| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
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| 3. |
- Menkveld, Albert J., et al.
(författare)
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Nonstandard Errors
- 2024
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Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 4. |
- Michel, M., et al.
(författare)
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Small-molecule activation of OGG1 increases oxidative DNA damage repair by gaining a new function
- 2022
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Ingår i: Science. - Stockholm : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 376:6600, s. 1471-1476
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Tidskriftsartikel (refereegranskat)abstract
- Oxidative DNA damage is recognized by 8-oxoguanine (8-oxoG) DNA glycosylase 1 (OGG1), which excises 8-oxoG, leaving a substrate for apurinic endonuclease 1 (APE1) and initiating repair. Here, we describe a small molecule (TH10785) that interacts with the phenylalanine-319 and glycine-42 amino acids of OGG1, increases the enzyme activity 10-fold, and generates a previously undescribed b,d-lyase enzymatic function. TH10785 controls the catalytic activity mediated by a nitrogen base within its molecular structure. In cells, TH10785 increases OGG1 recruitment to and repair of oxidative DNA damage. This alters the repair process, which no longer requires APE1 but instead is dependent on polynucleotide kinase phosphatase (PNKP1) activity. The increased repair of oxidative DNA lesions with a small molecule may have therapeutic applications in various diseases and aging. © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
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| 6. |
- Mehta, Shamir R, et al.
(författare)
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Complete Revascularization vs Culprit Lesion-Only Percutaneous Coronary Intervention for Angina-Related Quality of Life in Patients With ST-Segment Elevation Myocardial Infarction : Results From the COMPLETE Randomized Clinical Trial
- 2022
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Ingår i: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 7:11, s. 1091-1099
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: In patients with multivessel coronary artery disease (CAD) presenting with ST-segment elevation myocardial infarction (STEMI), complete revascularization reduces major cardiovascular events compared with culprit lesion-only percutaneous coronary intervention (PCI). Whether complete revascularization also improves angina-related health status is unknown.OBJECTIVE: To determine whether complete revascularization improves angina status in patients with STEMI and multivessel CAD.DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of a randomized, multinational, open label trial of patient-reported outcomes took place in 140 primary PCI centers in 31 countries. Patients presenting with STEMI and multivessel CAD were randomized between February 1, 2013, and March 6, 2017. Analysis took place between July 2021 and December 2021.INTERVENTIONS: Following PCI of the culprit lesion, patients with STEMI and multivessel CAD were randomized to receive either complete revascularization with additional PCI of angiographically significant nonculprit lesions or to no further revascularization.MAIN OUTCOMES AND MEASURES: Seattle Angina Questionnaire Angina Frequency (SAQ-AF) score (range, 0 [daily angina] to 100 [no angina]) and the proportion of angina-free individuals by study end.RESULTS: Of 4041 patients, 2016 were randomized to complete revascularization and 2025 to culprit lesion-only PCI. The mean (SD) age of patients was 62 (10.7) years, and 3225 (80%) were male. The mean (SD) SAQ-AF score increased from 87.1 (17.8) points at baseline to 97.1 (9.7) points at a median follow-up of 3 years in the complete revascularization group (score change, 9.9 [95% CI, 9.0-10.8]; P < .001) compared with an increase of 87.2 (18.4) to 96.3 (10.9) points (score change, 8.9 [95% CI, 8.0-9.8]; P < .001) in the culprit lesion-only group (between-group difference, 0.97 points [95% CI, 0.27-1.67]; P = .006). Overall, 1457 patients (87.5%) were free of angina (SAQ-AF score, 100) in the complete revascularization group compared with 1376 patients (84.3%) in the culprit lesion-only group (absolute difference, 3.2% [95% CI, 0.7%-5.7%]; P = .01). This benefit was observed mainly in patients with nonculprit lesion stenosis severity of 80% or more (absolute difference, 4.7%; interaction P = .02).CONCLUSIONS AND RELEVANCE: In patients with STEMI and multivessel CAD, complete revascularization resulted in a slightly greater proportion of patients being angina-free compared with a culprit lesion-only strategy. This modest incremental improvement in health status is in addition to the established benefit of complete revascularization in reducing cardiovascular events.
