| 1. |
- Ashar, Foram N., et al.
(författare)
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A comprehensive evaluation of the genetic architecture of sudden cardiac arrest
- 2018
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 39:44, s. 3961-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Sudden cardiac arrest (SCA) accounts for 10% of adult mortality in Western populations. We aim to identify potential loci associated with SCA and to identify risk factors causally associated with SCA.Methods and results: We carried out a large genome-wide association study (GWAS) for SCA (n = 3939 cases, 25 989 non-cases) to examine common variation genome-wide and in candidate arrhythmia genes. We also exploited Mendelian randomization (MR) methods using cross-trait multi-variant genetic risk score associations (GRSA) to assess causal relationships of 18 risk factors with SCA. No variants were associated with SCA at genome-wide significance, nor were common variants in candidate arrhythmia genes associated with SCA at nominal significance. Using cross-trait GRSA, we established genetic correlation between SCA and (i) coronary artery disease (CAD) and traditional CAD risk factors (blood pressure, lipids, and diabetes), (ii) height and BMI, and (iii) electrical instability traits (QT and atrial fibrillation), suggesting aetiologic roles for these traits in SCA risk.Conclusions: Our findings show that a comprehensive approach to the genetic architecture of SCA can shed light on the determinants of a complex life-threatening condition with multiple influencing factors in the general population. The results of this genetic analysis, both positive and negative findings, have implications for evaluating the genetic architecture of patients with a family history of SCA, and for efforts to prevent SCA in high-risk populations and the general community.
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| 2. |
- Böhm, Felix, et al.
(författare)
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FFR-Guided Complete or Culprit-Only PCI in Patients with Myocardial Infarction
- 2024
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 390:16, s. 1481-1492
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The benefit of fractional flow reserve (FFR)-guided complete revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease remains unclear. METHODS: In this multinational, registry-based, randomized trial, we assigned patients with STEMI or very-high-risk non-STEMI (NSTEMI) and multivessel disease who were undergoing primary percutaneous coronary intervention (PCI) of the culprit lesion to receive either FFR-guided complete revascularization of nonculprit lesions or no further revascularization. The primary outcome was a composite of death from any cause, myocardial infarction, or unplanned revascularization. The two key secondary outcomes were a composite of death from any cause or myocardial infarction and unplanned revascularization. RESULTS: A total of 1542 patients underwent randomization, with 764 assigned to receive FFR-guided complete revascularization and 778 assigned to receive culprit-lesion-only PCI. At a median follow-up of 4.8 years (interquartile range, 4.3 to 5.2), a primary-outcome event had occurred in 145 patients (19.0%) in the complete-revascularization group and in 159 patients (20.4%) in the culprit-lesion-only group (hazard ratio, 0.93; 95% confidence interval [CI], 0.74 to 1.17; P = 0.53). With respect to the secondary outcomes, no apparent between-group differences were observed in the composite of death from any cause or myocardial infarction (hazard ratio, 1.12; 95% CI, 0.87 to 1.44) or unplanned revascularization (hazard ratio, 0.76; 95% CI, 0.56 to 1.04). There were no apparent between-group differences in safety outcomes. CONCLUSIONS: Among patients with STEMI or very-high-risk NSTEMI and multivessel coronary artery disease, FFR-guided complete revascularization was not shown to result in a lower risk of a composite of death from any cause, myocardial infarction, or unplanned revascularization than culprit-lesion-only PCI at 4.8 years. (Funded by the Swedish Research Council and others; FULL REVASC ClinicalTrials.gov number, NCT02862119.).
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| 3. |
- El Farissi, Mohamed, et al.
(författare)
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A randomised trial of selective intracoronary hypothermia during primary PCI
- 2024
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Ingår i: EuroIntervention. - : European Society of Cardiology. - 1774-024X .- 1969-6213. ; 20:12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: While experimental data suggest that selective intracoronary hypothermia decreases infarct size, studies in patients with ST-elevation myocardial infarction (STEMI) are lacking.AIMS: We investigated the efficacy of selective intracoronary hypothermia during primary percutaneous coronary intervention (PCI) to decrease infarct size in patients with STEMI.METHODS: In this multicentre randomised controlled trial, 200 patients with large anterior wall STEMI were randomised 1:1 to selective intracoronary hypothermia during primary PCI or primary PCI alone. Using an over-the-wire balloon catheter for infusion of cold saline and a pressure-temperature wire to monitor the intracoronary temperature, the anterior myocardium distal to the occlusion was selectively cooled to 30-33°C for 7-10 minutes before reperfusion (occlusion phase), immediately followed by 10 minutes of cooling after reperfusion (reperfusion phase). The primary endpoint was infarct size as a percentage of left ventricular mass on cardiovascular magnetic resonance imaging after 3 months.RESULTS: Selective intracoronary hypothermia was performed in 94/100 patients randomised to cooling. Distal coronary temperature decreased by 6°C within 43 seconds (interquartile range [IQR] 18-113). The median duration of the occlusion phase and reperfusion phase were 8.2 minutes (IQR 7.2-9.0) and 9.1 minutes (IQR 8.2-10.0), respectively. The infarct size at 3 months was 23.1±12.5% in the selective intracoronary hypothermia group and 21.6±12.2% in the primary PCI alone group (p=0.43). The left ventricular ejection fraction at 3 months in each group were 49.1±10.2% and 50.1±10.4%, respectively (p=0.53).CONCLUSIONS: Selective intracoronary hypothermia during primary PCI in patients with anterior wall STEMI was feasible and safe but did not decrease infarct size compared with standard primary PCI. (ClinicalTrials.gov: NCT03447834).
