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  • 51.
    Alhede, Christina
    et al.
    Herlev Gentofte University Hospital, Denmark.
    Lauridsen, Trine K.
    Herlev Gentofte University Hospital, Denmark.
    Johannessen, Arne
    Herlev Gentofte University Hospital, Denmark.
    Dixen, Ulrik
    Hvidovre University Hospital, Denmark.
    Jensen, Jan S.
    Herlev Gentofte University Hospital, Denmark.
    Raatikainen, Pekka
    Helsinki University Hospital, Finland.
    Hindricks, Gerhard
    Leipzig University Hospital, Germany.
    Walfridsson, Håkan
    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.
    Kongstadf, Ole
    Lund University Hospital, Sweden.
    Pehrson, Steen
    Rigshosp, Denmark.
    Englund, Anders
    Örebro University Hospital, Sweden.
    Hartikainen, Juha
    Kupio University Hospital, Finland.
    Hansen, Peter S.
    Varde Heart Centre, Denmark.
    Nielsen, Jens C.
    Aarhus University Hospital, Denmark.
    Jons, Christian
    Rigshosp, Denmark.
    The impact of supraventricular ectopic complexes in different age groups and risk of recurrent atrial fibrillation after antiarrhythmic medication or catheter ablation2018In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 250, p. 122-127Article in journal (Refereed)
    Abstract [en]

    Introduction: Supraventricular ectopic complexes (SVEC) are known risk factors of recurrent atrial fibrillation (AF). However, the impact of SVEC in different age groups is unknown. We aimed to investigate the risk of AF recurrence with higher SVEC burden in patients +/- 57 years, respectively, after treatment with antiarrhythmic medication (AAD) or catheter ablation (CA). Methods: In total, 260 patients with LVEF amp;gt;40% and age amp;lt;= 70 years were randomized to AAD (N = 132) or CA (N = 128) as first-line treatment for paroxysmal AF. All patients underwent 7-day Holter monitoring at baseline, and after 3, 6, 12, 18 and 24 months and were categorized according to median age +/- 57 years. We used multi-variate Cox regression analyses and we defined high SVEC burden at 3 months of follow-up as the upper 75th percentile amp;gt;195 SVEC/day. AF recurrence was defined as AF amp;gt;= 1 min, AF-related cardioversion or hospitalization. Results: Age amp;gt;57 years were significantly associated with higher AF recurrence rate after CA (58% vs 36%, p = 0.02). After CA, we observed a higher SVEC burden during follow-up in patients amp;gt;57 years which was not observed in the younger age group treatedwith CA (p = 0.006). High SVEC burden at 3 months after CA was associated with AF recurrence in older patients but not in younger patients (amp;gt;57 years: HR 3.4 [1.4-7.9], p = 0.005). We did not find any age-related differences after AAD. Conclusion: We found that younger and older patients respond differently to CA and that SVEC burden was only associated with AF recurrence in older patients. (C) 2017 Elsevier B.V. All rights reserved.

  • 52.
    Ali, Zaheer
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Investigating mechanisms of angiogenesis in health and disease using zebrafish models2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Angiogenesis, the growth of blood vessels from an existing vasculature, can occur by sprouting from preexisting vessels or by vessel splitting (intussusception). Pathological angiogenesis drives choroidal neovascularization (CNV) in age related macular degeneration (AMD) which is commonly restricted under the retinal pigment epithelium (RPE), called occult CNV, but may also involve vessels penetrating through the RPE into the sub-retinal space. Pathological vessels are poorly developed, insufficiently perfused and highly leaky, phenotypes that are considered to drive disease progression and lead to poor prognosis. Currently, a number of anti-angiogenic drugs exists, the majority of which target vascular endothelial factor (VEGF), but although they often are highly beneficial for treating eye diseases in the short-term, they are generally of limited efficacy in other diseases such as cancer, and also have poorer efficacy when used for treatment of eye diseases in the long-term. A better understanding of the mechanisms underlying pathological angiogenesis can generate new targets for treatment leading to development of better drugs for cancer and retinopathies, but perhaps also other angiogenesis-dependent diseases, in the future. In this thesis mechanisms involved in developmental angiogenesis or pathological angiogenesis in the choroid, cornea or melanoma was identified. These findings highlight the need to further elaborate our knowledge related to angiogenesis in different tissues/conditions for a more targeted, and potentially effective treatment of diseases in the future.

    In paper I, we for the first time identified the choriocapillaries (CCs) in adult zebrafish and found that occult CNV could be induced by exposing the fish to severe hypoxia. Interestingly, we found that occult CNV relied on intussusception, involving not only de novo generation of intussusceptive pillars but also a previously poorly understood mechanism called pillar splitting. This involved HIF-VEGF-VEGFR2 signaling and evidence that this also occurred in both rats and humans suffering from AMD suggested that the mechanism was conserved and clinically relevant.

    In contrast, we found in paper II that the development of CCs in the zebrafish relies on sprouting angiogenesis, involve continuous remodeling, and delayed maturation of the vasculature in 2D. The initial development was found to occur by a unique process of tissuewide synchronized vasculogenesis. As expected, VEGFA via VEGFR2 was also critical for the development of these vessels in the zebrafish embryo, but surprisingly this was independent on hypoxia-inducible factor (HIF)-1.

    Inflammatory nuclear factor-kB (NF-kB) signaling is involved in the progression of angiogenesis, but this signaling pathway has mainly been studied in the inflammatory cells and the role of NF-kB in the endothelial cells during angiogenesis is poorly understood. In paper III, we found that blocking NF-kB signaling using a specific IKK2 blocker IMD0354, specifically blocks pathological as well as developmental angiogenesis by targeting endothelial cell NF-kB signaling in the endothelial cells. Using a rat model for suture-induced corneal neovascularization, IMD0354 treatment lead to reduced production of inflammatory C-C motif chemokine ligand 2 (CCL2), C-X-C motif chemokine ligand 5 (CXCL5) and VEGF, and thereby reduced pathological corneal angiogenesis in this model.

    Using the zebrafish tumor xenograft model in paper IV, we found an association between Microphthalmia associated transcription factor (MITF) and pigment epithelium derived factor (PEDF), which was involved in pathological tumor angiogenesis and metastasis. Similarly, in paper V we used zebrafish transplantation models to study and investigate the use of biocompatible polymers for the delivery of pro-angiogenic FGF-2 as a potential treatment strategy for ischemic diseases such as myocardial infarction (MI). Conclusively, this thesis provides new insights into diverse fields of angiogenic assays using zebrafish, and reveals new mechanisms of angiogenesis in health and disease. This work will hopefully provide a foundation for further studies into occult CNV related to AMD, a process that has not been possible to study previously in pre-clinical models. In addition, zebrafish xenograft or other transplantation models used in this work will likely be important to study cancer biology and to develop more attractive pharmaceutical preparations based on biocompatible hydrogels formulated as microspheres in the future.

    List of papers
    1. Selective IKK2 inhibitor IMD0354 disrupts NF-kappa B signaling to suppress corneal inflammation and angiogenesis
    Open this publication in new window or tab >>Selective IKK2 inhibitor IMD0354 disrupts NF-kappa B signaling to suppress corneal inflammation and angiogenesis
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    2018 (English)In: Angiogenesis, ISSN 0969-6970, E-ISSN 1573-7209, Vol. 21, no 2, p. 267-285Article in journal (Refereed) Published
    Abstract [en]

    Corneal neovascularization is a sight-threatening condition caused by angiogenesis in the normally avascular cornea. Neovascularization of the cornea is often associated with an inflammatory response, thus targeting VEGF-A alone yields only a limited efficacy. The NF-kappa B signaling pathway plays important roles in inflammation and angiogenesis. Here, we study consequences of the inhibition of NF-kappa B activation through selective blockade of the IKK complex I kappa B kinase beta (IKK2) using the compound IMD0354, focusing on the effects of inflammation and pathological angiogenesis in the cornea. In vitro, IMD0354 treatment diminished HUVEC migration and tube formation without an increase in cell death and arrested rat aortic ring sprouting. In HUVEC, the IMD0354 treatment caused a dose-dependent reduction in VEGF-A expression, suppressed TNF alpha-stimulated expression of chemokines CCL2 and CXCL5, and diminished actin filament fibers and cell filopodia formation. In developing zebrafish embryos, IMD0354 treatment reduced expression of Vegf-a and disrupted retinal angiogenesis. In inflammation-induced angiogenesis in the rat cornea, systemic selective IKK2 inhibition decreased inflammatory cell invasion, suppressed CCL2, CXCL5, Cxcr2, and TNF-alpha expression and exhibited anti-angiogenic effects such as reduced limbal vessel dilation, reduced VEGF-A expression and reduced angiogenic sprouting, without noticeable toxic effect. In summary, targeting NF-kappa B by selective IKK2 inhibition dampened the inflammatory and angiogenic responses in vivo by modulating the endothelial cell expression profile and motility, thus indicating an important role of NF-kappa B signaling in the development of pathologic corneal neovascularization.

    Place, publisher, year, edition, pages
    Springer Netherlands, 2018
    Keywords
    Cornea; Neovascularization; NF-kappa B; IMD0354; IKK2; VEGF
    National Category
    Cell and Molecular Biology
    Identifiers
    urn:nbn:se:liu:diva-147373 (URN)10.1007/s10456-018-9594-9 (DOI)000428924500007 ()29332242 (PubMedID)2-s2.0-85041334437 (Scopus ID)
    Note

    Funding Agencies|Swedish Research Council [2012-2472]; Swedish Foundation Stiftelsen Synframjandets Forskningsfond/Ogonfonden; Svenska Sallskapet for Medicinsk Forskning; Linkoping Universitet; Jeanssons Stiftelser

    Available from: 2018-05-18 Created: 2018-05-18 Last updated: 2019-05-01Bibliographically approved
    2. Regulatory and Functional Connection of Microphthalmia-Associated Transcription Factor and Anti-Metastatic Pigment Epithelium Derived Factor in Melanoma
    Open this publication in new window or tab >>Regulatory and Functional Connection of Microphthalmia-Associated Transcription Factor and Anti-Metastatic Pigment Epithelium Derived Factor in Melanoma
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    2014 (English)In: Neoplasia, ISSN 1522-8002, E-ISSN 1476-5586, Vol. 16, no 6, p. 529-542Article in journal (Refereed) Published
    Abstract [en]

    Pigment epithelium-derived factor (PEDF), a member of the serine protease inhibitor superfamily, has potent anti-metastatic effects in cutaneous melanoma through its direct actions on endothelial and melanoma cells. Here we show that PEDF expression positively correlates with microphthalmia-associated transcription factor ( MITF) in melanoma cell lines and human samples. High PEDF and MITF expression is characteristic of low aggressive melanomas classified according to molecular and pathological criteria, whereas both factors are decreased in senescent melanocytes and naevi. Importantly, MITF silencing down-regulates PEDF expression in melanoma cell lines and primary melanocytes, suggesting that the correlation in the expression reflects a causal relationship. In agreement, analysis of Chromatin immunoprecipitation coupled to high throughput sequencing (ChIP-seq) data sets revealed three MITF binding regions within the first intron of SERPINF1, and reporter assays demonstrated that the binding of MITF to these regions is sufficient to drive transcription. Finally, we demonstrate that exogenous PEDF expression efficiently halts in vitro migration and invasion, as well as in vivo dissemination of melanoma cells induced by MITF silencing. In summary, these results identify PEDF as a novel transcriptional target of MITF and support a relevant functional role for the MITF-PEDF axis in the biology of melanoma.