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| 7. |
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| 8. |
- Castaneda-Zegarra, S, et al.
(författare)
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Generation of a Mouse Model Lacking the Non-Homologous End-Joining Factor Mri/Cyren
- 2019
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Ingår i: Biomolecules. - : MDPI AG. - 2218-273X. ; 9:12
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Tidskriftsartikel (refereegranskat)abstract
- Classical non-homologous end joining (NHEJ) is a molecular pathway that detects, processes, and ligates DNA double-strand breaks (DSBs) throughout the cell cycle. Mutations in several NHEJ genes result in neurological abnormalities and immunodeficiency both in humans and mice. The NHEJ pathway is required for V(D)J recombination in developing B and T lymphocytes, and for class switch recombination in mature B cells. The Ku heterodimer formed by Ku70 and Ku80 recognizes DSBs and facilitates the recruitment of accessory factors (e.g., DNA-PKcs, Artemis, Paxx and Mri/Cyren) and downstream core factor subunits X-ray repair cross-complementing group 4 (XRCC4), XRCC4-like factor (XLF), and DNA ligase 4 (Lig4). Accessory factors might be dispensable for the process, depending on the genetic background and DNA lesion type. To determine the physiological role of Mri in DNA repair and development, we introduced a frame-shift mutation in the Mri gene in mice. We then analyzed the development of Mri-deficient mice as well as wild type and immunodeficient controls. Mice lacking Mri possessed reduced levels of class switch recombination in B lymphocytes and slow proliferation of neuronal progenitors when compared to wild type littermates. Human cell lines lacking Mri were as sensitive to DSBs as the wild type controls. Overall, we concluded that Mri/Cyren is largely dispensable for DNA repair and mouse development.
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| 9. |
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| 10. |
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| 11. |
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| 12. |
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| 13. |
- Redfors, B. Björn, et al.
(författare)
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Incidence and prognosis of the takotsubo syndrome compared to acute myocardial infarction
- 2019
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Ingår i: European Journal of Heart Failure. - : John Wiley & Sons. - 1388-9842 .- 1879-0844. ; 21, s. 267-267
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Takotsubo syndrome (TS) is a potentially life-threatening acute cardiac syndrome with a clinical presentation very similar to myocardial infarction (MI) and for which the natural history, management and outcome remain incompletely understood.Purpose: The aims of this study were to assess the relative short- and long-term mortality risk of TS , ST-elevation MI (STEMI) and non STEMI (NSTEMI) and to identify predictors of in-hospital complications and poor prognosis in patients with TS.Methods: Using the nationwide Swedish Angiography and Angioplasty Registry (SCAAR) we identified almost all (n=117,720) patients who underwent coronary angiography due to TS (N=2,898 [2.5%]), STEMI (N=48,493 [41.2%]) or NSTEMI (N=66,329 [56.3%]) in Sweden between January 2009 and February 2018.Results: Patients with TS were more often women as compared with patients with STEMI or NSTEMI. TS was associated with unadjusted and adjusted 30-day mortality risks lower than STEMI (adjusted hazard ratio [adjHR] 0.60, 95% confidence interval [CI]0.48-0.76, p<0.001), but higher than NSTEMI (adjHR 2.70, 95% CI 2.14-3.41, p<0.001). Compared to STEMI, TS was associated with similar risk of acute heart failure (adjHR 1.26, 95% CI 0.91–1.76, p=0.16) but lower risk of cardio-genic shock (adjHR 0.55, 95% CI 0.34–0.89, p=0.02). The relative 30-day mortality risk for TS versus STEMI and NSTEMI was higher for smokers than non-smokers (adjusted pinteractionSTEMI=0.01 and pinteractionNSTEMI=0.01).Conclusion: Thirty-day mortality in TS was higher than in NSTEMI but lower than STEMI, despite a similar risk of acute heart failure in TS and STEMI. Among patients with TS, smoking was an independent predictor of mortality
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| 14. |
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| 15. |
- Bonagas, Nadilly, et al.
(författare)
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Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
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Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
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Tidskriftsartikel (refereegranskat)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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| 16. |
- Costantini, E. A.C., et al.
