liu.seSearch for publications in DiVA
Change search
Refine search result
12 1 - 50 of 55
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Alehagen, Urban
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Alexander, J.
    Norwegian Inst Publ Hlth, Norway.
    Aaseth, J.
    Innlandet Hosp Trust, Norway.
    Larsson, A.
    Uppsala Univ, Sweden.
    Lindahl, Tomas
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Significant decrease of von Willebrand factor and plasminogen activator inhibitor-1 by providing supplementation with selenium and coenzyme Q10 to an elderly population with a low selenium status2020In: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215Article in journal (Refereed)
    Abstract [en]

    Purpose Endothelial dysfunction and inflammation are conditions which fuel atherosclerosis and ischaemic heart disease. We have previously reported reduced cardiovascular (CV) mortality following supplementation with selenium and coenzyme Q10 to 443 elderly individuals with low selenium status (mean 67 mu g/L) for 4 years. Here, we wanted to evaluate a possible association between the supplementation and the plasma concentrations of the von Willebrand factor (vWf), and the plasminogen activator inhibitor-1 (PAI-1), as they, besides other functions, are also strongly associated with endothelial function. Methods In this sub-study, 308 individuals (active substance: 157, placebo: 151) were included. Blood samples were drawn after 6 and 36 months and vWf and PAI-1 were determined in plasma by ELISA. Changes in concentrations of the biomarkers were evaluated by the use of T tests, repeated measures of variance, and ANCOVA analyses. Results The active treatment group presented a lower level of vWf after 36 months compared with the placebo group (1.08 U/mL vs. 5.10 U/mL; p = 0.0007). The results were validated through the repeated measures of variance evaluation. The PAI-1 levels showed an equally significant decrease in the active group (26.2 ng/mL vs. 49.2 ng/mL; p = 0.0002) and were also validated through repeated measures of variance evaluation. Conclusion In this sub-study on elderly receiving selenium and coenzyme Q10, or placebo we found significantly lower levels of vWf and PAI-1 in the active treatment group as compared to the placebo group. We interpret this as a better endothelial function because of the intervention, which accords with a previous finding of reduced CV mortality.

    Download full text (pdf)
    fulltext
  • 2.
    Ali, Zaheer
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Cui, Dongmei
    Sun Yat Sen Univ, Peoples R China.
    Yang, Yunlong
    Fudan Univ, Peoples R China.
    Tracey-White, Dhani
    UCL Inst Ophthalmol, England.
    Vazquez Rodriguez, Gabriela
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Moosajee, Mariya
    UCL Inst Ophthalmol, England.
    Ju, Rong
    Sun Yat Sen Univ, Peoples R China.
    Li, Xuri
    Sun Yat Sen Univ, Peoples R China.
    Cao, Yihai
    Karolinska Inst, Sweden.
    Jensen, Lasse
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Synchronized tissue-scale vasculogenesis and ubiquitous lateral sprouting underlie the unique architecture of the choriocapillaris2020In: Developmental Biology, ISSN 0012-1606, E-ISSN 1095-564X, Vol. 457, no 2, p. 206-214Article in journal (Refereed)
    Abstract [en]

    The choriocapillaris is an exceptionally high density, two-dimensional, sheet-like capillary network, characterized by the highest exchange rate of nutrients for waste products per area in the organism. These unique morphological and physiological features are critical for supporting the extreme metabolic requirements of the outer retina needed for vision. The developmental mechanisms and processes responsible for generating this unique vascular network remain, however, poorly understood. Here we take advantage of the zebrafish as a model organism for gaining novel insights into the cellular dynamics and molecular signaling mechanisms involved in the development of the choriocapillaris. We show for the first time that zebrafish have a choriocapillaris highly similar to that in mammals, and that it is initially formed by a novel process of synchronized vasculogenesis occurring simultaneously across the entire outer retina. This initial vascular network expands by un-inhibited sprouting angiogenesis whereby all endothelial cells adopt tip-cell characteristics, a process which is sustained throughout embryonic and early post-natal development, even after the choriocapillaris becomes perfused. Ubiquitous sprouting was maintained by continuous VEGF-VEGFR2 signaling in endothelial cells delaying maturation until immediately before stages where vision becomes important for survival, leading to the unparalleled high density and lobular structure of this vasculature. Sprouting was throughout development limited to two dimensions by Bruchs membrane and the sclera at the anterior and posterior surfaces respectively. These novel cellular and molecular mechanisms underlying choriocapillaris development were recapitulated in mice. In conclusion, our findings reveal novel mechanisms underlying the development of the choriocapillaris during zebrafish and mouse development. These results may explain the uniquely high density and sheet-like organization of this vasculature.

    Download full text (pdf)
    fulltext
  • 3.
    Ali, Zaheer
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Zang, Jingjing
    Univ Zurich, Switzerland.
    Lagali, Neil
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Speech Therapy, Otorhinolaryngology and Audiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Schmitner, Nicole
    Univ Innsbruck, Austria.
    Salvenmoser, Willi
    Univ Innsbruck, Austria.
    Mukwaya, Anthonny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Speech Therapy, Otorhinolaryngology and Audiology. Linköping University, Faculty of Medicine and Health Sciences.
    Neuhauss, Stephan C. F.
    Univ Zurich, Switzerland.
    Jensen, Lasse
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Kimmel, Robin A.
    Univ Innsbruck, Austria.
    Photoreceptor Degeneration Accompanies Vascular Changes in a Zebrafish Model of Diabetic Retinopathy2020In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 61, no 2, article id UNSP 43Article in journal (Refereed)
    Abstract [en]

    PURPOSE. Diabetic retinopathy (DR) is a leading cause of vision impairment and blindness worldwide in the working-age population, and the incidence is rising. Until now it has been difficult to define initiating events and disease progression at the molecular level, as available diabetic rodent models do not present the full spectrum of neural and vascular pathologies. Zebrafish harboring a homozygous mutation in the pancreatic transcription factor pdx1 were previously shown to display a diabetic phenotype from larval stages through adulthood. In this study, pdx1 mutants were examined for retinal vascular and neuronal pathology to demonstrate suitability of these fish for modeling DR. METHODS. Vessel morphology was examined in pdx1 mutant and control fish expressing the fli1a:EGFP transgene. We further characterized vascular and retinal phenotypes in mutants and controls using immunohistochemistry, histology, and electron microscopy. Retinal function was assessed using electroretinography. RESULTS. Pdx1 mutants exhibit clear vascular phenotypes at 2 months of age, and disease progression, including arterial vasculopenia, capillary tortuosity, and hypersprouting, could be detected at stages extending over more than 1 year. Neural-retinal pathologies are consistent with photoreceptor dysfunction and loss, but do not progress to blindness. CONCLUSIONS. This study highlights pdx1 mutant zebrafish as a valuable complement to rodent and other mammalian models of DR, in particular for research into the mechanistic interplay of diabetes with vascular and neuroretinal disease. They are furthermore suited for molecular studies to identify new targets for treatment of early as well as late DR.

    Download full text (pdf)
    fulltext
  • 4.
    Appelgren, Daniel
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Enocsson, Helena
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Skogman, Barbro H
    Center for Clinical Research Dalarna-Uppsala University, Region Dalarna and Faculty of Medicine and Health Sciences, Örebro University.
    Nordberg, Marika
    Åland Central Hospital, Department of Infectious Diseases, AX-22 100 Mariehamn, Åland, Finland.
    Perander, Linda
    Åland Central Hospital, Department of Infectious Diseases, AX-22 100 Mariehamn, Åland, Finland.
    Nyman, Dag
    Bimelix AB, AX-22 100 Mariehamn, Åland, Finland.
    Nyberg, Clara
    Åland Central Hospital, Department of Infectious Diseases, AX-22 100 Mariehamn, Åland, Finland.
    Knopf, Jasmin
    Department of Internal Medicine 3-Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), DE-91 054 Erlangen, Germany.
    Muñoz, Luis E
    Department of Internal Medicine 3-Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), DE-91 054 Erlangen, Germany.
    Sjöwall, Christopher
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöwall, Johanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Neutrophil Extracellular Traps (NETs) in the Cerebrospinal Fluid Samples from Children and Adults with Central Nervous System Infections.2020In: Cells, ISSN 2073-4409, Vol. 9, no 1, article id E43Article in journal (Refereed)
    Abstract [en]

    Neutrophils operate as part of the innate defence in the skin and may eliminate the Borrelia spirochaete via phagocytosis, oxidative bursts, and hydrolytic enzymes. However, their importance in Lyme neuroborreliosis (LNB) is unclear. Neutrophil extracellular trap (NET) formation, which is associated with the production of reactive oxygen species, involves the extrusion of the neutrophil DNA to form traps that incapacitate bacteria and immobilise viruses. Meanwhile, NET formation has recently been studied in pneumococcal meningitis, the role of NETs in other central nervous system (CNS) infections has previously not been studied. Here, cerebrospinal fluid (CSF) samples from clinically well-characterised children (N = 111) and adults (N = 64) with LNB and other CNS infections were analysed for NETs (DNA/myeloperoxidase complexes) and elastase activity. NETs were detected more frequently in the children than the adults (p = 0.01). NET presence was associated with higher CSF levels of CXCL1 (p < 0.001), CXCL6 (p = 0.007), CXCL8 (p = 0.003), CXCL10 (p < 0.001), MMP-9 (p = 0.002), TNF (p = 0.02), IL-6 (p < 0.001), and IL-17A (p = 0.03). NETs were associated with fever (p = 0.002) and correlated with polynuclear pleocytosis (rs = 0.53, p < 0.0001). We show that neutrophil activation and active NET formation occur in the CSF samples of children and adults with CNS infections, mainly caused by Borrelia and neurotropic viruses. The role of NETs in the early phase of viral/bacterial CNS infections warrants further investigation.

    Download full text (pdf)
    fulltext
  • 5.
    Beygui, Farzin
    et al.
    Caen Univ Hosp, France.
    Castren, Maaret
    Helsinki Univ Hosp, Finland; Univ Helsinki, Finland; Karolinska Inst, Sweden.
    Brunetti, Natale Daniele
    Univ Foggia, Italy.
    Rosell-Ortiz, Fernando
    Empresa Publ Emergencias Sanitarias Andalucia, Spain.
    Christ, Michael
    Paracelsus Med Univ, Germany.
    Zeymer, Uwe
    Klinikum Stadt Ludwigshafen Rhein gGmbH, Germany.
    Huber, Kurt
    Wilhelminenhospital, Austria.
    Folke, Fredrik
    Copenhagen Univ Hosp, Denmark.
    Svensson, Leif
    Karolinska Inst Solna, Sweden.
    Bueno, Hector
    Hosp 12 Octubre, Spain.
    vant Hof, Arnoud
    ISALA Acad, Netherlands.
    Nikolaou, Nikolaos
    Konstantopouleio Gen Hosp, Greece.
    Nibbe, Lutz
    Univ Med Berlin, Germany.
    Charpentier, Sandrine
    Univ Hosp Rangueil, France.
    Swahn, Eva
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Tubaro, Marco
    San Filippo Neri Hosp, Italy.
    Goldstein, Patrick
    Lille Univ Hosp, France; Lille Univ Hosp, France.
    Pre-hospital management of patients with chest pain and/or dyspnoea of cardiac origin. A position paper of the Acute Cardiovascular Care Association (ACCA) of the ESC.2020In: European heart journal. Acute cardiovascular care., ISSN 2048-8726, Vol. 9, no 1_SUPPL, p. 59-81Article in journal (Refereed)
    Abstract [en]

    Chest pain and acute dyspnoea are frequent causes of emergency medical services activation. The pre-hospital management of these conditions is heterogeneous across different regions of the world and Europe, as a consequence of the variety of emergency medical services and absence of specific practical guidelines. This position paper focuses on the practical aspects of the pre-hospital treatment on board and transfer of patients taken in charge by emergency medical services for chest pain and dyspnoea of suspected cardiac aetiology after the initial assessment and diagnostic work-up. The objective of the paper is to provide guidance, based on evidence, where available, or on experts opinions, for all emergency medical services health providers involved in the pre-hospital management of acute cardiovascular care.

  • 6.
    Cauwenberghs, Nicholas
    et al.
    Univ Leuven, Belgium.
    Cornelissen, Veronique
    Univ Leuven, Belgium.
    Christle, Jeffrey W.
    Stanford Sch Med, CA 94305 USA.
    Hedman, Kristofer
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Myers, Jonathan
    Stanford Sch Med, CA 94305 USA; Vet Adm Palo Alto Hlth Care Syst, CA USA.
    Haddad, Francois
    Stanford Univ, CA 94305 USA.
    Kuznetsova, Tatiana
    Univ Leuven, Belgium.
    Impact of age, sex and heart rate variability on the acute cardiovascular response to isometric handgrip exercise2020In: Journal of Human Hypertension, ISSN 0950-9240, E-ISSN 1476-5527Article in journal (Refereed)
    Abstract [en]

    Isometric handgrip exercise (IHG) triggers acute increases in cardiac output to meet the metabolic demands of the active skeletal muscle. An abnormal cardiovascular response to IHG might reflect early stages of cardiovascular disease. In a large community-based cohort, we comprehensively assessed the clinical correlates of acute cardiovascular changes during IHG. In total, 333 randomly recruited subjects (mean age, 53 +/- 13 years, 45% women) underwent simultaneous echocardiography and finger applanation tonometry at rest and during 3 min of IHG at 40% maximal handgrip force. We calculated time-domain measures of short-term heart rate variability (HRV) from finger pulse intervals. We assessed the adjusted associations of changes in blood pressure (BP) and echocardiographic indexes with clinical characteristics and HRV measures. During IHG, men presented a stronger absolute increase in heart rate, diastolic BP, left ventricular (LV) volumes and cardiac output than women, even after adjustment for covariables. In adjusted continuous and categorical analyses, age correlated positively with the increase in systolic BP and pulse pressure, but negatively with the increase in LV stroke volume and cardiac output during exercise. After full adjustment, a greater increase in systolic and diastolic BP during exercise was associated with lower absolute real variability (P amp;lt;= 0.026) and root mean square of successive differences (P amp;lt;= 0.032) in pulse intervals at rest. In a general population sample, women presented a weaker cardiovascular response to IHG than men. Older age was associated with greater rise in BP pulsatility and diminished cardiac reserve. Low HRV at rest predicted a higher BP increase during isometric exercise.

