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  • 301.
    Franck, Niclas
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Åstrand, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Lindström, Torbjön
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Primary Health Care in Motala.
    Nyström, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Cardiovascular risk factors related to the PPARγ Pro12Ala polymorphism in patients with type 2 diabetes are gender dependent2012In: Blood Pressure, ISSN 0803-7051, E-ISSN 1651-1999, Vol. 21, no 2, p. 122-127Article in journal (Refereed)
    Abstract [en]

    The interaction of the PPARγ Pro12Ala polymorphism with diabetes and cardiovascular risk is controversial. We studied 173 women and 309 men in the observational CARDIPP trial in which determination of left ventricular mass, carotid intima-media thickness (IMT) and pulse wave velocity (PWV) were performed. Blood pressures were measured with 24-h ambulatory technique (ABP). Heterozygotes and homozygotes of Ala were defined as Ala in the analyses. Men with Ala-isoform displayed higher waist circumference (Ala: 107 ± 14 cm, Pro: 104 ± 11 cm, p = 0.045) and body weight (Ala: 95.7 ± 18 kg, Pro: 91.6 ± 14 kg, p = 0.042) than Pro-homozygotes. Men with ALA-isoform also showed higher systolic ABP levels (Ala: 134 ± 15 mmHg, Pro: 130 ± 14 mmHg, p = 0.004), whereas left ventricular mass index, IMT and PWV were unrelated to isoforms. In contrast, carotid–radial PWV was lower in women with the Ala-isoform (Ala: 7.9 ± 1.0 m/s, Pro: 8.5 ± 1.3 m/s, p = 0.01) and levels of apolipoprotein A1 were higher (Ala: 1.43 ± 0.27 g/l, Pro: 1.35 ± 0.17 g/l, p = 0.03). In conclusion, we found that men with type 2 diabetes having the Ala-isoform of PPARγ Pro12Ala had an unfavorable cardiovascular risk profile, whereas women with this isoform had lower carotid–radial PWV and higher apolipoprotein A1 levels suggesting a beneficial prognosis. These differences according to gender of the ALA isoform in type 2 diabetes deserve further attention.

  • 302. Fransson, G
    et al.
    Edström, M
    Nilsson, L E
    Walther, Sten
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    High mortaility in bacteraemia and candidaemia in critically ill patients - report from Swedish Intensive Care Registry2012In: Proceedings of the 22nd European Congress of Clinical Microbiology and Infectious Diseases, 2012, p. P1060-Conference paper (Other academic)
    Abstract [en]

    Objective: Increasing prevalence of  bacteremia and candidemia with significant resistance to antimicrobial agents is an increasing concern among ICU patients. The objective of this report from Swedish Registry of Intensive care (SIR) was to study the frequency and cause of culture verified sepsis in critically ill patients and to analyse mortality in sepsis caused by Candida albicans, Candida non albicans and bacteria.

    Methods: Setting: Starting 10 years ago an increasing number of ICU:s in Sweden reports each episode of care (EOC) to the Swedish Intensive care Registry (SIR).  Mortality is followed weekly for all patients by link to the Swedish population registry. A specific routine for collection of microbial data directly from the laboratories connected individually to each EOC has been tested and implemented for laboratories covering 1/3 of the Swedish population. Participants: 47 ICU:s reported 1540 EOC:s during the period January 2005 to November 2011, with a diagnosis of sepsis (ICD10: A419, R572 or R651) and a positive blood culture within 14 days before admission until discharge.  For patients with more than one EOC was only the last EOC included which reduced the number of observations included in mortality calculations to 1416.

    Variables: Primary outcome was 30 day mortality calculated from admission to ICU.

    Results: 1 416 patients met inclusion criteria and were included in the analysis. The most common causes of sepsis were:  E. coli (24 %) followed by Coagulase Negative Staphylococci (CoNS) (21 %), Streptococcus spp (19 %), S. aureus (14 %), Klebsiella spp (8 %) and Candida spp (6 %) [Candida albicans 4 % and Candida non albicans 2 %]. The 30-days crude mortality was 34% for patients with sepsis caused by S. aureus. Correspondingly 30 days mortality was for  Candida non albicans 34%, Candida albicans 31%,  Klebsiella spp 26 % , CoNS 25 %, E. coli 22 %. Distribution of species in blood cultures from the 87 patients with candidemia were: C. albicans 62, C. glabrata 11, C. krusei 1, C. tropicalis 4, C. other 4, C. non specified 9.

    Conclusion: The highest (>30%) crude mortality in critically ill patients with sepsis was seen in patients with S. aureus and Candida infections. Further analysis of independent risk factors for mortality in sepsis caused by different pathogens are warranted.

  • 303.
    Fredriksson, Alexandru Grigorescu
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Örebrö University Hospital, Örebro, Sweden.
    Svalbring, Emil
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Eriksson, Jonatan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Dyverfeldt, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Faculty of Science & Engineering. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Carlhäll, Carl-Johan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    4D flow MRI can detect subtle right ventricular dysfunction in primary left ventricular disease.2016In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 43, no 3, p. 558-565Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate whether 4D flow magnetic resonance imaging (MRI) can detect subtle right ventricular (RV) dysfunction in primary left ventricular (LV) disease.

    MATERIALS AND METHODS: 4D flow and morphological 3T MRI data were acquired in 22 patients with mild ischemic heart disease who were stratified into two groups based on LV end-diastolic volume index (EDVI): lower-LVEDVI and higher-LVEDVI, as well as in 11 healthy controls. The RV volume was segmented at end-diastole (ED) and end-systole (ES). Pathlines were emitted from the ED volume and traced forwards and backwards in time to ES. The blood volume was separated into flow components. The Direct Flow (DF) component was defined as RV inflow passing directly to outflow. The kinetic energy (KE) of the DF component was calculated. Echocardiographic conventional RV indices were also assessed.

    RESULTS: The higher-LVEDVI group had larger LVEDVI and lower LV ejection fraction (98 ± 32 ml/m(2) ; 48 ± 13%) compared to the healthy (67 ± 12, P = 0.002; 64 ± 7, P < 0.001) and lower-LVEDI groups (62 ± 10; 68 ± 7, both P < 0.001). The RV 4D flow-specific measures "DF/EDV volume-ratio" and "DF/EDV KE-ratio at ED" were lower in the higher-LVEDVI group (38 ± 5%; 52 ± 6%) compared to the healthy (44 ± 6; 65 ± 7, P = 0.018 and P < 0.001) and lower-LVEDVI groups (44 ± 6; 64 ± 7, P = 0.011 and P < 0.001). There was no difference in any of the conventional MRI and echocardiographic RV indices between the three groups.

    CONCLUSION: We found that in primary LV disease mild impairment of RV function can be detected by 4D flow-specific measures, but not by the conventional MRI and echocardiographic indices. J. Magn. Reson. Imaging 2015.

  • 304.
    Fredriksson, Alexandru Grigorescu
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Trzebiatowska-Krzynska, Aleksandra
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Dyverfeldt, Petter
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Engvall, Jan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Ebbers, Tino
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Carlhäll, Carljohan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Turbulent kinetic energy in the right ventricle: Potential MR marker for risk stratification of adults with repaired Tetralogy of Fallot2018In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 47, no 4, p. 1043-1053Article in journal (Refereed)
    Abstract [en]

    Purpose: To assess right ventricular (RV) turbulent kinetic energy (TKE) in patients with repaired Tetralogy of Fallot (rToF) and a spectrum of pulmonary regurgitation (PR), as well as to investigate the relationship between these 4D flow markers and RV remodeling.

    Materials and Methods: Seventeen patients with rToF and 10 healthy controls were included in the study. Patients were divided into two groups based on PR fraction: one lower PR fraction group (11%) and one higher PR fraction group (>11%). Field strength/sequences: 3D cine phase contrast (4D flow), 2D cine phase contrast (2D flow), and balanced steady-state free precession (bSSFP) at 1.5T. Assessment: The RV volume was segmented in the morphologic short-axis images and TKE parameters were computed inside the segmented RV volume throughout diastole. Statistical tests: One-way analysis of variance with Bonferroni post-hoc test; unpaired t-test; Pearson correlation coefficients; simple and stepwise multiple regression models; intraclass correlation coefficient (ICC).

    Results: The higher PR fraction group had more remodeled RVs (140 6 25 vs. 107 6 22 [lower PR fraction, P < 0.01] and 93 6 15 ml/m2[healthy, P < 0.001] for RV end-diastolic volume index [RVEDVI]) and higher TKE values (5.95 6 3.15 vs. 2.23 6 0.81 [lower PR fraction, P < 0.01] and 1.91 6 0.78 mJ [healthy, P < 0.001] for Peak Total RV TKE). Multiple regression analysis between RVEDVI and 4D/2D flow parameters showed that Peak Total RV TKE was the strongest predictor of RVEDVI (R25 0.47, P 5 0.002).

    Conclusion: The 4D flow-specific TKE markers showed a slightly stronger association with RV remodeling than conventional 2D flow PR parameters. These results suggest novel hemodynamic aspects of PR in the development of late complications after ToF repair.

  • 305. Freter, W
    et al.
    Engerström, L
    Sellgren, J
    Öwall, A
    Jawad, J
    Walther, Sten
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Rekalibrering av Higgins' ICU admission score baserad på data från svensk thoraxintensivvård2012In: Thoraxmötet Göteborg, 2012Conference paper (Refereed)
  • 306.
    Fridell, Sara
    et al.
    Region Östergötland, Public Dental Health Care, Center for Oral Rehabilitation Linköping.
    Ström, Edvin
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Agebratt, Christian
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Leanderson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Guldbrand, Hans
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Nyström, Fredrik H.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    A randomised study in young subjects of the effects of eating extra fruit or nuts on periodontal inflammation2018In: BDJ open, ISSN 2056-807X, Vol. 3, article id 17022Article in journal (Refereed)
    Abstract [en]

    Objectives/Aims:

    Fruit is often advocated as a healthy source of nutrients and vitamins. However, the high contents of sugars in many fruits could potentially counteract positive effects on the teeth.

    Materials and methods:

    We recruited 30 healthy non-obese participants who were randomised to either supplement their diet with extra fruits or nuts, each at +7 kcal/kg body weight/day, for 2 months.

    Results:

    Fructose intake increased from 9.1±6.0 to 25.6±9.6 g/day, P<0.0001, in the fruit group and was reduced from 12.4±5.7 to 6.5±5.3 g/day, P=0.007, in the nut group. Serum-vitamin C increased in both groups (fruit: P=0.017; nuts: P=0.009). α-Tocopherol/cholesterol ratio increased in the fruit group (P=0.0033) while β-carotene/cholesterol decreased in the nut group (P<0.0001). The amount of subjects with probing pocket depths ⩾4 mm in the fruit group was reduced (P=0.045) according to blinded examinations, and the difference in the changes in probing pockets ⩾4 mm was also statistically significant between the food groups (P=0.010).

    Conclusion:

    A large increase of fruit intake, compared with nuts, had a favourable effect on periodontal status in some respects, despite the high sugar contents. To search for potential protective micronutrients in fruit that protect the teeth could be an aim for further research.

  • 307.
    Frobert, Ole
    et al.
    Örebro University, Sweden.
    Gotberg, Matthias
    University Hospital Lund, Sweden.
    Angeras, Oskar
    Sahlgrens University Hospital, Sweden.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Erlinge, David
    University Hospital Lund, Sweden.
    Engstrom, Thomas
    University of Copenhagen, Denmark.
    Persson, Jonas
    Karolinska Institute, Sweden.
    Jensen, Svend E.
    Aalborg University Hospital, Denmark.
    Omerovic, Elmir
    Sahlgrens University Hospital, Sweden.
    James, Stefan K.
    University Hospital Uppsala, Sweden.
    Lagerqvist, Bo
    University Hospital Uppsala, Sweden.
    Nilsson, Johan
    Umeå University, Sweden.
    Karegren, Amra
    Västerås County Hospital, Sweden.
    Moer, Rasmus
    Feiring Clin, Norway.
    Yang, Cao
    Örebro University, Sweden; Karolinska Institute, Sweden.
    Agus, David B.
    University of Southern Calif, CA 90089 USA.
    Erglis, Andrejs
    Pauls Stradins Clin University Hospital, Latvia.
    Jensen, Lisette O.
    Odense University Hospital, Denmark.
    Jakobsen, Lars
    Aarhus University Hospital, Denmark.
    Christiansen, Evald H.
    Aarhus University Hospital, Denmark.
    Pernow, John
    Karolinska Institute, Sweden.
    Design and rationale for the Influenza vaccination After Myocardial Infarction (IAMI) trial. A registry-based randomized clinical trial2017In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 189, p. 94-102Article in journal (Refereed)
    Abstract [en]

    Background Registry studies and case-control studies have demonstrated that the risk of acute myocardial infarction (AMI) is increased following influenza infection. Small randomized trials, underpowered for clinical end points, indicate that future cardiovascular events can be reduced following influenza vaccination in patients with established cardiovascular disease. Influenza vaccination is recommended by international guidelines for patients with cardiovascular disease, but uptake is varying and vaccination is rarely prioritized during hospitalization for AMI. Methods/design The Influenza vaccination After Myocardial Infarction (IAMI) trial is a double-blind, multicenter, prospective, registry-based, randomized, placebo-controlled, clinical trial. A total of 4,400 patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI undergoing coronary angiography will randomly be assigned either to in-hospital influenza vaccination or to placebo. Baseline information is collected from national heart disease registries, and follow-up will be performed using both registries and a structured telephone interview. The primary end point is a composite of time to all cause death, a new AMI, or stent thrombosis at 1 year. Implications The IAMI trial is the largest randomized trial to date to evaluate the effect of in-hospital influenza vaccination on death and cardiovascular outcomes in patients with STEMI or non-STEMI. The trial is expected to provide highly relevant clinical data on the efficacy of influenza vaccine as secondary prevention after AMI.