(författare)
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Local adaptation strategies to increase or maintain soil organic carbon content under arable farming in Europe : Inspirational ideas for setting operational groups within the European innovation partnership
- 2020
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Ingår i: Journal of Rural Studies. - : Elsevier BV. - 0743-0167. ; 79, s. 102-115
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Tidskriftsartikel (refereegranskat)abstract
- In the European Union, the setting of Operational Groups (OG) is supported by the European Innovation Partnership to tackle specific problems and favor innovation in agriculture. They constitute an important aspect of the current Common Agricultural Policy. Increasing or maintaining soil organic carbon (SOC) content under arable farming has been acknowledged as a primary target of European agriculture. SOC-preserving agriculture needs its techniques to be tailored to local conditions, namely, the combination of factors related to the environment (climate and soil characteristics), to the farming system (land use type, farm specialization, crop management), but also to the social and cultural context (market and availability of production means, subsidies, farmers’ education, propensity for innovation and change). In this paper we present inspirational ideas and show success examples of local adaptations strategies to increase or maintain SOC content in soils under arable farming in Europe. They include: · Adoption of soil management strategies to improve SOC storage in irrigated systems. · Precision farming and other high-tech solutions able to generate local diagnosis and adaptive strategies for increasing SOC and reducing greenhouse gasses emissions. · Innovative strategies for extending soil cover periods and introducing cover crops in rotations in areas with limited water availability or prone to harsh weather conditions. · Management of rainfed and low input crops to maintain and increase SOC in dry climates and erosive prone soils. These case studies could facilitate the setting up of OGs and the application of innovative practices in different European countries.
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| 17. |
- De Maria, Giovanni Luigi, et al.
(författare)
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Novel Indices of Coronary Physiology : Do We Need Alternatives to Fractional Flow Reserve?
- 2020
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Ingår i: Circulation. Cardiovascular Interventions. - 1941-7640 .- 1941-7632. ; 13:4
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Forskningsöversikt (refereegranskat)abstract
- Fractional flow reserve is the current invasive gold standard for assessing the ischemic potential of an angiographically intermediate coronary stenosis. Procedural cost and time, the need for coronary vessel instrumentation, and the need to administer adenosine to achieve maximal hyperemia remain integral components of invasive fractional flow reserve. The number of new alternatives to fractional flow reserve has proliferated over the last ten years using techniques ranging from alternative pressure wire metrics to anatomic simulation via angiography or intravascular imaging. This review article provides a critical description of the currently available or under-development alternatives to fractional flow reserve with a special focus on the available evidence, pros, and cons for each with a view towards their clinical application in the near future for the functional assessment of coronary artery disease.
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| 18. |
- Erlinge, David, et al.
(författare)
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Identification of vulnerable plaques and patients by intracoronary near-infrared spectroscopy and ultrasound (PROSPECT II) : a prospective natural history study
- 2021
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 397:10278, s. 985-995
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Tidskriftsartikel (refereegranskat)abstract
- Background: Near-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs).Methods: PROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065.Findings: Between June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17%] women, 745 [83%] men; median age 63 [IQR 55-70] years). Median follow-up was 3.7 (IQR 3.0-4.4) years. Adverse events within 4 years occurred in 112 (13.2%, 95% CI 11.0-15.6) of 898 patients, with 66 (8.0%, 95% CI 6.2-10.0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46.9% [SD 15.9]). Highly lipidic lesions (851 [24%] of 3500 lesions, present in 520 [59%] of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adjusted odds ratio 2.27, 95% CI 1.25-4.13) and nonculprit lesion-specific MACEs (7.83, 4.12-14.89). Large plaque burden (787 [22%] of 3629 lesions, present in 530 [59%] of 898 patients) was also an independent predictor of non-culprit lesion-related MACEs. Lesions with both large plaque burden by intravascular ultrasound and large lipid-rich cores by NIRS had a 4-year non-culprit lesion-related MACE rate of 7.0% (95% CI 4.0-10.0). Patients in whom one or more such lesions were identified had a 4-year non-culprit lesion-related MACE rate of 13.2% (95% CI 9.4-17.6).Interpretation: Combined NIRS and intravascular ultrasound detects angiographically non-obstructive lesions with a high lipid content and large plaque burden that are at increased risk for future adverse cardiac outcomes.