  • 7.
    Cavaliere, Carlo
    et al.
    IRCCS SDN, Italy.
    Longarzo, Mariachiara
    IRCCS SDN, Italy.
    Fogel, Stuart
    Western Univ, Canada; Univ Ottawa, Canada; Univ Ottawa, Canada; Univ Ottawa, Canada.
    Engström, Maria
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Soddu, Andrea
    Western Univ, Canada.
    Neuroimaging of Narcolepsy and Primary Hypersomnias2020In: The Neuroscientist, ISSN 1073-8584, E-ISSN 1089-4098, article id 1073858420905829Article, review/survey (Refereed)
    Abstract [en]

    Advances in neuroimaging open up the possibility for new powerful tools to be developed that potentially can be applied to clinical populations to improve the diagnosis of neurological disorders, including sleep disorders. At present, the diagnosis of narcolepsy and primary hypersomnias is largely limited to subjective assessments and objective measurements of behavior and sleep physiology. In this review, we focus on recent neuroimaging findings that provide insight into the neural basis of narcolepsy and the primary hypersomnias Kleine-Levin syndrome and idiopathic hypersomnia. We describe the role of neuroimaging in confirming previous genetic, neurochemical, and neurophysiological findings and highlight studies that permit a greater understanding of the symptoms of these sleep disorders. We conclude by considering some of the remaining challenges to overcome, the existing knowledge gaps, and the potential role for neuroimaging in understanding the pathogenesis and clinical features of narcolepsy and primary hypersomnias.

    Download full text (pdf)
    fulltext
  • 8.
    Chisalita, Ioana Simona
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Wijkman, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Davidson, Lee Ti
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Spångeus, Anna
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Nyström, Fredrik H
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Cityhälsan Centrum, Norrköping.
    Östgren, Carl Johan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Toe brachial index predicts major acute cardiovascular events in patients with type 2 diabetes independently of arterial stiffness2020In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 161, article id 108040Article in journal (Refereed)
    Abstract [en]

    Objective: Our aim was to analyze the predictive value of toe brachial index (TBI) as a risk marker for future major adverse cardiovascular events (MACE) and all-cause mortality in patients with type 2 diabetes (T2D). Methods: TBI was measured in 741 patients with T2D in 2005-2008. Conventional risk factors for vascular disease as well as non-invasive measurements such as pulse-wave velocity (PWV) and intima-media thickness (IMT) of the carotid arteries were estimated. MACE was defined as cardiovascular death or hospitalization for non fatal myocardial infarction or non fatal stroke. Patients were followed for incidence of MACE using the national Swedish Cause of Death Registry and the Inpatient Register. Results: During the follow-up for a period of 9 years MACE occurred in 97 patients and 85 patients died. TBI tertile, 1 versus 3, was significantly related to MACE (HR 2.67, 95%CI 1.60-4.50; p &lt; 0.001) and to all-cause mortality (HR 1.98, 95%CI 1.16-3.83; p = 0.01). TBI tertile 1 as compared to TBI tertile 3 predicted MACE, but not all-cause mortality, independently of age, sex, diabetes duration and treatment, antihypertensive treatment, previous cardiovascular diseases, office systolic blood pressure, HbA1c, LDL cholesterol, estimated glomerular filtration rate, body mass index, current smoking PWV, IMT and carotid plaque presence (HR 3.39, 95%CI 1.53-7.51; p = 0.003 and HR 1.81, 95%CI 0.87-3.76; p = 0.1, respectively). Conclusions: Low TBI predicts an increased risk for MACE independently of arterial stiffness in patients with type 2 diabetes. Trial registration: Clinical Trials.gov number NCT 01049737. Registered January 14, 2010. (C) 2020 Elsevier B.V. All rights reserved.

  • 9.
    Chougar, Lydia
    et al.
    Juntendo Univ, Japan; Hop Cochin, France.
    Hagiwara, Akifumi
    Juntendo Univ, Japan; Univ Tokyo, Japan.
    Takano, Nao
    Juntendo Univ, Japan.
    Andica, Christina
    Juntendo Univ, Japan.
    Cohen-Adad, Julien
    Juntendo Univ, Japan; Polytech Montreal, Canada; Univ Montreal, Canada.
    Warntjes, Marcel Jan Bertus
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). SyntheticMR AB, Linkoping, Sweden.
    Maekawa, Tomoko
    Juntendo Univ, Japan; Univ Tokyo, Japan.
    Hori, Masaaki
    Juntendo Univ, Japan.
    Koshino, Saori
    Juntendo Univ, Japan; Univ Tokyo, Japan.
    Nakazawa, Misaki
    Juntendo Univ, Japan.
    Abe, Osamu
    Univ Tokyo, Japan.
    Aoki, Shigeki
    Juntendo Univ, Japan.
    Signal Intensity within Cerebral Venous Sinuses on Synthetic MRI2020In: MAGNETIC RESONANCE IN MEDICAL SCIENCES, ISSN 1347-3182, Vol. 19, no 1, p. 56-63Article in journal (Refereed)
    Abstract [en]

    Purpose: Flowing blood sometimes appears bright on synthetic T-1-weighted images, which could be misdiagnosed as a thrombus. This study aimed to investigate the frequency of hyperintensity within cerebral venous sinuses on synthetic MR images and to evaluate the influence of increasing flow rates on signal intensity using a flow phantom. Materials and Methods: Imaging data, including synthetic and conventional MRI scans, from 22 patients were retrospectively analyzed. Signal intensities at eight locations of cerebral venous sinuses on synthetic images were graded using the following three-point scale: 0, "dark vessel"; 1, "hyperintensity within the walls"; and 2, "hyperintensity within the lumen:" A phantom with gadolinium solution inside a U-shaped tube was acquired without flow and then with increasing flow rates (60, 100, 200, 300, 400 ml/min). Results: Considering all sinus locations, the venous signal intensity on synthetic T-1-weighted images was graded as 2 in 79.8% of the patients. On synthetic T-2-weighted images, all sinuses were graded as 0. On fluid-attenuated inversion recovery (FLAIR) images, sinuses were almost always graded as 0 (99.4%). In the phantom study, the signal initially became brighter on synthetic T-1-weighted images as the flow rate increased. Above a certain flow rate, the signal started to decrease. Conclusion: High signal intensity within the cerebral venous sinuses is a frequent finding on synthetic T-1-weighted images. This corresponds to the hyperintensity noted at certain flow rates in the phantom experiment.

  • 10.
    Christiansen, Morten K.
    et al.
    Aarhus Univ Hosp, Denmark; Aarhus Univ, Denmark.
    Haugaa, Kristina H.
    Oslo Univ Hosp, Norway.
    Svensson, Anneli
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Gilljam, Thomas
    Sahlgrens Univ Hosp, Sweden.
    Madsen, Trine
    Aalborg Univ Hosp, Denmark.
    Hansen, Jim
    Univ Copenhagen, Denmark.
    Holst, Anders G.
    Rigshosp, Denmark; Univ Copenhagen, Denmark.
    Bundgaard, Henning
    Rigshosp, Denmark; Univ Copenhagen, Denmark.
    Edvardsen, Thor
    Oslo Univ Hosp, Norway.
    Svendsen, Jesper H.
    Rigshosp, Denmark; Univ Copenhagen, Denmark.
    Platonov, Pyotr G.
    Lund Univ, Sweden.
    Jensen, Henrik K.
    Aarhus Univ Hosp, Denmark; Aarhus Univ, Denmark.
    Incidence, Predictors, and Success of Ventricular Tachycardia Catheter Ablation in Arrhythmogenic Right Ventricular Cardiomyopathy (from the Nordic ARVC Registry)2020In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 125, no 5, p. 803-811Article in journal (Refereed)
    Abstract [en]

    Catheter ablation may reduce ventricular tachycardia (VT) burden in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients. However, little is known about factors predicting need for ablation. Therefore, we sought to investigate predictors and use of VT ablation and to evaluate the postprocedural outcome in ARVC patients. We studied 435 patients from the Nordic ARVC registry including 220 probands with definite ARVC according to the 2010 task force criteria and 215 mutation-carrying relatives identified through cascade screening. Patients were followed until first-time VT ablation, death, heart transplantation, or January 1st 2018. Additionally, patients undergoing VT ablation were further followed from the time of ablation for recurrent ventricular arrhythmias. The cumulative use of VT ablation was 4% (95% confidence interval [CI] 3% to 6%) and 11% (95% CI 8% to 15%) after 1 and 10 years. All procedures were performed in probands in whom cumulative use was 8% (95% CI 5% to 12%) and 20% (95% CI 15% to 26%). In adjusted analyses among probands, only young age predicted ablation. In patients undergoing ablation, risk of recurrent arrhythmias was 59% (95% CI 44% to 71%) and 74% (95% CI 59% to 84%) 1 and 5 years after the procedure. Despite high recurrence rates, the burden of ventricular arrhythmias was reduced after ablation (p = 0.0042). Young age, use of several antiarrhythmic drugs and inducibility to VT after ablation were associated with an unfavorable outcome. In conclusion, twenty percent of ARVC probands developed a clinical indication for VT ablation within 10 years whereas mutation-carrying relatives were without such need. Although the burden of ventricular arrhythmias decreased after ablation, risk of recurrence was substantial. (C) 2019 Elsevier Inc. All rights reserved.

  • 11.
    Cooper, Lauren B.
    et al.
    Inova Heart and Vasc Inst, VA 22042 USA; Duke Univ, NC 27706 USA.
    Benson, Lina
    Karolinska Inst, Sweden.
    Mentz, Robert J.
    Duke Univ, NC 27706 USA.
    Savarese, Gianluigi
    Karolinska Inst, Sweden.
    DeVore, Adam D.
    Duke Univ, NC 27706 USA.
    Carrero, Juan-Jesus
    Karolinska Inst, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Anker, Stefan D.
    Berlin Brandenburg Ctr Regenerat Therapies, Germany; Charite, Germany.
    Lainscak, Mitja
    Gen Hosp Murska Sobota, Slovenia; Univ Ljubljana, Slovenia.
    Hernandez, Adrian F.
    Duke Univ, NC 27706 USA.
    Pitt, Bertram
    Univ Michigan, MI USA.
    Lund, Lars H.
    Karolinska Inst, Sweden.
    Association between potassium level and outcomes in heart failure with reduced ejection fraction: a cohort study from the Swedish Heart Failure Registry2020In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844Article in journal (Refereed)
    Abstract [en]

    Aims Hyperkalaemia and hypokalaemia are common in heart failure and associated with worse outcomes. However, the optimal potassium range is unknown. We sought to determine the optimal range of potassium in patients with heart failure and reduced ejection fraction (amp;lt; 40%) by exploring the relationship between baseline potassium level and short- and long-term outcomes using the Swedish Heart Failure Registry from 1 January 2006 to 31 December 2012. Methods and results We assessed the association between baseline potassium level and all-cause mortality at 30 days, 12 months, and maximal follow-up, in uni- and multivariable stratified and restricted cubic spline Cox regressions. Of 13 015 patients, 93.3% had potassium 3.5-5.0 mmol/L, 3.7% had potassium amp;lt;3.5 mmol/L, and 3.0% had potassium amp;gt;5.0 mmol/L. Potassium 5.0 mmol/L were more common with lower estimated glomerular filtration rate and heart failure of longer duration and greater severity. The potassium level associated with the lowest hazard risk for mortality at 30 days, 12 months, and maximal follow-up was 4.2 mmol/L, and there was a steep increase in risk with both higher and lower potassium levels. In adjusted strata analyses, lower potassium was independently associated with all-cause mortality at 12 months and maximal follow-up, while higher potassium levels only increased risk at 30 days. Conclusion In this nationwide registry, the relationship between potassium and mortality was U-shaped, with an optimal potassium value of 4.2 mmol/L. After multivariable adjustment, hypokalaemia was associated with increased long-term mortality but hyperkalaemia was associated with increased short-term mortality.

  • 12.
    Cui, Xiaotong
    et al.
    Fudan Univ, Peoples R China; Shanghai Inst Cardiovasc Dis, Peoples R China; Univ Gothenburg, Sweden.
    Zhou, Jingmin
    Fudan Univ, Peoples R China; Shanghai Inst Cardiovasc Dis, Peoples R China.
    Pivodic, Aldina
    Stat Konsultgrp, Sweden; Univ Gothenburg, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Ge, Junbo
    Fudan Univ, Peoples R China; Shanghai Inst Cardiovasc Dis, Peoples R China.
    Fu, Michael
    Univ Gothenburg, Sweden.
    Temporal trends in cause-specific readmissions and their risk factors in heart failure patients in Sweden2020In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 306, p. 116-122Article in journal (Refereed)
    Abstract [en]

    Background: It remains unclear whether readmissions of patients with heart failure (HF) have decreased over time in an era of improved therapy and management of HF. This study aimed to determine the temporal short- and long-term trends of cause-specific rehospitalization and their risk factors in a Swedish context. Methods: HF patients in the Swedish Heart Failure Registry (SwedeHF) were investigated. Maximum follow-up time was 1 year. Outcomes included the first occurrence of all-cause, cardiovascular (CV) and HF rehospitalizations. Cox proportional hazards models were performed to determine the impact of increasing years on risk for rehospitalization and its known risk factors. Results: Totally, 25,644 index-hospitalized HF patients in SwedeHF from 2004 to 2011 were enrolled in the study. For 8 years, the incidence risk of 1-year all-cause rehospitalization remained unchanged, whereas the incidence risk of CV (P = 0.038) or HF (P = 0.0038) rehospitalization decreased. After adjustment for age and sex, a 3% decrease per every second year was observed for 1-year CV and HF rehospitalizations (P &lt; 0.05). However, time to the first occurring all-cause, CV and HF rehospitalization did not change significantly from 2004 to 2011 (P-values 0.13-0.87). When two study periods (2004-2005 vs. 2010-2011) were compared, the risk factor profile for rehospitalization was found to change. Conclusions: Throughout the 8-year study period, CV- and HF-related rehospitalizations decreased, whereas all-cause rehospitalization remained unchanged, indicating a parallel increase in non-CV rehospitalization in the HF patients. (c) 2020 Elsevier B.V. All rights reserved.

  • 13.
    Eleftheriou, Andreas
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology in Linköping.
    Blystad, Ida
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Tisell, Anders
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Region Östergötland, Center for Diagnostics, Medical radiation physics. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Gasslander, Johan
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Norrköping.
    Lundin, Fredrik
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology in Linköping.
    Indication of Thalamo-Cortical Circuit Dysfunction in Idiopathic Normal Pressure Hydrocephalus: A Tensor Imaging Study2020In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 10, no 1Article in journal (Refereed)
    Abstract [en]

    Idiopathic normal pressure hydrocephalus (iNPH) is a disorder with unclear pathophysiology. The diagnosis of iNPH is challenging due to its radiological similarity with other neurodegenerative diseases and ischemic subcortical white matter changes. By using Diffusion Tensor Imaging (DTI) we explored differences in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in iNPH patients (before and after a shunt surgery) and healthy individuals (HI) and we correlated the clinical results with DTI parameters. Thirteen consecutive iNPH-patients underwent a pre- and post-operative clinical work-up: 10m walk time (w10mt) steps (w10ms), TUG-time (TUGt) and steps (TUGs); for cognitive function MMSE. Nine HI were included. DTI was performed before and 3 months after surgery, HI underwent DTI once. DTI differences analyzed by manually placing 12 regions-of-interest. In patients motor and balance function improved significantly after surgery (p=0.01, p=0.025). Higher nearly significant FA values found in the patients vs HI pre-operatively in the thalamus (p=0.07) accompanied by an almost significant lower ADC (p=0.08). Significantly FA and ADC-values were found between patients and HI in FWM (p=0.02, p=0.001) and almost significant (p=0.057) pre- vs postoperatively. Postoperatively we found a trend towards the HIs FA values and a strong significant negative correlation between FA changes vs. gait results in the FWM (r=-0.7, p=0.008). Our study gives a clear indication of an ongoing pathological process in the periventricular white matter, especially in the thalamus and in the frontal white matter supporting the hypothesis of a shunt reversible thalamo-cortical circuit dysfunction in iNPH.

