| 1. |
- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 2. |
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| 3. |
- Braun, Oscar Ö., et al.
(författare)
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Continuous-flow LVADs in the Nordic countries : complications and mortality and its predictors
- 2019
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Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 53:1, s. 14-20
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The purpose of this study was to assess complications and mortality and its predictors, with continuous-flow left ventricular assist devices (CF-LVADs) in the Nordic Countries.Design: This was a retrospective, international, multicenter cohort study.Results: Between 1993 and 2013, 442 surgically implanted long-term mechanical assist devices were used among 8 centers in the Nordic countries. Of those, 238 were CF-LVADs (HVAD or HeartMate II) implanted in patients >18 years with complete data. Postoperative complications and survival were compared and Cox proportion hazard regression analysis was used to identify predictors of mortality. The overall Kaplan-Meier survival rate was 75% at 1 year, 69% at 2 years and 63% at 3 years. A planned strategy of destination therapy had poorer survival compared to a strategy of bridge to transplantation or decision (2-year survival of 41% vs. 76%, p < .001). The most common complications were non-driveline infections (excluding sepsis) (44%), driveline infection (27%), need for continuous renal replacement therapy (25%) and right heart failure (24%). In a multivariate model age and left ventricular diastolic dimension was left as independent risk factors for mortality with a hazard ratio of 1.35 (95% confidence interval (CI) [1.01-1.80], p = .046) per 10 years and 0.88 (95% CI [0.72-0.99], p = .044) per 5 mm, respectively.Conclusion: Outcome with CF LVAD in the Nordic countries was comparable to other cohorts. Higher age and destination therapy require particularly stringent selection.
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| 5. |
- Cakir, B., et al.
(författare)
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Thrombocytopenia is associated with severe retinopathy of prematurity
- 2018
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Ingår i: Jci Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 3:19
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Tidskriftsartikel (refereegranskat)abstract
- Retinopathy of prematurity (ROP) is characterized by abnormal retinal neovascularization in response to vessel loss. Platelets regulate angiogenesis and may influence ROP progression. In preterm infants, we assessed ROP and correlated with longitudinal postnatal platelet counts (n = 202). Any episode of thrombocytopenia (< 100 x 10(9)/l) at >= 30 weeks postmenstrual age (at onset of ROP) was independently associated with severe ROP, requiring treatment. Infants with severe ROP also had a lower weekly median platelet count compared with infants with less severe ROP. In a mouse oxygen-induced retinopathy model of ROP, platelet counts were lower at P17 (peak neovascularization) versus controls. Platelet transfusions at P15 and P16 suppressed neovascularization, and platelet depletion increased neovascularization. Platelet transfusion decreased retinal of vascular endothelial growth factor A (VEGFA) mRNA and protein expression; platelet depletion increased retinal VEGFA mRNA and protein expression. Resting platelets with intact granules reduced neovascularization, while thrombin-activated degranulated platelets did not. These data suggest that platelet releasate has a local antiangiogenic effect on endothelial cells to exert a downstream suppression of VEGFA in neural retina. Low platelet counts during the neovascularization phase in ROP is significantly associated with the development of severe ROP in preterm infants. In a murine model of retinopathy, platelet transfusion during the period of neovascularization suppressed retinopathy.
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| 6. |
- Chapman, Joanne R., et al.
(författare)
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The Evolution of Innate Immune Genes : Purifying and Balancing Selection on beta-Defensins in Waterfowl
- 2016
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 33:12, s. 3075-3087
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Tidskriftsartikel (refereegranskat)abstract
- In disease dynamics, high immune gene diversity can confer a selective advantage to hosts in the face of a rapidly evolving and diverse pathogen fauna. This is supported empirically for genes involved in pathogen recognition and signalling. In contrast, effector genes involved in pathogen clearance may be more constrained. beta-Defensins are innate immune effector genes; their main mode of action is via disruption of microbial membranes. Here, five beta-defensin genes were characterized in mallards (Anas platyrhynchos) and other waterfowl; key reservoir species for many zoonotic diseases. All five genes showed remarkably low diversity at the individual-, population-, and species-level. Furthermore, there was widespread sharing of identical alleles across species divides. Thus, specific beta-defensin alleles were maintained not only spatially but also over long temporal scales, with many amino acid residues being fixed across all species investigated. Purifying selection to maintain individual, highly efficacious alleles was the primary evolutionary driver of these genes in waterfowl. However, we also found evidence for balancing selection acting on the most recently duplicated beta-defensin gene (AvBD3b). For this gene, we found that amino acid replacements were more likely to be radical changes, suggesting that duplication of beta-defensin genes allows exploration of wider functional space. Structural conservation to maintain function appears to be crucial for avian beta-defensin effector molecules, resulting in low tolerance for new allelic variants. This contrasts with other types of innate immune genes, such as receptor and signalling molecules, where balancing selection to maintain allelic diversity has been shown to be a strong evolutionary force.
