessment.Conclusions: Hs-cTnT provides an excellent early diagnostic accuracy regarding non-STEMI already on admission. Neither H-FABP nor us-copeptin perform better or provide diagnostic increment to hs-cTnT levels.
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31.
  • Eggers, Kai M., et al. (författare)
  • Improving long-term risk prediction in patients with acute chest pain : The Global Registry of Acute Coronary Events (GRACE) risk score is enhanced by selected nonnecrosis biomarkers
  • 2010
  • Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 160:1, s. 88-94
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The Global Registry of Acute Coronary Events (GRACE) risk score is widely recommended for risk assessment in patients with acute coronary syndrome. However, there is limited knowledge regarding the utility of this score for long-term risk prediction in unselected patients with acute chest pain and whether it might be improved by the integration of nonnecrosis biomarkers. Methods We calculated the GRACE risk score in 453 chest pain patients and assessed its value for risk assessment together with the additive prognostic information obtained from N-terminal pro-B-type natriuretic peptide, C-reactive protein, growth differentiation factor-15 (GDF-15), and cystatin C. Results After a median follow-up of 5.8 years, 92 patients (20.7%) had died. The GRACE risk score was significantly higher in patients who died (median 146 vs 93, P < .001) and provided a c-statistic regarding mortality of 0.78. A significant increase of the c-statistic was achieved only after addition of GDF-15 (c-statistic 0.81, P = .003) and, to a minor extent, after addition of cystatin C (c-statistic 0.81, P = .035). Assessment of the integrated discriminative improvement yielded similar results. N-terminal pro-B-type natriuretic peptide had only limited incremental prognostic value, and C-reactive protein was not predictive for outcome. Conclusion The GRACE risk score allows for the prediction of mortality in chest pain patients even after almost 6 years of follow-up. However, its predictive value could be further enhanced by the addition of selected nonnecrosis biomarkers, in particular GDF-15 or cystatin C. (Am Heart J 2010; 160: 88-94.)
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32.
  • Eggers, Kai M., 1962-, et al. (författare)
  • Myeloperoxidase is not useful for the early assessment of patients with chest pain
  • 2010
  • Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 43:3, s. 240-245
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Myeloperoxidase (MPO) has been listed as a potentially useful risk marker in acute coronary syndrome. However, its clinical utility in patients with acute chest pain is not yet defined. DESIGN AND METHODS: MPO (Architect, Abbott Diagnostics) was measured in 120 healthy controls and 303 chest pain patients who had been admitted to the coronary care units of three Swedish hospitals. RESULTS: Chest pain patents had significantly higher median MPO levels compared to healthy controls (120.6 vs. 78. 9 pmol/L; p<0.001). However, MPO was not useful for the diagnosis of myocardial infarction (c-statistics 0.61 [95% CI 0.54-0.67]), and Cox regression analysis revealed no independent association between MPO and mortality (adjusted hazard ratio 1.3 [95% CI 0.8-2.0]) or the composite endpoint (adjusted hazard ratio 1.1 [95% CI 0.8-1.5]) after a median follow-up of 4.9 years. CONCLUSIONS: MPO provided no clinically relevant information in the present population of chest pain patients.
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33.