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| 4. |
- El Farissi, Mohamed, et al.
(författare)
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Safety of Selective Intracoronary Hypothermia During Primary Percutaneous Coronary Intervention in Patients With Anterior STEMI
- 2021
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Ingår i: JACC. - : Elsevier. - 1936-8798 .- 1876-7605. ; 14:18, s. 2047-2055
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this study was to determine the safety of selective intracoronary hypothermia during primary percutaneous coronary intervention (PPCI) in patients with anterior ST-segment elevation myocardial infarction (STEMI).BACKGROUND: Selective intracoronary hypothermia is a novel treatment designed to reduce myocardial reperfusion injury and is currently being investigated in the ongoing randomized controlled EURO-ICE (European Intracoronary Cooling Evaluation in Patients With ST-Elevation Myocardial Infarction) trial (NCT03447834). Data on the safety of such a procedure during PPCI are still limited.METHODS: The first 50 patients with anterior STEMI treated with selective intracoronary hypothermia during PPCI were included in this analysis and compared for safety with the first 50 patients randomized to the control group undergoing standard PPCI. In-hospital mortality, occurrence of rhythm or conduction disturbances, stent thrombosis, onset of heart failure during the procedure, and subsequent hospital admission were assessed.RESULTS: In-hospital mortality was 0%. One patient in both groups developed cardiogenic shock. Atrial fibrillation occurred in 0 and 3 patients (P = 0.24), and ventricular fibrillation occurred in 5 and 3 patients (P = 0.72) in the intracoronary hypothermia group and control group, respectively. Stent thrombosis occurred in 2 patients in the intracoronary hypothermia group; 1 instance was intraprocedural, and the other occurred following interruption of dual-antiplatelet therapy consequent to an intracranial hemorrhage 6 days after enrollment. No stent thrombosis was observed in the control group (P = 0.50).CONCLUSIONS: Selective intracoronary hypothermia during PPCI in patients with anterior STEMI can be implemented within the routine of PPCI and seems to be safe. The final safety results will be reported at the end of the trial.
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| 5. |
- Gaziano, Liam, et al.
(författare)
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Mild-to-moderate kidney dysfunction and cardiovascular disease : Observational and mendelian randomization analyses
- 2022
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 146:20, s. 1507-1517
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke.METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank.RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD.CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.
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| 6. |
- Glinge, Charlotte, et al.
(författare)
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Seasonality of ventricular fibrillation at first myocardial infarction and association with viral exposure
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:2
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Tidskriftsartikel (refereegranskat)abstract
- Aims To investigate seasonality and association of increased enterovirus and influenza activity in the community with ventricular fibrillation (VF) risk during first ST-elevation myocardial infarction (STEMI). Methods This study comprised all consecutive patients with first STEMI (n = 4,659; aged 18–80 years) admitted to the invasive catheterization laboratory between 2010–2016, at Copenhagen University Hospital, Rigshospitalet, covering eastern Denmark (2.6 million inhabitants, 45% of the Danish population). Hospital admission, prescription, and vital status data were assessed using Danish nationwide registries. We utilized monthly/weekly surveillance data for enterovirus and influenza from the Danish National Microbiology Database (2010–2016) that receives copies of laboratory tests from all Danish departments of clinical microbiology. Results Of the 4,659 consecutively enrolled STEMI patients, 581 (12%) had VF before primary percutaneous coronary intervention. In a subset (n = 807), we found that VF patients experienced more generalized fatigue and flu-like symptoms within 7 days before STEMI compared with the patients without VF (OR 3.39, 95% CI 1.76–6.54). During the study period, 2,704 individuals were diagnosed with enterovirus and 19,742 with influenza. No significant association between enterovirus and VF (OR 1.00, 95% CI 0.99–1.02), influenza and VF (OR 1.00, 95% CI 1.00–1.00), or week number and VF (p-value 0.94 for enterovirus and 0.89 for influenza) was found. Conclusion We found no clear seasonality of VF during first STEMI. Even though VF patients had experienced more generalized fatigue and flu-like symptoms within 7 days before STEMI compared with patients without VF, no relationship was found between enterovirus or influenza exposure and occurrence of VF.