  • 308.
    Fryk, Emanuel
    et al.
    University of Gothenburg, Sweden.
    Perman Sundelin, Jeanna
    University of Gothenburg, Sweden.
    Strindberg, Lena
    University of Gothenburg, Gothenburg, Sweden.
    Pereira, Maria J.
    Uppsala University, Sweden.
    Federici, Massimo
    University of Roma Tor Vergata, Italy.
    Marx, Nikolaus
    University Hospital RWTH Aachen, Germany.
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Schmelz, Martin
    Heidelberg University, Germany.
    Svensson, Per-Arne
    University of Gothenburg, Sweden.
    Eriksson, Jan W.
    Uppsala University, Sweden.
    Boren, Jan
    University of Gothenburg, Sweden.
    Jansson, Per-Anders
    University of Gothenburg, Sweden.
    Microdialysis and proteomics of subcutaneous interstitial fluid reveals increased galectin-1 in type 2 diabetes patients2016In: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 65, no 7, p. 998-1006Article in journal (Refereed)
    Abstract [en]

    Objective. To identify a potential therapeutic target for type 2 diabetes by comparing the subcutaneous interstitial fluid from type 2 diabetes patients and healthy men. Methods. Proteomics was performed on the interstitial fluid of subcutaneous adipose tissue obtained by microdialysis from 7 type 2 diabetes patients and 8 healthy participants. 851 proteins were detected, of which 36 (including galectin-1) showed significantly altered expression in type 2 diabetes. We also measured galectin-1 expression in: (1) adipocytes isolated from adipose tissue biopsies from these participants; (2) subcutaneous adipose tissue of 24 obese participants before, during and after 16 weeks on a very low calorie diet (VLCD); and (3) adipocytes isolated from 6 healthy young participants after 4 weeks on a diet and lifestyle intervention to promote weight gain. We also determined the effect of galectin-1 on glucose uptake in human adipose tissue. Results. Galectin-1 protein levels were elevated in subcutaneous dialysates from type 2 diabetes compared with healthy controls (p amp;lt; 0.05). In agreement, galectin-1 mRNA expression was increased in adipocytes from the type 2 diabetes patients (p amp;lt; 0.05). Furthermore, galectin-1 mRNA expression was decreased in adipose tissue after VLCD (p amp;lt; 0.05) and increased by overfeeding (p amp;lt; 0.05). Co-incubation of isolated human adipocytes with galectin-1 reduced glucose uptake (p amp;lt; 0.05) but this was independent of the insulin signal. Conclusion. Proteomics of the interstitial fluid in subcutaneous adipose tissue in vivo identified a novel adipokine, galectin-1, with a potential role in the pathophysiology of type 2 diabetes. (C) 2016 Elsevier Inc. All rights reserved.

  • 309.
    Fålun, Nina
    et al.
    Department of Heart Disease, Haukeland University Hospital, Norway.
    Moons, Philip
    Center for Health Services and Nursing Research, University of Leuven, Belgium.
    Fitzsimons, Donna
    Institute of Nursing and Health Research, Ulster University and Belfast Health and Social Care Trust, UK.
    Kirchhof, Paulus
    Centre for Cardiovascular Sciences, University of Birmingham, UK Sandwell and West Birmingham Hospitals National Health Service Trust, UK.
    Swahn, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Tubaro, Marco
    San Filippo Neri Hospital, Italy..
    Norekvål, Tone M
    Department of Heart Disease, Haukeland University Hospital, Norway Department of Clinical Science, University of Bergen, Norway.
    Editor's Choice - Practical challenges regarding in-hospital telemetry monitoring require the development of European practice standards2018In: European heart journal. Acute cardiovascular care, ISSN 2048-8734, Vol. 7, no 8, p. 774-776Article in journal (Other academic)
  • 310.
    Gabrielson, Marike
    et al.
    Karolinska Institute, Sweden.
    Vorkapic, Emina
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Folkesson, Maggie
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Welander, Martin
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Matussek, Andreas
    University of Coll Health Science, Sweden.
    Dimberg, Jan
    University of Coll Health Science, Sweden.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Skogberg, Josefin
    Karolinska Institute, Sweden.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Altered PPAR gamma Coactivator-1 Alpha Expression in Abdominal Aortic Aneurysm: Possible Effects on Mitochondrial Biogenesis2016In: Journal of Vascular Research, ISSN 1018-1172, E-ISSN 1423-0135, Vol. 53, no 1-2, p. 17-26Article in journal (Refereed)
    Abstract [en]

    Introduction: Abdominal aortic aneurysm (AAA) is a complex and deadly vascular disorder. The pathogenesis of AAA includes destruction and phenotypic alterations of the vascular smooth muscle cells (VSMCs) and aortic tissues. PPAR gamma coactivator-1 alpha (PGC1 alpha) regulates VSMC migration and matrix formation and is a major inducer of mitochondrial biogenesis and function, including oxidative metabolism. Methods: Protein and gene expression of PGC1 alpha and markers for mitochondria biogenesis and cell type-specificity were analysed in AAA aortas from humans and mice and compared against control aortas. Results: Gene expression of PPARGC1 A was decreased in human AAA and angiotensin (Ang) II-induced AAA in mice when compared to control vessels. However, high expression of PGC1 alpha was detected in regions of neovascularisation in the adventitia layer. In contract, the intima/media layer of AAA vessel exhibited defective mitochondrial biogenesis as indicated by low expression of PPARGC1 A, VDAC, ATP synthase and citrate synthase. Conclusion: Our results suggest that mitochondrial biogenesis is impaired in AAA in synthetic SMCs in the media, with the exception of newly formed supporting vessels in the adventitia where the mitochondrial markers seem to be intact. To our knowledge, this is the first study investigating PGC1 alpha and mitochondria biogenesis in AAA. (C) 2016 S. Karger AG, Basel

  • 311.
    Gaeta, Stephen
    et al.
    Duke Univ, NC USA.
    Dyverfeldt, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Eriksson, Jonatan
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Carlhäll, Carljohan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Bolger, Ann F
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Univ Calif San Francisco, CA 94143 USA.
    Fixed volume particle trace emission for the analysis of left atrial blood flow using 4D Flow MRI2018In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 47, p. 83-88Article in journal (Refereed)
    Abstract [en]

    4D Flow MRI has been used to quantify normal and deranged left ventricular blood flow characteristics on the basis of functionally distinct flow components. However, the application of this technique to the atria is challenging due to the presence of continuous inflow. This continuous inflow necessitates plane-based emission of particle traces from the inlet veins, leading to particles that represents different amounts of blood, and related quantification errors. The purpose of this study was to develop a novel fixed-volume approach for particle tracing and employ this method to develop quantitative analysis of 4D blood flow characteristics in the left atrium. 4D Flow MRI data were acquired during free-breathing using a navigator-gated gradient-echo sequence in three volunteers at 1.5 T. Fixed-volume particle traces emitted from the pulmonary veins were used to visualize left atrial blood flow and to quantitatively separate the flow into two functionally distinct flow components: Direct flow = particle traces that enter and leave the atrium in one heartbeat, Retained flow = particle traces that enter the atrium and remains there for one cardiac cycle. Flow visualization based on fixed-volume traces revealed that, beginning in early ventricular systole, flow enters the atrium and engages with residual blood volume to form a vortex. In early diastole during early ventricular filling, the organized vortical flow is extinguished, followed by formation of a second transient atrial vortex. Finally, in late diastole during atrial contraction, a second acceleration of blood into the ventricle is seen. The direct and retained left atrial flow components were between 44 and 57% and 43-56% of the stroke volume, respectively. In conclusion, fixed volume particle tracing permits separation of left atrial blood flow into different components based on the transit of blood through the atrium.

  • 312.
    Gaipov, Abduzhappar
    et al.
    Natl Sci Med Res Ctr, Kazakhstan.
    Molnar, Miklos Z.
    Methodist Univ Hosp, TN USA; Semmelweis Univ, Hungary.
    Potukuchi, Praveen K.
    Natl Sci Med Res Ctr, Kazakhstan.
    Sumida, Keiichi
    Natl Sci Med Res Ctr, Kazakhstan; Toranomon Hosp Kajigaya, Japan.
    Canada, Robert B.
    Natl Sci Med Res Ctr, Kazakhstan.
    Akbilgic, Oguz
    Kazakh Natl Med Univ, Kazakhstan.
    Kabulbayev, Kairat
    Kazakh Natl Med Univ, Kazakhstan.
    Szabo, Zoltán
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Koshy, Santhosh K. G.
    Univ Tennessee, TN 38104 USA.
    Kalantar-Zadeh, Kamyar
    Univ Calif Irvine, CA 92668 USA.
    Kovesdy, Csaba P.
    Natl Sci Med Res Ctr, Kazakhstan; Memphis VA Med Ctr, TN 38104 USA.
    Predialysis coronary revascularization and postdialysis mortality2019In: Journal of Thoracic and Cardiovascular Surgery, ISSN 0022-5223, E-ISSN 1097-685X, Vol. 157, no 3, p. 976-+Article in journal (Refereed)
    Abstract [en]

    Objectives: Coronary artery bypass grafting (CABG) is associated with better survival than percutaneous coronary intervention (PCI) in patients with mild-to-moderate chronic kidney disease (CKD) and end-stage renal disease (ESRD). However, the optimal strategy for coronary artery revascularization in patients with advanced CKD who transition to ESRD is unclear. Methods: We examined a contemporary national cohort of 971 US veterans with incident ESRD who underwent first CABG or PCI up to 5 years before dialysis initiation. We examined the association of a history of CABG versus PCI with all-cause mortality following transition to dialysis using Cox proportional hazards models adjusted for time between procedure and dialysis initiation, sociodemographics, comorbidities, and medications. Results: In total, 582 patients underwent CABG and 389 patients underwent PCI. The mean age was 64 +/- 8 years, 99% of patients were male, 79% were white, 19% were African American, and 84% had diabetes. The all-cause post-dialysis mortality rates after CABG and PCI were 229 per 1000 patient-years (95% confidence interval [CI], 205-256) and 311 per 1000 patient years (95% CI, 272-356), respectively. Compared with PCI, patients who underwent CABG had 34% lower risk of death (multivariable adjusted hazard ratio, 0.66; 95% CI, 0.51-0.86, P = .002) after initiation of dialysis. Results were similar in all subgroups of patients stratified by age, race, type of intervention, presence/absence of myocardial infarction, congestive heart failure, and diabetes. Conclusions: CABG in patients with advanced CKD was associated lower risk of death after initiation of dialysis compared with PCI.

  • 313.
    Gaipov, Abduzhappar
    et al.
    University of Tennessee Health Science Center, Memphis, TN, USA, National Scientific Medical Research Center, Astana, Kazakhstan.
    Molnar, Miklos Z
    University of Tennessee Health Science Center, Memphis, TN, USA, Semmelweis University, Budapest, Hungary.
    Potukuchi, Praveen K
    University of Tennessee Health Science Center, Memphis, TN, USA.
    Sumida, Keiichi
    University of Tennessee Health Science Center, Memphis, TN, USA,Toranomon Hospital Kajigaya, Kanagawa, Japan..
    Szabó, Zoltán
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Akbilgic, Oguz
    University of Tennessee Health Science Center, Memphis, TN, USA.
    Streja, Elani
    University of California, Irvine, Orange, CA, USA..
    Rhee, Connie M
    University of California, Irvine, Orange, CA, USA..
    Koshy, Santhosh K G
    University of Tennessee Health Science Center, Memphis, TN, USA.
    Canada, Robert B
    University of Tennessee Health Science Center, Memphis, TN, USA.
    Kalantar-Zadeh, Kamyar
    University of California, Irvine, Orange, CA, USA..
    Kovesdy, Csaba P
    University of Tennessee Health Science Center, Memphis, TN, USA, Memphis VA Medical Center, Memphis, TN, USA.
    Acute kidney injury following coronary revascularization procedures in patients with advanced CKD.2018In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385Article in journal (Refereed)
    Abstract [en]

    Background: Previous studies reported that compared with percutaneous coronary interventions (PCIs), coronary artery bypass grafting (CABG) is associated with a reduced risk of mortality and repeat revascularization in patients with mild to moderate chronic kidney disease (CKD) and end-stage renal disease (ESRD). Information about outcomes associated with CABG versus PCI in patients with advanced stages of CKD is limited. We evaluated the incidence and relative risk of acute kidney injury (AKI) associated with CABG versus PCI in patients with advanced CKD.