    Place, publisher, year, edition, pages
    Neoplasia, 2014
    National Category
    Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-110497 (URN)10.1016/j.neo.2014.06.001 (DOI)000340553600007 ()25030625 (PubMedID)
    Note

    Funding Agencies|Ministerio de Ciencia y Competitividad of Spain [SAF-2010-19256, SAF-2011-24225, SAF-2012-32117, FIS 11/02568, RD09/0076/0101, PT13/0010/0012, PI12/01552]; LiU-Cancer; Svenska Sallskapet for Medicinsk Forskning; Ake Wibergs Stiftelse; Goesta Fraenkels Stifelse; Fundacion Cientifica de la Asociacion Espanola Contra el Cancer

    Available from: 2014-09-15 Created: 2014-09-12 Last updated: 2018-12-07
    3. Adjustable delivery of pro-angiogenic FGF-2 by alginate: collagen microspheres
    Open this publication in new window or tab >>Adjustable delivery of pro-angiogenic FGF-2 by alginate: collagen microspheres
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    2018 (English)In: BIOLOGY OPEN, ISSN 2046-6390, Vol. 7, no 3, article id UNSP bio027060Article in journal (Refereed) Published
    Abstract [en]

    Therapeutic induction of blood vessel growth (angiogenesis) in ischemic tissues holds great potential for treatment of myocardial infarction and stroke. Achieving sustained angiogenesis and vascular maturation has, however, been highly challenging. Here, we demonstrate that alginate: collagen hydrogels containing therapeutic, pro-angiogenic FGF-2, and formulated as microspheres, is a promising and clinically relevant vehicle for therapeutic angiogenesis. By titrating the amount of readily dissolvable and degradable collagen with more slowly degradable alginate in the hydrogel mixture, the degradation rates of the biomaterial controlling the release kinetics of embedded proangiogenic FGF-2 can be adjusted. Furthermore, we elaborate a microsphere synthesis protocol allowing accurate control over sphere size, also a critical determinant of degradation/release rate. As expected, alginate: collagen microspheres were completely biocompatible and did not cause any adverse reactions when injected in mice. Importantly, the amount of pro-angiogenic FGF-2 released from such microspheres led to robust induction of angiogenesis in zebrafish embryos similar to that achieved by injecting FGF-2-releasing cells. These findings highlight the use of microspheres constructed from alginate: collagen hydrogels as a promising and clinically relevant delivery system for pro-angiogenic therapy.

    Place, publisher, year, edition, pages
    COMPANY OF BIOLOGISTS LTD, 2018
    Keywords
    Hydrogels; Microspheres; Angiogenesis; Vasculature; Zebrafish
    National Category
    Cell and Molecular Biology
    Identifiers
    urn:nbn:se:liu:diva-147419 (URN)10.1242/bio.027060 (DOI)000429100500002 ()29449216 (PubMedID)
    Note

    Funding Agencies|Svenska Sallskapet for Medicinsk Forskning; Ake-Wiberg Foundation; Goesta Fraenkel Foundation; Ahrens Stiftelse; Ollie och Elof Ericssons Stiftelse; Carmen och Bertil Ragners Stiftelse; KI Stiftelser och fonder; Loo och Hans Ostermans Stiftelse for Medicinsk Forskning; Vetenskapsradet; Linkoping University

    Available from: 2018-05-17 Created: 2018-05-17 Last updated: 2018-12-07
  • 53.
    Ali, Zaheer
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Islam, Anik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Sherrell, Peter
    Imperial Coll London, England.
    Le-Moine, Mark
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Lolas, Georgios
    Univ Athens, Greece.
    Syrigos, Konstantinos
    Univ Athens, Greece.
    Rafat, Mehrdad
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    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.
    Adjustable delivery of pro-angiogenic FGF-2 by alginate: collagen microspheres2018In: BIOLOGY OPEN, ISSN 2046-6390, Vol. 7, no 3, article id UNSP bio027060Article in journal (Refereed)
    Abstract [en]

    Therapeutic induction of blood vessel growth (angiogenesis) in ischemic tissues holds great potential for treatment of myocardial infarction and stroke. Achieving sustained angiogenesis and vascular maturation has, however, been highly challenging. Here, we demonstrate that alginate: collagen hydrogels containing therapeutic, pro-angiogenic FGF-2, and formulated as microspheres, is a promising and clinically relevant vehicle for therapeutic angiogenesis. By titrating the amount of readily dissolvable and degradable collagen with more slowly degradable alginate in the hydrogel mixture, the degradation rates of the biomaterial controlling the release kinetics of embedded proangiogenic FGF-2 can be adjusted. Furthermore, we elaborate a microsphere synthesis protocol allowing accurate control over sphere size, also a critical determinant of degradation/release rate. As expected, alginate: collagen microspheres were completely biocompatible and did not cause any adverse reactions when injected in mice. Importantly, the amount of pro-angiogenic FGF-2 released from such microspheres led to robust induction of angiogenesis in zebrafish embryos similar to that achieved by injecting FGF-2-releasing cells. These findings highlight the use of microspheres constructed from alginate: collagen hydrogels as a promising and clinically relevant delivery system for pro-angiogenic therapy.

  • 54.
    Ali, Zaheer
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Mukwaya, Anthonny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Biesemeier, Antje
    Univ Tubingen, Germany.
    Ntzouni, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Ramskold, Daniel
    Karolinska Inst, Sweden.
    Giatrellis, Sarantis
    Karolinska Inst, Sweden.
    Mammadzada, Parviz
    Karolinska Inst, Sweden.
    Cao, Renhai
    Karolinska Inst, Sweden.
    Lennikov, Anton
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Univ Missouri, MO 65211 USA.
    Marass, Michele
    Max Planck Inst Lung and Heart Res, Germany.
    Gerri, Claudia
    Max Planck Inst Lung and Heart Res, Germany.
    Hildesjö, Camilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Taylor, Michael
    Univ Wisconsin, WI 53706 USA.
    Deng, Qiaolin
    Karolinska Inst, Sweden.
    Peebo, Beatrice
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping. Bayer AB, Sweden.
    del Peso, Luis
    Universidad Autónoma de Madrid, Spain; Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM Madrid, Spain.
    Kvanta, Anders
    Karolinska Inst, Sweden.
    Sandberg, Rickard
    Karolinska Inst, Sweden.
    Schraermeyer, Ulrich
    Univ Tubingen, Germany.
    Andre, Helder
    Karolinska Inst, Sweden.
    Steffensen, John F.
    Univ Copenhagen, Denmark.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Cao, Yihai
    Karolinska Inst, Sweden.
    Kele, Julianna
    Karolinska Inst, Sweden.
    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. Univ Autonoma Madrid, Spain; UAM, Spain.
    Intussusceptive Vascular Remodeling Precedes Pathological Neovascularization2019In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 39, no 7, p. 1402-1418Article in journal (Refereed)
    Abstract [en]

    Objective—

    Pathological neovascularization is crucial for progression and morbidity of serious diseases such as cancer, diabetic retinopathy, and age-related macular degeneration. While mechanisms of ongoing pathological neovascularization have been extensively studied, the initiating pathological vascular remodeling (PVR) events, which precede neovascularization remains poorly understood. Here, we identify novel molecular and cellular mechanisms of preneovascular PVR, by using the adult choriocapillaris as a model.

    Approach and Results—

    Using hypoxia or forced overexpression of VEGF (vascular endothelial growth factor) in the subretinal space to induce PVR in zebrafish and rats respectively, and by analyzing choriocapillaris membranes adjacent to choroidal neovascular lesions from age-related macular degeneration patients, we show that the choriocapillaris undergo robust induction of vascular intussusception and permeability at preneovascular stages of PVR. This PVR response included endothelial cell proliferation, formation of endothelial luminal processes, extensive vesiculation and thickening of the endothelium, degradation of collagen fibers, and splitting of existing extravascular columns. RNA-sequencing established a role for endothelial tight junction disruption, cytoskeletal remodeling, vesicle- and cilium biogenesis in this process. Mechanistically, using genetic gain- and loss-of-function zebrafish models and analysis of primary human choriocapillaris endothelial cells, we determined that HIF (hypoxia-induced factor)-1α-VEGF-A-VEGFR2 signaling was important for hypoxia-induced PVR.

    Conclusions—

    Our findings reveal that PVR involving intussusception and splitting of extravascular columns, endothelial proliferation, vesiculation, fenestration, and thickening is induced before neovascularization, suggesting that identifying and targeting these processes may prevent development of advanced neovascular disease in the future.

    Visual Overview—

    An online visual overview is available for this article.

  • 55.
    Al-Karkhi, Isam
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Al-Rubaiy, Raad
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Rosenqvist, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Falk, Magnus
    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 Central Östergötland, Primary Health Care in Central County. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local 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.
    Comparisons of automated blood pressures in a primary health care setting with self-measurements at the office and at home using the Omron i-C10 device2015In: Blood Pressure Monitoring, ISSN 1359-5237, E-ISSN 1473-5725, Vol. 20, no 2, p. 98-103Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: We aimed to compare blood pressure (BP) levels recorded using the semiautomatic oscillometric Omron i-C10 BP device in patients with or without hypertension in three different settings: (a) when used by a doctor or a nurse at the office (OBP); (b) when used for self-measurement by the patient at the office (SMOBP); and (c) when used for 7 consecutive days at home (HBP).

    MATERIALS AND METHODS: A total of 247 individuals were invited to participate, but 78 of these individuals declined and a further seven were excluded, leaving a final cohort of 162 participants.

    RESULTS: The mean OBP was higher than HBP (difference 8.1±14/3.1±8.8 mmHg, P<0.0001) and so was SMOBP compared with HBP (difference 7.0±13/4.2±7.3 mmHg, P<0.0001). Sixteen participants (9.9%) had at least 10 mmHg higher systolic SMOBP than OBP and 28 (17%) participants had at least 10 mmHg lower systolic SMOBP than OBP. Participants who were current smokers had a larger mean difference between systolic OBP and SMOBP than nonsmokers (OBP-SMOBP in smokers: 6.6±9.4 mmHg, OBP-SMOBP in nonsmokers: 0.5±9.2 mmHg, P=0.011 between groups).

    CONCLUSION: Self-measurement of BP in the office does not preclude an increase in BP when levels in the individual patients are compared with HBP using the same equipment. Thus, SMOBP with a semiautomatic device does not lead to a reduction in the white-coat effect in the same manner as fully automatic devices.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.

  • 56.
    Allvin, Renée
    et al.
    Clinical Skills Centre, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro.
    Berndtzon, Magnus
    Metodikum - Skill Centre of Medical Simulation Region County Jönköping, Jönköping.
    Carlzon, Liisa
    Simulation Centre West, Department of Research, Education and Development, Sahlgrenska University Hospital, Gothenburg.
    Edelbring, Samuel
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm.
    Hult, Håkan
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Hultin, Magnus
    Department of Surgical and Perioperative Sciences, Anaesthesiology and Intensive Care, Medical Faculty, Umeå University, Umeå.
    Karlgren, Klas
    Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm; Department of Research, Education and Development and Innovation, Södersjukhuset Hospital, Stockholm.
    Masiello, Italo
    Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset Hospital, Stockholm.
    Södersved Källestedt, Marie-Louise
    Clinical Skills Centre, Centre for Clinical Research, Uppsala University, Västerås.
    Tamás, Éva
    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.
    Confident but not theoretically grounded: experienced simulation educators perceptions of their own professional development2017In: Advances in Medical Education and Practice, ISSN 1179-7258, E-ISSN 1179-7258, Vol. 8, p. 99-108Article in journal (Refereed)
    Abstract [en]

    Background: Medical simulation enables the design of learning activities for competency areas (eg, communication and leadership) identified as crucial for future health care professionals. Simulation educators and medical teachers follow different career paths, and their education backgrounds and teaching contexts may be very different in a simulation setting. Although they have a key role in facilitating learning, information on the continuing professional development (pedagogical development) of simulation educators is not available in the literature.

    Objectives: To explore changes in experienced simulation educators’ perceptions of their own teaching skills, practices, and understanding of teaching over time.

    Methods: A qualitative exploratory study. Fourteen experienced simulation educators participated in individual open-ended interviews focusing on their development as simulation educators. Data were analyzed using an inductive thematic analysis.

    Results: Marked educator development was discerned over time, expressed mainly in an altered way of thinking and acting. Five themes were identified: shifting focus, from following to utilizing a structure, setting goals, application of technology, and alignment with profession. Being confident in the role as an instructor seemed to constitute a foundation for the instructor’s pedagogical development.

    Conclusion: Experienced simulation educators’ pedagogical development was based on self-confidence in the educator role, and not on a deeper theoretical understanding of teaching and learning. This is the first clue to gain increased understanding regarding educational level and possible education needs among simulation educators, and it might generate several lines of research for further studies.