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| 19. |
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| 20. |
- Jemth, Ann-Sofie, et al.
(författare)
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MutT homologue 1 (MTH1) catalyzes the hydrolysis of mutagenic O6-methyl-dGTP
- 2018
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 46:20, s. 10888-10904
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Tidskriftsartikel (refereegranskat)abstract
- Nucleotides in the free pool are more susceptible to nonenzymatic methylation than those protected in the DNA double helix. Methylated nucleotides like O6-methyl-dGTP can be mutagenic and toxic if incorporated into DNA. Removal of methylated nucleotides from the nucleotide pool may therefore be important to maintain genome integrity. We show that MutT homologue 1 (MTH1) efficiently catalyzes the hydrolysis of O6-methyl-dGTP with a catalytic efficiency similar to that for 8-oxo-dGTP. O6-methyl-dGTP activity is exclusive to MTH1 among human NUDIX proteins and conserved through evolution but not found in bacterial MutT. We present a high resolution crystal structure of human and zebrafish MTH1 in complex with O6-methyl-dGMP. By microinjecting fertilized zebrafish eggs with O6-methyl-dGTP and inhibiting MTH1 we demonstrate that survival is dependent on active MTH1 in vivo. O6-methyl-dG levels are higher in DNA extracted from zebrafish embryos microinjected with O6-methyl-dGTP and inhibition of O6-methylguanine-DNA methyl transferase (MGMT) increases the toxicity of O6-methyl-dGTP demonstrating that O6-methyl-dGTP is incorporated into DNA. MTH1 deficiency sensitizes human cells to the alkylating agent Temozolomide, a sensitization that is more pronounced upon MGMT inhibition. These results expand the cellular MTH1 function and suggests MTH1 also is important for removal of methylated nucleotides from the nucleotide pool.
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| 21. |
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| 22. |
- Mohammad, Moman A., et al.
(författare)
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Incidence and outcome of myocardial infarction treated with percutaneous coronary intervention during COVID-19 pandemic
- 2020
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Ingår i: Heart. - : BMJ Publishing Group Ltd. - 1355-6037 .- 1468-201X. ; 106:23, s. 1812-1818
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Most reports on the declining incidence of myocardial infarction (MI) during the COVID-19 have either been anecdotal, survey results or geographically limited to areas with lockdowns. We examined the incidence of MI during the COVID-19 pandemic in Sweden, which has remained an open society with a different public health approach fighting COVID-19.METHODS: We assessed the incidence rate (IR) as well as the incidence rate ratios (IRRs) of all MI referred for coronary angiography in Sweden using the nationwide Swedish Coronary Angiography and Angioplasty Registry (SCAAR), during the COVID-19 pandemic in Sweden (1 March 2020-7 May 2020) in relation to the same days 2015-2019.RESULTS: A total of 2443 MIs were referred for coronary angiography during the COVID-19 pandemic resulting in an IR 36 MIs/day (204 MIs/100 000 per year) compared with 15 213 MIs during the reference period with an IR of 45 MIs/day (254 MIs/100 000 per year) resulting in IRR of 0.80, 95% CI (0.74 to 0.86), p<0.001. Results were consistent in all investigated patient subgroups, indicating no change in patient category seeking cardiac care. Kaplan-Meier event rates for 7-day case fatality were 439 (2.3%) compared with 37 (2.9%) (HR: 0.81, 95% CI (0.58 to 1.13), p=0.21). Time to percutaneous coronary intervention (PCI) was shorter during the pandemic and PCI was equally performed, indicating no change in quality of care during the pandemic.CONCLUSION: The COVID-19 pandemic has significantly reduced the incidence of MI referred for invasive treatment strategy. No differences in overall short-term case fatality or quality of care indicators were observed.
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| 23. |
- Mohammad, M. A., et al.