    Methods: We examined 730 US veterans with incident ESRD who underwent a first CABG or PCI up to 5 years prior to dialysis initiation. The association of CABG versus PCI with AKI was examined in multivariable adjusted logistic regression analyses.

    Results: A total of 466 patients underwent CABG and 264 patients underwent PCI. The mean age was 64 ± 8 years, 99% were male, 20% were African American and 84% were diabetic. The incidence of AKI in the CABG versus PCI group was 67% versus 31%, respectively (P < 0.001). The incidence of all stages of AKI were higher after CABG compared with PCI. CABG was associated with a 4.5-fold higher crude risk of AKI {odds ratio [OR] 4.53 [95% confidence interval (CI) 3.28-6.27]; P < 0.001}, which remained significant after multivariable adjustments [OR 3.50 (95% CI 2.03-6.02); P < 0.001].

    Conclusion: CABG was associated with a 4.5-fold higher risk of AKI compared with PCI in patients with advanced CKD. Despite other benefits of CABG over PCI, the extremely high risk of AKI associated with CABG should be considered in this vulnerable population when deciding on the optimal revascularization strategy.

  • 314.
    Gardner, Benjamin
    et al.
    UCL, England.
    Broström, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Nilsen, Per
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    Hrubos Strom, Harald
    Akershus University Hospital, Norway.
    Ulander, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Fridlund, Bengt
    Jonköping University, Sweden.
    Skagerström (Malmsten), Janna
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Johansson, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Editorial Material: From does it work? to what makes it work?: The importance of making assumptions explicit when designing and evaluating behavioural interventions in EUROPEAN JOURNAL OF CARDIOVASCULAR NURSING, vol 13, issue 4, pp 292-2942014In: European Journal of Cardiovascular Nursing, ISSN 1474-5151, E-ISSN 1873-1953, Vol. 13, no 4, p. 292-294Article in journal (Other academic)
    Abstract [en]

    n/a

  • 315.
    Garvin, Peter
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Nilsson, Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Falk, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Kristenson, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Plasma Matrix Metalloproteinase-9 Levels Predict First-Time Coronary Heart Disease: An 8-Year Follow-Up of a Community-Based Middle Aged Population2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 9, p. e0138290-Article in journal (Refereed)
    Abstract [en]

    Background The enzyme in matrix metalloproteinase (MMP)-9 has been suggested to be an important determinant of plaque degradation. While several studies have shown elevated levels in patients with coronary heart disease, results in prospective population based studies evaluating MMP-9 in relation to first time coronary events have been inconclusive. As of today, there are four published studies which have measured MMP-9 in serum and none using plasma. Measures of MMP-9 in serum have been suggested to have more flaws than measures in plasma. Aim To investigate the independent association between plasma levels of MMP-9 and first-time incidence of coronary events in an 8-year follow-up. Material and Methods 428 men and 438 women, aged 45-69 years, free of previous coronary events and stroke at baseline, were followed-up. Adjustments were made for sex, age, socioeconomic position, behavioral and cardiovascular risk factors, chronic disease at baseline, depressive symptoms, interleukin-6 and C-reactive protein. Results 53 events were identified during a risk-time of 6 607 person years. Hazard ratio (HR) for MMP-9 after adjustment for all covariates were HR = 1.44 (1.03 to 2.02, p = 0.033). Overall, the effect of adjustments for other cardiovascular risk factors was low. Conclusion Levels of plasma MMP-9 are independently associated with risk of first-time CHD events, regardless of adjustments. These results are in contrast to previous prospective population-based studies based on MMP-9 in serum. It is essential that more studies look at MMP-9 levels in plasma to further evaluate the association with first coronary events.

  • 316.
    Gawel, Danuta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Serra-Musach, Jordi
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Lilja, Sandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Aagesen, Jesper
    Reg Jonkoping Cty, Sweden.
    Arenas, Alex
    Univ Rovira and Virgili, Spain.
    Asking, Bengt
    Reg Jonkoping Cty, Sweden.
    Bengner, Malin
    Reg Jonkoping Cty, Sweden.
    Bjorkander, Janne
    Reg Jonkoping Cty, Sweden.
    Biggs, Sophie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Hjortswang, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Karlsson, Jan-Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Reg Jonkoping Cty, Sweden.
    Köpsén, Mattias
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Jung Lee, Eun Jung
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Yonsei Univ, South Korea.
    Lentini, Antonio
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Li, Xinxiu
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Magnusson, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Martinez, David
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Matussek, Andreas
    Reg Jonkoping Cty, Sweden; Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Schafer, Samuel
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Seifert, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Reg Jonkoping Cty, Sweden.
    Sonmez, Ceylan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Stjernman, Henrik
    Reg Jonkoping Cty, Sweden.
    Tjärnberg, Andreas
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Wu, Simon
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Åkesson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Reg Jonkoping Cty, Sweden.
    Shalek, Alex K.
    MIT, MA 02139 USA; Broad Inst MIT and Harvard, MA 02142 USA; Ragon Inst MGH MIT and Harvard, MA USA.
    Stenmarker, Margaretha
    Reg Jonkoping Cty, Sweden; Inst Clin Sci, Sweden.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Gustafsson, Mika
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases2019In: Genome Medicine, ISSN 1756-994X, E-ISSN 1756-994X, Vol. 11, article id 47Article in journal (Refereed)
    Abstract [en]

    Background

    Genomic medicine has paved the way for identifying biomarkers and therapeutically actionable targets for complex diseases, but is complicated by the involvement of thousands of variably expressed genes across multiple cell types. Single-cell RNA-sequencing study (scRNA-seq) allows the characterization of such complex changes in whole organs.

    Methods

    The study is based on applying network tools to organize and analyze scRNA-seq data from a mouse model of arthritis and human rheumatoid arthritis, in order to find diagnostic biomarkers and therapeutic targets. Diagnostic validation studies were performed using expression profiling data and potential protein biomarkers from prospective clinical studies of 13 diseases. A candidate drug was examined by a treatment study of a mouse model of arthritis, using phenotypic, immunohistochemical, and cellular analyses as read-outs.

    Results

    We performed the first systematic analysis of pathways, potential biomarkers, and drug targets in scRNA-seq data from a complex disease, starting with inflamed joints and lymph nodes from a mouse model of arthritis. We found the involvement of hundreds of pathways, biomarkers, and drug targets that differed greatly between cell types. Analyses of scRNA-seq and GWAS data from human rheumatoid arthritis (RA) supported a similar dispersion of pathogenic mechanisms in different cell types. Thus, systems-level approaches to prioritize biomarkers and drugs are needed. Here, we present a prioritization strategy that is based on constructing network models of disease-associated cell types and interactions using scRNA-seq data from our mouse model of arthritis, as well as human RA, which we term multicellular disease models (MCDMs). We find that the network centrality of MCDM cell types correlates with the enrichment of genes harboring genetic variants associated with RA and thus could potentially be used to prioritize cell types and genes for diagnostics and therapeutics. We validated this hypothesis in a large-scale study of patients with 13 different autoimmune, allergic, infectious, malignant, endocrine, metabolic, and cardiovascular diseases, as well as a therapeutic study of the mouse arthritis model.

    Conclusions

    Overall, our results support that our strategy has the potential to help prioritize diagnostic and therapeutic targets in human disease.

  • 317.
    Gelmi, Amy
    et al.
    Linköping University, Faculty of Science & Engineering. Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Imperial Coll London, England.
    Cieslar-Pobuda, Artur
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Silesian Technical University, Poland.
    de Muinck, Ebo
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Los, Marek Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Pomeranian Medical University, Poland.
    Rafat, Mehrdad
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Jager, Edwin
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Direct Mechanical Stimulation of Stem Cells: A Beating Electromechanically Active Scaffold for Cardiac Tissue Engineering2016In: Advanced Healthcare Materials, ISSN 2192-2640, E-ISSN 2192-2659, Vol. 5, no 12, p. 1471-1480Article in journal (Refereed)
    Abstract [en]

    The combination of stem cell therapy with a supportive scaffold is a promising approach to improving cardiac tissue engineering. Stem cell therapy can be used to repair nonfunctioning heart tissue and achieve myocardial regeneration, and scaffold materials can be utilized in order to successfully deliver and support stem cells in vivo. Current research describes passive scaffold materials; here an electroactive scaffold that provides electrical, mechanical, and topographical cues to induced human pluripotent stem cells (iPS) is presented. The poly(lactic-co-glycolic acid) fiber scaffold coated with conductive polymer polypyrrole (PPy) is capable of delivering direct electrical and mechanical stimulation to the iPS. The electroactive scaffolds demonstrate no cytotoxic effects on the iPS as well as an increased expression of cardiac markers for both stimulated and unstimulated protocols. This study demonstrates the first application of PPy as a supportive electroactive material for iPS and the first development of a fiber scaffold capable of dynamic mechanical actuation.

  • 318.
    Genaridis, Apostolos
    et al.
    Södersjukhuset, Stockholm, Sweden.
    Engerström, L
    Berkius, Johan
    Västerviks sjukhus, Västervik, Sweden.
    Wickerts, Carl-Johan
    Walther, Sten
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Can we predict who will benefit from non-invasive ventilation in hypoxemic acute respiratory failure?2015Conference paper (Other academic)
  • 319.
    Georgiopoulos, Charalampos
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Davidsson, Anette
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Larsson, Elna-Marie
    Uppsala University, Sweden.
    Zachrisson, Helene
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dizdar (Dizdar Segrell), Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    The diagnostic value of dopamine transporter imaging and olfactory testing in patients with parkinsonian syndromes2015In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 262, no 9, p. 2154-2163Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to compare the efficacy of olfactory testing and presynaptic dopamine imaging in diagnosing Parkinsons disease (PD) and atypical parkinsonian syndromes (APS); to evaluate if the combination of these two diagnostic tools can improve their diagnostic value. A prospective investigation of 24 PD patients, 16 APS patients and 15 patients with non-parkinsonian syndromes was performed during an 18-month period. Single photon emission computed tomography with the presynaptic radioligand I-123-FP-CIT (DaTSCAN (R)) and olfactory testing with the Brief 12-item Smell Identification Test (B-SIT) were performed in all patients. DaTSCAN was analysed semi-quantitatively, by calculating two different striatal uptake ratios, and visually according to a predefined ranking scale. B-SIT score was significantly lower for PD patients, but not significantly different between APS and non-parkinsonism. The visual assessment of DaTSCAN had higher sensitivity, specificity and diagnostic accuracy compared to olfactory testing. Most PD patients (75 %) had visually predominant dopamine depletion in putamen, while most APS patients (56 %) had visually severe dopamine depletion both in putamen and in caudate nucleus. The combination of DaTSCAN and B-SIT led to a higher rate of correctly classified patients. Olfactory testing can distinguish PD from non-parkinsonism, but not PD from APS or APS from non-parkinsonism. DaTSCAN is more efficient than olfactory testing and can be valuable in differentiating PD from APS. However, combining olfactory testing and DaTSCAN imaging has a higher predictive value than these two methods separately.