  • Eggers, Kai M., 1962-, et al. (författare)
  • Predictors of 10-year changes in levels of N-terminal pro B-type natriuretic peptide and cardiac troponin I in the elderly
  • 2018
  • Ingår i: International Journal of Cardiology. - : ELSEVIER IRELAND LTD. - 0167-5273 .- 1874-1754. ; 257, s. 300-305
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Measurement of N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) might be useful for monitoring of cardiovascular disease in the elderly. However, it is not clear whether changes in these biomarkers are associated with changes in the cardiovascular risk profile and if this pattern could be modified by changes in lifestyle habits or medications.Methods: We measured levels of NT-proBNP and cTnI in community-dwelling subjects (PIVUS study) upon visits scheduled at age 70 (n = 1007), 75 (n = 825) and 80 (n = 602). The associations of these biomarkers with repeated measurements of clinical variables (risk factors, lifestyle habits, echocardiographic data and medications) were investigated using sex-adjusted linear mixed random effect models.Results: NT-proBNP and cTnI were positively associated with increasing age. NT-proBNP, but not cTnI, was affected by changes of renal function and the degree of obesity. NT-proBNP was more closely related than cTnI to changes in echocardiographic estimates of cardiac geometry and function. Biomarker levels and/or their changes were inversely associated with a physically more active lifestyle (both NT-proBNP and cTnI) and statin treatment at age 70 (only cTnI). Changes in smoking status or antihypertensive treatment had no effect on biomarker levels.Conclusions: Changes in NT-proBNP and cTnI levels are associated with different patterns of cardiovascular disease burden when using a longitudinal approach. However, levels of both biomarkers and their changes also reflect changes in the cardiovascular risk profile that might be modifiable. This is an important aspect for the use of any cardiovascular biomarker in an elderly population.
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34.
  • Eggers, Kai M., et al. (författare)
  • Prognostic implications of changes in cardiac troponin I levels in patients with non-ST elevation acute coronary syndrome
  • 2013
  • Ingår i: Biomarkers. - 1354-750X .- 1366-5804. ; 18:8, s. 668-672
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Information is limited on the prognostic implications of cardiac troponin I (cTnI) changes during the first days of non-ST elevation acute coronary syndrome (NSTE-ACS). Methods: High-sensitivity cTnI levels were measured at study inclusion and after 48 h in 1615 conservatively managed NSTE-ACS patients from the Global Use of Strategies To Open Occluded Coronary Arteries (GUSTO) IV trial. Results: Patients with moderately increased cTnI levels and without a relevant decrease over time had a significantly raised mortality at 30 days and 1 year. No relevant associations between cTnI changes and recurrent myocardial infarction were seen. Conclusion: The cTnI change is predictive for subsequent mortality in selected conservatively managed NSTE-ACS patients.
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35.
  • Fornander, Louise, et al. (författare)
  • Airway symptoms and biological markers in nasal lavage fluid in subjects exposed to metalworking fluids
  • 2013
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:12, s. e83089-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUNDS: Occurrence of airway irritation among industrial metal workers was investigated. The aims were to study the association between exposures from water-based metal working fluids (MWF) and the health outcome among the personnel, to assess potential effects on the proteome in nasal mucous membranes, and evaluate preventive actions.METHODS: The prevalence of airway symptoms related to work were examined among 271 metalworkers exposed to MWF and 24 metal workers not exposed to MWF at the same factory. At the same time, air levels of potentially harmful substances (oil mist, morpholine, monoethanolamine, formaldehyde) generated from MWF was measured. Nasal lavage fluid was collected from 13 workers and 15 controls and protein profiles were determined by a proteomic approach.RESULTS: Airway symptoms were reported in 39% of the workers exposed to MWF although the measured levels of MWF substances in the work place air were low. Highest prevalence was found among workers handling the MWF machines but also those working in the same hall were affected. Improvement of the ventilation to reduce MWF exposure lowered the prevalence of airway problems. Protein profiling showed significantly higher levels of S100-A9 and lower levels of SPLUNC1, cystatin SN, Ig J and β2-microglobulin among workers with airway symptoms.CONCLUSIONS: This study confirms that upper airway symptoms among metal workers are a common problem and despite low levels of MWF-generated substances, effects on airway immune proteins are found. Further studies to clarify the role of specific MWF components in connection to airway inflammation and the identified biological markers are warranted.
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36.