(författare)
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Trends in Clinical Practice and Outcomes After Percutaneous Coronary Intervention of Unprotected Left Main Coronary Artery
- 2022
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Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Background The use of percutaneous coronary intervention (PCI) to treat unprotected left main coronary artery disease has expanded rapidly in the past decade. We aimed to describe nationwide trends in clinical practice and outcomes after PCI for left main coronary artery disease. Methods and Results Patients (n=4085) enrolled in the SCAAR (Swedish Coronary Angiography and Angioplasty Registry) as undergoing PCI for left main coronary artery disease from 2005 to 2017 were included. A count regression model was used to analyze time-related differences in procedural characteristics. The 3-year major adverse cardiovascular and cerebrovascular event rate defined as death, myocardial infarction, stroke, and repeat revascularization was calculated with the Kaplan-Meier estimator and Cox proportional hazard model. The number of annual PCI procedures grew from 121 in 2005 to 589 in 2017 (389%). The increase was greater for men (479%) and individuals with diabetes (500%). Periprocedural complications occurred in 7.9%, decreasing from 10% to 6% during the study period. A major adverse cardiovascular and cerebrovascular event occurred in 35.7% of patients, falling from 45.6% to 23.9% (hazard ratio, 0.56; 95% CI, 0.41-0.78; P=0.001). Radial artery access rose from 21.5% to 74.2% and intracoronary diagnostic procedures from 14.0% to 53.3%. Use of bare-metal stents and first-generation drug-eluting stents fell from 19.0% and 71.9%, respectively, to 0, with use of new-generation drug-eluting stents increasing to 95.2%. Conclusions Recent changes in clinical practice relating to PCI for left main coronary artery disease are characterized by a 4-fold rise in procedures conducted, increased use of evidence-based adjunctive treatment strategies, intracoronary diagnostics, newer stents, and more favorable outcomes.
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| 24. |
- Mohammad, Moman A., et al.
(författare)
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Trends in Clinical Practice and Outcomes After Percutaneous Coronary Intervention of Unprotected Left Main Coronary Artery
- 2022
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Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The use of percutaneous coronary intervention (PCI) to treat unprotected left main coronary artery disease has expanded rapidly in the past decade. We aimed to describe nationwide trends in clinical practice and outcomes after PCI for left main coronary artery disease. METHODS AND RESULTS: Patients (n=4085) enrolled in the SCAAR (Swedish Coronary Angiography and Angioplasty Registry) as undergoing PCI for left main coronary artery disease from 2005 to 2017 were included. A count regression model was used to analyze time-related differences in procedural characteristics. The 3-year major adverse cardiovascular and cerebrovascular event rate defined as death, myocardial infarction, stroke, and repeat revascularization was calculated with the KaplanMeier estimator and Cox proportional hazard model. The number of annual PCI procedures grew from 121 in 2005 to 589 in 2017 (389%). The increase was greater for men (479%) and individuals with diabetes (500%). Periprocedural complications occurred in 7.9%, decreasing from 10% to 6% during the study period. A major adverse cardiovascular and cerebrovascular event occurred in 35.7% of patients, falling from 45.6% to 23.9% (hazard ratio, 0.56; 95% CI, 0.41–0.78; P=0.001). Radial artery access rose from 21.5% to 74.2% and intracoronary diagnostic procedures from 14.0% to 53.3%. Use of bare-metal stents and first-generation drug-eluting stents fell from 19.0% and 71.9%, respectively, to 0, with use of new-generation drugeluting stents increasing to 95.2%. CONCLUSIONS: Recent changes in clinical practice relating to PCI for left main coronary artery disease are characterized by a 4-fold rise in procedures conducted, increased use of evidence-based adjunctive treatment strategies, intracoronary diagnostics, newer stents, and more favorable outcomes.
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| 25. |
- Sarno, Giovanna, et al.