  • 320.
    Georgiopoulos, Charalampos
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Warntjes, Marcel Jan Bertus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). SyntheticMR AB, Linkoping, Sweden.
    Dizdar Segrell, Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Zachrisson, Helene
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Haller, Sven
    Affidea CDRC Centre Diagnost Radiol Carouge SA, Switzerland; Uppsala University, Sweden.
    Larsson, Elna-Marie
    Uppsala University, Sweden.
    Olfactory Impairment in Parkinsons Disease Studied with Diffusion Tensor and Magnetization Transfer Imaging2017In: Journal of Parkinson's Disease, ISSN 1877-7171, E-ISSN 1877-718X, Vol. 7, no 2, p. 301-311Article in journal (Refereed)
    Abstract [en]

    Background: Olfactory impairment is an early manifestation of Parkinsons disease (PD). Diffusion Tensor Imaging (DTI) and Magnetization Transfer (MT) are two imaging techniques that allow noninvasive detection of microstructural changes in the cerebral white matter. Objective: To assess white matter alterations associated with olfactory impairment in PD, using a binary imaging approach with DTI and MT. Methods: 22 PD patients and 13 healthy controls were examined with DTI, MT and an odor discrimination test. DTI data were first analyzed with tract-based spatial statistics (TBSS) in order to detect differences in fractional anisotropy, mean, radial and axial diffusivity between PD patients and controls. Voxelwise randomized permutation was employed for the MT analysis, after spatial and intensity normalization. Additionally, ROI analysis was performed on both the DTI and MT data, focused on the white matter adjacent to olfactory brain regions. Results: Whole brain voxelwise analysis revealed decreased axial diffusivity in the left uncinate fasciculus and the white matter adjacent to the left olfactory sulcus of PD patients. ROI analysis demonstrated decreased axial diffusivity in the right orbitofrontal cortex, as well as decreased mean diffusivity and axial diffusivity in the white matter of the left entorhinal cortex of PD patients. There were no significant differences regarding fractional anisotropy, radial diffusivity or MT between patients and controls. Conclusions: ROI analysis of DTI could detect microstructural changes in the white matter adjacent to olfactory areas in PD patients, whereas MT imaging could not.

  • 321.
    Georgiopoulos, Charalampos
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Witt, Suzanne
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Haller, Sven
    Ctr Imagerie Rive Droite SA, Switzerland; Uppsala Univ, Sweden.
    Dizdar Segrell, Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology in Linköping.
    Zachrisson, Helene
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Larsson, Elna-Marie
    Uppsala Univ, Sweden.
    A study of neural activity and functional connectivity within the olfactory brain network in Parkinsons disease2019In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 23, article id UNSP 101946Article in journal (Refereed)
    Abstract [en]

    Olfactory dysfunction is an early manifestation of Parkinsons disease (PD). The present study aimed to illustrate potential differences between PD patients and healthy controls in terms of neural activity and functional connectivity within the olfactory brain network. Twenty PD patients and twenty healthy controls were examined with olfactory fMRI and resting-state fMRI. Data analysis of olfactory fMRI included data-driven tensorial independent component (ICA) and task-driven general linear model (GLM) analyses. Data analysis of resting-state fMRI included probabilistic ICA based on temporal concatenation and functional connectivity analysis within the olfactory network. ICA of olfactory fMRI identified an olfactory network consisting of the posterior piriform cortex, insula, right orbitofrontal cortex and thalamus. Recruitment of this network was less significant for PD patients. GLM analysis revealed significantly lower activity in the insula bilaterally and the right orbitofrontal cortex in PD compared to healthy controls but no significant differences in the olfactory cortex itself. Analysis of resting-state fMRI did not reveal any differences in the functional connectivity within the olfactory, default mode, salience or central executive networks between the two groups. In conclusion, olfactory dysfunction in PD is associated with less significant recruitment of the olfactory brain network. ICA could demonstrate differences in both the olfactory cortex and its main projections, compared to GLM that revealed differences only on the latter. Resting-state fMRI did not reveal any significant differences in functional connectivity within the olfactory, default mode, salience and central executive networks in this cohort.

  • 322.
    Georgiopoulos, Charalampos
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Witt, Suzanne Tyson
    Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Haller, Sven
    Affidea CDRC Ctr Diagnost Radiol Carouge SA, Switzerland; Uppsala Univ, Sweden.
    Dizdar Segrell, Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Zachrisson, Helene
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Larsson, Elna-Marie
    Uppsala Univ, Sweden.
    Olfactory fMRI: Implications of Stimulation Length and Repetition Time2018In: Chemical Senses, ISSN 0379-864X, E-ISSN 1464-3553, Vol. 43, no 6, p. 389-398Article in journal (Refereed)
    Abstract [en]

    Studying olfaction with functional magnetic resonance imaging (fMRI) poses various methodological challenges. This study aimed to investigate the effects of stimulation length and repetition time (TR) on the activation pattern of 4 olfactory brain regions: the anterior and the posterior piriform cortex, the orbitofrontal cortex, and the insula. Twenty-two healthy participants with normal olfaction were examined with fMRI, with 2 stimulation lengths (6 s and 15 s) and 2 TRs (0.901 s and 1.34 s). Data were analyzed using General Linear Model (GLM), Tensorial Independent Component Analysis (TICA), and by plotting the event-related time course of brain activation in the 4 olfactory regions of interest. The statistical analysis of the time courses revealed that short TR was associated with more pronounced signal increase and short stimulation was associated with shorter time to peak signal. Additionally, both long stimulation and short TR were associated with oscillatory time courses, whereas both short stimulation and short TR resulted in more typical time courses. GLM analysis showed that the combination of short stimulation and short TR could result in visually larger activation within these olfactory areas. TICA validated that the tested paradigm was spatially and temporally associated with a functionally connected network that included all 4 olfactory regions. In conclusion, the combination of short stimulation and short TR is associated with higher signal increase and shorter time to peak, making it more amenable to standard GLM-type analyses than long stimulation and long TR, and it should, thus, be preferable for olfactory fMRI.

  • 323.
    Gharehbaghi, Arash
    et al.
    Malardalen University, Sweden.
    Ask, Per
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, Faculty of Science & Engineering.
    Nylander, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Janerot-Sjoberg, Birgitta
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden; KTH Royal Institute Technology, Sweden.
    Ekman, Inger
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Linden, Maria
    Malardalen University, Sweden.
    Babic, Ankica
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. University of Bergen, Norway.
    A Hybrid Model for Diagnosing Sever Aortic Stenosis in Asymptomatic Patients using Phonocardiogram2015In: WORLD CONGRESS ON MEDICAL PHYSICS AND BIOMEDICAL ENGINEERING, 2015, VOLS 1 AND 2, Springer, 2015, Vol. 51, p. 1006-1009Conference paper (Refereed)
    Abstract [en]

    This study presents a screening algorithm for severe aortic stenosis (AS), based on a processing method for phonocardiographic (PCG) signal. The processing method employs a hybrid model, constituted of a hidden Markov model and support vector machine. The method benefits from a preprocessing phase for an enhanced learning. The performance of the method is statistically evaluated using PCG signals recorded from 50 individuals who were referred to the echocardiography lab at Linkoping University hospital. All the individuals were diagnosed as having a degree of AS, from mild to severe, according to the echocardiographic measurements. The patient group consists of 26 individuals with severe AS, and the rest of the 24 patients comprise the control group. Performance of the method is statistically evaluated using repeated random sub sampling. Results showed a 95% confidence interval of (80.5%-82.8%)/(77.8%-80.8%) for the accuracy/sensitivity, exhibiting an acceptable performance to be used as decision support system in the primary healthcare center.

  • 324.
    Gharehbaghi, Arash
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Ekman, Inger
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Ask, Per
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Nylander, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Janerot Sjöberg, Birgitta
    Departments of Clinical Science, Intervention and Technology, Karolinska Institutet & Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden.
    Severity assessments of aortic stenosis using intelligent phonocardiographyManuscript (preprint) (Other academic)
    Abstract [en]

    Objectives: To study capabilities of the intelligent phonocardiography (IPCG) in automatic grading severity of the aortic stenosis (AS).

    Methods: Phonocardiogram signals were recorded from the patients with AS, as diagnosed by echocardiography. The patient group is comprised of signals, recorded from 5 patients (2 recordings from each), mostly elderly referrals (>60 years) with mild to severe AS. An advanced processing algorithm, consisted of the wavelet transform and the stepwise regression analysis, characterizes the systolic murmur caused by the AS in order to predict the 5 indicators; mean pressure gradient over the aortic valve (MPG), maximum jet velocity (MJV), aortic valve area (AVA), velocity time integral and the ejection period. The automatic assessment is performed by an artificial neural network using the predicted values of the indicators as the input data. Reliability of the IPCG is validated by applying repeated random sub-sampling (RRSS) with 70%/30% of the training/testing data, and calculating the accuracy. The RRSS is also employed to validate reproducibility of the IPCG by using 70% of the signals for training and the second recording of the same individuals for  testing.

    Results: Accuracy of the IPCG is estimated to be and (95% confidence interval) for the reliability and the reproducibility, respectively. Linear correlation between the characterized systolic murmur and the MPG (r>0.81), the MJV (r>0.82) and the AVA (r>0.85) is observed.

    Conclusions: The IPCG has the potential to objectively serve as a clinical tool for grading severity of the aortic stenosis.

  • 325.
    Gharehbaghi, Arash
    et al.
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, Faculty of Science & Engineering.
    Ekman, Inger
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Ask, Per
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, Faculty of Science & Engineering.
    Nylander, Eva
    Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Janerot-Sjoberg, Birgitta
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden; Karolinska University Hospital, Sweden; KTH Royal Institute Technology, Sweden.
    Letter: Assessment of aortic valve stenosis severity using intelligent phonocardiography2015In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 198, p. 58-60Article in journal (Other academic)
    Abstract [en]

    n/a

  • 326.
    Gijsberts, Crystel M.
    et al.
    ICIN Netherlands Heart Institute, Netherlands; University of Medical Centre Utrecht, Netherlands.
    Benson, Lina
    Karolinska Institute, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Sim, David
    Singhealth, Singapore.
    Yeo, Daniel P. S.
    Tan Tock Seng Hospital, Singapore.
    Yee Ong, Hean
    Khoo Teck Puat Hospital, Singapore.
    Jaufeerally, Fazlur
    Singapore Gen Hospital, Singapore; Duke NUS, Singapore.
    Leong, Gerard K. T.
    Changi Gen Hospital, Singapore.
    Ling, Lieng H.
    National University of Singapore, Singapore; National University of Health Syst, Singapore.
    Mark Richards, A.
    National University of Singapore, Singapore; National University of Health Syst, Singapore; National University of Singapore, Singapore; University of Otago, New Zealand.
    de Kleijn, Dominique P. V.
    ICIN Netherlands Heart Institute, Netherlands; University of Medical Centre Utrecht, Netherlands; National University of Singapore, Singapore; National University of Singapore, Singapore.
    Lund, Lars H.
    Karolinska Institute, Sweden; Karolinska Institute, Sweden.
    Lam, Carolyn S. P.
    Singhealth, Singapore; National University of Singapore, Singapore; National University of Singapore, Singapore.
    Ethnic differences in the association of QRS duration with ejection fraction and outcome in heart failure2016In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 102, no 18, p. 1464-1471Article in journal (Refereed)
    Abstract [en]

    Background QRS duration (QRSd) criteria for device therapy in heart failure (HF) were derived from predominantly white populations and ethnic differences are poorly understood. Methods We compared the association of QRSd with ejection fraction (EF) and outcomes between 839 Singaporean Asian and 11221 Swedish white patients with HF having preserved EF (HFPEF)and HF having reduced EF (HFREF) were followed in prospective population-based HF studies. Results Compared with whites, Asian patients with HF were younger (62 vs 74years, pamp;lt;0.001), had smaller body size (height 163 vs 171cm, weight 70 vs 80kg, both pamp;lt;0.001) and had more severely impaired EF (EF was amp;lt;30% in 47% of Asians vs 28% of whites). Overall, unadjusted QRSd was shorter in Asians than whites (101 vs 104ms, pamp;lt;0.001). Lower EF was associated with longer QRSd (pamp;lt;0.001), with a steeper association among Asians than whites (p(interaction)amp;lt;0.001), independent of age, sex and clinical covariates (including body size). Excluding patients with left bundle branch block (LBBB) and adjusting for clinical covariates, QRSd was similar in Asians and whites with HFPEF, but longer in Asians compared with whites with HFREF (p=0.001). Longer QRSd was associated with increased risk of HF hospitalisation or death (absolute 2-year event rate for 120ms was 40% and for amp;gt;120ms it was 52%; HR for 10ms increase of QRSd was 1.04 (1.03 to 1.06), pamp;lt;0.001), with no interaction by ethnicity. Conclusion We found ethnic differences in the association between EF and QRSd among patients with HF. QRS prolongation was similarly associated with increased risk, but the implications for ethnicity-specific QRSd cut-offs in clinical decision-making require further study.