  • 57.
    Almeida, Nuno
    et al.
    Katholieke University of Leuven, Belgium; GE Vingmed Ultrasound AS, Norway.
    Papachristidis, Alexandros
    Kings Coll Hospital London, England.
    Pearson, Peter
    Kings Coll Hospital London, England.
    Imre Sarvari, Sebastian
    University of Oslo, Norway.
    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).
    Edvardsen, Thor
    University of Oslo, Norway.
    Monaghan, Mark
    Kings Coll Hospital London, England.
    Gerard, Olivier
    GE Vingmed Ultrasound AS, Norway.
    Samset, Eigil
    GE Vingmed Ultrasound AS, Norway; University of Oslo, Norway.
    Dhooge, Jan
    Katholieke University of Leuven, Belgium.
    Left atrial volumetric assessment using a novel automated framework for 3D echocardiography: a multi-centre analysis2017In: European Heart Journal Cardiovascular Imaging, ISSN 2047-2404, E-ISSN 2047-2412, Vol. 18, no 9, p. 1008-1015Article in journal (Refereed)
    Abstract [en]

    Aims This study aims at validating a software tool for automated segmentation and quantification of the left atrium (LA) from 3D echocardiography. Methods and results The LA segmentation tool uses a dual-chamber model of the left side of the heart to automatically detect and track the atrio-ventricular plane and the LA endocardium in transthoracic 3D echocardiography. The tool was tested in a dataset of 121 ultrasound images from patients with several cardiovascular pathologies (in a multi-centre setting), and the resulting volumes were compared with those assessed manually by experts in a blinded analysis using conventional contouring. Bland-Altman analysis showed good agreement between the automated method and the manual references, with differences (mean +/- 1.96 SD) of 0.5 +/- 5.7 mL for LA minimum volume and -1.6 +/- 9.7 mL for LA maximum volume (comparable to the inter-observer variability of manual tracings). The automated tool required no user interaction in 93% of the recordings, while 4% required a single click and only 2% required contour adjustments, reducing considerably the amount of time and effort required for LA volumetric analysis. Conclusion The automated tool was validated in a multi-centre setting, providing quantification of the LA volume over the cardiac cycle with minimal user interaction. The results of the automated analysis were in agreement with those estimated manually by experts. This study shows that such approach has clinical utility for the assessment of the LA morphology and function, automating and facilitating the time-consuming task of analysing 3D echocardiographic recordings.

  • 58.
    Almquist, Camilla
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Implementation of an automated,personalized model of the cardiovascularsystem using 4D Flow MRI2019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    A personalized cardiovascular lumped parameter model of the left-sided heart and thesystemic circulation has been developed by the cardiovascular medicine research groupat Linköping University. It provides information about hemodynamics, some of whichcould otherwise only have been retrieved by invasive measurements. The framework forpersonalizing the model is made using 4D Flow MRI data, containing volumes describinganatomy and velocities in three directions. Thus far, the inputs to this model have beengenerated manually for each subject. This is a slow and tedious process, unpractical touse clinically, and unfeasible for many subjects.This project aims to develop a tool to calculate the inputs and run the model for mul-tiple subjects in an automatic way. It has its basis in 4D Flow MRI data sets segmentedto identify the locations of left atrium (LA), left ventricle (LV), and aorta, along with thecorresponding structures on the right side.The process of making this tool started by calculation of the inputs. Planes were placedin the relevant positions, at the mitral valve, aortic valve (AV) and in the ascending aortaupstream the brachiocephalic branches, and flow rates were calculated through them. TheAV plane was used to calculate effective orifice area of AV and aortic cross-sectional area,while the LV end systolic and end diastolic volumes were extracted form the segmentation.The tool was evaluated by comparison with manually created inputs and outputs,using 9 healthy volunteers and one patient deemed to have normal left ventricular func-tion. The patient was chosen from a subject group diagnosed with chronic ischemic heartdisease, and/or a history of angina, together with fulfillment of the high risk score ofcardiovascular diseases of the European Society of Cardiology. This data was evaluatedusing coefficient of variation, Bland-Altman plots and sum squared error. The tool wasalso evaluated visually on some subjects with pathologies of interest.This project shows that it is possible to calculate inputs fully automatically fromsegmented 4D Flow MRI and run the cardiovascular avatar in an automatic way, withoutuser interaction. The method developed seems to be in good to moderate agreement withthose obtained manually, and could be the basis for further development of the model.

  • 59.
    Almroth, Gabriel
    et al.
    Linköping University, Department of Medicine and Care, Nephrology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Lonn, J
    University of Örebro, Sweden .
    Uhlin, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Andersson, B
    Sahlgrens University Hospital, Sweden .
    Hahn-Zoric, M
    Sahlgrens University Hospital, Sweden .
    Fibroblast Growth Factor 23, Hepatocyte Growth Factor, Interleukin-6, High-Sensitivity C-Reactive Protein and Soluble Urokinase Plasminogen Activator Receptor. Inflammation Markers in Chronic Haemodialysis Patients?2013In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 78, no 3, p. 285-290Article in journal (Refereed)
    Abstract [en]

    Sera from 84 haemodialysis (HD) patients and 68 healthy blood donors were analysed with commercially available ELISA techniques for fibroblast growth factor 23 (FGF-23), hepatocyte growth factor (HGF), interleukin-6 (Il-6), high-sensitivity C-reactive protein (hs-CRP) and soluble urokinase plasminogen activator receptor (suPAR), to find a possible correlation of FGF-23 and HGF with the earlier recognized inflammatory markers Il-6 and hs-CRP or suPAR. All patients studied had significantly elevated levels of FGF-23, HGF, hs-CRP and suPAR as compared to the controls. Il-6 and hs-CRP correlated for patients (R=0.6) as well as for patients and controls altogether. Ln (natural logarithm) of HGF correlated weakly with Ln Il-6 and Ln CRP (R 0.28-0.37). Ln FGF-23 correlated only with Ln HGF (r=-0.25) in controls. Ln HGF correlated with ln suPAR (r=0.6) in both patients and controls. Although elevated as compared to controls, we found no correlation of FGF-23 with the recognized inflammatory markers Il-6, hs-CRP, nor HGF or the new marker suPAR in HD patients. Ln HGF correlated with Ln Il-6, Ln CRP and Ln suPAR. Although probably involved in vessel disease, FGF-23 and HGF may play other roles than acting in inflammatory vessel disease in HD patients. Further studies are necessary to evaluate the role of these immunological markers in chronic haemodialysis patients with atherosclerosis.

  • 60.
    Almroth, Gabriel
    et al.
    Linköping University, Department of Medical and Health Sciences, Nephrology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Lönn, J
    School of Health and Medical Sciences, Örebro, Sweden.
    Uhlin, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Andersson, B
    Hahn-Zoric, M
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Tillväxtfaktorer och inflammationsmarkörer vid kronisk njursvikt2013In: Njurmedicinskt vårmöte Jönköping 12-14 maj 2013, 2013Conference paper (Refereed)
  • 61.
    Almroth, Gabriel
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Lönn, Johanna
    Örebro Universitet, Sweden.
    Uhlin, Fredrik
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Department of Physiology, County Hospital, Kalmar, Sweden.
    Andersson, Bengt Andersson
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Hahn-Zoric, Mirjana
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Sclerostin, TNF-alpha and Interleukin-18 Correlate and are Together with Klotho Related to Other Growth Factors and Cytokines in Haemodialysis Patients2016In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 83, no 1, p. 58-63Article in journal (Refereed)
    Abstract [en]

    Patients with chronic renal failure are known to have renal osteodystrophy (bone disease) and increased calcification of vessels. A new marker of bone disease, sclerostin, the two pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-18 (IL-18), and the fibroblast growth factor-23 (FGF-23) receptor-associated marker Klotho were tested in 84 haemodialysis (HD) patients and in healthy controls. The patients had significantly higher levels of the three former markers than of the controls while Klotho was significantly higher in the controls. Low level, but significant, correlations were observed in the patient group when the levels of these four markers were compared to each other and to those of 5 cytokines and growth factors tested earlier; high-sensitive CRP (hsCRP), interleukin-6 (IL-6), hepatocyte growth factor (HGF), fibroblast growth factor-23 (FGF-23) and soluble urokinase plasminogen activator (suPAR). Ln sclerostin correlated positively to Ln hsTNF-alpha, Ln HGF and Ln suPAR. Ln hsTNF-alpha correlated positively to Ln sclerostin, Ln hsCRP, Ln IL-6, Ln FGF-23, Ln suPAR and Ln IL-18. Ln IL-18 correlated positively to Ln suPAR and Ln TNF-alpha. Ln Klotho correlated negatively to Ln hsCRP but did not correlate to Ln FGF-23. The markers studied here may be involved in the calcification of vessels seen in HD patients due to a combination of inflammation and bone disease. The mechanisms are still not fully known but may be of importance for future therapeutic possibilities in this group of patients.

  • 62.
    Andell, Pontus
    et al.
    Lund Univ, Sweden.
    Berntorp, Karolina
    Lund Univ, Sweden.
    Christiansen, Evald H.
    Aarhus Univ Hosp, Denmark.
    Gudmundsdottir, Ingibjorg J.
    Univ Hosp Iceland, Iceland.
    Sandhall, Lennart
    Helsingborg Hosp, 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.
    Erlinge, David
    Lund Univ, Sweden.
    Frobert, Ole
    Orebro Univ, Sweden.
    Koul, Sasha
    Lund Univ, Sweden.
    Reitan, Christian
    Lund Univ, Sweden.
    Gotberg, Matthias
    Lund Univ, Sweden.
    Reclassification of Treatment Strategy With Instantaneous Wave-Free Ratio and Fractional Flow Reserve A Substudy From the iFR-SWEDEHEART Trial2018In: JACC: Cardiovascular Interventions, ISSN 1936-8798, E-ISSN 1876-7605, Vol. 11, no 20, p. 2084-2094Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES The authors sought to compare reclassification of treatment strategy following instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR). BACKGROUND iFR was noninferior to FFR in 2 large randomized controlled trials in guiding coronary revascularization. Reclassification of treatment strategy by FFR is well-studied, but similar reports on iFR are lacking. METHODS The iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome Trial) study randomized 2,037 participants with stable angina or acute coronary syndrome to treatment guided by iFR or FFR. Interventionalists entered the preferred treatment (optimal medical therapy [OMT], percutaneous coronary intervention [PCI], or coronary artery bypass grafting [CABG]) on the basis of coronary angiograms, and the final treatment decision was mandated by the iFR/FFR measurements. RESULTS In the iFR/FFR (n = 1,009/n = 1,004) populations, angiogram-based treatment approaches were similar (p = 0.50) with respect to OMT (38%/35%), PCI of 1 (37%/39%), 2 (15%/16%), and 3 vessels (2%/2%) and CABG (8%/8%). iFR and FFR reclassified 40% and 41% of patients, respectively (p = 0.78). The majority of reclassifications were conversion of PCI to OMT in both the iFR/FFR groups (31.4%/29.0%). Reclassification increased with increasing number of lesions evaluated (odds ratio per evaluated lesion for FFR: 1.46 [95% confidence interval: 1.22 to 1.76] vs. iFR 1.37 [95% confidence interval: 1.18 to 1.59]). Reclassification rates for patients with 1, 2, and 3 assessed vessels were 36%, 52%, and 53% (p amp;lt; 0.01). CONCLUSIONS Reclassification of treatment strategy of intermediate lesions was common and occurred in 40% of patients with iFR or FFR. The most frequent reclassification was conversion from PCI to OMT regardless of physiology modality. Irrespective of the physiological index reclassification of angiogram-based treatment strategy increased with the number of lesions evaluated. (c) 2018 by the American College of Cardiology Foundation.