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| 7. |
- Laursen, Peter Nørkjær, et al.
(författare)
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Comparison between patients included in randomized controlled trials of ischemic heart disease and real-world data. A nationwide study
- 2018
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703. ; 204, s. 128-138
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Tidskriftsartikel (refereegranskat)abstract
- Background: The objective was to compare patients with ischemic heart disease (IHD) undergoing percutaneous coronary intervention (PCI) who were included in randomized controlled trials (RCTs) (trial participants) with patients who were not included (nonparticipants) on a trial-by-trial basis and according to indication for PCI. Methods: In this cohort study, we compared patients with IHD who were randomized in RCTs in relation to undergoing PCI in Denmark between 2011 and 2015 were considered as RCT-participants in this study. The RCT-participants were compared with contemporary nonparticipants with IHD undergoing PCI in the same period, and they were identified using unselected national registry data. The primary end point was all-cause mortality. Results: A total of 10,317 (30%) patients were included in 10 relevant RCTs (trial participants), and a total of 23,644 (70%) contemporary patients did not participate (nonparticipants). In all the included RCTs, nonparticipants had higher hazard ratios for mortality compared to trial participants (P <.001). Among all patients treated with PCI, the pooled estimates showed a significantly higher mortality rate for nonparticipants compared to trial participants (hazard ratio: 2.03, 95% CI: 1.88-2.19) (P <.001). When patients were stratified according to indication for PCI, the pooled estimates showed a significantly lower mortality rate for trial participants compared to nonparticipants in all strata (P for all <.001). Conclusions: Trial participants in recently performed RCTs including patients undergoing PCI were not representative of the general population of patients with IHD treated with PCI according to clinical characteristics and mortality. The difference in mortality was found irrespective of the indication for PCI. Thus, results from RCTs including patients undergoing PCI should be extrapolated with caution to the general patient population.
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| 8. |
- Laursen, Peter Nørkjær, et al.
(författare)
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Unreported exclusion and sampling bias in interpretation of randomized controlled trials in patients with STEMI
- 2019
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 289, s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To assess the impact of sampling bias due to reported as well as unreported exclusion of the target population in a multi-center randomized controlled trial (RCT)of ST-elevation myocardial infarction (STEMI). Methods and Results: We compared clinical characteristics and mortality between participants in the DANAMI-3 trial to contemporary non-participants with STEMI using unselected registries. A total of 179 DANAMI-3 participants (8%)and 617 contemporary non-participants (22%)had died (Log-Rank: P < 0.001)after a median follow-up of 1333 days (range: 1–2021 days). In an unadjusted Cox regression model all groups of non-participants had a higher hazard ratio to predict mortality compared to participants: eligible excluded (n = 144)(hazard ratio: 3.41 (95% CI: (2.69–4.32)), ineligible excluded (n = 472)(hazard ratio: 3.42 (95% CI: (2.44–4.80), eligible non-screened (n = 154)(hazard ratio: 3.37 (95% CI: (2.36–4.82)), ineligible non-screened (n = 154)(hazard ratio: 6.48 (95% CI: (4.77–8.80). Conclusion: Sampling bias had occurred due to both reported and unreported exclusion of eligible patients and the difference in mortality between participants and non-participants could not be explained only by the trial exclusion criteria. Thus, screening logs may not be suited to address the risks of sampling bias.
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| 9. |
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| 10. |
- Akhtar, Zubair, et al.
(författare)
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Optimal timing of influenza vaccination among patients with acute myocardial infarction - Findings from the IAMI trial
- 2023
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Ingår i: Vaccine. - : Elsevier. - 0264-410X .- 1873-2518. ; 41:48, s. 7159-7165
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Tidskriftsartikel (refereegranskat)abstract
- Influenza vaccination reduces the risk of adverse cardiovascular events. The IAMI trial randomly assigned 2571 patients with acute myocardial infarction (AMI) to receive influenza vaccine or saline placebo during their index hospital admission. It was conducted at 30 centers in 8 countries from October 1, 2016 to March 1, 2020. In this post-hoc exploratory sub-study, we compare the trial outcomes in patients receiving early season vaccination (n = 1188) and late season vaccination (n = 1344). The primary endpoint was the composite of all-cause death, myocardial infarction (MI), or stent thrombosis at 12 months. The cumulative incidence of the primary and key secondary endpoints by randomized treatment and early or late vaccination was estimated using the Kaplan-Meier method. In the early vaccinated group, the primary composite endpoint occurred in 36 participants (6.0%) assigned to influenza vaccine and 49 (8.4%) assigned to placebo (HR 0.69; 95% CI 0.45 to 1.07), compared to 31 participants (4.7%) assigned to influenza vaccine and 42 (6.2%) assigned to placebo (HR 0.74; 95% CI 0.47 to 1.18) in the late vaccinated group (P = 0.848 for interaction on HR scale at 1 year). We observed similar estimates for the key secondary endpoints of all-cause death and CV death. There was no statistically significant difference in vaccine effectiveness against adverse cardiovascular events by timing of vaccination. The effect of vaccination on all-cause death at one year was more pronounced in the group receiving early vaccination (HR 0.50; 95% CI, 0.29 to 0.86) compared late vaccination group (HR 0.75; 35% CI, 0.40 to 1.40) but there was no statistically significant difference between these groups (Interaction P = 0.335). In conclusion, there is insufficient evidence from the trial to establish whether there is a difference in efficacy between early and late vaccination but regardless of vaccination timing we strongly recommend influenza vaccination in all patients with cardiovascular diseases.