  • Fors, Per, 1988- (författare)
  • Problematizing Sustainable ICT
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • How should we understand the relationship between information and communication technology (ICT) and sustainability? Generally, it is assumed that while ICT products contribute to many environmental and social problems as they are produced and disposed of, the potential of using ICT to achieve a more sustainable society is immense. However, despite the fact that such a discourse is favored not only in the industrial but also in the political and academic spheres, we have yet to see this presumed sustainability-related potential of ICT fully exploited.This thesis argues that conventional assumptions and understandings related to three abstractions in sustainable ICT research and practice – namely the technological, the social, and the sustainable – contribute to an overly optimistic discourse of sustainable ICT, which favors certain research approaches and practical applications. Adhering to such a discourse risks reinforcing, rather than breaking loose from, an unsustainable status quo. Through problematization, this thesis aims to unveil and challenge such underlying assumptions and understandings, based on insights from the social sciences and philosophy. New assumptions and understandings of sustainable ICT research and practice are suggested, and contribute with a perspective that among other things emphasize the ontological inseparability of the technological and the social, implying an anti-essentialist position embracing the value-ladenness and value and meaning mediatory aspects of such phenomena. The normative contributions include theoretical and methodological approaches to sustainable ICT design and sustainable ICT entrepreneurship – identified as two central practices for sustainable ICT to promote sustainability – that aim to mobilize politically charged discourses of our being together with each other, technologies and nature in order to facilitate collaborative action towards sustainable futures. This thesis should be seen as a critical contribution to fields interested in sustainable ICT, such as ICT for Sustainability (ICT4S) and Sustainable Human-Computer Interaction (SHCI).
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37.
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38.
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39.
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40.
  • Gul, Nadia, 1980, et al. (författare)
  • The MTH1 inhibitor TH588 is a microtubule-modulating agent that eliminates cancer cells by activating the mitotic surveillance pathway
  • 2019
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • The mut-T homolog-1 (MTH1) inhibitor TH588 has shown promise in preclinical cancer studies but its targeting specificity has been questioned. Alternative mechanisms for the anti-cancer effects of TH588 have been suggested but the question remains unresolved. Here, we performed an unbiased CRISPR screen on human lung cancer cells to identify potential mechanisms behind the cytotoxic effect of TH588. The screen identified pathways and complexes involved in mitotic spindle regulation. Using immunofluorescence and live cell imaging, we showed that TH588 rapidly reduced microtubule plus-end mobility, disrupted mitotic spindles, and prolonged mitosis in a concentration-dependent but MTH1-independent manner. These effects activated a USP28-p53 pathway -the mitotic surveillance pathway -that blocked cell cycle reentry after prolonged mitosis; USP28 acted upstream of p53 to arrest TH588-treated cells in the G1-phase of the cell cycle. We conclude that TH588 is a microtubule-modulating agent that activates the mitotic surveillance pathway and thus prevents cancer cells from re-entering the cell cycle.
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41.
  • Gunneriusson, Håkan, 1970-, et al. (författare)
  • Defensiven : begrepp och doktrinbakgrund
  • 2018
  • Ingår i: Tankar om defensiven. - Stockholm : Kungl. Krigsvetenskapsakademien. - 9789188581051 ; , s. 32-55
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • I DENNA ARTIKEL kommer defensiven att belysas utifrån två olika perspektiv och genom två historiska exempel tagna från första respektive andra världskriget. Inledningsvis betraktas defensiven utifrån försvararen perspektiv och med ett exempel från Estland (Narva) 1944. Efter en historik bakgrundsbeskrivning, där bl a doktrinutvecklingen beskrivs, följer ett avsnitt avseende doktrin- och reglementsjämförelse mellan dåtida tyska och nutida svenska reglementen. Vi har i den delen valt att som metod söka efter vissa militärteoretiska indikatorer – fyra typiska begrepp inom defensiv och offensiv strid – för att diskutera likheter och olikheter mellan dåtid och nutid. De fyra valda begreppen är eldens (verkans) betydelse, terrängens betydelse, djupets betydelse och slutligen reservernas betydelse. Jämförelsen appliceras sedan på det taktiska exemplet innan denna del avslutas med en kort sammanfattning.
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42.
  • Hagberg, Carolina E, et al. (författare)
  • Vascular endothelial growth factor B controls endothelial fatty acid uptake.