  • 63.
    Andersson, Charlotta
    et al.
    Region Östergötland, Center for Diagnostics, Department of Clinical Physiology in Norrköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Kihlberg, Johan
    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 Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    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).
    Lindström, Lena
    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).
    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).
    Phase-contrast MRI volume flow - a comparison of breath held and navigator based acquisitions2016In: BMC Medical Imaging, ISSN 1471-2342, E-ISSN 1471-2342, Vol. 16, no 26Article in journal (Refereed)
    Abstract [en]

    Background: Magnetic Resonance Imaging (MRI) 2D phase-contrast flow measurement has been regarded as the gold standard in blood flow measurements and can be performed with free breathing or breath held techniques. We hypothesized that the accuracy of flow measurements obtained with segmented phase-contrast during breath holding, and in particular higher number of k-space segments, would be non-inferior compared to navigator phase-contrast. Volumes obtained from anatomic segmentation of cine MRI and Doppler echocardiography were used for additional reference. Methods: Forty patients, five women and 35 men, mean age 65 years (range 53-80), were randomly selected and consented to the study. All underwent EKG-gated cardiac MRI including breath hold cine, navigator based free-breathing phase-contrast MRI and breath hold phase-contrast MRI using k-space segmentation factors 3 and 5, as well as transthoracic echocardiography within 2 days. Results: In navigator based free-breathing phase-contrast flow, mean stroke volume and cardiac output were 79.7 +/- 17.1 ml and 5071 +/- 1192 ml/min, respectively. The duration of the acquisition was 50 +/- 6 s. With k-space segmentation factor 3, the corresponding values were 77.7 ml +/- 17.5 ml and 4979 +/- 1211 ml/min (p = 0.15 vs navigator). The duration of the breath hold was 17 +/- 2 s. K-space segmentation factor 5 gave mean stroke volume 77.9 +/- 16.4 ml, cardiac output 5142 +/- 1197 ml/min (p = 0.33 vs navigator), and breath hold time 11 +/- 1 s. Anatomical segmentation of cine gave mean stroke volume and cardiac output 91.2 +/- 20.8 ml and 5963 +/- 1452 ml/min, respectively. Echocardiography was reliable in 20 of the 40 patients. The mean diameter of the left ventricular outflow tract was 20.7 +/- 1.5 mm, stroke volume 78.3 ml +/- 15.2 ml and cardiac output 5164 +/- 1249 ml/min. Conclusions: In forty consecutive patients with coronary heart disease, breath holding and segmented k-space sampling techniques for phase-contrast flow produced stroke volumes and cardiac outputs similar to those obtained with free-breathing navigator based phase-contrast MRI, using less time. The values obtained agreed fairly well with Doppler echocardiography while there was a larger difference when compared with anatomical volume determinations using SSFP (steady state free precession) cine MRI.

  • 64.
    Andersson, Magnus
    et al.
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, Faculty of Science & Engineering.
    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).
    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).
    Characterization and estimation of turbulence-related wall shear stress in patient-specific pulsatile blood flow2019In: Journal of Biomechanics, ISSN 0021-9290, E-ISSN 1873-2380, Vol. 85, p. 108-117Article in journal (Refereed)
    Abstract [en]

    Disturbed, turbulent-like blood flow promotes chaotic wall shear stress (WSS) environments, impairing essential endothelial functions and increasing the susceptibility and progression of vascular diseases. These flow characteristics are today frequently detected at various anatomical, lesion and intervention-related sites, while their role as a pathological determinant is less understood. To present-day, numerous WSS-based descriptors have been proposed to characterize the spatiotemporal nature of the WSS disturbances, however, without differentiation between physiological laminar oscillations and turbulence-related WSS (tWSS) fluctuations. Also, much attention has been focused on magnetic resonance (MR) WSS estimations, so far with limited success; promoting the need of a near-wall surrogate marker. In this study, a new approach is explored to characterize the tWSS, by taking advantage of the tensor characteristics of the fluctuating WSS correlations, providing both a magnitude and an anisotropy measure of the disturbances. These parameters were studied in two patient-specific coarctation models (sever and mild), using large eddy simulations, and correlated against near-wall reciprocal Reynolds stress parameters. Collectively, results showed distinct regions of differing tWSS characteristics, features which were sensitive to changes in flow conditions. Generally, the post-stenotic tWSS was governed by near axisymmetric fluctuations, findings that where not consistent with conventional WSS disturbance predictors. At the 2-3 mm wall-offset range, a strong linear correlation was found between tWSS magnitude and near-wall turbulence kinetic energy (TKE), in contrast to the anisotropy indices, suggesting that MR-measured TKE can be used to assess elevated tWSS regions while tWSS anisotropy estimates request well-resolved simulation methods. (C) 2019 Elsevier Ltd. All rights reserved.

  • 65.
    Andersson, Magnus
    et al.
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, Faculty of Science & Engineering. Swedish E Science Research Centre SeRC, Sweden.
    Lantz, Jonas
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Swedish E Science Research Centre SeRC, Sweden.
    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). Swedish E Science Research Centre SeRC, Sweden.
    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). Swedish E Science Research Centre SeRC, Sweden.
    Correction: Quantitative Assessment of Turbulence and Flow Eccentricity in an Aortic Coarctation: Impact of Virtual Interventions (vol 6, pg 281, 2015)2015In: Cardiovascular Engineering and Technology, ISSN 1869-408X, E-ISSN 1869-4098, Vol. 6, no 4, p. 577-589Article in journal (Refereed)
    Abstract [en]

    Turbulence and flow eccentricity can be measured by magnetic resonance imaging (MRI) and may play an important role in the pathogenesis of numerous cardiovascular diseases. In the present study, we propose quantitative techniques to assess turbulent kinetic energy (TKE) and flow eccentricity that could assist in the evaluation and treatment of stenotic severities. These hemodynamic parameters were studied in a pre-treated aortic coarctation (CoA) and after several virtual interventions using computational fluid dynamics (CFD), to demonstrate the effect of different dilatation options on the flow field. Patient-specific geometry and flow conditions were derived from MRI data. The unsteady pulsatile flow was resolved by large eddy simulation (LES) including non-Newtonian blood rheology. Results showed an inverse asymptotic relationship between the total amount of TKE and degree of dilatation of the stenosis, where the pre-stenotic hypoplastic segment may limit the possible improvement by treating the CoA alone. Spatiotem-poral maps of TKE and flow eccentricity could be linked to the characteristics of the post-stenotic jet, showing a versatile response between the CoA dilatations. By including these flow markers into a combined MRI-CFD intervention framework, CoA therapy has not only the possibility to produce predictions via simulation, but can also be validated pre-and immediate post treatment, as well as during follow-up studies.

  • 66.
    Andersson, Magnus
    et al.
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, Faculty of Science & Engineering.
    Lantz, Jonas
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    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).
    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).
    Multidirectional WSS disturbances in stenotic turbulent flows: A pre- and post-intervention study in an aortic coarctation2017In: Journal of Biomechanics, ISSN 0021-9290, E-ISSN 1873-2380, Vol. 51Article in journal (Refereed)
    Abstract [en]

    Wall shear stress (WSS) disturbances are commonly expressed at sites of abnormal flow obstructions and may play an essential role in the pathogenesis of various vascular diseases. In laminar flows these disturbances have recently been assessed by the transverse wall shear stress (transWSS), which accounts for the WSS multidirectionality. Site-specific estimations of WSS disturbances in pulsatile transitional and turbulent type of flows are more challenging due to continuous and unpredictable changes in WSS behavior. In these complex flow settings, the transWSS may serve as a more comprehensive descriptor for assessing WSS disturbances of general nature compared to commonly used parameters. In this study large eddy simulations (LES) were used to investigate the transWSS properties in flows subjected to different pathological turbulent flow conditions, governed by a patient-specific model of an aortic coarctation pre and post balloon angioplasty. Results showed that regions of strong near-wall turbulence were collocated with regions of elevated transWSS and turbulent WSS, while in more transitional-like near-wall flow regions a closer resemblance was found between transWSS and low, and oscillatory WSS. Within the frame of this study, the transWSS parameter demonstrated a more multi-featured picture of WSS disturbances when exposed to different types of flow regimes, characteristics which were not depicted by the other parameters alone. (C) 2016 Published by Elsevier Ltd.

  • 67.
    Andersson, Magnus
    et al.
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, The Institute of Technology.
    Lantz, Jonas
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, The Institute of Technology.
    Ebbers, Tino
    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 Clinical Physiology in Linköping.
    Karlsson, Matts
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Quantitative Assessment of Turbulence and Flow Eccentricity in an Aortic Coarctation - Impact of Virtual Interventions2015In: Cardiovascular Engineering and Technology, ISSN 1869-408X, E-ISSN 1869-4098, Vol. 6, no 6, p. 281-293Article in journal (Refereed)
    Abstract [en]

    Turbulence and flow eccentricity can be measured by magnetic resonance imaging (MRI) and may play an important role in the pathogenesis of numerous cardiovascular diseases. In the present study, we propose quantitative techniques to assess turbulent kinetic energy (TKE) and flow eccentricity that could assist in the evaluation and treatment of stenotic severities. These hemodynamic parameters were studied in a pre-treated aortic coarctation (CoA) and after several virtual interventions using computational fluid dynamics (CFD), to demonstrate the effect of different dilatation options on the flow field. Patient-specific geometry and flow conditions were derived from MRI data. The unsteady pulsatile flow was resolved by large eddy simulation (LES) including non-Newtonian blood rheology. Results showed an inverse asymptotic relationship between the total amount of TKE and degree of dilatation of the stenosis, where turbulent flow proximal the constriction limits the possible improvement by treating the CoA alone. Spatiotemporal maps of TKE and flow eccentricity could be linked to the characteristics of the jet, where improved flow conditions were favored by an eccentric dilatation of the CoA. By including these flow markers into a combined MRI-CFD intervention framework, CoA therapy has not only the possibility to produce predictions via simulation, but can also be validated pre- and immediate post treatment, as well as during follow-up studies.

  • 68.
    Andersson, Malin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Jägervall, Karl
    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).
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Department of Rheumatology. Linköping University, Faculty of Medicine and Health Sciences.
    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).
    Granerus, Göran
    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.
    Wang, Chunliang
    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). KTH Royal Institute Technology, Sweden.
    Smedby, Örjan
    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). KTH Royal Institute Technology, Sweden.
    How to measure renal artery stenosis - a retrospective comparison of morphological measurement approaches in relation to hemodynamic significance2015In: BMC Medical Imaging, ISSN 1471-2342, E-ISSN 1471-2342, Vol. 15, no 42Article in journal (Refereed)
    Abstract [en]

    Background: Although it is well known that renal artery stenosis may cause renovascular hypertension, it is unclear how the degree of stenosis should best be measured in morphological images. The aim of this study was to determine which morphological measures from Computed Tomography Angiography (CTA) and Magnetic Resonance Angiography (MRA) are best in predicting whether a renal artery stenosis is hemodynamically significant or not. Methods: Forty-seven patients with hypertension and a clinical suspicion of renovascular hypertension were examined with CTA, MRA, captopril-enhanced renography (CER) and captopril test (Ctest). CTA and MRA images of the renal arteries were analyzed by two readers using interactive vessel segmentation software. The measures included minimum diameter, minimum area, diameter reduction and area reduction. In addition, two radiologists visually judged the diameter reduction without automated segmentation. The results were then compared using limits of agreement and intra-class correlation, and correlated with the results from CER combined with Ctest (which were used as standard of reference) using receiver operating characteristics (ROC) analysis. Results: A total of 68 kidneys had all three investigations (CTA, MRA and CER + Ctest), where 11 kidneys (16.2 %) got a positive result on the CER + Ctest. The greatest area under ROC curve (AUROC) was found for the area reduction on MRA, with a value of 0.91 (95 % confidence interval 0.82-0.99), excluding accessory renal arteries. As comparison, the AUROC for the radiologists visual assessments on CTA and MRA were 0.90 (0.82-0.98) and 0.91 (0.83-0.99) respectively. None of the differences were statistically significant. Conclusions: No significant differences were found between the morphological measures in their ability to predict hemodynamically significant stenosis, but a tendency of MRA having higher AUROC than CTA. There was no significant difference between measurements made by the radiologists and measurements made with fuzzy connectedness segmentation. Further studies are required to definitely identify the optimal measurement approach.