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| 11. |
- Ali, Imran, et al.
(författare)
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Associations between cadmium exposure and circulating levels of sex hormones in postmenopausal women.
- 2014
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Ingår i: Environmental Research. - : Elsevier BV. - 1096-0953 .- 0013-9351. ; 134, s. 265-269
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Tidskriftsartikel (refereegranskat)abstract
- Recent epidemiological as well as in vivo and in vitro studies collectively suggest that the metalloestrogen cadmium (Cd) could be a potential risk factor for hormone-related cancers in particularly breast cancer. Assessment of the association between Cd exposure and levels of endogenous sex hormones is of pivotal importance, as increased levels of such have been associated with a higher risk of breast cancer in postmenopausal women. The present study investigated the perceived relationship (multivariable-adjusted linear regression analyses) between Cd exposure [blood Cd (B-Cd) and urinary Cd (U-Cd)], and serum levels of androstenedione, testosterone, estradiol, and sex-hormone binding globulin (SHBG), in 438 postmenopausal Swedish women without hormone replacement therapy (HRT). A significant positive association between B-Cd (median 3.4nmol/L) and serum testosterone levels, as well as a significant inverse association between B-Cd and serum estradiol levels and with the estradiol/testosterone ratio were encountered. However, U-Cd (median 0.69nmol/mmol creatinine) was inversely associated with serum estradiol levels only. Our data may suggest that Cd interferes with the levels of testosterone and estradiol in postmenopausal women, which might have implications for breast cancer risk.
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| 12. |
- Alzuhairi, Karam Sadoon, et al.
(författare)
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Sub-acute cardiac magnetic resonance to predict irreversible reduction in left ventricular ejection fraction after ST-segment elevation myocardial infarction : A DANAMI-3 sub-study
- 2020
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 301, s. 215-219
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To predict irreversible reduction in left ventricular ejection fraction (LVEF) during admission for ST-segment elevation myocardial infarction (STEMI) using cardiac magnetic resonance (CMR) in addition to classical clinical parameters. Irreversible reduction in LVEF is an important prognostic factor after STEMI which necessitates medical therapy and implantation of prophylactic implantable cardioverter defibrillator (ICD). Methods and results: A post-hoc analysis of DANAMI-3 trial program (Third DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction) which recruited 649 patients who had CMR performed during index hospitalization and after 3 months. Patients were divided into two groups according to CMR-LVEF at 3 months: Group 1 with LVEF≤35% and Group 2 with LVEF>35%. Group 1 included 15 patients (2.3%) while Group 2 included 634 patients (97.7%). A multivariate analysis showed that: Killip class >1 (OR 7.39; CI:1.47–36.21, P = 0.01), symptom onset-to-wire ≥6 h (OR 7.19; CI 1.07–50.91, P = 0.04), LVEF≤35% using index echocardiography (OR 7.11; CI: 1.27–47.43, P = 0.03), and infarct size ≥40% of LV on index CMR (OR 42.62; CI:7.83–328.29, P < 0.001) independently correlated with a final LVEF≤35%. Clinical models consisted of these parameters could identify 7 out of 15 patients in Group 1 with 100% positive predictive value. Conclusion: Together with other clinical measurements, the assessment of infarct size using late Gadolinium enhancement by CMR during hospitalization is a strong predictor of irreversible reduction in CMR_LVEF ≤35. That could potentially, after validation with future research, aids the selection and treatment of high-risk patients after STEMI, including implantation of prophylactic ICD during index hospitalization.
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| 13. |
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| 14. |
- Andersson, Thomas K., et al.