    Download full text (pdf)
    fulltext
  • 14.
    Engström, Karolina
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Vanky, Farkas
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Rehnberg, Malin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Trinks, Cecilia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Jonasson, Jon
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Green, Anna
    Orebro Univ, Sweden.
    Gunnarsson, Cecilia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Novel SMAD3 p.Arg386Thr genetic variant co-segregating with thoracic aortic aneurysm and dissection2020In: Molecular Genetics & Genomic Medicine, ISSN 2324-9269, article id e1089Article in journal (Refereed)
    Abstract [en]

    Background Pathogenic variants in the SMAD3 gene affecting the TGF-beta/SMAD3 signaling pathway with aortic vessel involvement cause Loeys-Dietz syndrome 3, also known as aneurysms-osteoarthritis syndrome. Methods Description of clinical history of a family in Sweden using clinical data, DNA sequencing, bioinformatics, and pedigree analysis. Results We report a novel SMAD3 variant, initially classified as a genetic variant of uncertain clinical significance (VUS), and later found to be co-segregating with aortic dissection in the family. The index patient presented with a dissecting aneurysm of the aorta including the ascending, descending, and abdominal parts. Genotype analysis revealed a heterozygous missense SMAD3 variant: NM_005902.3(SMAD3): c.11576G amp;gt; C (p.Arg386Thr). The same variant was also identified in a 30 years old formalin-fixed paraffin-embedded block of tissue from a second cousin, who died at 26 years of age from a dissecting aneurysm of the aorta. Conclusion A "variant of uncertain significance" according to the ACMG guidelines has always a scope for reappraisal. Genetic counselling to relatives, and the offering of surveillance service is important to families with aortic aneurysm disease. The report also highlight the potential use of FFPE analysis from deceased relatives to help in the interpretation of variants.

    Download full text (pdf)
    fulltext
  • 15.
    Gawel, Danuta
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Serra I Musach, Jordi
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Lilja, Sandra
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Aagesen, Jesper
    Reg Jonkoping Cty, Sweden.
    Arenas, Alex
    Univ Rovira and Virgili, Spain.
    Asking, Bengt
    Reg Jonkoping Cty, Sweden.
    Bengner, Malin
    Reg Jonkoping Cty, Sweden.
    Bjorkander, Janne
    Reg Jonkoping Cty, Sweden.
    Biggs, Sophie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Hjortswang, Henrik
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Karlsson, Jan-Erik
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Reg Jonkoping Cty, Sweden.
    Köpsen, Mattias
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Jung Lee, Eun Jung
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Yonsei Univ, South Korea.
    Lentini, Antonio
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Li, Xinxiu
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Magnusson, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Martinez, David
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Matussek, Andreas
    Reg Jonkoping Cty, Sweden; Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Nestor, Colm
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Schäfer, Samuel
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Seifert, Oliver
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Reg Jonkoping Cty, Sweden.
    Sonmez, Ceylan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Stjernman, Henrik
    Reg Jonkoping Cty, Sweden.
    Tjärnberg, Andreas
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Wu, Simon
    Not Found:Linkoping Univ, Dept Phys Chem and Biol, Bioinformat, Linkoping, Sweden.
    Åkesson, Karin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Reg Jonkoping Cty, Sweden.
    Shalek, Alex K.
    MIT, MA 02139 USA; MIT, MA 02139 USA; MIT, MA 02139 USA; Broad Inst MIT and Harvard, MA 02142 USA; Ragon Inst MGH MIT and Harvard, MA USA.
    Stenmarker, Margaretha
    Reg Jonkoping Cty, Sweden; Inst Clin Sci, Sweden.
    Zhang, Huan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Gustafsson, Mika
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Benson, Mikael
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases (vol 11, 47, 2019)2020In: Genome Medicine, ISSN 1756-994X, E-ISSN 1756-994X, Vol. 12, no 1, article id 37Article in journal (Refereed)
    Abstract [en]

    An amendment to this paper has been published and can be accessed via the original article.

  • 16. Order onlineBuy this publication >>
    Gutefeldt, Kerstin
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Upper extremity impairments in type 1 diabetes in comparison to matched controls without diabetes: associations to the IGF-system, metabolic factors, disability and quality of life2020Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Compared with the general population, people with type 1 diabetes (T1D) more often exhibit pathological alterations in musculoskeletal tissue (impairments). Some of these impairments involve the upper extremities, i.e., the shoulders, hands, and fingers. Although present in diabetes, these complications are underdiagnosed and not actively searched for during routine clinical examinations. Furthermore, much is still unclear about these impairments, specifically regarding their etiology, risk factors, and consequences on daily life activities and quality of life. The growth hormone (GH)/insulinlike growth factor (IGF)-system is known to be affected in diabetes, but whether this is involved in upper extremity impairments (UEIs) is unclear. The aim of this thesis was to describe the prevalence of UEIs in patients with diabetes compared with controls. Furthermore, we aimed to search for risk factors of UEIs, and elucidate the impact of UEIs on daily life activities and health-related quality of life (HRQOL). We used two cohorts; the LedIG cohort (papers I–III), a large population-based study in which all patients with a long duration of T1D (>20 years), aged <67 years, living in the south-east region of Sweden were invited to participate, as well as matched controls without diabetes. This study was based on questionnaires as well as blood samples from the participants. The last paper (IV) included a smaller cohort (n=69) of patients with T1D, who both completed a questionnaire and were the subjects of a clinical examination.

    Paper I: The UEIs were common in diabetes, with a prevalence of up to 48%. Hand paresthesia was the most common impairment, followed by shoulder pain and stiffness. The prevalence of UEIs was 2–4 times higher in patients than in controls and was associated with more activity limitations. Risk factors were heterogeneous for the different UEIs and included female sex, increasing age, longer duration of diabetes, and poor glycemic control.

    Paper II: The GH-IGF-axis is important for the growth and function of musculoskeletal tissues. We examined differences in the IGF system between patients with T1D on subcutaneous insulin treatment and controls. We found lower levels of IGF-I and insulinlike growth factor-binding protein (IGFBP)-3 and higher levels of GH and IGFBP-1 in patients with T1D than in controls. The largest difference was found in IGFBP-1, and this probably reflected insulin deficiency. The IGF-I levels were increased with increasing insulin doses. However, even at very high insulin doses (>1 U/kg) the IGF-I Z-score was subnormal, indicating that IGF-I cannot be normalized by subcutaneous insulin treatment. Residual endogenous insulin secretion counteracted these alterations. Furthermore, we investigated possible relationships between UEIs and IGF-I, and found no association.

    Paper III: The HRQOL was lower in patients with T1D than in controls. Patients with shoulder impairments, hand paresthesia, and hand stiffness, but not finger impairments, had lower HRQOL scores than patients without these impairments. The patients with T1D showed a higher frequency of sick leave than controls, and a common reason for this was musculoskeletal impairments.

    Paper IV: In addition to the self-reported UEIs, the prevalence of UEIs was also investigated by clinical examination. Clinical UEIs were found in 65% of the participants, with shoulder test (hands against back), prayer sign test, and the Phalen’s and Tinel’s tests being most prevalent. We compared self-reported UEIs to clinical UEIs and found that self-reported impairments were associated with clinical examination. We also found that self-reported shoulder impairments, reduced hand strength, and previous surgery for carpal tunnel syndrome and trigger finger were associated with several other UEIs.

    In current diabetic care, there is no established routine to capture UEIs, as opposed to other known diabetes complications. We show that UEIs are more common in patients with T1D than in controls, and that they are related to impaired HRQOL and daily life activity limitations. Clinical routines including self-reported UEIs, e.g. shoulder stiffness and reduced hand strength, might be used to identify patients with UEIs in need of clinical investigation, enhanced preventive and therapeutic strategies, as well as rehabilitative interventions.

    List of papers
    1. Upper extremity impairments in type 1 diabetes with long duration: common problems with great impact on daily life
    Open this publication in new window or tab >>Upper extremity impairments in type 1 diabetes with long duration: common problems with great impact on daily life
    Show others...
    2019 (English)In: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165, Vol. 41, no 6, p. 633-640Article in journal (Refereed) Published
    Abstract [en]

    PURPOSE: To investigate the prevalence, activity limitations and potential risk factors of upper extremity impairments in type 1 diabetes in comparison to controls.

    METHODS: In a cross-sectional population-based study in the southeast of Sweden, patients with type 1 diabetes <35 years at onset, duration ≥20 years, <67 years old and matched controls were invited to answer a questionnaire on upper extremity impairments and activity limitations and to take blood samples.

    RESULTS: Seven hundred and seventy-three patients (ages 50 ± 10 years, diabetes duration 35 ± 10 years) and 708 controls (ages 54 ± 9 years) were included. Shoulder pain and stiffness, hand paraesthesia and finger impairments were common in patients with a prevalence of 28-48%, which was 2-4-folds higher than in controls. Compared to controls, the patients had more bilateral impairments, often had coexistence of several upper extremity impairments, and in the presence of impairments, reported more pronounced activity limitations. Female gender (1.72 (1.066-2.272), p = 0.014), longer duration (1.046 (1.015-1.077), p = 0.003), higher body mass index (1.08 (1.017-1.147), p = 0.013) and HbA1c (1.029 (1.008-1.05), p = 0.007) were associated with upper extremity impairments.

    CONCLUSIONS: Compared to controls, patients with type 1 diabetes have a high prevalence of upper extremity impairments, often bilateral, which are strongly associated with activity limitations. Recognising these in clinical practise is crucial, and improved preventative, therapeutic and rehabilitative interventions are needed. Implications for rehabilitation Upper extremity impairments affecting the shoulder, hand and fingers are common in patients with type 1 diabetes, the prevalence being 2-4-fold higher compared to non-diabetic persons. Patients with diabetes type 1 with upper extremity impairments have more pronounced limitations in daily activities compared to controls with similar impairments. Recognising upper extremity impairments and activity limitations are important and improved preventive, therapeutic and rehabilitation methods are needed.

    Place, publisher, year, edition, pages
    Taylor & Francis, 2019
    Keywords
    Dupuytren’s disease, Type 1 diabetes, carpal tunnel syndrome, frozen shoulder, trigger finger disorder
    National Category
    Endocrinology and Diabetes
    Identifiers
    urn:nbn:se:liu:diva-144020 (URN)10.1080/09638288.2017.1397202 (DOI)000461521100002 ()29105514 (PubMedID)2-s2.0-85033477270 (Scopus ID)
    Note

    Funding agencies: Medical Research Council of Southeast Sweden (FORSS); County council of Region Ostergotland, Sweden; Stiftelseforvaltningen of Region Ostergotland, Sweden

    Available from: 2018-01-03 Created: 2018-01-03 Last updated: 2020-04-27Bibliographically approved
    2. Dysregulated growth hormone-insulin-like growth factor-1 axis in adult type 1 diabetes with long duration
    Open this publication in new window or tab >>Dysregulated growth hormone-insulin-like growth factor-1 axis in adult type 1 diabetes with long duration
    Show others...
    2018 (English)In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 89, no 4, p. 424-430Article in journal (Refereed) Published
    Abstract [en]

    ContextIn type 1 diabetes (T1D), dysregulation of the GH-IGF-1 axis has been reported. Whether this is related to upper extremity impairments (UEI) is unknown. ObjectiveExamine differences in GH-IGF-1 axis between T1D on subcutaneous insulin treatment and matched controls without diabetes and possible associations between GH-IGF-1 axis and UEI. DesignCross-sectional population-based study. Patients with T1D, onset amp;lt;35years, duration 20years, amp;lt;67years old and controls were invited to answer questionnaires and take blood samples. SubjectsA total of 605 patients with T1D and 533 controls accepted to participate. OutcomesFasting levels of IGF-1, IGF-1 Z-score, IGFBP-1, IGFBP-3, C-peptide, GH and UEI. ResultsPatients with T1D had lower IGF-1 and IGFBP-3 and higher IGFBP-1 and GH than controls. The difference in IGF-1 persisted with age. Insulin dose was associated with increasing IGF-1 Z-score but even at a very high insulin dose (amp;gt;1U/kg) IGF-1 Z-score was subnormal compared to controls. IGF-1 Z-score was unaffected by glycaemic control (HbA1c) but increased with residual insulin secretion, (C-peptide 1-99 pmol/L). IGFBP-1 was associated with fasting blood glucose, negatively in controls and positively in patients with T1D probably reflecting insulin resistance and insulin deficiency, respectively. There was no association between lower IGF-1 Z-score and UEI in T1D. ConclusionIn adult T1D with fair glycaemic control, the GH-IGF-1 axis is dysregulated exhibiting GH resistance, low IGF-1 and elevated IGFBP-1. Subcutaneous insulin cannot normalize these changes while endogenous insulin secretion has marked effects on IGF-1 pointing to a role of portal insulin.

    Place, publisher, year, edition, pages
    WILEY, 2018
    Keywords
    GH; insulin-like growth factor-1; insulin-like growth factor-binding protein-1; insulin; type 1 diabetes; upper extremity impairments
    National Category
    Endocrinology and Diabetes
    Identifiers
    urn:nbn:se:liu:diva-151773 (URN)10.1111/cen.13810 (DOI)000444539600006 ()29989677 (PubMedID)
    Note

    Funding Agencies|Medical Research Council of Southeast Sweden FORSS; County council and Stiftelseforvaltningen of Region Ostergotland, Sweden

    Available from: 2018-10-08 Created: 2018-10-08 Last updated: 2020-03-24
    3. Low health-related quality of life is strongly linked to upper extremity impairments in type 1 diabetes with a long duration
    Open this publication in new window or tab >>Low health-related quality of life is strongly linked to upper extremity impairments in type 1 diabetes with a long duration
    Show others...
    2020 (English)In: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165Article in journal (Refereed) Epub ahead of print
    Abstract [en]

    Purpose: To compare health-related quality of life (HRQOL) in type 1 diabetes and non-diabetic controls and possible links to upper extremity impairments (UEIs). Prevalence of sick-leave and causes were investigated.

    Materials and methods: This Swedish population-based case-control study included type 1 diabetes patients <67 years old and with a diabetes duration ≥20 years. Participants completed a postal questionnaire including Short Form 36, and questions regarding UEIs, and sick-leave.

    Results: In total, 773 patients, aged 50 ± 10 years (diabetes duration 35 ± 10 years), and 708 non-diabetic controls, aged 54 ± 9 years, completed the study. Patients reported significantly lower HRQOL compared with controls. The difference was greatest for general health, vitality, and bodily pain. Patients with shoulder or hand but not finger impairments scored significantly lower than asymptomatic patients. The prevalence of sick leave was higher in patients vs. controls (23% vs. 9%, p < 0.001), and nearly half cited impairments from back, muscles, or joints as the main reason.