  • 2010
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 464:7290, s. 917-21
  • Tidskriftsartikel (refereegranskat)abstract
    • The vascular endothelial growth factors (VEGFs) are major angiogenic regulators and are involved in several aspects of endothelial cell physiology. However, the detailed role of VEGF-B in blood vessel function has remained unclear. Here we show that VEGF-B has an unexpected role in endothelial targeting of lipids to peripheral tissues. Dietary lipids present in circulation have to be transported through the vascular endothelium to be metabolized by tissue cells, a mechanism that is poorly understood. Bioinformatic analysis showed that Vegfb was tightly co-expressed with nuclear-encoded mitochondrial genes across a large variety of physiological conditions in mice, pointing to a role for VEGF-B in metabolism. VEGF-B specifically controlled endothelial uptake of fatty acids via transcriptional regulation of vascular fatty acid transport proteins. As a consequence, Vegfb(-/-) mice showed less uptake and accumulation of lipids in muscle, heart and brown adipose tissue, and instead shunted lipids to white adipose tissue. This regulation was mediated by VEGF receptor 1 and neuropilin 1 expressed by the endothelium. The co-expression of VEGF-B and mitochondrial proteins introduces a novel regulatory mechanism, whereby endothelial lipid uptake and mitochondrial lipid use are tightly coordinated. The involvement of VEGF-B in lipid uptake may open up the possibility for novel strategies to modulate pathological lipid accumulation in diabetes, obesity and cardiovascular diseases.
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43.
  • Hammar, Per, et al. (författare)
  • Unrecognized myocardial infarctions assessed by cardiovascular magnetic resonance are associated with the severity of the stenosis in the supplying coronary artery
  • 2015
  • Ingår i: Journal of Cardiovascular Magnetic Resonance. - : BioMed Central. - 1097-6647 .- 1532-429X. ; 17
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A previous study has shown an increased prevalence of late gadolinium enhancement cardiovascular magnetic resonance (LGE CMR) detected unrecognized myocardial infarction (UMI) with increasing extent and severity of coronary artery disease. However, the coronary artery disease was evaluated on a patient level assuming normal coronary anatomy. Therefore, the aims of the present study were to investigate the prevalence of UMI identified by LGE CMR imaging in patients with stable angina pectoris and no known previous myocardial infarction; and to investigate whether presence of UMI is associated with stenotic lesions in the coronary artery supplying the segment of the myocardium in which the UMI is located, using coronary angiography to determine the individual coronary anatomy in each patient.Methods: In this prospective multicenter study, we included patients with stable angina pectoris and without prior myocardial infarction, scheduled for coronary angiography. A LGE CMR examination was performed prior to the coronary angiography. The study cohort consisted of 235 patients (80 women, 155 men) with a mean age of 64.8 years.Results: UMIs were found in 25 % of patients. There was a strong association between stenotic lesions (>= 70 % stenosis) in a coronary artery and the presence of an UMI in the myocardial segments supplied by the stenotic artery; it was significantly more likely to have an UMI downstream a stenosis >= 70 % as compared to <70 % (OR 5.1, CI 3.1-8.3, p < 0.0001). 56 % of the UMIs were located in the inferior and infero-lateral myocardial segments, despite predominance for stenotic lesions in the left anterior descending artery.Conclusion: UMI is common in patients with stable angina and the results indicate that the majority of the UMIs are of ischemic origin due to severe coronary atherosclerosis. In contrast to what is seen in recognized myocardial infarctions, UMIs are predominately located in the inferior and infero-lateral myocardial segments.
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44.