(författare)
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Perceptions of Experiences of Recovery After Pancreaticoduodenectomy-A Phenomenographic Interview Study
- 2022
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Ingår i: Cancer Nursing. - : Ovid Technologies (Wolters Kluwer Health). - 0162-220X .- 1538-9804. ; 45:3, s. 172-180
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Tidskriftsartikel (refereegranskat)abstract
- Background Pancreatic surgery in the context of enhanced recovery has mainly been evaluated using clinical variables. However, there is limited knowledge about patients' perceptions of recovery in this context. Hence, the aim of this study was to explore patients' perceptions of recovery after pancreatic surgery within an enhanced recovery program. Objective To explore the variations in patients' perceptions, a qualitatively designed study was undertaken. Methods Data in this phenomenographic study consisted of interviews with 19 patients at 4 to 6 weeks after surgery. Results Recovery after pancreatic surgery was classified into 5 categories, based on patients' perceptions: to be as before, affected by symptoms, physical activity, understanding the process, and facilitated by other people. Conclusion The study focused on various areas of recovery, which took place between the in-hospital and after-discharge phases. Physical experiences were found to disturb recovery, in contrast to social and emotional experiences, which facilitated recovery. Variations in perceptions of recovery suggest that care may need to be more individualized, both in the preoperative and the postoperative phase. Working with realistic expectations and early patient education might better prepare patients to continue working on their own recovery after discharge from the hospital. Implications for Practice Major cancer surgery needs to be perceived as a personal journey for the patient, even in enhanced recovery program care. Preoperative education is good, but adding continuous and individually adopted education during recovery is better. Knowledge about both hindering and facilitating factors for recovery is important for the healthcare personal.
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| 15. |
- Antonsson, Åsa, 1972-
(författare)
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Regulation of NF-κB by Calmodulin
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cells experience numerous external signals which they must respond to. Such signals arriving at the cell surface are transduced via various signal transduction pathways and often ultimately result in regulation of transcription. NF-κB is a family of transcription factors involved in the regulation of genes important for processes such as immune and inflammatory responses, cell growth, development and cell survival. NF-κB proteins are normally kept inactive in the cytoplasm due to masking of their nuclear localisation signal (NLS) by inhibitory IκB proteins. A large number of stimuli lead to the activation of IκB-kinase (IKK). Active IKK phosphorylates IκB and thereby labels it for ubiquitination and, subsequently, degradation by the proteasome. Liberated NF-κB enters the nucleus, where it takes part in the regulation of its target genes.Calmodulin (CaM) is a ubiquitous Ca2+-binding protein which is considered to be the predominant intracellular Ca2+ sensor. CaM plays a major role in the Ca2+-dependent regulation of a wide variety of cellular processes, including transcription. CaM regulates transcription both indirectly through CaM-dependent kinases and phosphatases and directly through interaction with transcription factors.CaM was found to bind directly and in a Ca2+-dependent fashion to the two NF-κB family members c-Rel and RelA. The CaM-NF-κB interactions were strongly enhanced by NF-κB activating stimuli and this enhancement was blocked by the addition of IκB, suggesting that c-Rel and RelA can bind CaM after their signal-induced release from IκB. Compared to wild-type c-Rel, CaM binding-deficient mutants were shown to exhibit an increased nuclear accumulation and transcriptional activity on Ca2+-regulated cytokine promoters. The results suggest that CaM can inhibit transport of c-Rel, but not of RelA, to the nucleus and thereby differentially regulate the activation of NF-κB proteins following cell stimulation. CaM was also found to affect NF-κB activity indirectly through the action of a CaM-dependent kinase (CaMK). Studies of the events leading to IκBα phosphorylation revealed that CaM and CaMKII inhibitors blocked phorbol ester induced activation of IKK. Furthermore, CaM and CaMKII inhibitors also blocked T cell receptor/CD3 induced IκBα degradation, and expression of an inhibitor-resistant derivative of the γ isoform of CaMKII caused the inhibitors lose their effect on phorbol ester induced IκBα degradation. Finally, expression of a constitutively active CaMKII resulted in the activation of NF-κB. These results identify CaMKII as a mediator of IKK activation, specifically in response to T cell receptor/CD3 and phorbol ester stimulation.In conclusion, this thesis describes the identification of CaM as a dual regulator of NF-κB proteins, acting both directly and indirectly to affect the activity of this family of transcription factors.
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| 16. |
- Axelsson, Sara, et al.
(författare)
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Prednisolone in Bell's Palsy Related to Treatment Start and Age
- 2011
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Ingår i: Otology and Neurotology. - 1531-7129 .- 1537-4505. ; 32:1, s. 141-146
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate if treatment start and age are related to the outcome in Bell's palsy patients treated with prednisolone. Study Design: Prospective, randomized, double-blind, placebo-controlled, multicenter trial. Setting: Sixteen otorhinolaryngologic centers in Sweden and 1 in Finland. Patients: Data were collected from the Scandinavian Bell's palsy study. A total of 829 patients were treated within 72 hours of onset of palsy. Follow-up was 12 months. Intervention: Patients were randomly assigned to treatment with placebo plus placebo (n = 206), prednisolone plus placebo (n = 210), valacyclovir plus placebo (n = 207), or prednisolone plus valacyclovir (n = 206). Main Outcome Measures: Facial function was assessed with the Sunnybrook grading system, and complete recovery was defined as Sunnybrook = 100. Time from onset of palsy to treatment start was registered. Results: Patients treated with prednisolone within 24 hours and 25 to 48 hours had significantly higher complete recovery rates, 66% (103/156) and 76% (128/168), than patients given no prednisolone, 51% (77/152) and 58% (102/177) (p = 0.008 and p = 0.0003, respectively). For patients treated within 49 to 72 hours of palsy onset, there were no significant differences. Patients aged 40 years or older had significantly higher complete recovery rates if treated with prednisolone, whereas patients aged younger than 40 years did not differ with respect to prednisolone treatment. However, synkinesis was significantly less in patients younger than 40 years given prednisolone (p = 0.002). Conclusion: Treatment with prednisolone within 48 hours of onset of palsy resulted in significantly higher complete recovery rates and less synkinesis compared with no prednisolone.