  • 69.
    Andersson, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences.
    Östholm Balkhed, Åse
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Holmbom, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Hällgren, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Berg, Sören
    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.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Delay of appropriate antibiotic treatment is associated with high mortality in patients with community-onset sepsis in a Swedish setting2019In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 38, no 7, p. 1223-1234Article in journal (Refereed)
    Abstract [en]

    Early appropriate antimicrobial therapy is crucial in patients with sepsis and septic shock. Studies often focus on time to first dose of appropriate antibiotics, but subsequent dosing is equally important. Our aim was to investigate the impact of fulfillment of early treatment, with focus on appropriate administration of first and second doses of antibiotics, on 28-day mortality in patients with community-onset severe sepsis and septic shock. A retrospective study on adult patients admitted to the emergency department with community-onset sepsis and septic shock was conducted 2012-2013. The criterion early appropriate antibiotic treatment was defined as administration of the first dose of adequate antibiotics within 1h, and the second dose given with less than 25% delay after the recommended dose interval. A high-risk patient was defined as a septic patient with either shock within 24h after arrival or red triage level on admittance according to the Medical Emergency Triage and Treatment System Adult. Primary endpoint was 28-day mortality. Of 90 patients, less than one in four (20/87) received early appropriate antibiotic treatment, and only one in three (15/44) of the high-risk patients. The univariate analysis showed a more than threefold higher mortality among high-risk patients not receiving early appropriate antibiotic treatment. Multivariable analysis identified early non-appropriate antibiotic treatment as an independent predictor of mortality with an odds ratio for mortality of 10.4. Despite that the importance of early antibiotic treatment has been established for decades, adherence to this principle was very poor.

  • 70.
    Andersson, Per
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Karlsson, Jan-Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Department of Internal Medicine, County Council of Jönköping, Jönköping.
    Landberg, Eva
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Festin, Karin
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Norrköping, Sweden.
    Consequences of high-sensitivity troponin T testing applied in a primary care population with chest pain compared with a commercially available point-of-care troponin T analysis: an observational prospective study2015In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 8, no 1, p. 1-9Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:There is a demand for a highly sensitive and specific point-of care test to detect acute myocardial infarction (AMI). It is unclear if a high-sensitivity troponin assay will have enough discriminative power to become a decision support in primary care. The aim of this study was to evaluate a high-sensitivity troponin T assay performed in three primary health care centres in southeast Sweden and to compare the outcome with a point-of-care troponin T test.METHODS:This study included 115 patients who consulted their general practitioner for chest pain, dyspnoea on exertion, unexplained weakness and/or fatigue in the last 7days. Troponin T was analysed by a point-of-care test and a high-sensitivity method together with N-terminal pro-B-type natriuretic peptide (NT-proBNP) and creatinine. All patients were checked for AMI or unstable angina (UA) within 30days of study enrolment. Univariate and multivariate logistic regression was carried out to examine possible connections between troponin T[greater than or equal to]15ng/L, clinical variables and laboratory findings at baseline. In addition, 21 patients with troponin T[greater than or equal to]15ng/L and no signs of AMI or UA were followed up for 2-3years.RESULTS:Three patients were diagnosed with AMI and three with UA. At the [greater than or equal to]15ng/L cut-off, the troponin T method had 100% sensitivity, 75% specificity for AMI and a positive predictive value of 10%. The troponin T point-of-care test missed one case of AMI and the detection limit was 50ng/L. Troponin T[greater than or equal to]15ng/L was correlated to age [greater than or equal to]65years (odds ratio (OR), 10.9 95% CI 2.28-51.8) and NT-proBNP in accordance with heart failure (OR 8.62 95% CI 1.61-46.1). Fourteen of the 21 patients, without signs of AMI or UA at baseline, still had increased troponin T at follow-up after 2-3years.CONCLUSIONS:A high-sensitivity troponin T assay could become useful in primary care as a point-of-care test for patients <65years. For patients older than 65-70years, a higher decision limit than [greater than or equal to]15ng/L should be considered and used in conjunction with clinical parameters and possibly with NT-proBNP.

  • 71.
    Andersson, Per
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ljungsbro.
    Sederholm Lawesson, Sofia
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Karlsson, Jan-Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Dept Internal Med, Sweden.
    Nilsson, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Vikbolandet.
    Thylén, Ingela
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Characteristics of patients with acute myocardial infarction contacting primary healthcare before hospitalisation: a cross-sectional study2018In: BMC Family Practice, ISSN 1471-2296, E-ISSN 1471-2296, Vol. 19, article id 167Article in journal (Refereed)
    Abstract [en]

    Background: The characteristics of patients with on-going myocardial infarction (MI) contacting the primary healthcare (PHC) centre before hospitalisation are not well known. Prompt diagnosis is crucial in patients with MI, but many patients delay seeking medical care. The aims of this study was to 1) describe background characteristics, symptoms, actions and delay times in patients contacting the PHC before hospitalisation when falling ill with an acute MI, 2) compare those patients with acute MI patients not contacting the PHC, and 3) explore factors associated with a PHC contact in acute MI patients. Methods: This was a cross-sectional multicentre study, enrolling consecutive patients with MI within 24 hours of admission to hospital from Nov 2012 until Feb 2014. Results: A total of 688 patients with MI, 519 men and 169 women, were included; the mean age was 66 +/- 11 years. One in five people contacted PHC instead of the recommended emergency medical services (EMS), and 94% of these patients experienced cardinal symptoms of an acute MI; i.e., chest pain, and/or radiating pain in the arms, and/or cold sweat. Median delay time from symptom-onset-to-decision-to-seek-care was 2:15 hours in PHC patients and 0:40 hours in non-PHC patients (pamp;lt;0.01). The probability of utilising the PHC before hospitalisation was associated with fluctuating symptoms (OR 1.74), pain intensity (OR 0.90) symptoms during off-hours (OR 0.42), study hospital (OR 3.49 and 2.52, respectively, for two of the county hospitals) and a final STEMI diagnosis (OR 0.58). Conclusions: Ambulance services are still underutilized in acute MI patients. A substantial part of the patients contacts their primary healthcare centre before they are diagnosed with MI, although experiencing cardinal symptoms such as chest pain. There is need for better knowledge in the population about symptoms of MI and adequate pathways to qualified care. Knowledge and awareness amongst primary healthcare professionals on the occurrence of MI patients is imperative.

  • 72.
    Andersson, Thord
    et al.
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Romu, Thobias
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Karlsson, Anette
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Norén, Bengt
    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.
    Forsgren, Mikael
    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 Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Smedby, Örjan
    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.
    Kechagias, Stergios
    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.
    Almer, Sven
    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, Department of Gastroentorology.
    Lundberg, Peter
    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 Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Borga, Magnus
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dahlqvist Leinhard, Olof
    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 Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Consistent intensity inhomogeneity correction in water–fat MRI2015In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 42, no 2, p. 468-476Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    To quantitatively and qualitatively evaluate the water-signal performance of the consistent intensity inhomogeneity correction (CIIC) method to correct for intensity inhomogeneities METHODS: Water-fat volumes were acquired using 1.5 Tesla (T) and 3.0T symmetrically sampled 2-point Dixon three-dimensional MRI. Two datasets: (i) 10 muscle tissue regions of interest (ROIs) from 10 subjects acquired with both 1.5T and 3.0T whole-body MRI. (ii) Seven liver tissue ROIs from 36 patients imaged using 1.5T MRI at six time points after Gd-EOB-DTPA injection. The performance of CIIC was evaluated quantitatively by analyzing its impact on the dispersion and bias of the water image ROI intensities, and qualitatively using side-by-side image comparisons.

    RESULTS:

    CIIC significantly ( P1.5T≤2.3×10-4,P3.0T≤1.0×10-6) decreased the nonphysiological intensity variance while preserving the average intensity levels. The side-by-side comparisons showed improved intensity consistency ( Pint⁡≤10-6) while not introducing artifacts ( Part=0.024) nor changed appearances ( Papp≤10-6).

    CONCLUSION:

    CIIC improves the spatiotemporal intensity consistency in regions of a homogenous tissue type. J. Magn. Reson. Imaging 2014.

  • 73.
    Andreassen, A. K.
    et al.
    Oslo University Hospital, Norway.
    Andersson, B.
    Sahlgrens University Hospital, Sweden.
    Gustafsson, F.
    Rigshosp, Denmark.
    Eiskjaer, H.
    Aarhus University Hospital, Denmark.
    Radegran, G.
    Lund University, Sweden; Lund University, Sweden.
    Gude, E.
    Oslo University Hospital, 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 Clinical Physiology in Linköping.
    Solbu, D.
    Novartis Norge AS, Norway.
    Karason, K.
    Sahlgrens University Hospital, Sweden.
    Arora, S.
    Oslo University Hospital, Norway.
    Dellgren, G.
    Sahlgrens University Hospital, Sweden.
    Gullestad, L.
    Oslo University Hospital, Norway; University of Oslo, Norway; University of Oslo, Norway.
    Everolimus Initiation With Early Calcineurin Inhibitor Withdrawal in De Novo Heart Transplant Recipients: Three-Year Results From the Randomized SCHEDULE Study2016In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 16, no 4, p. 1238-1247Article in journal (Refereed)
    Abstract [en]

    In a randomized, open-label trial, de novo heart transplant recipients were randomized to everolimus (3-6ng/mL) with reduced-exposure calcineurin inhibitor (CNI; cyclosporine) to weeks 7-11 after transplant, followed by increased everolimus exposure (target 6-10ng/mL) with cyclosporine withdrawal or standard-exposure cyclosporine. All patients received mycophenolate mofetil and corticosteroids. A total of 110 of 115 patients completed the 12-month study, and 102 attended a follow-up visit at month 36. Mean measured GFR (mGFR) at month 36 was 77.4mL/min (standard deviation [SD] 20.2mL/min) versus 59.2mL/min (SD 17.4mL/min) in the everolimus and CNI groups, respectively, a difference of 18.3mL/min (95% CI 11.1-25.6mL/min; p &lt; 0.001) in the intention to treat population. Multivariate analysis showed treatment to be an independent determinant of mGFR at month 36. Coronary intravascular ultrasound at 36 months revealed significantly reduced progression of allograft vasculopathy in the everolimus group compared with the CNI group. Biopsy-proven acute rejection grade 2R occurred in 10.2% and 5.9% of everolimus- and CNI-treated patients, respectively, during months 12-36. Serious adverse events occurred in 37.3% and 19.6% of everolimus- and CNI-treated patients, respectively (p=0.078). These results suggest that early CNI withdrawal after heart transplantation supported by everolimus, mycophenolic acid and steroids with lymphocyte-depleting induction is safe at intermediate follow-up. This regimen, used selectively, may offer adequate immunosuppressive potency with a sustained renal advantage. A follow-up study of the SCHEDULE trial, which randomized de novo heart transplant recipients to everolimus with cyclosporine discontinuation or to standard-exposure cyclosporine, shows that measured glomerular filtration rate remains significantly higher in the everolimus group at three years posttransplant, with significantly reduced progression of allograft vasculopathy compared to cyclosporine therapy.

  • 74.
    Andreassen, A.K.
    et al.
    University of Oslo, Norway .
    Andersson, B.
    Sahlgrens University Hospital, Sweden .
    Gustafsson, F.
    Rigshosp, Denmark .
    Eiskjaer, H.
    Aarhus University Hospital, Denmark .
    Rdegran, G.
    Skåne University Hospital, Sweden Lund University, Sweden .
    Gude, E.
    University of Oslo, Norway .
    Jansson, Kjell
    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.
    Solbu, D.
    Novartis Norge AS, Norway .
    Sigurdardottir, V.
    Sahlgrens University Hospital, Sweden .
    Arora, S.
    University of Oslo, Norway .
    Dellgren, G.
    Sahlgrens University Hospital, Sweden .
    Gullestad, L.
    University of Oslo, Norway University of Oslo, Norway University of Oslo, Norway .
    Everolimus Initiation and Early Calcineurin Inhibitor Withdrawal in Heart Transplant Recipients: A Randomized Trial2014In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 14, no 8, p. 1828-1838Article in journal (Refereed)
    Abstract [en]

    In a randomized, open-label trial, everolimus was compared to cyclosporine in 115 de novo heart transplant recipients. Patients were assigned within 5 days posttransplant to low-exposure everolimus (3-6 ng/mL) with reduced-exposure cyclosporine (n 56), or standard-exposure cyclosporine (n = 59), with both mycophenolate mofetil and corticosteroids. In the everolimus group, cyclosporine was withdrawn after 7-11 weeks and everolimus exposure increased (6-10 ng/mL). The primary efficacy end point, measured GFR at 12 months posttransplant, was significantly higher with everolimus versus cyclosporine (mean +/- SD: 79.8 +/- 17.7 mL/min/1.73m 2 vs. 61.5 +/- 19.6 mL/min/1.73m 2; pless than0.001). Coronary intravascular ultrasound showed that the mean increase in maximal intimal thickness was smaller (0.03 mm [95% CI 0.01, 0.05 mm] vs. 0.08 mm [95% CI 0.05, 0.12 mm], p = 0.03), and the incidence of cardiac allograft vasculopathy (CAV) was lower (50.0% vs. 64.6%, p = 0.003), with everolimus versus cyclosporine at month 12. Biopsy-proven acute rejection after weeks 7-11 was more frequent with everolimus (p = 0.03). Left ventricular function was not inferior with everolimus versus cyclosporine. Cytomegalovirus infection was less common with everolimus (5.4% vs. 30.5%, pless than0.001); the incidence of bacterial infection was similar. In conclusion, everolimus-based immunosuppression with early elimination of cyclosporine markedly improved renal function after heart transplantation. Since postoperative safety was not jeopardized and development of CAV was attenuated, this strategy may benefit long-term outcome.