  • Hellstrom-Lindahl, Ewa, et al. (författare)
  • In vitro binding of [H-3]PIB to human amyloid deposits of different types
  • 2014
  • Ingår i: Amyloid. - : Informa UK Limited. - 1350-6129 .- 1744-2818. ; 21:1, s. 21-27
  • Tidskriftsartikel (refereegranskat)abstract
    • Systemic amyloidosis is caused by extracellular deposition of insoluble fibrillar proteins arranged in beta-pleated sheets. [C-11] PIB has been used in PET studies to assess A beta deposition in brain of patients with Alzheimer's disease (AD). The possibility to visualize other types of amyloid deposits with [C-11] PIB would be of potential clinical importance in early diagnosis and for following therapeutic effects. In the present study, we evaluated in vitro binding of [3 H] PIB to tissues containing transthyretin (ATTR), immunoglobulin light-chain (AL), amyloid protein A (AA) and Ab amyloid. We found significantly higher binding of [H-3] PIB in tissue from systemic amyloidoses than in control tissue, i.e. 4.7 times higher (p<0.05). [H-3] PIB showed the highest affinity to cortex of AD brain (IC50 = 3.84 nM), while IC50 values were much higher for ATTR, AA and AL type of amyloidosis and large variations in affinity were observed even within tissues having the same type of amyloidosis. Extraction with guanidine-HCl, which disrupts the beta-sheet structure, decreased the protein levels and, concomitantly, the binding of [H-3] PIB in all four types of amyloidoses.
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45.
  • Hellström, Thomas, et al. (författare)
  • An intelligent rollator for mobility impaired persons, especially stroke patients
  • 2016
  • Ingår i: Journal of Medical Engineering & Technology. - : Taylor & Francis. - 0309-1902 .- 1464-522X. ; 40:5, s. 270-279
  • Tidskriftsartikel (refereegranskat)abstract
    • An intelligent rollator (IRO) was developed that aims at obstacle detection and guidance to avoid collisions and accidental falls. The IRO is a retrofit four-wheeled rollator with an embedded computer, two solenoid brakes, rotation sensors on the wheels and IR-distance sensors. The value reported by each distance sensor was compared in the computer to a nominal distance. Deviations indicated a present obstacle and caused activation of one of the brakes in order to influence the direction of motion to avoid the obstacle. The IRO was tested by seven healthy subjects with simulated restricted and blurred sight and five stroke subjects on a standardised indoor track with obstacles. All tested subjects walked faster with intelligence deactivated. Three out of five stroke patients experienced more detected obstacles with intelligence activated. This suggests enhanced safety during walking with IRO. Further studies are required to explore the full value of the IRO.
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46.
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47.
  • Hjelmgren, Ola, et al. (författare)
  • Increased Vascularization in the Vulnerable Upstream Regions of Both Early and Advanced Human Carotid Atherosclerosis.
  • 2016
  • Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 11:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Vascularization of atherosclerotic plaques has been linked to plaque vulnerability. The aim of this study was to test if the vascularization was increased in upstream regions of early atherosclerotic carotid plaques and also to test if the same pattern of vascularization was seen in complicated, symptomatic plaques.We enrolled 45 subjects with early atherosclerotic lesions for contrast enhanced ultrasound and evaluated the percentage of plaque area in a longitudinal ultrasound section which contained contrast agent. Contrast-agent uptake was evaluated in both the upstream and downstream regions of the plaque. We also collected carotid endarterectomy specimens from 56 subjects and upstream and downstream regions were localized using magnetic resonance angiography and analyzed using histopathology and immunohistochemistry.Vascularization was increased in the upstream regions of early carotid plaques compared with downstream regions (30% vs. 23%, p = 0.033). Vascularization was also increased in the upstream regions of advanced atherosclerotic lesions compared with downstream regions (4.6 vs. 1.4 vessels/mm2, p = 0.001) and was associated with intra-plaque hemorrhage and inflammation.Vascularization is increased in the upstream regions of both early and advanced plaques and is in advanced lesions mainly driven by inflammation.
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48.