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| 17. |
- Ay, Hakan, et al.
(författare)
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Pathogenic Ischemic Stroke Phenotypes in the NINDS-Stroke Genetics Network
- 2014
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Ingår i: Stroke. - 0039-2499. ; 45:12, s. 3589-3596
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: NINDS (National Institute of Neurological Disorders and Stroke)-SiGN (Stroke Genetics Network) is an international consortium of ischemic stroke studies that aims to generate high-quality phenotype data to identify the genetic basis of pathogenic stroke subtypes. This analysis characterizes the etiopathogenetic basis of ischemic stroke and reliability of stroke classification in the consortium. METHODS: Fifty-two trained and certified adjudicators determined both phenotypic (abnormal test findings categorized in major pathogenic groups without weighting toward the most likely cause) and causative ischemic stroke subtypes in 16954 subjects with imaging-confirmed ischemic stroke from 12 US studies and 11 studies from 8 European countries using the web-based Causative Classification of Stroke System. Classification reliability was assessed with blinded readjudication of 1509 randomly selected cases. RESULTS: The distribution of pathogenic categories varied by study, age, sex, and race (P<0.001 for each). Overall, only 40% to 54% of cases with a given major ischemic stroke pathogenesis (phenotypic subtype) were classified into the same final causative category with high confidence. There was good agreement for both causative (κ 0.72; 95% confidence interval, 0.69-0.75) and phenotypic classifications (κ 0.73; 95% confidence interval, 0.70-0.75). CONCLUSIONS: This study demonstrates that pathogenic subtypes can be determined with good reliability in studies that include investigators with different expertise and background, institutions with different stroke evaluation protocols and geographic location, and patient populations with different epidemiological characteristics. The discordance between phenotypic and causative stroke subtypes highlights the fact that the presence of an abnormality in a patient with stroke does not necessarily mean that it is the cause of stroke.
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| 18. |
- Barregård, Lars, 1948, et al.
(författare)
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Cadmium Exposure and Coronary Artery Atherosclerosis: A Cross-Sectional Population-Based Study of Swedish Middle-Aged Adults
- 2021
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Ingår i: Environmental health perspectives. - 1552-9924 .- 0091-6765. ; 129:6
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Tidskriftsartikel (refereegranskat)abstract
- The general population is ubiquitously exposed to the toxic metal cadmium through the diet and smoking. Cadmium exposure is associated with increased morbidity and mortality in myocardial infarction and stroke. Atherosclerosis is the main underlying mechanism of myocardial infarction. However, associations between cadmium and coronary artery atherosclerosis have not been examined.Our study sought to examine the hypothesis that blood cadmium (B-Cd) is positively associated with coronary artery calcification, as a measure of coronary artery atherosclerosis in the population-based Swedish SCAPIS study.Our analysis included 5,627 individuals (51% women), age 50-64 y, enrolled from 2013 to 2018. The coronary artery calcium score (CACS) was obtained from computed tomography. Blood cadmium was determined by inductively coupled plasma mass spectrometry (ICP-MS). Associations between B-Cd and coronary artery calcium score (CACS Agatston score) were evaluated using prevalence ratios (PRs) in models adjusted for sex, age, smoking, hypertension, diabetes, low-density cholesterol/high-density cholesterol ratio, and family history.The median B-Cd concentration was 0.24 μ g / L . The prevalence of positive coronary artery calcium ( CACS > 0 ) was 41% and the prevalence of CACS ≥ 100 was 13%. Relative to the lowest quartile (Q) of B-Cd ( < 0.16 μ g / L ), the highest quartile (median 0.63 μ g / L ) was associated with a small but significant increase in CACS > 0 (PR 1.1; 95% CI: 1.0, 1.3), and a greater relative increase in CACS ≥ 100 (PR 1.6; 95% CI: 1.3, 2.0). When restricted to 2,446 never-smokers, corresponding PRs were 1.1 (95% CI 0.9, 1.3) for CACS > 0 (63 cases in Q4) and 1.7 (95% CI 1.1, 2.7) for CACS ≥ 100 (17 cases in Q4).Blood cadmium in the highest quartile was associated with CACS in a general population sample with low to moderate cadmium exposure. This supports the hypothesis that atherosclerosis is an important mechanism underlying the associations between cadmium and incident cardiovascular disease. The findings suggest that public health measures to reduce cadmium exposure are warranted. https://doi.org/10.1289/EHP8523.