    Conclusions: Health-related quality of life is lower in type 1 diabetes than controls and in patients with shoulder and hand impairments than in asymptomatic. Musculoskeletal impairments (back/muscle/joints) have impact on work ability. Identification of UEIs is important for initiating preventative-, therapeutic-, and rehabilitative interventions.

    • Implications for rehabilitation
    • Upper extremity impairments (UEIs) that are common in type 1 diabetes, and associated with reduced health-related quality of life, should preferably be screened for on a regular basis along with other known diabetes complications.

    • Early identification of UEIs is important to improve health by initiating preventive as well as therapeutic multi-professional rehabilitative interventions.

    • Sick leave is higher in type 1 diabetes than in controls. Musculoskeletal impairments, including the back, muscles, and joints, are a common cause for sick leave warranting further studies.

    Place, publisher, year, edition, pages
    Taylor & Francis, 2020
    Keywords
    Quality of life; type 1 diabetes; upper extremity impairments; work ability; disability
    National Category
    General Practice
    Identifiers
    urn:nbn:se:liu:diva-163405 (URN)10.1080/09638288.2019.1705924 (DOI)000505880400001 ()31906725 (PubMedID)2-s2.0-85078623672 (Scopus ID)
    Note

    Funding Agencies|Medical Research Council South-east Sweden (FORSS); County Council; Stiftelseforvaltningen of Region Ostergotland, Sweden

    Available from: 2020-02-04 Created: 2020-02-04 Last updated: 2020-03-24Bibliographically approved
    4. Clinical Examination and Self-Reported Upper Extremity Impairments in Patients with Long-Standing Type 1 Diabetes Mellitus
    Open this publication in new window or tab >>Clinical Examination and Self-Reported Upper Extremity Impairments in Patients with Long-Standing Type 1 Diabetes Mellitus
    Show others...
    2020 (English)In: Journal of Diabetes Research, ISSN 2314-6745, E-ISSN 2314-6753, Journal of Diabetes Research, Vol. 2020, article id 4172635Article in journal (Refereed) Published
    Abstract [en]

    Aim. The aims of the current study were (1) to determine the prevalence of upper extremity impairments (UEIs) in patients with type 1 diabetes by clinical investigation; (2) to investigate if self-reported impairments were concordant with clinical findings and if key questions could be identified; and (3) to investigate if answers to our self-reported questionnaire regarding UEIs are reliable. Methods. Patients with type 1 diabetes were invited to participate in a cross-sectional study of clinical and self-reported (12 items) UEIs in adjunction to ordinary scheduled clinical visit. Before the visit, a questionnaire on UEIs was filled in twice (test-retest) followed by clinical testing at the planned visit. Results. In total, 69 patients aged and with diabetes duration were included in the study. In the clinical examination, two-thirds (65%) of the patients showed one or more UEI, with failure to perform hand against back as the most common clinical finding (40%) followed by positive Phalen’s test (27%), Tinel’s test (26%), and Prayer’s sign (24%). UEIs observed by clinical examination were often bilateral, and multiple impairments often coexisted. Self-reported shoulder stiffness was associated with impaired shoulder mobility and with Prayer’s sign. Self-reported reduced hand strength was associated to lower grip force, Prayer’s sign, trigger finger, fibrosis string structures, and reduced thenar strength as well as reduced shoulder mobility. In addition, self-reporting previous surgery of carpal tunnel and trigger finger was associated with several clinical UEIs including shoulder, hand, and finger. The test-retest of the questionnaire showed a high agreement of 80-98% for reported shoulder, hand, and finger impairments. Conclusion. UEIs are common in type 1 diabetes. Self-reported shoulder stiffness and reduced hand strength might be used to capture patients with UEIs in need of clinical investigation and enhanced preventive and therapeutic strategies, as well as rehabilitative interventions.

    Place, publisher, year, edition, pages
    Hindawi Publishing Corporation, 2020
    National Category
    Physiotherapy
    Identifiers
    urn:nbn:se:liu:diva-164549 (URN)10.1155/2020/4172635 (DOI)000522278400001 ()
    Note

    Funding agencies:  Medical Research Council of Southeast Sweden (FORSS); County council; Stiftelseforvaltningen of Region ostergotland, Sweden

    Available from: 2020-03-24 Created: 2020-03-24 Last updated: 2020-04-15Bibliographically approved
    Download full text (pdf)
    fulltext
    Download (png)
    presentationsbild
  • 17.
    Gutefeldt, Kerstin
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Hedman, Christina
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Thyberg, Ingrid
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Bachrack Lindström, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Arnqvist, Hans
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    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.
    Low health-related quality of life is strongly linked to upper extremity impairments in type 1 diabetes with a long duration2020In: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165Article in journal (Refereed)
    Abstract [en]

    Purpose: To compare health-related quality of life (HRQOL) in type 1 diabetes and non-diabetic controls and possible links to upper extremity impairments (UEIs). Prevalence of sick-leave and causes were investigated.

    Materials and methods: This Swedish population-based case-control study included type 1 diabetes patients <67 years old and with a diabetes duration ≥20 years. Participants completed a postal questionnaire including Short Form 36, and questions regarding UEIs, and sick-leave.

    Results: In total, 773 patients, aged 50 ± 10 years (diabetes duration 35 ± 10 years), and 708 non-diabetic controls, aged 54 ± 9 years, completed the study. Patients reported significantly lower HRQOL compared with controls. The difference was greatest for general health, vitality, and bodily pain. Patients with shoulder or hand but not finger impairments scored significantly lower than asymptomatic patients. The prevalence of sick leave was higher in patients vs. controls (23% vs. 9%, p < 0.001), and nearly half cited impairments from back, muscles, or joints as the main reason.

    Conclusions: Health-related quality of life is lower in type 1 diabetes than controls and in patients with shoulder and hand impairments than in asymptomatic. Musculoskeletal impairments (back/muscle/joints) have impact on work ability. Identification of UEIs is important for initiating preventative-, therapeutic-, and rehabilitative interventions.

    • Implications for rehabilitation
    • Upper extremity impairments (UEIs) that are common in type 1 diabetes, and associated with reduced health-related quality of life, should preferably be screened for on a regular basis along with other known diabetes complications.

    • Early identification of UEIs is important to improve health by initiating preventive as well as therapeutic multi-professional rehabilitative interventions.

    • Sick leave is higher in type 1 diabetes than in controls. Musculoskeletal impairments, including the back, muscles, and joints, are a common cause for sick leave warranting further studies.

    Download full text (pdf)
    fulltext
  • 18.
    Gutefeldt, Kerstin
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology. Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine.
    Lundstedt, Simon
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Thyberg, Ingrid
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Region Östergötland, Heart and Medicine Center, Department of Rheumatology. Linköping University, Faculty of Medicine and Health Sciences.
    Bachrach-Lindström, Margareta
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Nursing Sciences and Reproductive Health. Linköping University, Faculty of Medicine and Health Sciences.
    Arnqvist, Hans
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology. Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology.
    Spångeus, Anna
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology. Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine.
    Clinical Examination and Self-Reported Upper Extremity Impairments in Patients with Long-Standing Type 1 Diabetes Mellitus2020In: Journal of Diabetes Research, ISSN 2314-6745, E-ISSN 2314-6753, Journal of Diabetes Research, Vol. 2020, article id 4172635Article in journal (Refereed)
    Abstract [en]

    Aim. The aims of the current study were (1) to determine the prevalence of upper extremity impairments (UEIs) in patients with type 1 diabetes by clinical investigation; (2) to investigate if self-reported impairments were concordant with clinical findings and if key questions could be identified; and (3) to investigate if answers to our self-reported questionnaire regarding UEIs are reliable. Methods. Patients with type 1 diabetes were invited to participate in a cross-sectional study of clinical and self-reported (12 items) UEIs in adjunction to ordinary scheduled clinical visit. Before the visit, a questionnaire on UEIs was filled in twice (test-retest) followed by clinical testing at the planned visit. Results. In total, 69 patients aged and with diabetes duration were included in the study. In the clinical examination, two-thirds (65%) of the patients showed one or more UEI, with failure to perform hand against back as the most common clinical finding (40%) followed by positive Phalen’s test (27%), Tinel’s test (26%), and Prayer’s sign (24%). UEIs observed by clinical examination were often bilateral, and multiple impairments often coexisted. Self-reported shoulder stiffness was associated with impaired shoulder mobility and with Prayer’s sign. Self-reported reduced hand strength was associated to lower grip force, Prayer’s sign, trigger finger, fibrosis string structures, and reduced thenar strength as well as reduced shoulder mobility. In addition, self-reporting previous surgery of carpal tunnel and trigger finger was associated with several clinical UEIs including shoulder, hand, and finger. The test-retest of the questionnaire showed a high agreement of 80-98% for reported shoulder, hand, and finger impairments. Conclusion. UEIs are common in type 1 diabetes. Self-reported shoulder stiffness and reduced hand strength might be used to capture patients with UEIs in need of clinical investigation and enhanced preventive and therapeutic strategies, as well as rehabilitative interventions.

    Download full text (pdf)
    fulltext
  • 19.
    Hedman, Kristofer
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Lindow, Thomas
    Vaxjo Cent Hosp, Sweden; Lund Univ, Sweden.
    Elmberg, Viktor
    Lund Univ, Sweden; Blekinge Hosp, Sweden.
    Brudin, Lars
    Kalmar Cty Hosp, Sweden.
    Ekstrom, Magnus
    Lund Univ, Sweden.
    Age- and gender-specific upper limits and reference equations for workload-indexed systolic blood pressure response during bicycle ergometry2020In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, article id UNSP 2047487320909667Article in journal (Refereed)
    Abstract [en]

    Background Guidelines recommend considering workload in interpretation of the systolic blood pressure (SBP) response to exercise, but reference values are lacking. Design This was a retrospective, consecutive cohort study. Methods From 12,976 subjects aged 18-85 years who performed a bicycle ergometer exercise test at one centre in Sweden during the years 2005-2016, we excluded those with prevalent cardiovascular disease, comorbidities, cardiac risk factors or medications. We extracted SBP, heart rate and workload (watt) from &gt;= 3 time points from each test. The SBP/watt-slope and the SBP/watt-ratio at peak exercise were calculated. Age- and sex-specific mean values, standard deviations and 90th and 95th percentiles were determined. Reference equations for workload-indexed and peak SBP were derived using multiple linear regression analysis, including sex, age, workload, SBP at rest and anthropometric variables as predictors. Results A final sample of 3839 healthy subjects (n = 1620 female) were included. While females had lower mean peak SBP than males (188 +/- 24 vs 202 +/- 22 mmHg, p &lt; 0.001), workload-indexed SBP measures were markedly higher in females; SBP/watt-slope: 0.52 +/- 0.21 versus 0.41 +/- 0.15 mmHg/watt (p &lt; 0.001); peak SBP/watt-ratio: 1.35 +/- 0.34 versus 0.90 +/- 0.21 mmHg/watt (p &lt; 0.001). Age, sex, exercise capacity, resting SBP and height were significant predictors of the workload-indexed SBP parameters and were included in the reference equations. Conclusions These novel reference values can aid clinicians and exercise physiologists in interpreting the SBP response to exercise and may provide a basis for future research on the prognostic impact of exercise SBP. In females, a markedly higher SBP in relation to workload could imply a greater peripheral vascular resistance during exercise than in males.

    Download full text (pdf)
    fulltext
  • 20.
    Hedman, Kristofer
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Stanford University, Stanford, USA.
    Moneghetti, Kegan J.
    Stanford University, Stanford, USA.
    Hsu, David
    Stanford University, Stanford, USA.
    Christle, Jeffrey W.
    Stanford University, Stanford, USA.
    Patti, Alessandro
    Stanford University, Stanford, USA; Univ Padua, Italy.
    Ashley, Euan
    Stanford University, Stanford, USA.
    Hadley, David
    Cardiac Insight Inc, WA USA.
    Haddad, Francois
    Stanford University, Stanford, USA.
    Froelicher, Victor
    Stanford University, Stanford, USA.
    Limitations of Electrocardiography for Detecting Left Ventricular Hypertrophy or Concentric Remodeling in Athletes2020In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 133, no 1, p. 123-132.e8Article in journal (Refereed)
    Abstract [en]

    Background

    Electrocardiography (ECG) is used to screen for left ventricular hypertrophy (LVH), but common ECG-LVH criteria have been found less effective in athletes. The purpose of this study was to comprehensively evaluate the value of ECG for identifying athletes with LVH or a concentric cardiac phenotype.

    Methods

    A retrospective analysis of 196 male Division I college athletes routinely screened with ECG and echocardiography within the Stanford Athletic Cardiovascular Screening Program was performed. Left-ventricular mass and volume were determined using echocardiography. LVH was defined as left ventricular mass (LVM) > 102 g/m²; a concentric cardiac phenotype as LVM-to-volume (M/V) ≥ 1.05 g/mL. Twelve-lead electrocardiograms including high-resolution time intervals and QRS voltages were obtained. Thirty-seven previously published ECG-LVH criteria were applied, of which the majority have never been evaluated in athletes. C-statistics, including area under the receiver operating curve (AUC) and likelihood ratios were calculated.

    Results

    ECG lead voltages were poorly associated with LVM (r = 0.18-0.30) and M/V (r = 0.15-0.25). The proportion of athletes with ECG-LVH was 0%-74% across criteria, with sensitivity and specificity ranging between 0% and 91% and 27% and 99.5%, respectively. The average AUC of the criteria in identifying the 11 athletes with LVH was 0.57 (95% confidence interval [CI] 0.56-0.59), and the average AUC for identifying the 8 athletes with a concentric phenotype was 0.59 (95% CI 0.56-0.62).

    Conclusion

    The diagnostic capacity of all ECG-LVH criteria were inadequate and, therefore, not clinically useful in screening for LVH or a concentric phenotype in athletes. This is probably due to the weak association between LVM and ECG voltage.