(författare)
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Morphological and functional evaluation of the bioresorption of the bioresorbable everolimus-eluting vascular scaffold using IVUS, echogenicity and vasomotion testing at two year follow-up : a patient level insight into the ABSORB A clinical trial
- 2012
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Ingår i: The international journal of cardiovascular imaging. - : Springer Science and Business Media LLC. - 1875-8312 .- 1569-5794 .- 1573-0743. ; 28:1, s. 51-58
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to describe vaso-reactivity (by Acetylcholine and Methergine tests) at 2 year follow-up in parallel with the individual changes in the echogenicity characteristics of the polymer struts of the everolimus eluting bioresorbable vascular scaffold (BVS), from post-treatment to 2 year follow-up, in patients enrolled in the ABSORB Cohort A study. Intravascular ultrasound assessment was performed with a phased array catheter (EagleEye, Volcano Corporation, Cordova, CA, USA) with automated pullback at 0.5 mm per second. The % ratio at 6 months and 2 years [(Scaffold Area post PCI- Lumen Area)/Scaffold Area post PCI] was calculated as a measure of scaffold shrinkage. The % change of hyperechogenicity was defined as: ([post-procedural hyperechogenicity] - [2 year follow up hyperechogenicity])/[post-procedural hyperechogenicity]) × 100. The vasomotion test with intracoronary acetylcholine (10(-6) M) or intravenous methergine (0.4 mg) was performed at 2 years. Overall nine patients received all these analyses and were enrolled in the present analysis. A 50-96% reduction in hyperechogenicity was observed between baseline and 2 years, which corresponded to a change in vasoreactivity between 2 and 22%. A vasoconstriction of the scaffolded segment was observed in the 5 patients, who underwent the methergine test, with a mean decrease in lumen diameter after methergine of 9 ± 7% (P = 0.06), while vasodilatation occurred in the 4 patients who underwent the acetylcholine test with a mean increase in lumen diameter after acetylcholine of 8 ± 5% (P = 0.125). Bioresorption of the BVS is accompanied by re-establishment of both endothelial and non-endothelial dependent vasomotion.
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| 26. |
- Shin, Eun-Seok, et al.
(författare)
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Reproducibility of Shin's method for necrotic core and calcium content in atherosclerotic coronary lesions treated with bioresorbable everolimus-eluting vascular scaffolds using volumetric intravascular ultrasound radiofrequency-based analysis
- 2012
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Ingår i: The international journal of cardiovascular imaging. - : Springer Science and Business Media LLC. - 1875-8312 .- 1569-5794 .- 1573-0743. ; 28:1, s. 43-49
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Tidskriftsartikel (refereegranskat)abstract
- Although Virtual Histology intravascular ultrasound (VH-IVUS) is increasingly used in clinical research, the reproducibility of plaque composition remains unexplored in significant coronary artery and stented lesions. The purpose of this study was to assess the reproducibility of necrotic core and calcium content in atherosclerotic coronary lesions that were treated with a bioresorbable everolimus-eluting vascular scaffold (BVS) using a new measurement method (Shin's method) by VH-IVUS. Eight patients treated with a BVS (Abbott Vascular, Santa Clara, CA, USA) were analyzed with serial VH-IVUS assessments, i.e., pre- and post-stenting, and at 6 months and 2 years follow-up. A total of 32 coronary segments were imaged to evaluate the reproducibility of volumetric VH-IVUS measurements. In Shin's method, contours are drawn around the IVUS catheter (instead of the lumen) and vessel. Overall, in the imaged coronary segment, for necrotic core and dense calcium volumes, the relative intra-observer differences were 0.30 ± 0.22, 0.19 ± 0.16% for observer 1 and 0.45 ± 0.41, 0.36 ± 0.47% for observer 2, respectively. The inter-observer relative differences of necrotic core and dense calcium volumes were 0.51 ± 0.79 and 0.56 ± 1.01%, respectively. The present study demonstrates a good reproducibility for both, intra-observer and inter-observer measurements using Shin's method. This method is suitable for the measurement of necrotic core and dense calcium using VH-IVUS in longitudinal studies, especially studies on bioresorbable scaffolds, because the degradation process will be fully captured independently of the location of the struts and their greyscale appearance.
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| 27. |
- Velders, Matthijs A., et al.