  • 75.
    Angelin, Bo
    et al.
    Karolinska University, Sweden; Karolinska University, Sweden.
    Kristensen, Jens D.
    Karo Bio AB, Sweden.
    Eriksson, Mats
    Karolinska University, Sweden; Karolinska University, Sweden.
    Carlsson, Bo
    Karo Bio AB, Sweden.
    Klein, Irwin
    NYU, NY USA.
    Olsson, Anders
    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 Endocrinology. Stockholm Heart Centre, Sweden.
    Chester Ridgway, E.
    University of Colorado, CO USA.
    Ladenson, Paul W.
    Johns Hopkins University, MD 21205 USA.
    Reductions in serum levels of LDL cholesterol, apolipoprotein B, triglycerides and lipoprotein(a) in hypercholesterolaemic patients treated with the liver-selective thyroid hormone receptor agonist eprotirome2015In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 277, no 3, p. 331-342Article in journal (Refereed)
    Abstract [en]

    BackgroundLiver-selective thyromimetic agents could provide a new approach for treating dyslipidaemia. MethodsWe performed a multicentre, randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of eprotirome, a liver-selective thyroid hormone receptor agonist, in 98 patients with primary hypercholesterolaemia. After previous drug wash-out and dietary run-in, patients received 100 or 200gday(-1) eprotirome or placebo for 12weeks. The primary end-point was change in serum LDL cholesterol; secondary end-points included changes in other lipid parameters and safety measures. ResultsEprotirome treatment at 100 and 200g daily reduced serum LDL cholesterol levels by 235% and 31 +/- 4%, respectively, compared with 2 +/- 6% for placebo (Pless than0.0001). Similar reductions were seen in non-HDL cholesterol and apolipoprotein (apo) B, whereas serum levels of HDL cholesterol and apo A-I were unchanged. There were also considerable reductions in serum triglycerides and lipoprotein(a), in particular in patients with elevated levels at baseline. There was no evidence of adverse effects on heart or bone and no changes in serum thyrotropin or triiodothyronine, although the thyroxine level decreased. Low-grade increases in liver enzymes were evident in most patients. ConclusionIn hypercholesterolaemic patients, the liver-selective thyromimetic eprotirome decreased serum levels of atherogenic lipoproteins without signs of extra-hepatic side effects. Selective stimulation of hepatic thyroid hormone receptors may be an attractive way to modulate lipid metabolism in hyperlipidaemia.

  • 76.
    Arbring, Kerstin
    et al.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine.
    Chaireti, Roza
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine.
    Janzon, Magnus
    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.
    Uppugunduri, Srinivas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Jansson, Kjell
    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.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    First experience of structured introduction of new oral anticoagulants in a Swedish health care district: dabigatran as an alternative to warfarin in atrial fibrillation2013Conference paper (Refereed)
  • 77.
    Arjonen, Antti
    et al.
    VTT Technical Research Centre Finland, Finland University of Turku, Finland .
    Kaukonen, Riina
    VTT Technical Research Centre Finland, Finland University of Turku, Finland .
    Mattila, Elina
    VTT Technical Research Centre Finland, Finland University of Turku, Finland .
    Rouhi, Pegah
    Karolinska Institute, Sweden .
    Hognas, Gunilla
    VTT Technical Research Centre Finland, Finland University of Turku, Finland .
    Sihto, Harri
    University of Helsinki, Finland .
    Miller, Bryan W.
    University of Glasgow, Scotland .
    Morton, Jennifer P.
    University of Glasgow, Scotland .
    Bucher, Elmar
    VTT Technical Research Centre Finland, Finland .
    Taimen, Pekka
    University of Turku, Finland Turku University Hospital, Finland .
    Virtakoivu, Reetta
    VTT Technical Research Centre Finland, Finland University of Turku, Finland .
    Cao, Yihai
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Sansom, Owen J.
    University of Glasgow, Scotland .
    Joensuu, Heikki
    University of Helsinki, Finland University of Helsinki, Finland .
    Ivaska, Johanna
    VTT Technical Research Centre Finland, Finland University of Turku, Finland University of Turku, Finland .
    Mutant p53-associated myosin-X upregulation promotes breast cancer invasion and metastasis2014In: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 124, no 3, p. 1069-1082Article in journal (Refereed)
    Abstract [en]

    Mutations of the tumor suppressor TP53 are present in many forms of human cancer and are associated with increased tumor cell invasion and metastasis. Several mechanisms have been identified for promoting dissemination of cancer cells with TP53 mutations, including increased targeting of integrins to the plasma membrane. Here, we demonstrate a role for the filopodia-inducing motor protein Myosin-X (Myo10) in mutant p53-driven cancer invasion. Analysis of gene expression profiles from 2 breast cancer data sets revealed that MYO10 was highly expressed in aggressive cancer subtypes. Myo10 was required for breast cancer cell invasion and dissemination in multiple cancer cell lines and murine models of cancer metastasis. Evaluation of a Myo10 mutant without the integrin-binding domain revealed that the ability of Myo10 to transport 131 integrins to the filopodia tip is required for invasion. Introduction of mutant p53 promoted Myo10 expression in cancer cells and pancreatic ductal adenocarcinoma in mice, whereas suppression of endogenous mutant p53 attenuated Myo10 levels and cell invasion. In clinical breast carcinomas, Myo10 was predominantly expressed at the invasive edges and correlated with the presence of TP53 mutations and poor prognosis. These data indicate that Myo10 upregulation in mutant p53-driven cancers is necessary for invasion and that plasma-membrane protrusions, such as filopodia, may serve as specialized metastatic engines.

  • 78. Aronsson, M
    et al.
    Janzon, Magnus
    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.
    Walfridsson, Håkan
    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.
    Walfridsson, Ulla
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    Cost-effectivesness of catheter ablation as first-line treatment for paroxysmal atrial fibrillation2013Conference paper (Refereed)
  • 79.
    Aronsson, Mattias
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Walfridsson, Håkan
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Janzon, Magnus
    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.
    Walfridsson, Ulla
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nielsen, Jens Cosedis
    Aarhus University Hospital, Denmark.
    Hansen, Peter Steen
    Aarhus University Hospital, Denmark.
    Johannessen, Arne
    Gentofte University Hospital, Denmark.
    Raatikainen, Pekka
    Tampere University Hospital, Finland.
    Hindricks, Gerhard
    Leipzig University Hospital, Germany.
    Kongstad, Ole
    Lund University Hospital, Sweden.
    Pehrson, Steen
    Rigshospitalet, Denmark.
    Englund, Anders
    University Hospital, Örebro, Sweden.
    Hartikainen, Juha
    Kuopio University Hospital, Finland.
    Mortensen, Leif Spange
    Danish Information Technology Centre for Education and Research, Aarhus, Denmark.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    The cost-effectiveness of radiofrequency catheter ablation as first-line treatment for paroxysmal atrial fibrillation: results from a MANTRA-PAF substudy.2015In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 17, no 1, p. 48-55Article in journal (Refereed)
    Abstract [en]

    AIM: The aim of this prospective substudy was to estimate the cost-effectiveness of treating paroxysmal atrial fibrillation (AF) with radiofrequency catheter ablation (RFA) compared with antiarrhythmic drugs (AADs) as first-line treatment.

    METHODS AND RESULTS: A decision-analytic Markov model, based on MANTRA-PAF (Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation) study data, was developed to study long-term effects and costs of RFA compared with AADs as first-line treatment. Positive clinical effects were found in the overall population, a gain of an average 0.06 quality-adjusted life years (QALYs) to an incremental cost of €3033, resulting in an incremental cost-effectiveness ratio of €50 570/QALY. However, the result of the subgroup analyses showed that RFA was less costly and more effective in younger patients. This implied an incremental cost-effectiveness ratio of €3434/QALY in ≤50-year-old patients respectively €108 937/QALY in >50-year-old patients.

    CONCLUSION: Radiofrequency catheter ablation as first-line treatment is a cost-effective strategy for younger patients with paroxysmal AF. However, the cost-effectiveness of using RFA as first-line therapy in older patients is uncertain, and in most of these AADs should be attempted before RFA (MANTRA-PAF ClinicalTrials.gov number; NCT00133211).

  • 80.
    Babic, Ankica
    et al.
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. University of Bergen, Norway.
    Peterzen, Bengt
    Östergötlands Läns Landsting, Heart and Medicine Center.
    Lönn, Urban
    Östergötlands Läns Landsting, Heart and Medicine Center.
    Casimir Ahn, Henrik
    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.
    Case Based Reasoning in a Web Based Decision Support System for Thoracic Surgery2013In: IFMBE Proceedings 41 / [ed] L.M. Roa Romero, Springer, 2013, p. 1413-1416Conference paper (Refereed)
    Abstract [en]

    Case Based Reasoning (CBR) methodology provides means of collecting patients cases and retrieving them following the clinical criteria. By studying previously treated patients with similar backgrounds, the physician can get a better base for deciding on treatment for a current patient and be better prepared for complications that might occur during and after surgery. This could be taken advantage of when there is not enough data for a statistical analysis, but electronic patient records that provide all the relevant information to assure a timely and accurate clinical insight into a patient particular situation.

    We have developed and implemented a CBR engine using the Nearest Neighbor algorithm. A patient case is represented as a combination of perioperative variable values and operation reports. Physicians could review a selected number of cases by browsing through the electronic patient record and operational narratives which provides an exhaustive insight into the previously treated cases. An evaluation of the search algorithm suggests a very good functionality.

  • 81.
    Backteman, Karin
    et al.
    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 Immunology and Transfusion Medicine.
    Ernerudh, Jan
    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 Immunology and Transfusion Medicine.
    Jonasson, Lena
    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.
    Cytomegalovirus seropositivity is a major determinant of CD28null T cell expansion in patients with coronary artery disease2014Manuscript (preprint) (Other academic)
    Abstract [en]

    Objective: Accumulation of CD4+28null cells, with a proinflammatory and senescent phenotype, has been associated with unstable conditions of coronary artery disease (CAD). Human cytomegalovirus (HCMV) is known to exert profound effects on T cells, including loss of CD28. Here, we longitudinally assessed the proportions of CD28null and CD28nullCD57+ cells in CD4+ and CD8+ T cell populations of patients with CAD and related the findings to HCMV seropositivity.

    Methods: HCMV antibody levels and expression of CD28 and CD57 on CD4+ and CD8+ T cells were analysed in 31 patients with acute coronary syndrome (ACS), 34 patients with stable angina (SA) and 37 healthy controls. Samples were taken prior to 34 coronary angiography and after 3 and 12 months. In a subsample, HCMV-specific IFN-γ and  TNF production was assessed ex vivo.

    Results: Increased proportions of CD4+CD28null, but not CD8+CD28null cells, were significantly associated with presence of CAD. Significant increases in CD28null 37 and CD28nullCD57+ cells occurred within CD4+ and CD8+ T cell compartments in both ACS and SA patients during 12-month follow-up. HCMV was the major determinant of CD28null and CD28nullCD57+ T cell levels in both patients and controls (p <0.001). There were no obvious signs of CMV reactivation in patients.

    Conclusion: HCMV was a major determinant of the presence of CD28null and CD28nullCD57+ T cells in patients with CAD, independent of clinical stage. Findings also indicate that HCMV might have a large impact on the T cell aging process that occurred in patients after a cardiac event.