    The full text will be freely available from 2020-11-15 08:52
  • 21.
    Henriksson, Hanna
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Linköping University, Faculty of Medicine and Health Sciences. Univ Granada, Spain.
    Henriksson, Pontus
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Linköping University, Faculty of Medicine and Health Sciences. Univ Granada, Spain; Karolinska Inst, Sweden.
    Tynelius, Per
    Karolinska Inst, Sweden; Stockholm Cty Council, Sweden.
    Ekstedt, Mattias
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Berglind, Daniel
    Karolinska Inst, Sweden; Stockholm Cty Council, Sweden.
    Labayen, Idoia
    Univ Publ Navarra, Spain.
    Ruiz, Jonatan R.
    Univ Granada, Spain; Karolinska Inst, Sweden.
    Lavie, Carl J.
    Univ Queensland, LA 70121 USA.
    Ortega, Francisco B.
    Univ Granada, Spain; Karolinska Inst, Sweden.
    Cardiorespiratory fitness, muscular strength, and obesity in adolescence and later chronic disability due to cardiovascular disease: a cohort study of 1 million men2020In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 41, no 15, p. 1503-+Article in journal (Refereed)
    Abstract [en]

    Aims Cardiorespiratory fitness, muscular strength, and obesity in adulthood are risk factors for cardiovascular disease (CVD). However, Little is known regarding the associations of these risk factors, already in adolescence, with later disability due to chronic CVD. Hence, we investigated associations of cardiorespiratory fitness, muscular strength, and body mass index (BMI) in adolescence with Later chronic disability due to specific causes of CVD disability (i.e. cerebrovascutar disease, ischaemic heart disease and heart failure). Methods and results This population-based cohort study included 1 078 685 male adolescents (16-19 years) from the Swedish military conscription register from 1972 to 1994. Cardiorespiratory fitness (bicycle ergometer test), muscular strength (knee extension strength), and BMI were measured during the conscription examination. Information about disability pension due to CVD was retrieved from the Social Insurance Agency during a mean follow-up of 28.4 years. Cardiorespiratory fitness was strongly and inversely associated with later risk of chronic CVD disability for all investigated causes. The association was particularly strong for ischaemic heart diseases (hazard ratio 0.11, 95% confidence interval 0.05-0.29 for highest vs. lowest fitness-quintiles). Furthermore, overweight/obesity were associated with CVD disability for all investigated causes. Conversely, associations of muscular strength with CVD disability were generally weak. Conclusions This study provides evidence for associations between low levels of cardiorespiratory fitness and obesity with later risk of chronic disability due to CVD. Preventive actions may begin at young ages and include promotion of cardiorespiratory fitness and healthy body weight.

  • 22.
    Holm, Jonasta
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland.
    Cederholm, Ingemar
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Alehagen, Urban
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lindahl, Tomas
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Szabo, Zoltán
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Biomarker dynamics in cardiac surgery: a prospective observational study on MR-proADM, MR-proANP, hs-CRP and sP-selectin plasma levels in the perioperative period2020In: Biomarkers, ISSN 1354-750X, E-ISSN 1366-5804Article in journal (Refereed)
    Abstract [en]

    Background: For many biomarkers in cardiac surgery, there is a lack of knowledge regarding the normal dynamics of plasma levels during the perioperative course. The aim of this study was to investigate the perioperative dynamics of MR-proADM, MR-proANP, hs-CRP and sP-selectin in cardiac surgery. Method: A prospective observational pilot study with 20 patients scheduled for open cardiac surgery procedures with cardiopulmonary bypass (CPB). Plasma samples were taken for each patient and biomarker during the pre-, per- and postoperative period until Day 6 postoperatively. Results: MR-proADM increased significantly from 0.62 [IQR; 0.54-0.93] nmol/L preoperatively to 1.20 [1.04-1.80] nmol/L postoperative Day 1. MR-proANP increased significantly from 125 [77-152] pmol/L preoperatively to 198 [168-307] pmol/L on weaning from CPB. hs-CRP increased significantly from 2.5 mg/L [0.4-12] preoperatively to peak at 208 mg/L [186-239] postoperative Day 3. The preoperative level of sP-selectin at 23.0 [21.3-26.3] ng/mL initially fell at weaning from CPB, followed by a significant peak of 25.5 [22.7-27.7] ng/mL 8 h postoperatively. Conclusions: The findings in this study may help to understand the physiology of the biomarkers analysed and their response to cardiac surgical trauma including CPB. Furthermore, these findings will guide us in further research on the clinical usefulness of these biomarkers.

    Download full text (pdf)
    fulltext
  • 23.
    Holm Nielsen, S.
    et al.
    Nordic Biosci, Denmark; Tech Univ Denmark, Denmark.
    Jonasson, Lena
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Kalogeropoulos, K.
    Tech Univ Denmark, Denmark.
    Karsdal, M. A.
    Nordic Biosci, Denmark.
    Reese-Petersen, A. L.
    Nordic Biosci, Denmark.
    Keller, U. Auf Dem
    Tech Univ Denmark, Denmark.
    Genovese, F.
    Nordic Biosci, Denmark.
    Nilsson, J.
    Lund Univ, Sweden.
    Goncalves, I
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Exploring the role of extracellular matrix proteins to develop biomarkers of plaque vulnerability and outcome2020In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796Article, review/survey (Refereed)
    Abstract [en]

    Cardiovascular disease (CVD) is the most common cause of death in industrialized countries. One underlying cause is atherosclerosis, which is a systemic disease characterized by plaques of retained lipids, inflammatory cells, apoptotic cells, calcium and extracellular matrix (ECM) proteins in the arterial wall. The biologic composition of an atherosclerotic plaque determines whether the plaque is more or less vulnerable, that is prone to rupture or erosion. Here, the ECM and tissue repair play an important role in plaque stability, vulnerability and progression. This review will focus on ECM remodelling in atherosclerotic plaques, with focus on how ECM biomarkers might predict plaque vulnerability and outcome.

  • 24.
    Jarkman, Sofia
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Lindvall, Martin
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Hedlund, Joel
    Linköping University, National Supercomputer Centre (NSC). Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Treanor, Darren
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Clinical pathology.
    Lundström, Claes
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    van der Laak, Jeroen
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Axillary lymph nodes in breast cancer cases2019Data set
  • 25.
    Karason, Kristjan
    et al.
    Sahlgrens Univ Hosp, Sweden.
    Lund, Lars H.
    Karolinska Univ Hosp, Sweden.
    Dalen, Magnus
    Karolinska Univ Hosp, Sweden.
    Bjorklund, Erik
    Uppsala Univ Hosp, Sweden.
    Grinnemo, Karl
    Uppsala Univ Hosp, Sweden.
    Braun, Oscar
    Skane Univ Hosp, Sweden.
    Nilsson, Johan
    Skane Univ Hosp, Sweden.
    van der Wal, Henriette
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Holm, Jonas
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Hübbert, Laila
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Norrköping.
    Lindmark, Krister
    Umea Univ Hosp, Sweden.
    Szabo, Barna
    Orebro Univ Hosp, Sweden.
    Holmberg, Erik
    Sahlgrens Univ Hosp, Sweden.
    Dellgren, Goran
    Sahlgrens Univ Hosp, Sweden.
    Randomized trial of a left ventricular assist device as destination therapy versus guideline-directed medical therapy in patients with advanced heart failure. Rationale and design of the SWEdish evaluation of left Ventricular Assist Device (SweVAD) trial2020In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844Article in journal (Refereed)
    Abstract [en]

    Aims Patients with advanced heart failure (AdHF) who are ineligible for heart transplantation (HTx) can become candidates for treatment with a left ventricular assist device (LVAD) in some countries, but not others. This reflects the lack of a systematic analysis of the usefulness of LVAD systems in this context, and of their benefits, limitations and cost-effectiveness. The SWEdish evaluation of left Ventricular Assist Device (SweVAD) study is a Phase IV, prospective, 1:1 randomized, non-blinded, multicentre trial that will examine the impact of assignment to mechanical circulatory support with guideline-directed LVAD destination therapy (GD-LVAD-DT) using the HeartMate 3 (HM3) continuous flow pump vs. guideline-directed medical therapy (GDMT) on survival in a population of AdHF patients ineligible for HTx. Methods A total of 80 patients will be recruited to SweVAD at the seven university hospitals in Sweden. The study population will comprise patients with AdHF (New York Heart Association class IIIB-IV, INTERMACS profile 2-6) who display signs of poor prognosis despite GDMT and who are not considered eligible for HTx. Participants will be followed for 2 years or until death occurs. Other endpoints will be determined by blinded adjudication. Patients who remain on study-assigned interventions beyond 2 years will be asked to continue follow-up for outcomes and adverse events for up to 5 years. Conclusion The SweVAD study will compare survival, medium-term benefits, costs and potential hazards between GD-LVAD-DT and GDMT and will provide a valuable reference point to guide destination therapy strategies for patients with AdHF ineligible for HTx.

    Download full text (pdf)
    fulltext
  • 26.
    Karjosukarso, Dyah W.
    et al.
    Radboud Univ Nijmegen, Netherlands.
    Ali, Zaheer
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Peters, Theo A.
    Radboud Univ Nijmegen, Netherlands.
    Zhang, Jia Qi Cheng
    Radboud Univ Nijmegen, Netherlands.
    Hoogendoorn, Anita D. M.
    Radboud Univ Nijmegen, Netherlands.
    Garanto, Alejandro
    Radboud Univ Nijmegen, Netherlands.
    van Wijk, Erwin
    Radboud Univ Nijmegen, Netherlands.
    Jensen, Lasse
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Collin, Rob W. J.
    Radboud Univ Nijmegen, Netherlands.
    Modeling ZNF408-Associated FEVR in Zebrafish Results in Abnormal Retinal Vasculature2020In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 61, no 2, article id UNSP 39Article in journal (Refereed)
    Abstract [en]

    PURPOSE. Familial exudative vitreoretinopathy (FEVR) is an inherited retinal disease in which the retinal vasculature is affected. Patients with FEVR typically lack or have abnormal vasculature in the peripheral retina, the outcome of which can range from mild visual impairment to complete blindness. A missense mutation (p.His455Tyr) in ZNF408 was identified in an autosomal dominant FEVR family. Little, however, is known about the molecular role of ZNF408 and how its defect leads to the clinical features of FEVR. METHODS. Using CRISPR/Cas9 technology, two homozygous mutant zebrafish models with truncated znf408 were generated, as well as one heterozygous and one homozygous missense znf408 model in which the human p.His455Tyr mutation is mimicked. RESULTS. Intriguingly, all three znf408-mutant zebrafish strains demonstrated progressive retinal vascular pathology, initially characterized by a deficient hyaloid vessel development at 5 days postfertilization (dpf) leading to vascular insufficiency in the retina. The generation of stable mutant lines allowed long-term follow up studies, which showed ectopic retinal vascular hyper-sprouting at 90 dpf and extensive vascular leakage at 180 dpf. CONCLUSIONS. Together, our data demonstrate an important role for znf408 in the development and maintenance of the vascular system within the retina.

    Download full text (pdf)
    fulltext
  • 27.
    Kaveckyte, Vaiva
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Univ Hosp, Sweden.
    Persson, Linda
    Swedish Radiat Safety Author, Sweden.
    Malusek, Alexandr
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Benmakhlouf, Hamza
    Karolinska Univ Hosp, Sweden.
    Alm Carlsson, Gudrun
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Carlsson Tedgren, Åsa
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Karolinska Univ Hosp, Sweden.
    Investigation of a synthetic diamond detector response in kilovoltage photon beams2020In: Medical physics (Lancaster), ISSN 0094-2405Article in journal (Refereed)
    Abstract [en]

    Purpose An important characteristic of radiation dosimetry detectors is their energy response which consists of absorbed-dose and intrinsic energy responses. The former can be characterized using Monte Carlo (MC) simulations, whereas the latter (i.e., detector signal per absorbed dose to detector) is extracted from experimental data. Such a characterization is especially relevant when detectors are used in nonrelative measurements at a beam quality that differs from the calibration beam quality. Having in mind the possible application of synthetic diamond detectors (microDiamond PTW 60019, Freiburg, Germany) for nonrelative dosimetry of low-energy brachytherapy (BT) beams, we determined their intrinsic and absorbed-dose energy responses in 25-250 kV beams relative to a Co-60 beam, which is usually the reference beam quality for detector calibration in radiotherapy. Material and Methods Three microDiamond detectors and, for comparison, two silicon diodes (PTW 60017) were calibrated in terms of air-kerma free in air in six x-ray beam qualities (from 25 to 250 kV) and in terms of absorbed dose to water in a Co-60 beam at the national metrology laboratory in Sweden. The PENELOPE/penEasy MC radiation transport code was used to calculate the absorbed-dose energy response of the detectors (modeled based on blueprints) relative to air and water depending on calibration conditions. The MC results were used to extract the relative intrinsic energy response of the detectors from the overall energy response. Measurements using an independent setup with a single ophthalmic BEBIG I25.S16 I-125 BT seed (effective photon energy of 28 keV) were used as a qualitative check of the extracted intrinsic energy response correction factors. Additionally, the impact of the thickness of the active volume as well as the presence of extra-cameral components on the absorbed-dose energy response of a microDiamond detector was studied using MC simulations. Results The relative intrinsic energy response of the microDiamond detectors was higher by a factor of 2 in 25 and 50 kV beams compared to the Co-60 beam. The variation in the relative intrinsic energy response of silicon diodes was within 10% over the investigated photon energy range. The use of relative intrinsic energy response correction factors improved the agreement among the absorbed dose to water values determined using microDiamond detectors and silicon diodes, as well as with the TG-43 formalism-based calculations for the I-125 seed. MC study of microDiamond detector design features provided a possible explanation for inter-detector response variation at low-energy photon beams by differences in the effective thickness of the active volume. Conclusions MicroDiamond detectors had a non-negligible variation in the relative intrinsic energy response (factor of 2) which was comparable to that in the absorbed-dose energy response relative to water at low-energy photon beams. Silicon diodes, in contrast, had an absorbed-dose energy dependence on photon energy that varied by a factor of 6, whereas the intrinsic energy dependence on beam quality was within 10%. It is important to decouple these two responses for a full characterization of detector energy response especially when the user and reference beam qualities differ significantly, and MC alone is not enough.