  • 327.
    Gilljam, Thomas
    et al.
    University of Gothenburg, Sweden.
    Haugaa, Kristina H.
    Oslo University Hospital, Norway; University of Oslo, Norway.
    Jensen, Henrik K.
    Aarhus University, Denmark; Aarhus University, Denmark.
    Svensson, Anneli
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Bundgaard, Henning
    University of Copenhagen, Denmark.
    Hansen, Jim
    University of Copenhagen, Denmark.
    Dellgren, Goran
    University of Gothenburg, Sweden.
    Gustafsson, Finn
    University of Copenhagen, Denmark.
    Eiskjaer, Hans
    Aarhus University, Denmark; Aarhus University, Denmark.
    Andreassen, Arne K.
    Oslo University Hospital, Norway.
    Sjogren, Johan
    Lund University, Sweden.
    Edvardsen, Thor
    Oslo University Hospital, Norway; University of Oslo, Norway.
    Holst, Anders G.
    University of Copenhagen, Denmark.
    Hastrup Svendsen, Jesper
    University of Copenhagen, Denmark.
    Platonov, Pyotr G.
    Lund University, Sweden; Skåne University Hospital, Sweden.
    Heart transplantation in arrhythmogenic right ventricular cardiomyopathy - Experience from the Nordic ARVC Registry2018In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 250, p. 201-206Article in journal (Refereed)
    Abstract [en]

    Objective: There is a paucity of data on heart transplantation (HTx) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), and specific recommendations on indications for listing ARVC patients for HTx are lacking. In order to delineate features pertinent to HTx assessment, we explored the pre-HTx characteristics and clinical history in a cohort of ARVC patients who received heart transplants. Methods: Data from 31 ARVC/HTx patients enrolled in the Nordic ARVC Registry, transplanted between 1988 and 2014 at a median age of 46 years (14-65), were compared with data from 152 non-transplanted probands with Definite ARVC according to 2010 Task Force Criteria from the same registry. Results: The HTx patients were younger at presentation, median 31 vs. 38 years (p = 0.001). Therewas no difference in arrhythmia-related events. The indication for HTx was heart failure in 28 patients (90%) and ventricular arrhythmias in 3 patients (10%). During median follow-up of 4.9 years (0.04-28), there was one early death and two late deaths. Survival was 91% at 5 years after HTx. Age at first symptoms under 35 years independently predicted HTx in our cohort (OR = 7.59, 95% CI 2.69-21.39, p amp;lt; 0.001). Conclusion: HTx in patientswith ARVC is performed predominantly due to heart failure. This suggests that current 2016 International Society for Heart and Lung Transplantation heart transplant listing recommendations for other cardiomyopathies could be applicable in many cases when taking into account the haemodynamic consequences of right ventricular failure in conjunction with ventricular arrhythmia. (C) 2017 Elsevier B.V. All rights reserved.

  • 328.
    Glad, Camilla A. M.
    et al.
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Svensson, Per-Arne
    Univ Gothenburg, Sweden.
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Cityhälsan Centrum, Norrköping.
    Jacobson, Peter
    Univ Gothenburg, Sweden.
    Carlsson, Lena M. S.
    Univ Gothenburg, Sweden.
    Johannsson, Gudmundur
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Andersson-Assarsson, Johanna C.
    Univ Gothenburg, Sweden.
    Expression of GHR and Downstream Signaling Genes in Human Adipose Tissue-Relation to Obesity and Weight Change2019In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 104, no 5, p. 1459-1470Article in journal (Refereed)
    Abstract [en]

    Context: GH is a strong regulator of metabolism. In obesity, both GH secretion and adipose tissue GHR gene expression are decreased. More detailed information on the regulation of GHR, STAT3/5, and downstream-regulated genes in human adipose tissue during diet-induced weight loss and weight gain is lacking. Objective: The aim of the present study was to investigate the gene expression patterns of GHR and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway (JAK2, STAT3, STAT5A, and STAT5B) in human subcutaneous adipose tissue in relation to energy restriction and overfeeding. Design, Patients, and Interventions: Tissue distribution was analyzed in a data set generated by RNA sequencing containing information on global expression in human tissues. Subcutaneous adipose tissue or adipocyte gene expression (measured by DNA microarrays) was investigated in the following settings: (i) individuals with obesity vs individuals with normal weight; (ii) energy restriction; and (iii) overfeeding. Results: GHR expression was decreased in subjects with obesity compared with subjects with normal weight (P amp;lt; 0.001). It was increased in response to energy restriction and decreased in response to overfeeding (P = 0.015 and P = 0.030, respectively). STAT3 expression was increased in subjects with obesity (P amp;lt; 0.001). It was decreased during energy restriction and increased during overfeeding (P = 0.004 and P = 0.006, respectively). STAT3-regulated genes showed an overall view of overexpression in obesity. Conclusions: The results of the present study have shown that GHR, STAT3, and STAT3-regulated genes are dynamically, and reciprocally, regulated at the tissue level in response to energy restriction and overfeeding, suggesting that GH signaling is perturbed in obesity.

  • 329.
    Gnosa, Sebastian
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Capodanno, Alessandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Dahl Ejby Jensen, Lasse
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    AEG-1 knockdown in colon cancer cell lines inhibits radiation-enhanced migration and invasion in vitro and in a novel in vivo zebrafish model2016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 49, p. 81634-81644Article in journal (Refereed)
    Abstract [en]

    Background Radiotherapy is a well-established anti-cancer treatment. Although radiotherapy has been shown to significantly decrease the local relapse in rectal cancer patients, the rate of distant metastasis is still very high. Several studies have shown that radiation enhances migration and invasion both in vitro and in vivo. The aim of this study was to evaluate whether AEG-1 is involved in radiation-enhanced migration and invasion in vitro and in a novel in vivo zebrafish model.

    Materials and Methods We evaluated the involvement of AEG-1 in migration and invasion and radiation-enhanced migration and invasion by Boyden chamber assay in three colon cancer cell lines and respective AEG-1 knockdown cell lines. Furthermore, we injected the cells in zebrafish embryos and evaluated the amount of disseminated cells into the tail.

    Results Migration and invasion was decreased in all the AEG-1 knockdown cell lines. Furthermore, radiation enhanced migration and invasion, while AEG-1 knockdown could abolish this effect. The results from the zebrafish model confirmed the results obtained in vitro. MMP-9 secretion and expression were decreased in AEG-1 knockdown cells.

    Conclusion Our results demonstrate that AEG-1 knockdown inhibits migration and invasion, as well as radiation-enhanced migration and invasion. We speculate that this is done via the downregulation of the intrinsic or radiation-enhanced MMP-9 expression. The zebrafish model can be used to study early events in radiation-enhanced invasion.

  • 330.
    Goetze, Jens P
    et al.
    Rigshospitalet, University of Copenhagen, Denmark .
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Flyvbjerg, Allan
    Aarhus University Hospital, Denmark.
    Rehfeld, Jens F
    Rigshospitalet, University of Copenhagen, Denmark .
    Chromogranin A as a biomarker in cardiovascular disease2014In: Biomarkers in Medicine, ISSN 1752-0363, E-ISSN 1752-0371, Vol. 8, no 1, p. 133-140Article, review/survey (Refereed)
    Abstract [en]

    Chromogranin A is known as an important marker of neuroendocrine tumors. In cardiovascular medicine, however, chromogranin A measurement has only recently gained interest, since increased concentrations in the circulation are associated with risk of clinical worsening and death in patients with acute coronary syndromes or chronic heart failure. In this article, we summarize the current clinical data on chromogranin A as a biomarker in cardiovascular disease from high-risk conditions; for example, obesity, hypertension and diabetes, to overt heart failure. Biological activity of the various chromogranin A fragments, including the intact precursor itself, will not be covered in the present review. Instead, we highlight the complexity of chromogranin A as a plasma marker, where the protein is extensively and variably processed to a plethora of peptide fragments. Current immunological methods for clinical measurement differ dramatically with respect to both epitope choice and clinical validation.

  • 331.
    Goetze, Jens P
    et al.
    Rigshospitalet, University of Copenhagen, Denmark .
    Hilsted, Linda M
    Rigshospitalet, University of Copenhagen, Denmark .
    Rehfeld, Jens F
    Rigshospitalet, University of Copenhagen, Denmark .
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Plasma chromogranin A is a marker of death in elderly patients presenting with symptoms of heart failure2014In: Endocrine Connections, ISSN 2049-3614, E-ISSN 2049-3614, Vol. 3, no 1, p. 47-56Article in journal (Refereed)
    Abstract [en]

    Cardiovascular risk assessment remains difficult in elderly patients. We examined whether chromogranin A (CgA) measurement in plasma may be valuable in assessing risk of death in elderly patients with symptoms of heart failure in a primary care setting. A total of 470 patients (mean age 73 years) were followed for 10 years. For CgA plasma measurement, we used a two-step method including a screening test and a confirmative test with plasma pre-treatment with trypsin. Cox multivariable proportional regression and receiver-operating curve (ROC) analyses were used to assess mortality risk. Assessment of cardiovascular mortality during the first 3 years of observation showed that CgA measurement contained useful information with a hazard ratio (HR) of 5.4 (95% CI 1.7–16.4) (CgA confirm). In a multivariate setting, the corresponding HR was 5.9 (95% CI 1.8–19.1). When adding N-terminal proBNP (NT-proBNP) to the model, CgA confirm still possessed prognostic information (HR: 6.1; 95% CI 1.8–20.7). The result for predicting all-cause mortality displayed the same pattern. ROC analyses in comparison to NT-proBNP to identify patients on top of clinical variables at risk of cardiovascular death within 5 years of follow-up showed significant additive value of CgA confirm measurements compared with NT-proBNP and clinical variables. CgA measurement in the plasma of elderly patients with symptoms of heart failure can identify those at increased risk of short- and long-term mortality.

  • 332.
    Goetze, Jens P.
    et al.
    University of Copenhagen, Denmark; Aarhus University, Denmark.
    Rehfeld, Jens F.
    University of Copenhagen, Denmark.
    Alehagen, Urban
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Cholecystokinin in plasma predicts cardiovascular mortality in elderly females2016In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 209, p. 37-41Article in journal (Refereed)
    Abstract [en]

    Background: Cholecystokinin (CCK) and gastrin are related gastrointestinal hormones with documented cardiovascular effects of exogenous administration. It is unknown whether measurement of endogenous CCK or gastrin in plasma contains information regarding cardiovascular mortality. Methods: Mortality risk was evaluated using Cox proportional hazard regression and Kaplan-Meier analyses. Elderly patients in a primary care setting with symptoms of cardiac disease, i.e. shortness of breath, peripheral edema, and/or fatigue, were evaluated (n = 470). Primary care patients were followed for 13 years (from 1999); the 5-year all-cause and cardiovascular mortality was used as end point. Results: In univariate analysis, patients in the 4th CCK quartile had an increased risk of 5-year cardiovascular mortality (hazard ratio 3.9, 95% confidence interval: 2.1-7.0, p &lt; 0.0001). In multivariate analysis including established factors associated with cardiovascular mortality, CCK concentrations in the 4th quartile were still associated with increased 5-year cardiovascular mortality risk (HR 3.1, 95% C.I.: 1.7-5.7, p = 0.0004), even when including 4th quartile NT-proBNP concentrations in the same model. We observed a marked difference between the genders, where CCK concentrations in the 4th quartile were associated with a higher 5-year cardiovascular mortality in female patients (HR 8.99, 95% C.I.: 3.49-102.82, p = 0.0007) compared to men (1.47, 95% C.I.: 0.7-3.3, p = 0.35). In contrast, no significant information was obtained from 4th quartile gastrin concentrations on 5-year cardiovascular mortality risk. Conclusions: CCK in plasma is an independent marker of cardiovascular mortality in elderly female patients. The study thus introduces measurement of plasma CCK in gender-specific cardiovascular risk assessment. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  • 333.
    Gonon, Adrian
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Richter, Arina
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Cederholm, Ingemar
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Khan, Jehangir
    Karolinska Univ Hosp, Sweden.
    Novak, Jacek
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Milovanovic, Micha
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Janerot-Sjoberg, Birgitta
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; Karolinska Univ Hosp, Sweden.
    Effects of thoracic epidural analgesia on exercise-induced myocardial ischaemia in refractory angina pectoris2019In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 63, no 4, p. 515-522Article in journal (Refereed)
    Abstract [en]

    Background Thoracic epidural analgesia (TEDA) was offered to patients with refractory angina pectoris. Our primary objectives were to evaluate TEDAs influence on quality of life (QoL, base for power analysis), and hypothesising that TEDA with bupivacaine during 1 month counteracts exercise-induced myocardial hypoperfusion and increase physical performance. Methods Patients with refractory angina and exercise inducible hypoperfusion, as demonstrated by myocardial perfusion imaging (MPI), were randomised to 1-month treatment with TEDA with bupivacaine (B-group, n = 9) or saline (P-group, n = 10) in a double-blind fashion. MPI and bicycle ergometry were performed before TEDA and after 1 month while subjective QoL on a visual analogue scale (VAS) reported by the patients was checked weekly. Results During this month VAS (mean [95%CI]) increased similarly in both groups (B-group from 33 [18-50] to 54 [30-78] P P amp;lt; 0.05). The B-group reduced their exertional-induced myocardial hypoperfusion (from 32% [12-52] to 21% [3-39]; n = 9; P amp;lt; 0.05), while the P-group showed no significant change (before 21% [6-35]; at 1 month 23% [6-40]; n = 10). MPI at rest did not change and no improvement in physical performance was detected in neither of the groups. Conclusions In refractory angina, TEDA with bupivacaine inhibits myocardial ischaemia in contrast to TEDA with saline. Regardless of whether bupivacaine or saline is applied intermittently every day, TEDA during 1 month improves the quality of life and reduces angina, even when physical performance remains low. A significant placebo effect has to be considered.