  • 82.
    Backteman, Karin
    et al.
    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 Immunology and Transfusion Medicine.
    Ernerudh, Jan
    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 Immunology and Transfusion Medicine.
    Jonasson, Lena
    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.
    Natural killer (NK) cell deficit in coronary artery disease: no aberrations in phenotype but sustained reduction of NK cells is associated with low-grade inflammation2014In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 175, no 1, p. 104-112Article in journal (Refereed)
    Abstract [en]

    Although reduced natural killer (NK) cell levels have been reported consistently in patients with coronary artery disease (CAD), the clinical significance and persistence of this immune perturbation is not clarified. In this study we characterized the NK cell deficit further by determining (i) differentiation surface markers and cytokine profile of NK cell subsets and (ii) ability to reconstitute NK cell levels over time. Flow cytometry was used to analyse NK cell subsets and the intracellular cytokine profile in 31 patients with non-ST elevation myocardial infarction (non-STEMI), 34 patients with stable angina (SA) and 37 healthy controls. In blood collected prior to coronary angiography, the proportions of NK cells were reduced significantly in non-STEMI and SA patients compared with controls, whereas NK cell subset analyses or cytokine profile measurements did not reveal any differences across groups. During a 12-month follow-up, the proportions of NK cells increased, although not in all patients. Failure to reconstitute NK cell levels was associated with several components of metabolic syndrome. Moreover, interleukin (IL)-6 levels remained high in patients with sustained NK cell deficit, whereas a decline in IL-6 (P < 0·001) was seen in patients with a pronounced increase in NK cells. In conclusion, we found no evidence that reduction of NK cells in CAD patients was associated with aberrations in NK cell phenotype at any clinical stage of the disease. Conversely, failure to reconstitute NK cell levels was associated with a persistent low-grade inflammation, suggesting a protective role of NK cells in CAD.

  • 83.
    Bagai, Akshay
    et al.
    Univ Toronto, Canada.
    Goodman, Shaun G.
    Univ Toronto, Canada; Univ Toronto, Canada.
    Cantor, Warren J.
    Univ Toronto, England.
    Vicaut, Eric
    Hop Lariboisiere, France.
    Bolognese, Leonardo
    Azienda Osped Arezzo, Italy.
    Cequier, Angel
    Univ Barcelona, Spain.
    Chettibi, Mohamed
    Ctr Hosp Univ Frantz Fanon, Algeria.
    Hammett, Christopher J.
    Royal Brisbane and Womens Hosp, Australia.
    Huber, Kurt
    Wilhelminenhosp, Austria; Sigmund Freud Private Univ, Austria.
    Janzon, Magnus
    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.
    Lapostolle, Frederic
    Hop Avicenne, France.
    Lassen, Jens Flensted
    Univ Copenhagen, Denmark.
    Merkely, Bela
    Semmelweis Univ, Hungary.
    Storey, Robert F.
    Univ Sheffield, England.
    ten Berg, Jurrien M.
    St Antonius Hosp Nieuwegein, Netherlands.
    Zeymer, Uwe
    Klinikum Ludwigshafen, Germany; Inst Herzinfarktforsch Ludwigshafen, Germany.
    Diallo, Abdourahmane
    Hop Lariboisiere, France; Hop Fernand Widal, France.
    Hamm, Christian W.
    Kerckhoff Klin, Germany.
    Tsatsaris, Anne
    AstraZeneca, France.
    El Khoury, Jad
    AstraZeneca, England.
    vant Hof, Arnoud W.
    Maastricht Hart Vaat Ctr MUMC, Netherlands.
    Montalescot, Gilles
    Sorbonne Univ Paris 6, France.
    Duration of ischemia and treatment effects of pre- versus in-hospital ticagrelor in patients with ST-segment elevation myocardial infarction: Insights from the ATLANTIC study2018In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 196, p. 56-64Article in journal (Refereed)
    Abstract [en]

    Background Among patients with STEMI in the ATLANTIC study, pre-hospital administration of ticagrelor improved post-PCI ST-segment resolution and 30-day stent thrombosis. We investigated whether this clinical benefit with pre-hospital ticagrelor differs by ischemic duration. Methods In a post hoc analysis we compared absence of ST-segment resolution post-PCI and stent thrombosis at 30 days between randomized treatment groups (pre-versus in-hospital ticagrelor) stratified by symptom onset to first medical contact (FMC) duration [amp;lt;= 1 hour (n = 773), amp;gt;1 to amp;lt;= 3 hours (n = 772), and amp;gt;3 hours (n = 311)], examining the interaction between randomized treatment strategy and duration of symptom onset to FMC for each outcome. Results Patients presenting later after symptom onset were older, more likely to be female, and have higher baseline risk. Patients with symptom onset to FMC amp;gt;3 hours had the greatest improvement in post-PCI ST-segment elevation resolution with pre-versus in-hospital ticagrelor (absolute risk difference: amp;lt;= 1 hour, 2.9% vs. amp;gt;1 to amp;lt;= 3 hours, 3.6% vs. amp;gt;3 hours, 12.2%; adjusted p for interaction = 0.13), while patients with shorter duration of ischemia had greater improvement in stent thrombosis at 30 days with pre-versus in-hospital ticagrelor (absolute risk difference: amp;lt;= 1 hour, 1.3% vs. amp;gt;1 hour to amp;lt;= 3hours, 0.7% vs. amp;gt;3 hours, 0.4%; adjusted p for interaction = 0.55). Symptom onset to active ticagrelor administration was independently associated with stent thrombosis at 30 days (adjusted OR 1.89 per 100 minute delay, 95% CI 1.20-2.97, P amp;lt; .01), but not post-PCI ST-segment resolution (P = .41). Conclusions The effect of pre-hospital ticagrelor to reduce stent thrombosis was most evident when given early within 3 hours after symptom onset, with delay in ticagrelor administration after symptom onset associated with higher rate of stent thrombosis. These findings re-emphasize the need for early ticagrelor administration in primary PCI treated STEMI patients.

  • 84.
    Banck, M
    et al.
    Hallands Hospital, Halmstad, Sweden.
    Heller, Ute
    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.
    Samuelsson, C
    Hallands Hospital, Halmstad, Sweden.
    Wickerts, CJ
    Danderyd Hospital and Karolinska Institutet, Stockholm, Sweden.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    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.
    Women with out-of-hospital cardiac arrest are less likely to receive therapeutic hypothermia and more likely to die than men: Swedish nationwide cohort study2013Conference paper (Refereed)
  • 85.
    Banck, M
    et al.
    Svenska Intensivvårdsregistret, Karlstad.
    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.
    Karlström, G
    Svenska Intensivvårdsregistret, Karlstad.
    Nolin, T
    Svenska Intensivvårdsregistret, Kristianstad.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Samuelsson, C
    Svenska Intensivvårdsregistret, Karlstad.
    Är svensk intensivvård könsjämlik?2013Conference paper (Refereed)
  • 86.
    Banck, Malin
    et al.
    Hallands sjukhus, Halmstad.
    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.
    Karlström, Göran
    Centralsjukhuset, Karlstad.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Samuelsson, Carolina
    Hallands sjukhus, Halmstad.
    Män intensivvårdas mer än kvinnor: Med det är ändå oklart om intensivvården i Sverige är könsojämlik2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 9-10, p. 388-390Article in journal (Other academic)
  • 87.
    Bandaru, S.
    et al.
    University of Gothenburg, Sweden.
    Zhou, A-X
    University of Gothenburg, Sweden.
    Rouhi, P.
    Karolinska Institute, Sweden.
    Zhang, Y.
    Karolinska Institute, Sweden.
    Bergo, M. O.
    University of Gothenburg, Sweden.
    Cao, Yihai
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Karolinska Institute, Sweden.
    Akyurek, L. M.
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Targeting filamin B induces tumor growth and metastasis via enhanced activity of matrix metalloproteinase-9 and secretion of VEGF-A2014In: Oncogenesis, E-ISSN 2157-9024, Vol. 3, p. e119-Article in journal (Refereed)
    Abstract [en]

    Filamins regulate cell locomotion and associate with diverse signaling molecules. We have recently found that targeting filamin A (FLNA) reduces RAS-induced lung adenocarcinomas. In this study, we explored the role of another major filamin isoform, filamin B (FLNB), in tumor development. In contrast to FLNA, we report that targeting FLNB enhances RAS-induced tumor growth and metastasis which is associated with higher matrix metallopeptidase-9 (MMP-9) and extracellular signal-regulated kinase (ERK) activity. Flnb deficiency in mouse embryonic fibroblasts results in increased proteolytic activity of MMP-9 and cell invasion mediated by the RAS/ERK pathway. Similarly, silencing FLNB in multiple human cancer cells increases the proteolytic activity of MMP-9 and tumor cell invasion. Furthermore, we observed that Flnb-deficient RAS-induced tumors display more capillary structures that is correlated with increased vascular endothelial growth factor-A (VEGF-A) secretion. Inhibition of ERK activation blocks phorbol myristate acetate-induced MMP-9 activity and VEGF-A secretion in vitro. In addition, silencing FLNB in human ovarian cancer cells increases secretion of VEGF-A that induces endothelial cells to form more vascular structures in vitro. We conclude that FLNB suppresses tumor growth and metastasis by regulating the activity of MMP-9 and secretion of VEGF-A which is mediated by the RAS/ERK pathway.

  • 88.
    Banefelt, J.
    et al.
    Quantify Res, Sweden.
    Akesson, K. E.
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Spångeus, Anna
    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.
    Ljunggren, O.
    Uppsala Univ Hosp, Sweden.
    Karlsson, L.
    Quantify Res, Sweden.
    Strom, O.
    Quantify Res, Sweden; Karolinska Inst, Sweden.
    Ortsater, G.
    Quantify Res, Sweden.
    Libanati, C.
    UCB Biopharma Sprl, Belgium.
    Toth, E.
    UCB Biopharma Sprl, Belgium.
    Risk of imminent fracture following a previous fracture in a Swedish database study2019In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 30, no 3, p. 601-609Article in journal (Refereed)
    Abstract [en]

    The SummaryThis study examined the imminent risk of a future fracture within 1 and 2years following a first fracture in women aged 50years and older and assessed independent factors associated with risk of subsequent fractures. The study highlights the need to intervene rapidly after a fracture to prevent further fractures.IntroductionThis study aims to determine the imminent risk of subsequent fractures within 1 and 2years following a first fracture and to assess independent factors associated with subsequent fractures.MethodsRetrospective, observational cohort study of women aged 50years with a fragility fracture was identified from Swedish national registers. Clinical/demographic characteristics at the time of index fracture and cumulative fracture incidences up to 12 and 24months following index fracture were calculated. Risk factors for subsequent fracture were identified using multivariate regression analysis.ResultsTwo hundred forty-two thousand one hundred eight women (mean [SD] age 74 [12.5] years) were included. The cumulative subsequent fracture incidence at 12months was 7.1% (95% confidence interval [CI], 6.9-7.2) and at 24months was 12.0% (95% CI, 11.8-12.1). The rate of subsequent fractures was highest in the first month (similar to 15 fractures per 1000 patient-years) and remained steady between 4 and 24months (similar to 5 fractures/1000 patient-years). Higher age was an independent risk factor for imminent subsequent fractures (at 24months, sub-distribution hazard ratio [HR], 3.07; pamp;lt;0.001 for women 80-89years [reference 50-59years]). Index vertebral fracture was a strong independent risk factor for subsequent fracture (sub-distribution HR, 2.72 versus hip fracture; pamp;lt;0.001 over 12months; HR, 2.23; pamp;lt;0.001 over 24months).ConclusionsOur findings highlight the need to intervene rapidly after any fragility fracture in postmenopausal women. The occurrence of a fragility fracture provides healthcare systems with a unique opportunity to intervene to reduce the increased risk of subsequent fractures.