    The full text will be freely available from 2020-12-27 08:12
  • 28.
    Lu, Yingying
    et al.
    Zhejiang Univ, Peoples R China; State Adm Tradit Chinese Med PR China, Peoples R China; Minist Hlth, Peoples R China; Key Lab Nephropathy, Peoples R China.
    Jiang, Hong
    Zhejiang Univ, Peoples R China; State Adm Tradit Chinese Med PR China, Peoples R China; Minist Hlth, Peoples R China; Key Lab Nephropathy, Peoples R China.
    Li, Bingjue
    Zhejiang Univ, Peoples R China; State Adm Tradit Chinese Med PR China, Peoples R China; Minist Hlth, Peoples R China; Key Lab Nephropathy, Peoples R China.
    Cao, Luxi
    Zhejiang Univ, Peoples R China; State Adm Tradit Chinese Med PR China, Peoples R China; Minist Hlth, Peoples R China; Key Lab Nephropathy, Peoples R China.
    Shen, Qixia
    Zhejiang Univ, Peoples R China; State Adm Tradit Chinese Med PR China, Peoples R China; Minist Hlth, Peoples R China; Key Lab Nephropathy, Peoples R China.
    Yi, Weiwei
    Hangzhou Normal Univ, Peoples R China.
    Ju, Zhenyu
    Hangzhou Normal Univ, Peoples R China.
    Chen, Liangliang
    Zhejiang Univ, Peoples R China; State Adm Tradit Chinese Med PR China, Peoples R China; Minist Hlth, Peoples R China; Key Lab Nephropathy, Peoples R China.
    Han, Fei
    Zhejiang Univ, Peoples R China; State Adm Tradit Chinese Med PR China, Peoples R China; Minist Hlth, Peoples R China; Key Lab Nephropathy, Peoples R China.
    Appelgren, Daniel
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Segelmark, Mårten
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology.
    de Buhr, Nicole
    Univ Vet Med Hannover, Germany.
    von Koeckritz-Blickwede, Maren
    Univ Vet Med Hannover, Germany.
    Chen, Jianghua
    Zhejiang Univ, Peoples R China; State Adm Tradit Chinese Med PR China, Peoples R China; Minist Hlth, Peoples R China; Key Lab Nephropathy, Peoples R China.
    Telomere dysfunction promotes small vessel vasculitis via the LL37-NETs-dependent mechanism2020In: Annals of Translational Medicine, ISSN 2305-5839, E-ISSN 2305-5847, Vol. 8, no 6, article id 357Article in journal (Refereed)
    Abstract [en]

    Background: Small vessel vasculitis (SVV) is a group of systemic autoimmune diseases that are mediated by neutrophil extracellular traps (NETs) in response to cathelicidin LL37, an aging molecular marker, which could be induced by telomere dysfunction. Therefore, in this study, we evaluated the hypothesis that telomere dysfunction in neutrophils may promote SVV via an LL37-NETs-dependent mechanism. Methods: We contrasted the release of neutrophil NETs from mice with telomere dysfunction, mice with DNA damage and wide-type mice. Neutrophil telomere length, the expression of LL37, and the formation of NETs were measured in SVV patients and healthy controls (HCs). The co-expression of gamma H2AX, LL37, and NETs were detected in SVV patients to evaluate the association of the immune aging of neutrophils and pro-inflammatory conditions. LL37 inhibitor was used to verify its key role in NETs release in SVV patients and DNA damage mice. Results: We found that NETs were over-induced by telomere dysfunction and DNA damage in mice, which may be associated with a marked increase in LL37. For patients with SVV, telomeres in neutrophils were significantly shortened, which was also associated with higher levels of LL37 and NETs. Inhibition of LL37 reduced the NETs released from neutrophils. Conclusions: Taken together, the results of these studies suggest that dysfunction of telomeres may promote SVV through the mechanism of LL37-dependent NETs. Thus, targeting the LL37-NETs may be a novel therapy for SVV.

    Download full text (pdf)
    fulltext
  • 29.
    Moltubak, Elin
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Cty Hosp Ryhov, Sweden.
    Landerholm, Kalle
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Cty Hosp Ryhov, Sweden.
    Blomberg, Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Redéen, Stefan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Andersson, Roland
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Cty Hosp Ryhov, Sweden.
    Major Variation in the Incidence of Appendicitis Before, During and After Pregnancy: A Population-Based Cohort Study2020In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323Article in journal (Refereed)
    Abstract [en]

    Background Previous studies indicate a low incidence of appendicitis in third-trimester pregnancy, suggesting a protecting effect of pregnancy. This large population-based cohort study analyzes the association of appendicitis with pregnancy in more detail. The aim of the study was to investigate the incidence of appendicitis and negative appendectomy before, during and after pregnancy. Methods Cross-linking between two Swedish health registries provided data on appendectomy for all women in Sweden giving birth between 1973 and 2013. We analyzed the incidence rates (IR) of perforated and non-perforated appendicitis and negative appendectomy before, during and after pregnancy, and secular trends during the study period. Standardized incidence ratios (SIR) were estimated using age-, sex- and period-specific IR from the background population in Sweden. Results Some 3,888,452 pregnancies resulted in birth during the study period. An appendectomy was registered for 27,575 women in the interval starting one year before and ending two years after pregnancy. The incidence of appendicitis varied substantially during and after pregnancy. SIR for perforated appendicitis was 0.47 (95% CI 0.38-0.59) in the third trimester, 3.89 (2.92-5.18) peripartum, 2.20 (1.89-2.55) in the puerperium and 1.27 (1.19-1.36) in the year postpartum. The pattern was similar for non-perforated appendicitis. Negative appendectomy decreased postpartum. Incidence rate of non-perforated appendicitis and negative appendectomy decreased for both pregnant and non-pregnant women during the study period. Conclusions The findings in this study suggest a protecting effect of pregnancy on the development of appendicitis, which is followed by a rebound effect after birth.

  • 30.
    Nasr, Patrik
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Blomdahl, Julia
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Kechagias, Stergios
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Ekstedt, Mattias
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Modifiers of Liver-Related Manifestation in the Course of NAFLD2020In: Current pharmaceutical design, ISSN 1381-6128, E-ISSN 1873-4286, Vol. 26, no 10, p. 1062-1078Article, review/survey (Refereed)
    Abstract [en]

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease affecting approximately 25% of the global population. There is a strong association between the severity, of NAFLD and the components of the metabolic syndrome. NAFLD is also independently associated with cardiovascular disease and type 2 diabetes mellitus (T2DM). The progressive potential of non-alcoholic fatty liver disease (NAFLD) is indisputable today, and the histological spectrum of NAFLD ranges from isolated steatosis to nonalcoholic steatohepatitis (NASH), with risk of developing :fibrosis and subsequent cirrhosis and hepatocellular carcinoma. There is a substantial inter-patient variation in disease progression, therefore, this review will focus on potential modifiers of fibrosis progression, development of liver cirrhosis, decompensation and liver-related mortality. The potential drivers of disease progression that is discussed are; T2DM and Insulin Resistance, body weight, alcohol consumption, genetics (including HFE and alfa-1-antitrypsin) as well as histological features predictive of disease progression.

  • 31.
    Nasr, Patrik
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Fredrikson, Mats
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences, Forum Östergötland.
    Ekstedt, Mattias
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Kechagias, Stergios
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    The Amount of Liver Fat Predicts Mortality and Development of Type 2 Diabetes in Non-alcoholic Fatty Liver Disease.2020In: Liver international (Print), ISSN 1478-3223, E-ISSN 1478-3231Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is a risk factor for development of type 2 diabetes mellitus (T2DM). We aimed to evaluate whether conventional histological grading of steatosis and accurate quantification of fat content in liver biopsies using stereological point counting (SPC) can predict mortality and future development of T2DM in NAFLD patients.

    METHODS: 129 patients with biopsy proven NAFLD, enrolled between 1988 and 1992, were re-evaluated on two occasions, after 13.7 (±1.5) and 23.2 (±6.8) years. In patients accepting to undergo the procedure, repeat liver biopsies were performed on each follow-up and were evaluated with conventional histopathological methodology and SPC.

    RESULTS: Of the 106 patients without T2DM at baseline, 66 (62%) developed T2DM during a mean follow-up of 23.2 (± 6.8) years. Steatosis grade and liver fat measured with SPC independently (adjusted for age, BMI, fibrosis stage) predicted development of T2DM with an aHR of 1.60 per grade and 1.03 for each SPC percentage increase, respectively. Overall mortality and development of T2DM was more common in patients with grade 3 steatosis compared to lower grades of steatosis. Liver fat measured with SPC was significant for overall mortality (aHR 1.04). In patients that underwent repeat biopsy, reduction of liver fat measured with SPC was associated with decreased risk of developing T2DM (aHR 0.91 for each SPC percentage decrease).

    CONCLUSION: Steatosis grade and liver fat measured with SPC predict mortality and the risk of developing T2DM in NAFLD. Reduction of liver fat decreases the risk of developing T2DM.

    Download full text (pdf)
    fulltext
  • 32.
    Nelzén, Oskar
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Skoog, Johan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Öster, Malin
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Zachrisson, Helene
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Impact on venous haemodynamics after treatment of great saphenous vein incompetence using plethysmography and duplex ultrasound2020In: Phlebology, ISSN 0268-3555, E-ISSN 1758-1125, article id 0268355519898952Article in journal (Refereed)
    Abstract [en]

    Objectives

    To evaluate postoperative venous haemodynamics and quality of life after treatment of great saphenous vein (GSV) incompetence.

    Methods

    Radiofrequency ablation and high ligation and stripping were performed in 62 patients (65 limbs) and 58 (65 limbs), respectively. Phlebectomies were performed in both modalities. Strain-gauge plethysmography on the foot combined with superficial venous occlusion was used to measure refilling time after knee bends. Strain-gauge plethysmography, duplex ultrasound and quality of life were assessed before and one month after treatment.

    Results

    Duplex ultrasound displayed successful intervention in all but two limbs. Refilling time increased similar in radiofrequency ablation and high ligation and stripping after treatment (p < 0.001). Postoperatively, strain-gauge plethysmography detected remaining reflux in 71% of the patients. Multivariate analysis showed that two or more incompetent calf branches were associated with remaining reflux (OR 4.82 (95% CI: 1.33–17.5), p = 0.02). No difference in quality of life was seen in patients with remaining reflux.

    Conclusions

    Despite successful treatment, a majority of the limbs showed remaining reflux, in which incompetent calf branches appear to play an important role.

    Clinicaltials.gov: Lower Limb Venous Insufficiency and the Effect of Radiofrequency Treatment Versus Open Surgery. Nr: NCT02397226

  • 33.
    Ong, Kwok Leung
    et al.
    Univ New South Wales, Australia.
    Chung, Rosanna
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hui, Nicholas
    Univ New South Wales, Australia.
    Festin, Karin
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Linköping University, Faculty of Medicine and Health Sciences.
    Lundberg, Anna
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Rye, Kerry-Anne
    Univ New South Wales, Australia.
    Jonasson, Lena
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Kristenson, Margareta
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Linköping University, Faculty of Medicine and Health Sciences.
    Usefulness of Certain Protein Biomarkers for Prediction of Coronary Heart Disease2020In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 125, no 4, p. 542-548Article in journal (Refereed)
    Abstract [en]

    Identification of biomarkers can help monitor and prevent cardiovascular disease (CVD) risk. We performed an exploratory analysis to identify potential biomarkers for coronary heart disease (CHD) in participants from the Life Conditions, Stress, and Health study. A total of 1,007 participants (50% women), randomly selected from the general population, were followed for incident CHD at 8 and 13 years of follow-up. Plasma levels of 184 CVD-related biomarkers were measured in samples collected at baseline in 86 cases with CHD and 184 age- and sex-matched controls by proximity extension assay. Biomarker levels were presented as normalized protein expression values (log 2 scale). After adjusting for confounding factors, 6 biomarkers showed significant association with incident CHD at 13 years. In a sensitivity analysis, this association remained significant at 8 years for 3 biomarkers; collagen alpha-1(I) chain (COL1A1), bone morphogenetic protein-6 (BMP-6), and interleukin-6 receptor alpha chain (IL-6R alpha). When entering these biomarkers in the full adjustment model simultaneously, their association with incident CHD at 13 years remained significant, hazards ratio being 0.671, 0.335, and 2.854, respectively per unit increase in normalized protein expression values. Subjects with low COL1A1, low BMP-6, and high IL-6R alpha levels had a hazards ratio of 5.097 for incident CHD risk (p = 0.019), compared with those without. In conclusion, we identified COL1A1, BMP-6 and IL-6Ra as biomarkers for incident CHD over a long-term follow-up in this exploratory analysis. For COL1A1 and BMP-6 this has not been previously reported. Further studies are needed to confirm our findings and establish their clinical relevance. (C) 2019 Elsevier Inc. All rights reserved.

  • 34.
    Ouellette, R.
    et al.
    Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden; A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, United States; Harvard Medical School, Boston, MA, United States.
    Mangeat, G.
    A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, United States; NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, QC, Canada.
    Polyak, I.
    Invicro, Boston, MA, United States.
    Warntjes, Marcel Jan Bertus
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). SyntheticMR, Linköping, Sweden.
    Forslin, Y.
    Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden.
    Bergendal, Å.
    Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Department of Medical Psychology, Karolinska University Hospital, Stockholm, Sweden.
    Plattén, M.
    Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden; School of Engineering Sciences in Chemistry, Biology, and Health, Royal Institute of Technology, Stockholm, Sweden.
    Uppman, M.
    Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden.
    Treaba, C.A.
    A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, United States; Harvard Medical School, Boston, MA, United States.
    Cohen-Adad, J.
    NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, QC, Canada.
    Piehl, F.
    Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
    Kristoffersen, Wiberg M.
    Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden.
    Fredrikson, S.
    Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
    Mainero, C.
    A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, United States; Harvard Medical School, Boston, MA, United States.
    Granberg, T.
    Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden; A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, United States; Harvard Medical School, Boston, MA, United States.
    Validation of Rapid Magnetic Resonance Myelin Imaging in Multiple Sclerosis2020In: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 87, no 5, p. 710-724Article in journal (Refereed)
    Abstract [en]

    Objective: Magnetic resonance imaging (MRI) is essential for multiple sclerosis diagnostics but is conventionally not specific to demyelination. Myelin imaging is often hampered by long scanning times, complex postprocessing, or lack of clinical approval. This study aimed to assess the specificity, robustness, and clinical value of Rapid Estimation of Myelin for Diagnostic Imaging, a new myelin imaging technique based on time-efficient simultaneous T1/T2 relaxometry and proton density mapping in multiple sclerosis. Methods: Rapid myelin imaging was applied using 3T MRI ex vivo in 3 multiple sclerosis brain samples and in vivo in a prospective cohort of 71 multiple sclerosis patients and 21 age/sex-matched healthy controls, with scan–rescan repeatability in a subcohort. Disability in patients was assessed by the Expanded Disability Status Scale and the Symbol Digit Modalities Test at baseline and 2-year follow-up. Results: Rapid myelin imaging correlated with myelin-related stains (proteolipid protein immunostaining and Luxol fast blue) and demonstrated good precision. Multiple sclerosis patients had, relative to controls, lower normalized whole-brain and normal-appearing white matter myelin fractions, which correlated with baseline cognitive and physical disability. Longitudinally, these myelin fractions correlated with follow-up physical disability, even with correction for baseline disability. Interpretation: Rapid Estimation of Myelin for Diagnostic Imaging provides robust myelin quantification that detects diffuse demyelination in normal-appearing tissue in multiple sclerosis, which is associated with both cognitive and clinical disability. Because the technique is fast, with automatic postprocessing and US Food and Drug Administration/CE clinical approval, it can be a clinically feasible biomarker that may be suitable to monitor myelin dynamics and evaluate treatments aiming at remyelination.