  • 334.
    Good, Elin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    de Muinck, Ebo
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Editorial Material: Targeting systemic inflammation in atherosclerosis: Who will benefit? in EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY, vol 25, issue 9, pp 921-9222018In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 25, no 9, p. 921-922Article in journal (Other academic)
    Abstract [en]

    n/a

  • 335.
    Good, Elin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Wilhelm, Elisabeth
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Perk, Joep
    3Department of Health and Caring Sciences, Linnaeus University, Sweden.
    Jaarsma, Tiny
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    de Muinck, Ebo
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    High-grade carotid artery stenosis: A forgotten area in cardiovascular risk management2016In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, no 13, p. 1453-1460Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Patients with high-grade (≥70%) carotid artery stenosis (CAS) rank in the highest risk category for future cardiovascular (CV) events, but the quality of cardiovascular risk management in this patient group is unknown.

    DESIGN: Cross-sectional retrospective study.

    METHODS: Data were collected for all patients diagnosed with high-grade CAS in Östergötland county, Sweden between 1 January 2009 and 31 July 2012 regarding the quality of cardiovascular risk management, co-morbidity and outcomes during the 2-year follow-up period after a diagnosis of CAS with a carotid ultrasound scan. Patients were included regardless of whether they underwent carotid endarterectomy (CEA).

    RESULTS: A total of 393 patients with CAS were included in the study; 133 (33.8%) underwent CEA and 260 (66.2%) were assigned to a conservative management (CM) group. In both groups of patients the prescription of platelet inhibitors, statins and antihypertensive drugs increased significantly (p < 0.001) after diagnosis. However treatment targets were not met in the majority of patients and the low-density lipoprotein level was on target in only 13.5% of patients. During follow-up, low-density lipoprotein levels were not measured in 19.8% of patients who underwent CEA and 44.2% of patients in the CM group (p < 0.001); HbA1c was not measured in 24.4% of patients with diabetes in the CEA group and in 18.8% of patients in the CM group (p = 0.560). There was no documentation of counselling on diet, exercise, smoking cessation or adherence to medication. The combined clinical event rate (all-cause mortality, cardiovascular mortality and non-fatal cardiovascular events) was high in both groups (CEA 36.8% and CM 36.9%; p = 1.00) with no difference in the occurrence of ipsilateral ischaemic stroke.

    CONCLUSIONS: The clinical event rate was high in patients with high-grade CAS and the management of cardiovascular risk was deficient in all aspects.

  • 336.
    Gotberg, M.
    et al.
    Lund University, Sweden.
    Christiansen, E. H.
    Aarhus University Hospital, Denmark.
    Gudmundsdottir, I. J.
    Reykjavik University Hospital, Iceland.
    Sandhall, L.
    Helsingborg Hospital, Sweden.
    Danielewicz, M.
    Karlstad Hospital, Sweden.
    Jakobsen, L.
    Aarhus University Hospital, Denmark.
    Olsson, S. -E.
    Helsingborg Hospital, Sweden.
    Ohagen, P.
    Uppsala University, Sweden.
    Olsson, H.
    Karlstad Hospital, Sweden.
    Omerovic, E.
    Sahlgrenska University, Sweden.
    Calais, F.
    Örebro University, Sweden.
    Lindroos, P.
    St Goran Hospital, Sweden.
    Maeng, M.
    Aarhus University Hospital, Denmark.
    Todt, T.
    Lund University, Sweden.
    Venetsanos, Dimitrios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    James, S. K.
    Uppsala University, Sweden.
    Karegren, A.
    Västmanland Hospital Västerås, Sweden.
    Nilsson, M.
    Lund University, Sweden.
    Carlsson, J.
    Kalmar County Hospital, Sweden; Linnaeus University, Sweden.
    Hauer, D.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Jensen, J.
    Karolinska Institute, Sweden; Capio St Gorans Sjukhus, Sweden; Sundsvall Hospital, Sweden.
    Karlsson, A. -C.
    Halmstad County Hospital, Sweden.
    Panayi, G.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Erlinge, D.
    Lund University, Sweden.
    Frobert, O.
    Örebro University, Sweden.
    Instantaneous Wave-free Ratio versus Fractional Flow Reserve to Guide PCI2017In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 376, no 19, p. 1813-1823Article in journal (Refereed)
    Abstract [en]

    BACKGROUND The instantaneous wave-free ratio (iFR) is an index used to assess the severity of coronary-artery stenosis. The index has been tested against fractional flow reserve (FFR) in small trials, and the two measures have been found to have similar diagnostic accuracy. However, studies of clinical outcomes associated with the use of iFR are lacking. We aimed to evaluate whether iFR is noninferior to FFR with respect to the rate of subsequent major adverse cardiac events. METHODS We conducted a multicenter, randomized, controlled, open-label clinical trial using the Swedish Coronary Angiography and Angioplasty Registry for enrollment. A total of 2037 participants with stable angina or an acute coronary syndrome who had an indication for physiologically guided assessment of coronary-artery stenosis were randomly assigned to undergo revascularization guided by either iFR or FFR. The primary end point was the rate of a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization within 12 months after the procedure. RESULTS A primary end-point event occurred in 68 of 1012 patients (6.7%) in the iFR group and in 61 of 1007 (6.1%) in the FFR group (difference in event rates, 0.7 percentage points; 95% confidence interval [CI], -1.5 to 2.8; P = 0.007 for noninferiority; hazard ratio, 1.12; 95% CI, 0.79 to 1.58; P = 0.53); the upper limit of the 95% confidence interval for the difference in event rates fell within the prespecified noninferiority margin of 3.2 percentage points. The results were similar among major subgroups. The rates of myocardial infarction, target-lesion revascularization, restenosis, and stent thrombosis did not differ significantly between the two groups. A significantly higher proportion of patients in the FFR group than in the iFR group reported chest discomfort during the procedure. CONCLUSIONS Among patients with stable angina or an acute coronary syndrome, an iFR-guided revascularization strategy was noninferior to an FFR-guided revascularization strategy with respect to the rate of major adverse cardiac events at 12 months.

  • 337.
    Gottsäter, M.
    et al.
    Lund University, Malmö, Sweden.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Nilsson, P.M.
    Lund University, Malmö, Sweden.
    Predictive markers of abdominal aortic stiffness measured by echo-tracking in subjects with varying insulin sensitivity2014In: Journal of Human Hypertension, ISSN 0950-9240, E-ISSN 1476-5527, Vol. 28, no 7, p. 456-460Article in journal (Refereed)
    Abstract [en]

    Arterial stiffness is influenced by advancing age and vascular disease and is an independent risk factor for cardiovascular events and death. Using ultrasound measurements, arterial stiffness in a specific arterial segment can be assessed. The aim of this observational study was to explore the prospective and cross- sectional associations between arterial stiffness measured by ultrasound locally in the abdominal aorta and cardiovascular risk factors/markers including insulin resistance measured by the homeostatic model assessment- insulin resistance (HOMA- IR), lipids and abdominal obesity. This study includes 335 subjects from Malmo ", Sweden, examined in 1991- 1994 and again at follow- up in 1998- 2000 (mean age 64 years, 42% men). Ultrasound measurement of the abdominal aorta was performed at follow- up investigation. In the female subgroup, there was a positive association between HOMA-IR at baseline and abdominal aortic stiffness at follow-up (beta = 0.18, P 0.03) and a negative association between high-density lipoprotein and aortic stiffness (beta = 0.23, P 0.005), independently of classical cardiovascular risk factors. These associations were not found among men. The results suggest a greater or different role of impaired glucose metabolism in the pathophysiology of arterial stiffness in women than in men.

  • 338.
    Grams, M
    et al.
    John Hopkins University, USA.
    Sang, Yingying
    John Hopkins University, USA.
    Ballew, Shoshana
    John Hopkins University, USA.
    Szabó, Zoltán
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Matsushita, Kunihiro
    John Hopkins University, USA.
    Kalantar-Zadeh, Kamyar
    UC Irvine, USA.
    Coresh, Josef
    John Hopkins University, USA.
    Kovesdy, Csaba
    Memphis VA, USA.
    Incidence of and risk factors for acute kidney injury after major surgery2014Conference paper (Refereed)
  • 339.
    Grams, Morgan E
    et al.
    Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
    Sang, Yingying
    Departments of Epidemiology, Baltimore, Maryland, USA.
    Coresh, Josef
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
    Ballew, Shoshana H
    Departments of Epidemiology, Baltimore, Maryland, USA.
    Matsushita, Kunihiro
    Departments of Epidemiology, Baltimore, Maryland, USA.
    Levey, Andrew S
    Departments of Epidemiology, Baltimore, Maryland, USA.
    Greene, Tom H
    5Division of Clinical Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah, USA.
    Molnar, Miklos Z
    6Division of Nephrology, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
    Szabó, Zoltán
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Kalantar-Zadeh, Kamyar
    University of California Irvine Medical Center, Irvine, California, USA.
    Kovesdy, Csaba P
    University of Tennessee Health Science Center, Memphis, Tennessee, USA.
    Candidate Surrogate End Points for ESRD after AKI2016In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 27, no 9, p. 2851-2859Article in journal (Refereed)
    Abstract [en]

    AKI, a frequently transient condition, is not accepted by the US Food and Drug Association as an end point for drug registration trials. We assessed whether an intermediate-term change in eGFR after AKI has a sufficiently strong relationship with subsequent ESRD to serve as an alternative end point in trials of AKI prevention and/or treatment. Among 161,185 United States veterans undergoing major surgery between 2004 and 2011, we characterized in-hospital AKI by Kidney Disease Improving Global Outcomes creatinine criteria and decline in eGFR from prehospitalization to postdischarge time points and quantified associations of these values with ESRD and mortality over a median of 3.8 years. An eGFR decline of ≥30% at 30, 60, and 90 days after discharge occurred in 3.1%, 2.5%, and 2.6%, of survivors without AKI and 15.9%, 12.2%, and 11.7%, of survivors with AKI. For patients with in-hospital AKI compared with those with no AKI and stable eGFR, a 30% decline in eGFR at 30, 60, and 90 days after discharge demonstrated adjusted hazard ratios (95% confidence intervals) of ESRD of 5.60 (4.06 to 7.71), 6.42 (4.76 to 8.65), and 7.27 (5.14 to 10.27), with corresponding estimates for 40% decline in eGFR of 6.98 (5.21 to 9.35), 8.03 (6.11 to 10.56), and 10.95 (8.10 to 14.82). Risks for mortality were smaller but consistent in direction. A 30%-40% decline in eGFR after AKI could be a surrogate end point for ESRD in trials of AKI prevention and/or treatment, but additional trial evidence is needed.

  • 340.
    Grams, Morgan E
    et al.
    Johns Hopkins University School of Medicine, Baltimore, MD.
    Sang, Yingying
    Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
    Coresh, Josef
    Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
    Ballew, Shoshana
    Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
    Matsushita, Kunihiro
    Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
    Molnar, Miklos Z
    Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
    Szabó, Zoltán
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Kalantar-Zadeh, Kamyar
    Harold Simmons Center for Chronic Disease Research & Epidemiology, University of California Irvine Medical Center, Irvine.
    Kovesdy, Csaba P
    Nephrology Section, Memphis Veterans Affairs Medical Center, Memphis, TN.
    Acute Kidney Injury After Major Surgery: A Retrospective Analysis of Veterans Health Administration Data.2016In: American Journal of Kidney Diseases, ISSN 0272-6386, E-ISSN 1523-6838, Vol. 67, no 6, p. 872-880Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Few trials of acute kidney injury (AKI) prevention after surgery have been conducted, and most observational studies focus on AKI following cardiac surgery. The frequency of, risk factors for, and outcomes after AKI following other types of major surgery have not been well characterized and may present additional opportunities for trials in AKI.

    STUDY DESIGN: Observational cohort study.

    SETTING & PARTICIPANTS: 3.6 million US veterans followed up from 2004 to 2011 for the receipt of major surgery (cardiac; general; ear, nose, and throat; thoracic; vascular; urologic; and orthopedic) and postoperative outcomes.

    FACTORS: Demographics, health characteristics, and type of surgery.

    OUTCOMES: Postoperative AKI defined by the KDIGO creatinine criteria, postoperative length of stay, end-stage renal disease, and mortality.