(författare)
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Prognosis of elderly patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention in 2001 to 2011 : a report from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) registry
- 2014
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Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 167:5, s. 666-673
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Elderly patients constitute a growing part of the population presenting with ST-elevation myocardial infarction (STEMI). The use of primary percutaneous coronary intervention (PCI) in this high-risk population remains poorly investigated.METHODS: Using the Swedish Coronary Angiography and Angioplasty Registry (SCAAR), we identified consecutive patients with STEMI 80 years or older undergoing primary PCI during a 10-year period. Temporal trends in care and 1-year prognosis were investigated, and long-term outcome was compared with a reference group of patients with STEMI aged 70 to 79 years. Relative survival was calculated by dividing the observed survival rate with the expected survival rate of the general population. Adjusted end points were calculated using Cox regression.RESULTS: In total, 4,876 elderly patients with STEMI were included. During the study period, average age and presence of comorbidity increased, as well as the use of antithrombotic therapy. Procedural success remained constant. One-year mortality was exclusively reduced between the most recent vs the earliest cohort, whereas the risk of reinfarction, heart failure, stroke, and bleeding remained similar. The risk of death was higher for elderly patients early after PCI, after which the prognosis was slightly better compared with the general population. Long-term risk of adverse events increased markedly with age.CONCLUSIONS: The prognosis of patients older than 80 years treated with primary PCI for STEMI was relatively unchanged during the 10-year inclusion period, despite changes in patient characteristics and treatment. Advanced age increased the risk of adverse events, but survivors of the early phase after PCI had a slightly improved prognosis compared with the general population.
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| 29. |
- Visnes, Torkild, et al.
(författare)
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Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation
- 2018
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 362:6416, s. 834-
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Tidskriftsartikel (refereegranskat)abstract
- The onset of inflammation is associated with reactive oxygen species and oxidative damage to macromolecules like 7,8-dihydro-8-oxoguanine (8-oxoG) in DNA. Because 8-oxoguanine DNA glycosylase 1 (OGG1) binds 8-oxoG and because Ogg1-deficient mice are resistant to acute and systemic inflammation, we hypothesized that OGG1 inhibition may represent a strategy for the prevention and treatment of inflammation. We developed TH5487, a selective active-site inhibitor of OGG1, which hampers OGG1 binding to and repair of 8-oxoG and which is well tolerated by mice. TH5487 prevents tumor necrosis factor-alpha-induced OGG1-DNA interactions at guanine-rich promoters of proinflammatory genes. This, in turn, decreases DNA occupancy of nuclear factor kappa B and proinflammatory gene expression, resulting in decreased immune cell recruitment to mouse lungs. Thus, we present a proof of concept that targeting oxidative DNA repair can alleviate inflammatory conditions in vivo.
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| 30. |
- Yndigegn, Troels, et al.
(författare)
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Long-term Safety of Revascularization Deferral Based on Instantaneous Wave-Free Ratio or Fractional Flow Reserve
- 2023
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Ingår i: Journal of the Society for Cardiovascular Angiography & Interventions. - : Elsevier. - 2772-9303. ; 2:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Deferral of coronary revascularization is safe whether guided by instantaneous wave-free ratio (iFR) or by fractional flow reserve (FFR). We aimed to assess long-term outcomes in patients deferred from revascularization based on iFR or FFR in a large real-world population.Methods: From 2013 through 2017, 201,933 coronary angiographies were registered in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART). We included all patients (n = 11,324) with at least 1 coronary lesion deferred from PCI during an index procedure using iFR (>0.89; n = 1998) or FFR (>0.80; n = 9326). The primary outcome was major adverse cardiac events (MACE) defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization. A multivariable-adjusted Cox proportional hazards model was used, with analysis for interaction of prespecified subgroups.Results: Patients presented with stable angina pectoris (iFR 46.9% vs FFR 48.6%), unstable angina or non–ST-elevation myocardial infarction (iFR 37.7% vs FFR 33.1%), ST-elevation myocardial infarction (iFR 1.9% vs FFR 1.6%), and other indications (iFR 12.5% vs FFR 15.7%). The median follow-up was 2 years for both iFR and FFR groups. At the conclusion of the study, the cumulative MACE risks were 26.7 for the iFR group and 25.9% for FFR group. In the adjusted analysis, no difference was found between the 2 groups (adjusted hazard ratio: iFR vs FFR, 0.947; 95% CI, 0.84-1.08; P = 39). Consistent with the overall findings, the prespecified subgroups showed no interaction with the FFR/iFR results.Conclusions: Deferral of revascularization showed similar long-term safety whether based on iFR or on FFR.
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