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| 8. |
- Ghandriz, Toheed, 1982, et al.
(författare)
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Optimization Based Design of Heterogeneous Truck Fleet and Electric Propulsion
- 2016
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Ingår i: Proceedings, ITSC. IEEE 19th International Conference on Intelligent Transportation Systems (ITSC), November 1-4, 2016, Rio de Janeiro, Brazil. - 9781509018895 ; , s. Art no 7795575, Pages 328-335
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Konferensbidrag (refereegranskat)abstract
- Many researches have been focused on vehicle routing problem during past decades where subject vehicles are previously fully designed and ready to start operation. Further, extensive studies have been done on powertrain design irrespective of the routes where the vehicle is going to be employed. In the present paper, we try to define a new branch of problems where the vehicle design, in particular its propulsion system and loading capacity, is treated simultaneously with the routing problem. The focus is on optimization based design of heterogeneous electric truck fleet to perform a prescribed task with a lowest cost on an available set of routes. The approach is illustrated in a simple case study problem. It is shown that long heavy combination vehicles are energy-efficient but not cost-optimal on short routes.
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| 9. |
- Ghandriz, Toheed, 1982, et al.
(författare)
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Sensitivity Analysis of Optimal Energy Management in Plug-in Hybrid Heavy Vehicles
- 2017
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Ingår i: 2017 2nd IEEE International Conference on Intelligent Transportation Engineering (ICITE). - 9781509062737 ; , s. 320-327
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Konferensbidrag (refereegranskat)abstract
- Optimal energy management strategies of hybrid vehicles are computationally expensive when considering the entire trip ahead rather than a short upcoming horizon. Considering the entire representative trip is already needed in concept design stages of the vehicle. In order to come up with an appropriate design while minimizing the total ownership cost the energy management strategies must already be used together with early concept evaluations. To investigate the possibility of replacing the optimal energy management with simpler approaches, here, the sensitivity of optimal solution to some of vehicle parameters and traffic flow is studied. It is seen that a simpler approach, i.e. an instantaneous optimization, can be used, in case of smooth traffic flow, since the gain of optimal strategy in reduction of operational cost is less than 4% for different vehicle hardware setup and for selected representative driving cycle. Dynamic programming is used as a solution method for finding the optimal strategy.
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| 10. |
- Hellgren, K., et al.
(författare)
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Cancer risk in patients with spondyloarthritis treated with TNF inhibitors: a collaborative study from the ARTIS and DANBIO registers
- 2017
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:1, s. 105-111
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Tidskriftsartikel (refereegranskat)abstract
- Background Safety data on cancer risks following tumour necrosis factor alpha inhibitors (TNFi) in patients with spondyloarthritis (SpA) (here defined as ankylosing spondylitis (AS), undifferentiated spondarthropaties (SpA UNS), psoriatic arthritis (PsA)) are scarce. Our objective was to assess risks for cancer overall and for common subtypes in patients with SpA treated with TNFi compared with TNFi-naive patients with SpA and to the general population. Methods From the Swedish (Anti-Rheumatic Therapy in Sweden (ARTIS)) and Danish (DANBIO) biologics registers, we assembled 8703 (ARTIS=5448, DANBIO=3255) patients with SpA initiating a first TNFi 2001-2011. From the Swedish National Patient and Population Registers we assembled a TNFi-naive SpA cohort (n=28,164) and a Swedish age-matched and sex-matched general population comparator cohort (n=131 687). We identified incident cancers by linkage with the nationwide Swedish and Danish Cancer Registers 2001-2011, and calculated age-standardised and sex-standardised incidence ratios as measures of relative risk (RR). Results Based on 1188 cancers among the TNFi-naive patients with SpA, RR of cancer overall was 1.1 (95% Cl 1.0 to 1.2). Based on 147 cancers among TNFi initiators with SpA, RR versus TNFi-naive was 0.8 (95% CI 0.7 to 1.0) and results were similar for AS and PsA when analysed separately. Site-specific cancer RRs: prostate 0.5 (95% CI 0.3 to 0.8), lung 0.6 (95% CI 0.3 to 1.3), colorectal 1.0 (95% CI 0.5 to 2.0), breast 1.3 (95% Cl 0.9 to 2.0), lymphoma 0.8 (95% CI 0.4 to 1.8) and melanoma 1.4 (95% CI 0.7 to 2.6). Conclusions In patients with SpA, treatment with TNFi was not associated with increased risks of cancer, neither overall nor for the six most common cancer types.
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