  • Hjort, Marcus, et al. (författare)
  • Increased Inflammatory Activity in Patients 3 Months after Myocardial Infarction with Nonobstructive Coronary Arteries
  • 2019
  • Ingår i: Clinical Chemistry. - : AMER ASSOC CLINICAL CHEMISTRY. - 0009-9147 .- 1530-8561. ; 65:8, s. 1023-1030
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Around 5%-10% of patients with myocardial infarction (MI) present with nonobstructive coronary arteries (MINOCA). We aimed to assess pathophysiological mechanisms in MINOCA by extensively evaluating cardiovascular biomarkers in the stable phase after an event, comparing MINOCA patients with cardiovascular healthy controls and MI patients with obstructive coronary artery disease (MI-CAD).METHODS: Ninety-one biomarkers were measured with a proximity extension assay 3 months after MI in 97 MINOCA patients, 97 age-and sex-matched MI-CAD patients, and 98 controls. Lasso analyses (penalized logistic regression models) and adjusted multiple linear regression models were used for statistical analyses.RESULTS: In the Lasso analysis (MINOCA vs MI-CAD), 8 biomarkers provided discriminatory value: P-selectin glycoprotein ligand 1, C-X-C motif chemokine 1, TNF-related activation-induced cytokine, and pappalysin-1 (PAPPA) with increasing probabilities of MINOCA, and tissue-type plasminogen activator, B-type natriuretic peptide, myeloperoxidase, and interleukin-1 receptor antagonist protein with increasing probabilities of MI-CAD. Comparing MINOCA vs controls, 7 biomarkers provided discriminatory value: N-terminal pro-B-type natriuretic peptide, renin, NF-kappa-B essential modulator, PAPPA, interleukin-6, and soluble urokinase plasminogen activator surface receptor with increasing probabilities of MINOCA, and agouti-related protein with increasing probabilities of controls. Adjusted multiple linear regression analyses showed that group affiliation was associated with the concentrations of 7 of the 8 biomarkers in the comparison MINOCA vs MI-CAD and 5 of the 7 biomarkers in MINOCA vs controls.CONCLUSIONS: Three months after the MI, the biomarker concentrations indicated greater inflammatory activity in MINOCA patients than in both MI-CAD patients and healthy controls, and a varying degree of myocardial dysfunction among the 3 cohorts. 
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49.
  • Hjort, Marcus, et al. (författare)
  • Prognosis in relation to high-sensitivity cardiac troponin T levels in patients with myocardial infarction and non-obstructive coronary arteries
  • 2018
  • Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 200, s. 60-66
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) is a recently recognized condition where biomarkers and prognosis are less well studied than in MI with obstructive coronary artery disease (MI-CAD). We therefore aimed to investigate the one-year prognostic value of high-sensitivity cardiac troponin T (hs-cTnT) levels in MINOCA in comparison to MI-CAD.Methods: In this registry-based cohort study, we used data frompatientswith a discharge diagnosis ofMI, admitted between 2009 and 2013 to Swedish hospitals using the hs-cTnT assay. Only patients without previously known coronary artery disease were considered. Patients with and without coronary stenosis N50% were regarded to haveMI-CAD andMINOCA, respectively. Assessed outcomes included all-cause mortality, cardiovascular (CV) mortality and major CV events (MACE), defined as the composite of CV death or admissions for nonfatal MI, heart failure (HF) or ischemic stroke.Results: The study cohort consisted of 1639 MINOCA and 17,304 MI-CAD patients. In adjusted analyses, hs-cTnT (ln) in MINOCA patients predicted all-cause mortality (HR 1.32 [95% CI 1.11-1.56]), CVmortality (HR 2.11 [95% CI 1.51-2.96]) and MACE (HR 1.44 [95% CI 1.20-1.72]). Hs-cTnT (ln) also predicted readmissions for HF (HR 1.51 [95% CI 1.51-2.96]) but not non-fatal MI or stroke. Interaction analyses suggested that hs-cTnT (ln) was at least as prognostic in patients with MINOCA compared to MI-CAD.Conclusions: Hs-cTnT levels inMINOCA patients are strong and independent predictors of adverse outcome. Consideration of hs-cTnT levels is important for risk assessment of MINOCA patients.
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