    Download full text (pdf)
    fulltext
  • 35.
    Paats, Joosep
    et al.
    Tallinn Univ Technol, Estonia.
    Adoberg, Annika
    North Estonia Med Ctr, Estonia.
    Arund, Jurgen
    Tallinn Univ Technol, Estonia.
    Dhondt, Annemieke
    Ghent Univ Hosp, Belgium.
    Fernström, Anders
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Drug Research. Region Östergötland, Heart and Medicine Center, Department of Nephrology. Linköping University, Faculty of Medicine and Health Sciences.
    Fridolin, Ivo
    Tallinn Univ Technol, Estonia.
    Glorieux, Griet
    Ghent Univ Hosp, Belgium.
    Leis, Liisi
    North Estonia Med Ctr, Estonia.
    Luman, Merike
    Tallinn Univ Technol, Estonia; North Estonia Med Ctr, Estonia.
    Gonzalez-Parra, Emilio
    Fdn Jimenez Diaz Univ Hosp, Spain.
    Perez-Gomez, Vanessa Maria
    Fdn Jimenez Diaz Univ Hosp, Spain.
    Pilt, Kristjan
    Tallinn Univ Technol, Estonia.
    Sanchez-Ospina, Didier
    Fdn Jimenez Diaz Univ Hosp, Spain.
    Segelmark, Mårten
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology.
    Uhlin, Fredrik
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology. Tallinn Univ Technol, Estonia.
    Ortiz, Alberto Arduan
    Fdn Jimenez Diaz Univ Hosp, Spain.
    Serum Levels and Removal by Haemodialysis and Haemodiafiltration of Tryptophan-Derived Uremic Toxins in ESKD Patients2020In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol. 21, no 4, article id 1522Article in journal (Refereed)
    Abstract [en]

    Tryptophan is an essential dietary amino acid that originates uremic toxins that contribute to end-stage kidney disease (ESKD) patient outcomes. We evaluated serum levels and removal during haemodialysis and haemodiafiltration of tryptophan and tryptophan-derived uremic toxins, indoxyl sulfate (IS) and indole acetic acid (IAA), in ESKD patients in different dialysis treatment settings. This prospective multicentre study in four European dialysis centres enrolled 78 patients with ESKD. Blood and spent dialysate samples obtained during dialysis were analysed with high-performance liquid chromatography to assess uremic solutes, their reduction ratio (RR) and total removed solute (TRS). Mean free serum tryptophan and IS concentrations increased, and concentration of IAA decreased over pre-dialysis levels (67%, 49%, -0.8%, respectively) during the first hour of dialysis. While mean serum total urea, IS and IAA concentrations decreased during dialysis (-72%, -39%, -43%, respectively), serum tryptophan levels increased, resulting in negative RR (-8%) towards the end of the dialysis session (p &lt; 0.001), despite remarkable Trp losses in dialysate. RR and TRS values based on serum (total, free) and dialysate solute concentrations were lower for conventional low-flux dialysis (p &lt; 0.001). High-efficiency haemodiafiltration resulted in 80% higher Trp losses than conventional low-flux dialysis, despite similar neutral Trp RR values. In conclusion, serum Trp concentrations and RR behave differently from uremic solutes IS, IAA and urea and Trp RR did not reflect dialysis Trp losses. Conventional low-flux dialysis may not adequately clear Trp-related uremic toxins while high efficiency haemodiafiltration increased Trp losses.

    Download full text (pdf)
    fulltext
  • 36.
    Persson, Lennart
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Lyth, Johan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Region Östergötland, Operations management Region Östergötland, Research and Development Unit.
    Lind, Leili
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    The Health Diary Telemonitoring and Hospital-Based Home Care Improve Quality of Life Among Elderly Multimorbid COPD and Chronic Heart Failure Subjects2020In: The International Journal of Chronic Obstructive Pulmonary Disease, ISSN 1176-9106, E-ISSN 1178-2005, Vol. 15, p. 527-541Article in journal (Refereed)
    Abstract [en]

    Background: Elderly, multimorbid patients with advanced chronic obstructive pulmonary disease (COPD) and/or chronic heart failure (CHF) exhibit poor health-related quality of life (HRQoL). Telemonitoring, based on digital pen technology, supported by hospital-based home care (HBHC) significantly reduces the number of hospitalizations. We hypothesized that the same intervention would prevent the deterioration of HRQoL that follows upon disease progression. Methods: Elderly computer-illiterate subjects with amp;gt;= 2 hospitalizations the previous year were included. HRQoL was assessed at inclusion (baseline) and at 1, 6 and 12 months employing EuroQol-5 Dimensions (EQ-5D) and RAND-36 for general HRQoL, and Minnesota Living with Heart Failure Questionnaire (MLHFQ) and St. Georges Respiratory Questionnaire (SGRQ) for disease-specific HRQoL. Healthcare contacts, hospitalizations, as-needed medications, prescription changes and healthcare costs were registered. Results: Ninety-four patients were enrolled of which 53 subjects completed the 12-month study period. Compared to baseline, most domains of RAND-36 were improved significantly at 1 time-point or more. Only among COPD subjects, the disease-specific HRQoL was worsened at the 12 month evaluation. Measures of healthcare dependency were associated with poor HRQoL. Conclusion: The Health Diary system and HBHC together improve general HRQoL, and measures of healthcare dependency are associated with HRQoL variables.

    Download full text (pdf)
    fulltext
  • 37.
    Salahuddin, Taufiq
    et al.
    VA Med Ctr, CO 80045 USA; Univ Colorado, CO USA.
    Kittelson, John
    VA Med Ctr, CO 80045 USA.
    Tardif, Jean-Claude
    Univ Montreal, Canada.
    Shah, Prediman K.
    Cedars Sinai Med Ctr, CA 90048 USA.
    Olsson, Anders
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Nicholls, Stephen J.
    Monash Univ, Australia.
    Leitersdorf, Eran
    Hadassah Hebrew Univ, Israel.
    Leiter, Lawrence A.
    Univ Toronto, Canada.
    Kallend, David
    Medicines Co, Switzerland.
    Black, Donald M.
    Dalcor Pharmaceut, Switzerland.
    Barter, Philip J.
    Univ New South Wales, Australia.
    Ballantyne, Christie M.
    Baylor Coll Med, TX 77030 USA.
    Schwartz, Gregory G.
    VA Med Ctr, CO 80045 USA; Univ Colorado, CO USA.
    Association of high-density lipoprotein particle concentration with cardiovascular risk following acute coronary syndrome: A case-cohort analysis of the dal-Outcomes trial2020In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 221, p. 60-66Article in journal (Refereed)
    Abstract [en]

    Background High-density lipoprotein cholesterol (HDL-C) concentration is inversely related to risk of major adverse cardiovascular events (MACE) in epidemiologic studies but is a poorer predictor of MACE in patients with established coronary heart disease. HDL particle concentration (HDLP) has been proposed as a better predictor of risk. We investigated whether HDLP is associated with risk of MACE after acute coronary syndrome (ACS). Methods The dal-Outcomes trial compared the CETP inhibitor dalcetrapib with placebo in patients with recent ACS. In a nested case-cohort analysis, total, large, medium, and small HDLPs were measured by nuclear magnetic resonance spectroscopy at baseline (4-12 weeks after ACS) in 476 cases with MACE and 902 controls. Hazard ratios (HRs; case-control) for 1-SD increment of HDLP or HDL-C at baseline were calculated with and without adjustment for demographic, clinical, laboratory, and treatment variables. Similarly, HRs for MACE were calculated for changes in HDLP or HDL-C from baseline to month 3 of assigned treatment. Results Over median follow-up of 28 months, the risk of MACE was not associated with baseline HDLP (adjusted HR = 0.98, 95% CI = 0.84-1.15, P =.81), any HDLP subclass, or HDL-C. Dalcetrapib increased HDL-C and total, medium, and large HDLP and decreased small HDLP but had no effect on MACE compared with placebo. There were no association of risk of MACE with change in HDLP or HDL-C and no interaction with assigned study treatment. Conclusions Neither baseline HDLP nor the change in HDLP on treatment with dalcetrapib or placebo was associated with risk of MACE after ACS.

  • 38.
    Sandstedt, Mårten
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Henriksson, Lilian
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. 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.
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Nyberg, Gusten
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Engvall, Jan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist 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).
    de Geer, Jakob
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. 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.
    Alfredsson, Joakim
    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.
    Persson, Anders
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. 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).
    Evaluation of an AI-based, automatic coronary artery calcium scoring software2020In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 30, no 3, p. 1671-1678Article in journal (Refereed)
    Abstract [en]

    Objectives

    To evaluate an artificial intelligence (AI)–based, automatic coronary artery calcium (CAC) scoring software, using a semi-automatic software as a reference.

    Methods

    This observational study included 315 consecutive, non-contrast-enhanced calcium scoring computed tomography (CSCT) scans. A semi-automatic and an automatic software obtained the Agatston score (AS), the volume score (VS), the mass score (MS), and the number of calcified coronary lesions. Semi-automatic and automatic analysis time were registered, including a manual double-check of the automatic results. Statistical analyses were Spearman’s rank correlation coefficient (⍴), intra-class correlation (ICC), Bland Altman plots, weighted kappa analysis (κ), and Wilcoxon signed-rank test.

    Results

    The correlation and agreement for the AS, VS, and MS were  = 0.935, 0.932, 0.934 (p < 0.001), and ICC = 0.996, 0.996, 0.991, respectively (p < 0.001). The correlation and agreement for the number of calcified lesions were  = 0.903 and ICC = 0.977 (p < 0.001), respectively. The Bland Altman mean difference and 1.96 SD upper and lower limits of agreements for the AS, VS, and MS were − 8.2 (− 115.1 to 98.2), − 7.4 (− 93.9 to 79.1), and − 3.8 (− 33.6 to 25.9), respectively. Agreement in risk category assignment was 89.5% and κ = 0.919 (p < 0.001). The median time for the semi-automatic and automatic method was 59 s (IQR 35–100) and 36 s (IQR 29–49), respectively (p < 0.001).

    Conclusions

    There was an excellent correlation and agreement between the automatic software and the semi-automatic software for three CAC scores and the number of calcified lesions. Risk category classification was accurate but showing an overestimation bias tendency. Also, the automatic method was less time-demanding.

    Key Points

    • Coronary artery calcium (CAC) scoring is an excellent candidate for artificial intelligence (AI) development in a clinical setting.

    • An AI-based, automatic software obtained CAC scores with excellent correlation and agreement compared with a conventional method but was less time-consuming.

    Download full text (pdf)
    fulltext
  • 39.
    Schwartz, Gregory G.
    et al.
    Vet Affairs Med Ctr, CO 80012 USA; Univ Colorado, CO 80045 USA.
    Leiter, Lawrence A.
    Univ Toronto, Canada.
    Ballantyne, Christie M.
    Baylor Coll Med, TX 77030 USA.
    Barter, Philip J.
    Univ New South Wales, Australia.
    Black, Donald M.
    DalCor Pharmaceut, Switzerland.
    Kallend, David
    Medicines Co, Switzerland.
    Laghrissi-Thode, Fouzia
    DalCor Pharmaceut, Switzerland.
    Leitersdorf, Eran
    Hadassah Hebrew Univ, Israel.
    McMurray, John J. V.
    Univ Glasgow, Scotland.
    Nicholls, Stephen J.
    Monash Univ, Australia.
    Olsson, Anders
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Preiss, David
    Univ Oxford, England; Univ Oxford, England.
    Shah, Prediman K.
    Cedars Sinai Heart Inst, CA USA.
    Tardif, Jean-Claude
    Univ Montreal, Canada.
    Kittelson, John
    Univ Colorado, CO USA.
    Dalcetrapib Reduces Risk of New-Onset Diabetes in Patients With Coronary Heart Disease2020In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 43, no 5, p. 1077-1084Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE Incident type 2 diabetes is common among patients with recent acute coronary syndrome and is associated with an adverse prognosis. Some data suggest that cholesteryl ester transfer protein (CETP) inhibitors reduce incident type 2 diabetes. We compared the effect of treatment with the CETP inhibitor dalcetrapib or placebo on incident diabetes in patients with recent acute coronary syndrome. RESEARCH DESIGN AND METHODS In the dal-OUTCOMES trial, 15,871 patients were randomly assigned to treatment with dalcetrapib 600 mg daily or placebo, beginning 4-12 weeks after an acute coronary syndrome. Absence of diabetes at baseline was based on medical history, no use of antihyperglycemic medication, and hemoglobin A(1c) and serum glucose levels below diagnostic thresholds. Among these patients, incident diabetes after randomization was defined by any diabetes-related adverse event, new use of antihyperglycemic medication, hemoglobin A(1c) &gt;= 6.5%, or a combination of at least two measurements of serum glucose &gt;= 7.0 mmol/L (fasting) or &gt;= 11.1 mmol/L (random). RESULTS At baseline, 10,645 patients (67% of the trial cohort) did not have diabetes. During a median follow-up of 30 months, incident diabetes was identified in 403 of 5,326 patients (7.6%) assigned to dalcetrapib and in 516 of 5,319 (9.7%) assigned to placebo, corresponding to absolute risk reduction of 2.1%, hazard ratio of 0.77 (95% CI 0.68-0.88; P &lt; 0.001), and a need to treat 40 patients for 3 years to prevent 1 incident case of diabetes. Considering only those with prediabetes at baseline, the number needed to treat for 3 years to prevent 1 incident case of diabetes was 25. Dalcetrapib also decreased the number of patients who progressed from normoglycemia to prediabetes and increased the number who regressed from diabetes to no diabetes. CONCLUSIONS In patients with a recent acute coronary syndrome, incident diabetes is common and is reduced substantially by treatment with dalcetrapib.

  • 40.
    Silverio, Angelo
    et al.
    Uppsala Univ, Sweden.
    Buccheri, Sergio
    Uppsala Univ, Sweden.
    Venetsanos, Dimitrios
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Alfredsson, Joakim
    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.
    Lagerqvist, Bo
    Uppsala Univ, Sweden.
    Persson, Jonas
    Danderyd Hosp, Sweden.
    Witt, Nils
    Karolinska Inst, Sweden.
    James, Stefan
    Uppsala Univ, Sweden.
    Sarno, Giovanna
    Uppsala Univ, Sweden.
    Percutaneous Treatment and Outcomes of Small Coronary Vessels A SCAAR Report2020In: JACC: Cardiovascular Interventions, ISSN 1936-8798, E-ISSN 1876-7605, Vol. 13, no 7, p. 793-804Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES The aim of this study was to investigate the outcomes of patients with de novo lesions in small coronary vessels undergoing percutaneous coronary intervention (PCI) with drug-coated balloons (DCBs) or newer-generation drug-eluting stents (n-DES). BACKGROUND Notwithstanding the available evidence from a few randomized clinical trials and meta-analyses, the best device for PCI in patients with small-vessel coronary artery disease is not yet established. METHODS The study included all consecutive patients with de novo lesions in small coronary vessels undergoing PCI in Sweden from April 2009 to July 2017. A small coronary vessel was defined by a device diameter &lt;= 2.5 mm. The primary outcomes were restenosis and definite target lesion thrombosis at 3-year follow-up. The secondary outcomes were the occurrence of all-cause death and myocardial infarction. RESULTS The study population included 14,788 patients: 1,154 treated with DCBs and 13,634 with n-DES. Overall, 35,541 PCIs were performed using 2,503 DCBs and 33,038 n-DES. The propensity score-adjusted regression analysis showed a significantly higher risk for restenosis in the DCB group compared with the n-DES group (adjusted hazard ratio [HR]: 2.027; 95% confidence interval [CI]: 1.537 to 2.674). Conversely, no difference in the risk for target lesion thrombosis (adjusted HR: 0.741; 95% CI: 0.412 to 1.331) was detected. The risk for all-cause death (adjusted HR: 1.178; 95% CI: 0.992 to 1.399) and myocardial infarction (adjusted HR: 1.251; 95% CI: 0.960 to 1.629) was comparable between groups. CONCLUSIONS Because of the significantly higher risk for restenosis up to 3 years, this research suggests that DCBs are not an equally effective alternative to n-DES for percutaneous treatment of small coronary vessels. (C) 2020 by the American College of Cardiology Foundation.