  • 89.
    Bank, Ingrid E. M.
    et al.
    University of Medical Centre Utrecht, Netherlands.
    Gijsberts, Crystel M.
    University of Medical Centre Utrecht, Netherlands; ICIN Netherlands Heart Institute, Netherlands.
    Teng, Tiew-Hwa K.
    Singhealth, Singapore.
    Benson, Lina
    Karolinska Institute, Sweden.
    Sim, David
    Singhealth, Singapore.
    Shuan Daniel Yeo, Poh
    Tan Tock Seng Hospital, Singapore.
    Yee Ong, Hean
    Khoo Teck Puat Hospital, Singapore.
    Jaufeerally, Fazlur
    Singapore Gen Hospital, Singapore.
    Leong, Gerard K. T.
    Changi Gen Hospital, Singapore.
    Ling, Lieng H.
    National University, Singapore; National University of Health Syst, Singapore.
    Richards, A. Mark
    National University, Singapore; University of Otago, New Zealand.
    de Kleijn, Dominique P. V.
    University of Medical Centre Utrecht, Netherlands; National University, Singapore.
    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.
    Lund, Lars H.
    Karolinska University Hospital, Sweden.
    Lam, Carolyn S. P.
    Singhealth, Singapore; National University, Singapore; National University, Singapore; Duke NUS Medical Sch, Singapore.
    Prevalence and Clinical Significance of Diabetes in Asian Versus White Patients With Heart Failure2017In: JACC. Heart failure, ISSN 2213-1779, E-ISSN 2213-1787, Vol. 5, no 1, p. 14-24Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES The study sought to compare the prevalence, clinical correlates and prognostic impact of diabetes in Southeast Asian versus white patients with heart failure (HF) with preserved or reduced ejection fraction. BACKGROUND Diabetes mellitus is common in HF and is associated with impaired prognosis. Asia is home to the majority of the worlds diabetic population, yet data on the prevalence and clinical significance of diabetes in Asian patients with HF are sparse, and no studies have directly compared Asian and white patients. METHODS Two contemporary population-based HF cohorts were combined: from Singapore (n 1,002, median [25th to 75th percentile] age 62 [54 to 70] years, 76% men, 19.5% obesity) and Sweden (n =19,537, 77 [68 to 84] years, 60% men, 24.8% obesity). The modifying effect of ethnicity on the relationship between diabetes and clinical correlates or prognosis (HF hospitalization and all-cause mortality) was examined using interaction terms. RESULTS Diabetes was present in 569 (57%) Asian patients versus 4,680 (24%) white patients (p amp;lt; 0.001). Adjusting for clinical covariates, obesity was more strongly associated with diabetes in white patients (odds ratio [OR]: 3.45;. 95% confidence interval [CI]: 2.86 to 4.17) than in Asian patients (OR: 1.82; 95% CI: 1.13 to 2.96; P-interaction = 0.026). Diabetes was more strongly associated with increased HF hospitalization and all-cause mortality in Asian patients (hazard ratio: 1.50; 95% CI: 1.21 to 1.87) than in white patients (hazard ratio: 1.29; 95% CI: 1.22 to 1.36; P-interaction = 0.045). CONCLUSIONS Diabetes was 3-fold more common in Southeast Asian compared to white patients with HF, despite younger age and less obesity, and more strongly associated with poor outcomes in Asian patients than white patients. These results underscore the importance of ethnicity-tailored aggressive strategies to prevent diabetes and its complications. (C) 2017 by the American College of Cardiology Foundation.

  • 90.
    Baranowski, Jacek
    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.
    Catheter based valve interventions2014Conference paper (Refereed)
  • 91.
    Baranowski, Jacek
    et al.
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Dahlin, Lars-Göran
    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.
    Nielsen, Niels-Erik
    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.
    Nylander, Eva
    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.
    Wallby, Lars
    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.
    Ahn, Henrik
    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.
    Transcatheter aortic valve implantation without prior balloon dilatation - a non-randomized single centre experience2013Conference paper (Other academic)
  • 92.
    Baranowski, Jacek
    et al.
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Myasnikova, Irina
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Ahn, Henrik
    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.
    Implanterbar trycksensor för monitorering av hjärtsvikt-första humanapplikation.2013Conference paper (Refereed)
  • 93. Baranowski, Jacek
    et al.
    Nielsen, Niels-Erik
    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.
    TAVI without BAV2014Conference paper (Refereed)
  • 94.
    Baranowski, Jacek
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nielsen, Niels-Erik
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ahn, 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 Thoracic and Vascular Surgery.
    A simplified protocol for transcatheter aortic valve implantation that reduces procedure-related risk2016In: Journal of Cardiovascular Diseases & Diagnosis, E-ISSN 2329-9517, Vol. 4, no 3, article id 1000241Article in journal (Refereed)
    Abstract [en]

    Objectives: Transcatheter Aortic Valve Implantation is now a well-established procedure and continuous development has improved the technique. The object of this paper is to describe the successive steps taken at our department to improve our protocol, resulting in a more effective and patient-safe procedure.

    Design: An echo-guided method for aortic cusp alignment was used in 229 patients. In 139 patients pre-dilatation was excluded from the protocol. In the last 47 of the patients we exchanged the stiff guide-wire in the left ventricle with a soft wire for valve placement.

    Results: There was a significant decrease in the use of contrast medium during the period with 90% of patients receiving less than 50 ml contrast and 35% no contrast at all. In more than half the patients we only used rapid pacing in association with deployment of the stent valve. We had six cases ofpericardial bleeding due to penetration of the stiff guide wire through the left ventricular (LV) wall. This complication was avoided in all subsequent patients where we exchanged the stiff catheter to a soft guidewire in the ascending aorta before introduction of the wire and stent valve into the LV.

    Conclusions: We have successively modified our standard protocol for implantation of a balloon-expandable transcatheter aortic valve. This has simplified the procedure and reduced the risk for certain procedure-related complications.

  • 95. Baranowski, Jacek
    et al.
    Nielsen, Niels-Erik
    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.
    Ahn, Henrik
    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.
    Total percutaneuous transcatheter valve implantation in native mitral stenosis in a patient with previous transapical TAVI2014Conference paper (Refereed)
  • 96. Baranowski, Jacek
    et al.
    Wallby, Lars
    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.
    Ahn, Henrik
    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.
    Dahlin, Lars-Göran
    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.
    Nylander, Eva
    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. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Lindgren, B
    Freter, W
    Johansson, M
    Nielsen, Niels-Erik
    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.
    TAVI without balloon predilation. A ramdomized single centre study.2014Conference paper (Refereed)
  • 97.
    Baranowski, Jacek
    et al.
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Wallby, Lars
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Nylander, Eva
    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.
    Boano, Gabriella
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Vanky, Farkas
    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.
    Löfström, Lars
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Johansson, Mats
    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.
    Nielsen, Nils-Erik
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    MitraClip efter hjärtinfarkt med akut papillarmuskelruptur och som behandling vid SAM efter mitralisplastik - 2 fallbeskrivningar2013Conference paper (Refereed)
  • 98. Baranowski, Jacek
    et al.
    Wallby, Lars
    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.
    Nylander, Eva
    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. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Boano, Gabriella
    Vanky, Farkas
    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.
    Löfstöm, Lars
    Johansson, Mats
    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.
    Nielsen, Niels-Erik
    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.
    MitraClip after myocardial infarction with papillary muscle rupture and as treatment of systolic anterior motion of the mitral valve.2014Conference paper (Refereed)
  • 99.
    Barmano, Neshro
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Cty Hosp Ryhov, Sweden.
    Charitakis, Emmanouil
    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.
    Karlsson, Jan-Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Cty Hosp Ryhov, 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, Heart and Medicine Center, Department of Endocrinology. Primary Hlth Care Ctr Ctr, Sweden.
    Walfridsson, Håkan
    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.
    Walfridsson, Ulla
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Predictors of improvement in arrhythmia-specific symptoms and health-related quality of life after catheter ablation of atrial fibrillation2019In: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 42, no 2, p. 247-255Article in journal (Refereed)
    Abstract [en]

    Background The primary goal of radiofrequency ablation (RFA) of atrial fibrillation (AF) is to improve symptoms and health-related quality of life (HRQoL). However, most studies have focused on predictors of AF recurrence rather than on predictors of improvement in symptoms and HRQoL. Hypothesis We sought to explore predictors of improvement in arrhythmia-specific symptoms and HRQoL after RFA of AF, and to evaluate the effects on symptoms, HRQoL, anxiety, and depression. Methods We studied 192 patients undergoing their first RFA of AF. The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), arrhythmia-specific questionnaire in tachycardia and arrhythmia (ASTA), and hospital anxiety and depression scale (HADS) questionnaires were filled out at baseline, at 4 months, and at a 1-year follow-up. Results All questionnaire scale scores improved significantly over time. In the ASTA symptom scale score, female gender and amp;gt; 10 AF episodes the month before RFA were significant positive predictors of improvement, while diabetes and AF recurrence within 12 months after RFA were significant negative predictors (R-2 = 0.18; P amp;lt; 0.001). In the ASTA HRQoL scale score, the presence of heart failure and amp;gt; 10 AF episodes the month before RFA were significant positive predictors of improvement, while diabetes, maximum left atrial volume and AF recurrence were significant negative predictors (R-2 = 0.20; P amp;lt; 0.001). Conclusion Left atrial volume, gender, diabetes, heart failure, the frequency of AF attacks prior to RFA, and recurrence of AF after RFA were significant factors affecting improvement in symptoms and HRQoL after RFA of AF. Future studies are warranted to confirm these findings.

  • 100.
    Barmano, Neshro
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Department of Internal Medicine, County Hospital Ryhov, Jönköping, Sweden,.
    Charitakis, Emmanouil
    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.
    Kronstrand, Robert
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. National Board of Forensic Medicine, Linko¨ping, Sweden.
    Walfridsson, Ulla
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Karlsson, Jan-Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Department of Internal Medicine, County Hospital Ryhov, Jönköping, Sweden.
    Walfridsson, Håkan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    The association between alcohol consumption, cardiac biomarkers, left atrial size and re-ablation in patients with atrial fibrillation referred for catheter ablation2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 4, article id e0215121Article in journal (Refereed)
    Abstract [en]

    Background

    Information on alcohol consumption in patients undergoing radiofrequency ablation (RFA) of atrial fibrillation (AF) is often limited by the reliance on self-reports. The aim of this study was to describe the long-term alcohol consumption, measured as ethyl glucuronide in hair (hEtG), in patients undergoing RFA due to AF, and to examine potential associations with cardiac biomarkers, left atrial size and re-ablation within one year after the initial RFA.

    Methods

    The amount of hEtG was measured in patients referred for RFA, and a cut-off of 7 pg/mg was used. N-terminal pro B-type natriuretic peptide (NT-proBNP) and the mid-regional fragment of pro atrial natriuretic peptide (MR-proANP) were examined and maximum left atrium volume index (LAVI) was measured. The number of re-ablations was examined up to one year after the initial RFA. Analyses were stratified by gender, and adjusted for age, systolic blood pressure, body mass index, presence of heart failure and heart rhythm for analyses regarding NT-proBNP, MR-proANP and LAVI and heart rhythm being replaced by type of AF for analyses regarding re-ablation.

    Results

    In total, 192 patients were included in the study. Median (25th– 75th percentile) NT-proBNP in men with hEtG ≥ 7 vs. < 7 pg/mg was 250 (96–695) vs. 130 (49–346) pg/ml (p = 0.010), and in women it was 230 (125–480) vs. 230 (125–910) pg/ml (p = 0.810). Median MR-proANP in men with hEtG ≥ 7 vs. < 7 pg/mg was 142 (100–224) vs. 117 (83–179) pmol/l (p = 0.120) and in women it was 139 (112–206) vs. 153 (93–249) pmol/l (p = 0.965). The median of maximum LAVI was 30.1 (26.7–33.9) vs. 25.8 (21.4–32.0) ml/m2 (p = 0.017) in men, and 25.0 (18.9–29.6) vs. 25.7 (21.7–34.6) ml/m2 (p = 0.438) in women, with hEtG ≥ 7 vs. < 7 pg/ml, respectively. Adjusted analyses showed similar results, except for MR-proANP turning out significant in men with hEtG ≥ 7 vs. < 7 pg/mg (p = 0.047). The odds ratio of having a re-ablation was 3.5 (95% CI 1.3–9.6, p = 0.017) in men with hEtG ≥ 7 vs. < 7 pg/mg, while there was no significant difference in women.

    Conclusions

    In male patients with AF and hEtG ≥ 7 pg/mg, NT-proBNP and MR-proANP were higher, LA volumes larger, and there was a higher rate of re-ablations, as compared to men with hEtG < 7 pg/mg. This implies that men with an alcohol consumption corresponding to an hEtG-value ≥ 7, have a higher risk for LA remodelling that could potentially lead to a deterioration of the AF situation.

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