    RESULTS: Postoperative AKI occurred in 11.8% of the 161,185 major surgery hospitalizations (stage 1, 76%; stage 2, 15%, stage 3 [without dialysis], 7%; and AKI requiring dialysis, 2%). Cardiac surgery had the highest postoperative AKI risk (relative risk [RR], 1.22; 95% CI, 1.17-1.27), followed by general (reference), thoracic (RR, 0.92; 95% CI, 0.87-0.98), orthopedic (RR, 0.70; 95% CI, 0.67-0.73), vascular (RR, 0.68; 95% CI, 0.64-0.71), urologic (RR, 0.65; 95% CI, 0.61-0.69), and ear, nose, and throat (RR, 0.32; 95% CI, 0.28-0.37) surgery. Risk factors for postoperative AKI included older age, African American race, hypertension, diabetes mellitus, and, for estimated glomerular filtration rate < 90mL/min/1.73m(2), lower estimated glomerular filtration rate. Participants with postoperative AKI had longer lengths of stay (15.8 vs 8.6 days) and higher rates of 30-day hospital readmission (21% vs 13%), 1-year end-stage renal disease (0.94% vs 0.05%), and mortality (19% vs 8%), with similar associations by type of surgery and more severe stage of AKI relating to poorer outcomes.

    LIMITATIONS: Urine output was not available to classify AKI; cohort included mostly men.

    CONCLUSIONS: AKI was common after major surgery, with similar risk factor and outcome associations across surgery type. These results can inform the design of clinical trials in postoperative AKI to the noncardiac surgery setting.

  • 341.
    Grams, Morgan
    et al.
    John Hopkins University.
    Sang, Yingying
    John Hopkins University.
    Coresh, Josef
    John Hopkins University.
    Ballew, Shoshana
    John Hopkins University.
    Matsushita, Kunihiro
    John Hopkins University.
    Greene, Tom
    University of Utah.
    Levey, Adrew S
    Tufts Medical Center.
    Molnar, Miklos Z
    University of Tennessee Health Science Center.
    Szabó, Zoltán
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Decline in Estimated Glomerular Filtration Rate After Acute Kidney Injury: A Surrogate Endpoint?2015In: ASN (American Society of Nephrology), 2015, Vol. 26Conference paper (Refereed)
    Abstract [en]

    Background: Often a transient condition, acute kidney injury (AKI) is not currently accepted as an endpoint for drug registration trials by the US FDA. We sought to determine whether an intermediate-term change in eGFR after AKI has a sufficiently strong relationship with subsequent ESRD to serve as an alternative endpoint in clinical trials of AKI preventionand/or treatment.

    Methods: We evaluated 161,185 US veterans who underwent major surgery between2004-2011. Post-surgical AKI was defined by the KDIGO creatinine criteria;decline in eGFR was calculated from pre-hospitalization value to two time-points post-discharge (60-days, 90-days) and related to ESRD and mortality using Cox proportional hazards regression.

    Results: In-hospital mortality varied by AKI status, ranging from 1% for patients without AKI to 35% for those with dialysis-requiring AKI. An eGFR decline of ³30% at 60-days was relatively frequent: 2.5%, 9.7%, 17.2%, and 28.6% in those with no AKI, Stage 1 AKI, Stage 2 AKI, and Stage 3 AKI, respectively. There was a graded relationship between eGFR decline at 60-days and risk of ESRD in persons both with and without AKI (Figure). Compared to stable eGFR/no in-hospital AKI, the adjusted hazard ratio (HR) of ESRD associated with a 30% decline at 60-days after AKI was 6.42 (95% CI: 4.8-8.7). Risks for mortality associated with eGFR decline were smaller: the HR for 30% decline 60-days after in-hospital AKI was 1.59 (95% CI: 1.46-1.73). Risk relationships were similar at 90-days.

    Conclusions: A 30% decline in eGFR from pre-hospitalization baseline to 60-days or 90-days after an episode of AKI may be an acceptable surrogate endpoint in trials of AKI prevention and/or treatment.

  • 342.
    Grigorescu Fredriksson, Alexandru
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Blood flow specific assessment of ventricular function: Visualization and quantification using 4D flow CMR2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The spectrum of cardiovascular diseases is the leading cause of morbidity and mortality globally. Early assessment and treatment of these conditions, acquired as well as congenital, is therefore of paramount importance.

     

    The human heart has a great ability to adapt to various hemodynamic conditions by cardiac remodeling. Pathologic cardiac remodeling can occur as a result of cardiovascular disease in an effort to maintain satisfactory cardiac function. With time, cardiac function diminishes leading to disease progression and subsequent heart failure, the end-point of many heart diseases, associated with very poor prognosis.

     

    Within the normal cardiac ventricles blood flows in highly organized patterns, and changes in cardiac configuration or function will affect these flow patterns. Conversely, altered flows and pressures can bring about cardiac remodeling. In congenital heart disease, even after corrective surgery, cardiac anatomy and thereby intracardiac blood flow patterns are inherently altered. The clinically most available imaging technique, ultrasound with Doppler, allows only for one-directional flow assessment and is limited by the need of clear examination windows, thus failing to fully assess the complex three-dimensional blood flow within the beating heart. Cardiovascular magnetic resonance imaging (CMR) with phase-contrast has the ability to acquire three-dimensional (3D), three-directional time resolved velocity data (3D + time = 4D flow data) from which visualization and quantification of blood flow patterns over the complete cardiac cycle can be performed. Four functional blood flow components have previously been defined based on the blood route and distribution through the ventricle, where the inflowing blood that passes directly to the outflow is called Direct flow. From these components, various quantitative measures can be derived, such as component volumes and kinetic energy (KE) throughout the cardiac cycle. In addition, the 4D flow technique has the ability to quantify and visualize turbulent flow with increased velocity fluctuations in the heart and vessels, turbulent kinetic energy (TKE).

     

    The technique has been developed and evaluated for assessment of left ventricular (LV) blood flow in healthy subjects and in patients with dilated dysfunctional left ventricles, showing significant changes in blood flow patterns and energetics with disease. There is however still no study addressing the gap in the spectrum from the healthy cohorts to patients with moderate to severe left ventricular remodeling. In Paper III, 4D flow CMR was utilized to assess LV blood flow in patients with subtle LV dysfunction, and a shift in blood flow component volumes and KE was seen from the Direct flow to the non-ejecting blood flow components.

     

    In patients with both left- and right-sided acquired and congenital heart disease, right ventricular (RV) function is of great prognostic significance, however this ventricle has historically been somewhat overseen. With its complex geometry, advanced physiology and retrosternal location, assessment of the RV is still challenging and the right ventricular blood flow is still incompletely described. In Paper I, the RV blood flow in healthy subjects was assessed, and the proportionally larger Direct flow component was located in the most basal region of the ventricle and possessed higher levels of KE at end-diastole than the other flow components suggesting that this portion of blood was prepared for efficient systolic ejection. In Paper II, the blood flow was assessed in the RV of patients with subtle primary LV disease, and even if conventional echocardiographic or CMR RV parameters did not show any RV dysfunction, alterations of flow patterns suggestive of RV impairment were found in the patients with the more remodeled LVs.

     

    With improvements of the cardiovascular health care, including the surgical techniques, the number of adult patients with surgically corrected complex congenital heart diseases increases, one of which is tetralogy of Fallot (ToF). Surgical repair of ToF involves widening of the pulmonary stenosis, which postoperatively may cause pulmonary insufficiency and regurgitation (PR). Disturbed or turbulent flow patterns are rare in the healthy cardiovascular system. With pathological changes, such as valvular insufficiency, increased amounts of TKE have been demonstrated. Turbulence is known to be harmful to organic tissues and could be significant in the development of ventricular remodeling, such as dilation and other complications seen in Fallot patients. In Paper IV, the RV intraventricular TKE levels were assessed in relation to conventional measures of PR. Results showed that RV TKE was increased in ToF patients with PR compared to healthy controls, and that these 4D flow-specific measures related slightly stronger to indices of RV remodeling than the conventional measures of PR.

     

    4D flow CMR analysis of the intracardiac blood flow has the potential of adding to pathophysiological understanding, and thereby provide useful diagnostic information and contribute to optimization of treatment of heart disease at earlier stages before irreversible and clinically noticeable changes occur. The flow specific measures used in this thesis could be utilized to detect these alterations of intracardiac blood flow and could thus act as potential markers of progressing ventricular dysfunction, pathological remodeling or used for risk stratification in adults with early repair tetralogy of Fallot. Visualizations of intracardiac flow patterns could provide useful information to cardiac/thoracic surgeons pre- and post-operatively.

  • 343.
    Guldbrand, Hans
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Primary Health Care in Motala.
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Dizdar, B.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Bunjaku, B.
    Östergötlands Läns Landsting. Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, West County Primary Health Care.
    Nyström, Fredrik H.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Bachrach-Lindström, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Randomization to a low-carbohydrate diet advice improves health related quality of life compared with a low-fat diet at similar weight-loss in Type 2 diabetes mellitus2014In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 106, no 2, p. 221-227Article in journal (Refereed)
    Abstract [en]

    Aims

    To compare the effects on health-related quality of life (HRQoL) of a 2-year intervention with a low-fat diet (LFD) or a low-carbohydrate diet (LCD) based on four group-meetings to achieve compliance. To describe different aspects of taking part in the intervention following the LFD or LCD.

    Methods

    Prospective, randomized trial of 61 adults with Type 2 diabetes mellitus. The SF-36 questionnaire was used at baseline, 6, 12 and 24 months. Patients on LFD aimed for 55–60 energy percent (E%) and those on LCD for 20 E% from carbohydrates. The patients were interviewed about their experiences of the intervention.

    Results

    Mean body-mass-index was 32.7 ± 5.4 kg/m2 at baseline. Weight-loss did not differ between groups and was maximal at 6 months, LFD: −3.99 ± 4.1 kg, LCD: −4.31 ± 3.6 kg (p < 0.001 within groups). There was an increase in the physical component score of SF-36 from 44.1 (10.0) to 46.7 (10.5) at 12 months in the LCD group (p < 0.009) while no change occurred in the LFD group (p < 0.03 between groups). At 12 months the physical function, bodily pain and general health scores improved within the LCD group (p values 0.042–0.009) while there was no change within the LFD group.

    Conclusions

    Weight-changes did not differ between the diet groups while improvements in HRQoL only occurred after one year during treatment with LCD. No changes of HRQoL occurred in the LFD group in spite of a similar reduction in body weight.

     

  • 344.
    Gullestad, Lars
    et al.
    Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, University of Oslo, Oslo, Norway.
    Eiskjaer, Hans
    Department of Cardiology, Aarhus University Hospital, Skejby, Aarhus, Denmark.
    Gustafsson, Finn
    Department of Cardiology, Rigshospitalet, Copenhagen, Denmark.
    Riise, Gerdt C
    Department of Respiratory Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Karason, Kristjan
    Department of Cardiology and Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Dellgren, Göran
    Department of Cardiology and Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Rådegran, Göran
    Department of Clinical Sciences Lund, Cardiology, Lund University and the Section for Heart Failure and Valvular Disease, Skåne University Hospital, Lund, Sweden.
    Hansson, Lennart
    Department of Respiratory Medicine, Lund University Hospital and Skåne University Hospital, Lund, Sweden.
    Gude, Einar
    Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, University of Oslo, Oslo, Norway.
    Bjørtuft, Øystein
    Department of Respiratory Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
    Jansson, Kjell
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Schultz, Hans Henrik
    Division of Lung Transplantation, Department of Cardiology, Rigshospitalet, Copenhagen, Denmark.
    Solbu, Dag
    Novartis Norge AS, Oslo, Norway.
    Iversen, Martin
    Division of Lung Transplantation, Department of Cardiology, Rigshospitalet, Copenhagen, Denmark.
    Long-term outcomes of thoracic transplant recipients following conversion to everolimus with reduced calcineurin inhibitor in a multicenter, open-label, randomized trial2016In: Transplant International, ISSN 0934-0874, E-ISSN 1432-2277, Vol. 29, no 7, p. 819-829Article in journal (Refereed)
    Abstract [en]

    The NOCTET study randomized 282 patients ≥1 year after heart or lung transplantation to continue conventional calcineurin inhibitor (CNI) therapy or to start everolimus with reduced-exposure CNI. Last follow-up, at ≥5 years postrandomization (mean: 5.6 years) was attended by 72/140 everolimus patients (51.4%) and 91/142 controls (64.1%). Mean measured GFR remained stable in the everolimus group from randomization (51.3 ml/min) to last visit (51.4 ml/min) but decreased in controls (from 50.5 ml/min to 45.3 ml/min) and was significantly higher with everolimus at last follow-up (P = 0.004). The least squares mean (SE) change from randomization was -1.5 (1.7)ml/min with everolimus versus -7.2 (1.7)ml/min for controls (difference: 5.7 [95% CI 1.7; 9.6]ml/min; P = 0.006). The difference was accounted for by heart transplant patients (difference: 6.9 [95% 2.3; 11.5]ml/min; P = 0.004). Lung transplant patients showed no between-group difference at last follow-up. Rates of rejection, death, and major cardiac events were similar between groups, as was graft function. Pneumonia was more frequent with everolimus (18.3% vs. 6.4%). In conclusion, introducing everolimus in maintenance heart transplant patients, with reduced CNI, achieves a significant improvement in renal function which is maintained for at least 5 years, but an early renal benefit in lung transplant patients was lost. Long-term immunosuppressive efficacy was maintained.