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| 19. |
- Baykal, Yunus, et al.
(författare)
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Detrital zircon U–Pb age analysis of last glacial loess sources and proglacial sediment dynamics in the Northern European Plain
- 2021
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Ingår i: Quaternary Science Reviews. - : Elsevier. - 0277-3791 .- 1873-457X. ; 274
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Tidskriftsartikel (refereegranskat)abstract
- Loess deposits along the northern fringe of the European loess belt potentially record past changes in dust emission from areas proximal to former ice sheets. Recent chronologies from loess deposits across this region generally agree on greatly enhanced dust deposition rates when the Fennoscandian Ice Sheet reached its maximum extent during the late last glacial. However, uncertainties over the material's source and origin limit understanding of the causes of this enhanced dust activity. In particular, loess in southwestern Poland has been attributed to multiple origins, mainly involving glaciofluvial outwash plains along the Fennoscandian Ice Sheet margin and/or local sources in the mountainous areas of the Sudetes and Western Carpathians. Here we apply detrital zircon U–Pb age analyses for a large number of grains recovered from four loess samples taken from different stratigraphic units exposed at Biały Kościół in southwestern Poland, previously luminescence dated to MIS 4–2, to assess loess provenance as well as its temporal evolution during last glacial Fennoscandian Ice Sheet fluctuations. Furthermore, we analysed the detrital zircon U–Pb age spectra of five samples from potential source sediments to constrain the history of sediment recycling and mixing within the Northern European Plain prior to deflation and loess deposition. The broad range of zircon age components detected in the four loess samples suggests both Fennoscandian and closer Peri-Gondwanan proto-sources while a narrow, dominant Carboniferous age peak is consistent with sourcing from the local Strzelin Hills in the Sudetic foreland. However, the presence of both Fennoscandian and Peri-Gondwanan derived grains in samples from potential source sediments reveals that this mixture of sediment sources is widespread across the Northern European Plain, as a result of long-term glacial and fluvial reworking of cover sediments in the proglacial area throughout the Quaternary. Local rivers draining the Sudetic foreland transported this Fennoscandian-Peri-Gondwanan sediment mixture along with particles denuded from the Strzelin Hills, resulting in a nearby, temporally stable dust source for the Biały Kościół loess during MIS 4–2, while dust emission rates were substantially increased during the last glacial maximum. Given that our model for loess formation at Biały Kościół essentially involves sediment distribution via rivers prior to short distance aeolian transport, we infer that the proportion of northern ice sheet derived particles in European loess deposits is mainly controlled by the drainage pattern of major rivers in relation to Pleistocene ice margins where glaciofluvial sediment is abundant. Based on the presence of Fennoscandian derived zircon grains in European loess deposits, we constrain a southern limit of the influence of northern ice sheet dust sources along the central European highlands that currently divide drainage between the Northern European Plain and the Danube Basins.
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| 20. |
- Berg, Thomas, et al.
(författare)
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Agreement between the Sunnybrook, House-Brackmann, and Yanagihara facial nerve grading systems in Bell´s Palsy
- 2004
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Ingår i: Otology and Neurotology. - 1531-7129 .- 1537-4505. ; 25:6, s. 1020-1026
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the agreement between the Sunnybrook facial nerve grading system and the House-Brackmann and Yanagihara systems. STUDY DESIGN: Prospective clinical facial nerve grading. SETTING: Tertiary referral center. PATIENTS: One-hundred assessments, 94 in patients with Bell's palsy and 6 with herpes zoster. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: Evaluation according to the weighted regional Sunnybrook system, the gross House-Brackmann system, and the unweighted regional Yanagihara system. Weighted kappa statistics was used to measure agreement between the grading systems. RESULTS: The average weighted kappa value between the Sunny-brook, House-Brackmann, and Yanagihara grading systems was 0.65; kappa values increased temporally (but not statistically significantly) up to day 180. The highest agreement value, 0.72, was found between the Sunnybrook and Yanagihara grading systems. The weighted kappa value between the Sunnybrook and House-Brackmann systems was 0.59. In Sunnybrook gradings less than 63, there was an overlap between House-Brackmann scores of III to VI. Reliable conversion tables between the gross House-Brackmann system and the regional Sunnybrook and Yanagihara systems could not be established. CONCLUSION: The Sunnybrook system scores at the same agreement level as the House-Brackmann and Yanagihara grading systems. There is an evaluative difference between the weighted regional Sunnybrook and the gross House-Brackmann systems. Substantial agreement was found between the regional Sunnybrook and Yanagihara scales. Sunnybrook grading is easy and quick. By adding objective measurements and additional secondary defects, the Sunnybrook system can be an alternative to the other predominating grading systems.