  • 345.
    Gulyas, Miklos
    et al.
    Genetics and Pathology , Uppsala University , Uppsala , Sweden.
    Mattsson, Johanna Sofia Margareta
    Genetics and Pathology , Uppsala University , Uppsala , Sweden.
    Lindgren, Andrea
    Region Östergötland, Heart and Medicine Center, Allergy Center. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ek, Lars
    Skane University Hospital , Lund , Sweden.
    Lamberg Lundström, Kristina
    Akademiska Hospital , Uppsala , Sweden.
    Behndig, Annelie
    Norrland University Hospital , Umeå , Sweden.
    Holmberg, Erik
    Sahlgrenska Academy at University of Gothenburg , Sweden.
    Micke, Patrick
    Genetics and Pathology , Uppsala University , Uppsala , Sweden.
    Bergman, Bengt
    Sahlgrenska Academy at University of Gothenburg , Sweden..
    COX-2 expression and effects of celecoxib in addition to standard chemotherapy in advanced non-small cell lung cancer2018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 2, p. 244-250Article in journal (Refereed)
    Abstract [en]

    AIM: Inhibition of cyclooxygenase-2 (COX-2) is proposed as a treatment option in several cancer types. However, in non-small cell lung cancer (NSCLC), phase III trials have failed to demonstrate a benefit of adding COX-2 inhibitors to standard chemotherapy. The aim of this study was to analyze COX-2 expression in tumor and stromal cells as predictive biomarker for COX-2 inhibition.

    METHODS: In a multicenter phase III trial, 316 patients with advanced NSCLC were randomized to receive celecoxib (400 mg b.i.d.) or placebo up to one year in addition to a two-drug platinum-based chemotherapy combination. In a subset of 122 patients, archived tumor tissue was available for immunohistochemical analysis of COX-2 expression in tumor and stromal cells. For each compartment, COX-2 expression was graded as high or low, based on a product score of extension and intensity of positively stained cells.

    RESULTS: An updated analysis of all 316 patients included in the original trial, and of the 122 patients with available tumor tissue, showed no survival differences between the celecoxib and placebo arms (HR 1.01; 95% CI 0.81-1.27 and HR 1.12; 95% CI 0.78-1.61, respectively). High COX-2 scores in tumor (n = 71) or stromal cells (n = 55) was not associated with a superior survival outcome with celecoxib vs. placebo (HR =0.96, 95% CI 0.60-1.54; and HR =1.51; 95% CI 0.86-2.66), and no significant interaction effect between COX-2 score in tumor or stromal cells and celecoxib effect on survival was detected (p = .48 and .25, respectively).

    CONCLUSIONS: In this subgroup analysis of patients with advanced NSCLC treated within the context of a randomized trial, we could not detect any interaction effect of COX-2 expression in tumor or stromal cells and the outcome of celecoxib treatment in addition to standard chemotherapy.

  • 346.
    Gupta, Vikas
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Bustamante, Mariana
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Fredriksson, Alexandru
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Carlhäll, Carljohan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Improving left ventricular segmentation in four-dimensional flow MRI using intramodality image registration for cardiac blood flow analysis2018In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 79, no 1, p. 554-560Article in journal (Refereed)
    Abstract [en]

    PurposeAssessment of blood flow in the left ventricle using four-dimensional flow MRI requires accurate left ventricle segmentation that is often hampered by the low contrast between blood and the myocardium. The purpose of this work is to improve left-ventricular segmentation in four-dimensional flow MRI for reliable blood flow analysis. MethodThe left ventricle segmentations are first obtained using morphological cine-MRI with better in-plane resolution and contrast, and then aligned to four-dimensional flow MRI data. This alignment is, however, not trivial due to inter-slice misalignment errors caused by patient motion and respiratory drift during breath-hold based cine-MRI acquisition. A robust image registration based framework is proposed to mitigate such errors automatically. Data from 20 subjects, including healthy volunteers and patients, was used to evaluate its geometric accuracy and impact on blood flow analysis. ResultsHigh spatial correspondence was observed between manually and automatically aligned segmentations, and the improvements in alignment compared to uncorrected segmentations were significant (Pamp;lt;0.01). Blood flow analysis from manual and automatically corrected segmentations did not differ significantly (Pamp;gt;0.05). ConclusionOur results demonstrate the efficacy of the proposed approach in improving left-ventricular segmentation in four-dimensional flow MRI, and its potential for reliable blood flow analysis. Magn Reson Med 79:554-560, 2018. (c) 2017 International Society for Magnetic Resonance in Medicine.

  • 347.
    Gupta, Vikas
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Lantz, Jonas
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Henriksson, Lilian
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Karlsson, Matts
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Persson, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Automated three-dimensional tracking of the left ventricular myocardium in time-resolved and dose-modulated cardiac CT images using deformable image registration2018In: Journal of Cardiovascular Computed Tomography, ISSN 1934-5925, Vol. 12, no 2, p. 139-148Article in journal (Refereed)
    Abstract [en]

    Background Assessment of myocardial deformation from time-resolved cardiac computed tomography (4D CT) would augment the already available functional information from such an examination without incurring any additional costs. A deformable image registration (DIR) based approach is proposed to allow fast and automatic myocardial tracking in clinical 4D CT images.

    Methods Left ventricular myocardial tissue displacement through a cardiac cycle was tracked using a B-spline transformation based DIR. Gradient of such displacements allowed Lagrangian strain estimation with respect to end-diastole in clinical 4D CT data from ten subjects with suspected coronary artery disease. Dice similarity coefficient (DSC), point-to-curve error (PTC), and tracking error were used to assess the tracking accuracy. Wilcoxon signed rank test provided significance of tracking errors. Topology preservation was verified using Jacobian of the deformation. Reliability of estimated strains and torsion (normalized twist angle) was tested in subjects with normal function by comparing them with normal strain in the literature.

    Results Comparison with manual tracking showed high accuracy (DSC: 0.99± 0.05; PTC: 0.56mm± 0.47 mm) and resulted in determinant(Jacobian) > 0 for all subjects, indicating preservation of topology. Average radial (0.13 mm), angular (0.64) and longitudinal (0.10 mm) tracking errors for the entire cohort were not significant (p > 0.9). For patients with normal function, average strain [circumferential, radial, longitudinal] and peak torsion estimates were: [-23.5%, 31.1%, −17.2%] and 7.22°, respectively. These estimates were in conformity with the reported normal ranges in the existing literature.

    Conclusions Accurate wall deformation tracking and subsequent strain estimation are feasible with the proposed method using only routine time-resolved 3D cardiac CT.

  • 348.
    Gupta, Vikas
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Erasmus MC Canc Inst, Netherlands.
    Wang, Yibing
    Erasmus MC Canc Inst, Netherlands.
    Romero, Alejandra Mendez
    Erasmus MC Canc Inst, Netherlands.
    Myronenko, Andriy
    Accuray Inc, CA 94089 USA.
    Jordan, Petr
    Accuray Inc, CA 94089 USA.
    Maurer, Calvin
    Accuray Inc, CA 94089 USA.
    Heijmen, Ben
    Erasmus MC Canc Inst, Netherlands.
    Hoogeman, Mischa
    Erasmus MC Canc Inst, Netherlands.
    Fast and robust adaptation of organs-at-risk delineations from planning scans to match daily anatomy in pre-treatment scans for online-adaptive radiotherapy of abdominal tumors2018In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 127, no 2, p. 332-338Article in journal (Refereed)
    Abstract [en]

    Purpose: To validate a novel deformable image registration (DIR) method for online adaptation of planning organ-at-risk (OAR) delineations to match daily anatomy during hypo-fractionated RT of abdominal tumors. Materials and methods: For 20 liver cancer patients, planning OAR delineations were adapted to daily anatomy using the DIR on corresponding repeat CTs. The DIRs accuracy was evaluated for the entire cohort by comparing adapted and expert-drawn OAR delineations using geometric (Dice Similarity Coefficient (DSC), Modified Hausdorff Distance (MHD) and Mean Surface Error (MSE)) and dosimetric (D-max and D-mean) measures. Results: For all OARs, DIR achieved average DSC, MHD and MSE of 86%, 2.1 mm, and 1.7 mm, respectively, within 20 s for each repeat CT. Compared to the baseline (translations), the average improvements ranged from 2% (in heart) to 24% (in spinal cord) in DSC, and 25% (in heart) to 44% (in right kidney) in MHD and MSE. Furthermore, differences in dose statistics (D-max, D-mean and D-2%) using delineations from an expert and the proposed DIR were found to be statistically insignificant (p amp;gt; 0.01). Conclusion: The validated DIR showed potential for online-adaptive radiotherapy of abdominal tumors as it achieved considerably high geometric and dosimetric correspondences with the expert-drawn OAR delineations, albeit in a fraction of time required by experts. (C) 2018 The Authors. Published by Elsevier B.V.

  • 349.
    Gustafsson, Håkan
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Biomedical Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Lindgren, Mikael
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology. Norwegian University of Science and Technology, Norway.
    Kolbun, Natallia
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Jonson, Maria
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    de Muinck, Ebo
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Zachrisson, Helene
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Visualization of oxidative stress in ex vivo biopsies using electron paramagnetic resonance imaging2015In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 73, no 4, p. 1682-1691Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The purpose of this study was to develop an X-Band electron paramagnetic resonance imaging protocol for visualization of oxidative stress in biopsies.

    METHODS: The developed electron paramagnetic resonance imaging protocol was based on spin trapping with the cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. Computer software was developed for deconvolution and back-projection of the EPR image. A phantom containing radicals of known spatial characteristic was used for evaluation of the developed protocol. As a demonstration of the technique electron paramagnetic resonance imaging of oxidative stress was performed in six sections of atherosclerotic plaques. Histopathological analyses were performed on adjoining sections.

    RESULTS: The developed computer software for deconvolution and back-projection of the EPR images could accurately reproduce the shape of a phantom of known spatial distribution of radicals. The developed protocol could successfully be used to image oxidative stress in six sections of the three ex vivo atherosclerotic plaques.

    CONCLUSIONS: We have shown that oxidative stress can be imaged using a combination of spin trapping with the cyclic hydroxylamine spin probe cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. A thorough and systematic evaluation on different types of biopsies must be performed in the future to validate the proposed technique. Magn Reson Med, 2014.

  • 350.
    Gustafsson, Håkan
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Norell, M.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Lindgren, Mikael
    Norwegian University of Science and Technology, Trondheim, Norway.
    Engström, Maria
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences.
    Rosén, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Zachrisson, Helene
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Fe(III) distribution varies substantially within and between atherosclerotic plaques2014In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 2, no 71, p. 885-892Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    Vulnerable atherosclerotic plaques are structurally weak and prone to rupture, presumably due to local oxidative stress. Redox active iron is linked to oxidative stress and the aim of this study was to investigate the distribution of Fe(III) in carotid plaques and its relation to vulnerability for rupture.

    METHODS:

    Atherosclerotic plaques from 10 patients (three asymptomatic and seven symptomatic) were investigated. Plaque vulnerability was classified using ultrasound and immunohistochemistry and correlated to Fe(III) measured by electron paramagnetic resonance spectroscopy.

    RESULTS:

    Large intra-plaque Fe(III) variations were found. Plaques from symptomatic patients had a higher Fe(III) concentration as compared with asymptomatic plaques (0.36 ± 0.21 vs. 0.06 ± 0.04 nmol Fe(III)/mg tissue, P < 0.05, in sections adjoining narrowest part of the plaques). All but one plaque from symptomatic patients showed signs of cap rupture. No plaque from asymptomatic patients showed signs of cap rupture. There was a significant increase in cap macrophages in plaques from symptomatic patients compared with asymptomatic patients (31 ± 11% vs. 2.3 ± 2.3%, P < 0.01).

    CONCLUSION:

    Fe(III) distribution varies substantially within atherosclerotic plaques. Plaques from symptomatic patients had significantly higher concentrations of Fe(III), signs of cap rupture and increased cap macrophage activity.

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