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| 21. |
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| 22. |
- Berg, Thomas, et al.
(författare)
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Bells pares ger resttillstånd hos 30 procent av vuxna patienter - Tidig behandling med kortison ökar utläkningen.
- 2015
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Ingår i: Läkartidningen. - 0023-7205. ; 112
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Tidskriftsartikel (refereegranskat)abstract
- Bell's palsy is an acute unilateral weakness or paralysis of the face of unknown cause. The incidence of the disease is 30 individuals per 100,000 per year. It is a diagnosis of exclusion and other known causes for acute peripheral facial palsy must be ruled out. The prognosis is overall favorable and about 70% of the patients recover completely within 6 months without treatment. Recent randomized controlled Bell's palsy trials have shown that treatment with corticosteroids shortens time to recovery and improves recovery rates while antiviral treatment alone is not more effective than placebo. The combination of corticosteroids and antivirals has not been proven more effective than corticosteroids alone. We present an update of Bell's palsy in adults with focus on diagnosis, treatment and follow-up of these patients.
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| 23. |
- Berg, Thomas, 1975-
(författare)
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Medical Treatment and Grading of Bell's Palsy
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main aim of this thesis was to evaluate the effect of prednisolone and valaciclovir in a large number of Bell's palsy patients. The incidence and intensity of pain around the ear, in the face or in the neck during the first two months of palsy, and its prognostic value, was also assessed. We also investigated how study design and choice of analysis method affect the rate of facial recovery. Furthermore, the agreement between the Sunnybrook, House-Brackmann and Yanagihara facial grading systems was evaluated. From May 2001 to September 2007, a prospective, randomised, double-blind, placebo-controlled, multicentre trial with 12-month follow-up was performed in patients with Bell's palsy. Of 839 randomised patients, 829 were included in the intention-to-treat analysis; 206 received placebo plus placebo, 210 prednisolone plus placebo, 207 valaciclovir plus placebo, and 206 prednisolone plus valaciclovir. Time to recovery was significantly shorter in the 416 patients who received prednisolone compared with the 413 who did not (p<0.0001). At 12 months, 300 of 416 patients (72%) in the prednisolone group had recovered compared with 237 of 413 patients (57%) in the no prednisolone group (p<0.0001). Valaciclovir was not found to affect time to facial recovery or outcome at 12 months. Prednisolone and/or valaciclovir did not affect the incidence or intensity of pain. Presence of pain at day 11 to 17 indicated a worse prognosis for facial recovery at 12 months. We also found that recovery rates in a Bell's palsy trial are substantially affected by the choice of analysis method and definition of facial recovery. We used weighted Kappa statistics in 100 examinations of patients with facial palsy to assess the agreement between the Sunnybrook, House-Brackmann and Yanagihara scales. The highest agreement was found between the regional Sunnybrook and Yanagihara scales. An evaluative difference between the Sunnybrook and House-Brackmann systems was observed.
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| 24. |
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| 25. |
- Berg, Thomas, et al.
(författare)
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The Course of Pain in Bell's Palsy : Treatment With Prednisolone and Valacyclovir
- 2009
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Ingår i: Otology and Neurotology. - 1531-7129 .- 1537-4505. ; 30:6, s. 842-846
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the effect of prednisolone and valacyclovir on ipsilateral pain around the ear and in the face or neck in Bell's palsy. The incidence and intensity of pain during the first 2 months of palsy and its prognostic value were also assessed. Study Design: Prospective, randomized, double-blind, placebo-controlled, multicenter trial. Setting: Sixteen tertiary referral centers in Sweden and 1 in Finland. Patients: Data are part of the Scandinavian Bell's palsy study; 829 patients aged 18 to 75 years with onset of palsy within 72 hours were included. Follow-up time was 12 months. Intervention: Patients were assigned to 1 of 4 treatment arms in a factorial fashion: placebo plus placebo; prednisolone 60 mg daily for 5 days, then tapering for 5 days, plus placebo; valacyclovir 1,000 mg 3 times daily for 7 days plus placebo; or prednisolone plus valacyclovir. Main Outcome Measures: Pain was registered on a visual analog scale within 72 hours, at Days 11 to 17, 1 month, and 2 months. Facial function was assessed with the Sunnybrook and House-Brackmann systems. Results: Prednisolone and/or valacyclovir did not significantly affect the incidence or intensity of pain during the first 2 months. Pain was registered in 542 (65%) of 829 patients. At 2 months, 53 (8%) of 637 patients still reported pain. Subjects with pain at Days 11 to 17 had lower facial recovery rates at 12 months than those with no pain (p < 0.0001). Conclusion: Prednisolone and/or valacyclovir did not affect the incidence or intensity of ipsilateral pain in Bell's palsy. The incidence of pain was similar during the first 2 weeks and then decreased. Presence of pain at Days 11 to 17 indicated a worse prognosis for facial recovery.
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