  • 41.
    Skogman, Barbro H.
    et al.
    Uppsala Univ, Sweden; Orebro Univ, Sweden.
    Lager, Malin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Clin Microbiol, Sweden.
    Brudin, Lars
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Dept Clin Physiol, Sweden.
    Jenmalm, Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Tjernberg, Ivar
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Dept Clin Chem and Transfus Med, Sweden.
    Jonsson Henningsson, Anna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Clin Microbiol, Sweden.
    Cytokines and chemokines in cerebrospinal fluid in relation to diagnosis, clinical presentation and recovery in children being evaluated for Lyme neuroborreliosis2020In: Ticks and Tick-borne Diseases, ISSN 1877-959X, E-ISSN 1877-9603, Vol. 11, no 3, article id 101390Article in journal (Refereed)
    Abstract [en]

    In Lyme neuroborrelios (LNB), the immune response has been in focus, but the association between different cytokines/chemokines and clinical manifestations in LNB patients has not been fully investigated. The aim of this study was to evaluate a large number of cytokines and chemokines in cerebrospinal fluid (CSF) in relation to diagnosis, clinical presentation and recovery in children being evaluated for LNB. Materials and methods: Pediatric patients (n = 105) were recruited at seven Swedish pediatric departments during 2010-14. Serum and CSF samples were drawn on admission, before start of antibiotic treatment. Patients diagnosed as Definite LNB or Possible LNB were categorized as LNBtot patients, all LNBtot patients presented with pleocytosis in CSF. Patients diagnosed as Non-LNB or Other diagnosis were categorized as Controls(tot), all controls(tot) presented without pleocytosis in CSF. Multiplex bead array (Luminex) kits were used for analyses of 41 different cytokines/chemokines in CSF (Millipore). Results: Twenty-eight cytokines/chemokines were detectable in CSF and the levels of 26 of these mediators were significantly higher in LNBtot patients than in Controls(tot). In a discriminant analysis, a combination of four cytokines/chemokines (CXCL1, GM-CSF, IL-7 and IL-10) were shown to independently separate relevant patient groups. Furthermore, an IL-10/CXCL1 ratio was created and shown to have an improved diagnostic performance in distinguishing LNBtot vs Non-LNB patients, as compared to CXCL13 in CSF. No immune mediator differed significantly, when comparing LNBtot patients with different clinical presentation on admission or when comparing patients with or without recovery within 2 months of admission. Conclusion: A discriminant analysis was shown to be useful to distinguish the independently most important cytokines/chemokines (CXCL1, GM-CSF, IL-7 and IL-10) in CSF, in order to discriminate LNBtot patients from Non-LNB patients. An IL-10/CXCL1 ratio was shown to have a promising diagnostic profile with a better performance than the chemokine CXCL13 in CSF. However, further evaluation is required to address future possible usefulness of these cytokines and chemokines in laboratory diagnostics in LNB, including control groups with neuro-inflammation. No significant associations were found between CSF immune mediator levels and clinical presentation or recovery in pediatric LNB patients.

    Download full text (pdf)
    fulltext
  • 42.
    Soreskog, Emma
    et al.
    Quantify Res, Sweden.
    Strom, Oskar
    Quantify Res, Sweden; Karolinska Inst, Sweden.
    Spångeus, Anna
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Akesson, Kristina E.
    Lund Univ, Sweden.
    Borgstrom, Fredrik
    Quantify Res, Sweden; Karolinska Inst, Sweden.
    Banefelt, Jonas
    Quantify Res, Sweden.
    Toth, Emese
    UCB Pharma, Belgium.
    Libanati, Cesar
    UCB Pharma, Belgium.
    Charokopou, Mata
    UCB Pharma, Belgium.
    Risk of major osteoporotic fracture after first, second and third fracture in Swedish women aged 50 years and older2020In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 134, article id UNSP 115286Article in journal (Refereed)
    Abstract [en]

    Background: Osteoporosis affects approximately one in five European women and leads to fragility fractures, which result in poor health, social and economic consequences. Fragility fractures are a strong risk factor for subsequent major osteoporotic fracture (MOF), with risk of MOF being elevated in the 1-2 years following an earlier fracture, a concept described as "imminent risk". This study examines risk of subsequent MOF in patients with one, two or three prior fractures by age and type of fracture. Methods: In this retrospective, observational cohort study, Swedish women aged 50 years with 1 any clinical fragility fracture between July 1, 2006 and December 31, 2012 were identified from Swedens National Patient Register. Each patient was age- and sex-matched to three controls without history of fracture. Group 1 women included those with one fragility fracture during the study period; Group 2 included those with two fragility fractures; and Group 3 included those with three fragility fractures. "Index fracture" was defined as the first fracture during the study period for Group 1; the second for Group 2; and the third for Group 3. Patients in each cohort and matched controls were followed for up to 60 months or until subsequent MOF (hip, vertebra, forearm, humerus), death or end of data availability. Results: 231,769 women with at least one fracture were included in the study and therefore constituted Group 1; of these, 39,524 constituted Group 2 and of those, 7656 constituted Group 3. At five years, cumulative incidence of subsequent MOF was higher in patients with a history of fracture as compared to controls (Group 1: 20.7% vs 12.3%; Group 2: 32.0% vs 15.3%). Three-year cumulative incidence for Group 3 was 12.1% (vs 10.7% for controls). After adjusting for baseline covariates, risk of subsequent MOF was highest within 0-24 months following an index fracture, then decreased but remained elevated as compared to controls. Having two prior fractures, vertebral fractures and younger age at time of index fracture were associated with greater relative risk. Conclusions: Women with a history of osteoporotic fracture are at increased risk of subsequent fracture, which is highest during the first 24 months following a fracture. Younger women and those with vertebral fractures are at greatest relative risk, suggesting that treatment should target these patients and be timely enough to impact the period of imminent risk.

    Download full text (pdf)
    fulltext
  • 43.
    Spångeus, Anna
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Johansson, Simon
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Woisetschläger, Mischa
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Adherence to and persistence with zoledronic acid treatment for osteoporosis-reasons for early discontinuation2020In: ARCHIVES OF OSTEOPOROSIS, ISSN 1862-3522, Vol. 15, no 1, article id 58Article in journal (Refereed)
    Abstract [en]

    This retrospective study reports 81% long-term (&gt; 3 years) adherence to and 77% persistence with zoledronic acid (ZA) treatment in osteoporosis patients, with ZA being costfree for patients. Eight percent of patients discontinued treatment because of adverse events (AEs), with a tendency of higher discontinuation rate in older patients. Purpose This study investigated (1) long-term adherence to and persistence with ZA treatment in a real-world setting, (2) extent to which an adverse reaction to ZA impacted on adherence and persistence, and (3) whether there were sex or age differences in patients that had early treatment termination (ETT) due to AEs and those who adhered to the regimen. Methods All patients treated with ZA at the Endocrinology Department at Linkoping University Hospital, Linkoping, Sweden between 2012 and 2017 were included. ETT was defined as &lt; 3 ZA infusions, which was confirmed from patients medical records. Results A total of 414 patients were treated with ZA, with 81% receiving &gt; 3 ZA infusions. Three-year persistence was 77% for a treatment window of 365 days +/- 90 days (75% with 365 days +/- 60 days window). The most common reason for ETT was AEs (8%), followed by medical conditions (5%), biological aging (3%), and other (e.g., lost to follow-up [3%]). Most patients who discontinued treatment because of AEs reported symptoms of acute-phase reaction, and tended to be older than those who adhered to treatment (74 +/- 9 vs 70 +/- 13 years, p = 0.064). There was no difference in sex ratio between the 2 groups (85% vs 90% females, p = 0.367). Conclusion Rates of long-term adherence to and persistence with ZA treatment were high with a pre-scheduled 3-year treatment regimen in the tax-financed Swedish healthcare system. AEs-mainly acute-phase reaction-were the most common reason for ETT, occurring in nearly 1 out of 10 patients.

    Download full text (pdf)
    fulltext
  • 44.
    Strom, O.
    et al.
    Karolinska Inst, Sweden; Quantify Res, Sweden.
    Lauppe, R.
    Quantify Res, Sweden.
    Ljunggren, O.
    Uppsala Univ, Sweden.
    Spångeus, Anna
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Ortsater, G.
    Quantify Res, Sweden.
    OKelly, J.
    Amgen Ltd, England.
    Akesson, K.
    Lund Univ, Sweden.
    Real-world effectiveness of osteoporosis treatment in the oldest old2020In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965Article in journal (Refereed)
    Abstract [en]

    We studied effectiveness of osteoporosis treatment in women older than 80 years, who often are not included in clinical trials. Treatments were as effective on bone density and fractures as in younger women. Introduction To study real-world effectiveness of osteoporosis treatment on BMD and fractures in the oldest old women (&gt;= 80 years) compared with women (60-79 years) in the clinical setting using Swedish health register data. Methods National registers and data from DXA machines were used to study effectiveness of all available osteoporosis treatments in women 60-79 and &gt;= 80 years using three approaches: (1) Total Hip BMD change up to 8 years after treatment start; (2) fracture incidence where patients served as their own controls, comparing the first 3 months after treatment start with the subsequent 12 months; and (3) comparison of fracture incidence post-fracture in women &gt;= 80 years treated with osteoporosis treatment or calcium/vitamin D. Results Analysis 1: Total Hip BMD increased by up to 6.7% and 7.7% in women 60-79 and &gt;= 80 years old, respectively. The mean increase in BMD was 1.1%-units per year in both age groups. Analysis 2: Relative to the 3-month baseline, fracture incidence decreased during the subsequent 12 months of treatment. Incidence rate ratios were estimated at 0.65, 0.74, 0.29, and 0.81 for any, hip, vertebral, and non-hip-non-vertebral fracture, respectively. Analysis 3: A 24-month incidence of any fracture in women &gt;= 80 years given post-fracture osteoporosis treatment was lower (HR = 0.78) than in women given calcium/vitamin D, but treatment allocation was not random, with lower mortality (HR = 0.51) in patients receiving OP treatment. Conclusions Osteoporosis medication in women &gt; 80 years in clinical practice likely works, and the magnitude of effect is similar to what was estimated in younger women. The choice between osteoporosis treatment and calcium/vitamin D after fracture in women &gt;= 80 years is not random but appears associated with the patients health status and presence of vertebral fractures, rather than the known risk profile of sustaining a fracture at a high age.

    Download full text (pdf)
    fulltext
  • 45.
    Sundstrom, Johan
    et al.
    Uppsala Univ, Sweden; Univ New South Wales, Australia.
    Lind, Lars
    Uppsala Univ, Sweden.
    Lampa, Erik
    Uppsala Univ, Sweden.
    Angeras, Oskar
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Bachus, Erasmus
    Lund Univ, Sweden.
    Bergstrom, Goran
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Carlberg, Bo
    Umea Univ, Sweden.
    Engstrom, Gunnar
    Lund Univ, Sweden.
    Engvall, Jan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Eriksson, Mats
    Karolinska Univ Hosp, Sweden.
    Gigante, Bruna
    Danderyd Hosp, Sweden; Danderyd Hosp, Sweden.
    Hagstrom, Emil
    Uppsala Univ, Sweden; Uppsala Univ, Sweden.
    Hjelmgren, Ola
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Jansson, Jan-Hakan
    Umea Univ, Sweden.
    Jernberg, Tomas
    Danderyd Hosp, Sweden.
    Mannila, Maria
    Karolinska Univ Hosp, Sweden.
    Nyström, Fredrik H
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Cityhälsan Centrum, Norrköping.
    Oldgren, Jonas
    Uppsala Univ, Sweden; Uppsala Univ, Sweden.
    Persson, Margaretha
    Lund Univ, Sweden.
    Sandstrom, Anette
    Umea Univ, Sweden.
    Swahn, Eva
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Soderberg, Stefan
    Umea Univ, Sweden.
    Toren, Kjell
    Univ Gothenburg, Sweden; Sahlgrenska Univ, Sweden.
    Östgren, Carl Johan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Rosengren, Annika
    Univ Gothenburg, Sweden; Sahlgrenska Univ, Sweden.
    Weight gain and blood pressure2020In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 38, no 3, p. 387-394Article in journal (Refereed)
    Abstract [en]

    Objective: Although the causality of the obesity--hypertension association is established, the potential for prevention is not. We hypothesized that weight gain between early adulthood and mid-life is associated with higher mid-life blood pressure. Methods: We investigated the hypothesis using a large contemporaneous population-based mid-life cohort of men and women aged 50-64 years. Recalled body weight at age 20 years was self-reported, and mid-life body weight and office blood pressures were measured in accordance with a detailed protocol. Results: On average, men had gained 14.9 (95% CI 14.6-15.2) kg of weight, and women 14.6 (95% CI 14.4-14.9) kg, between age 20 years and the mid-life examination, corresponding to 0.40 (95% CI 0.39-0.41) kg/year for men and women. Both weight at age 20 years and weight at the mid-life examination were associated with mid-life blood pressures. On average, a 10 kg weight increase between age 20 years and mid-life was associated with 2.2 (95% CI 0.9-3.5) mmHg higher systolic and 1.7 (95% CI 0.9-2.5) mmHg higher diastolic mid-life blood pressure in men, and 3.2 (2.5-4.0) mmHg higher systolic and 2.4 (1.9-2.9) mmHg higher diastolic mid-life blood pressure in women. Mid-life weight was more closely associated than weight at age 20 years with mid-life blood pressure. For a given mid-life weight, blood pressure was higher in persons with higher weight gain from age 20 years. Conclusion: In sum, weight gain between early adulthood and mid-life was associated with higher mid-life blood pressure. The magnitude of the association indicates a potentially great public health impact of strategies to prevent weight gain throughout adulthood.

  • 46.
    Tamas, Eva
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Södersved Kallestedt, Marie-Louise
    Uppsala Univ, Sweden.
    Hult, Hakan
    Karolinska Inst, Sweden.
    Carlzon, Liisa
    Sahlgrens Univ Hosp, Sweden.
    Karlgren, Klas
    Sodersjukhuset Hosp, Sweden; Karolinska Inst, Sweden.
    Berndtzon, Magnus
    Reg Cty Jonkoping, Sweden.
    Hultin, Magnus
    Umea Univ, Sweden.
    Masiello, Italo
    Karolinska Inst, Sweden.
    Allvin, Renee
    Orebro Univ, Sweden.
    Simulation educators in clinical work: the managers perspective2020In: Journal of Health Organisation & Management, ISSN 1477-7266, E-ISSN 1758-7247, Vol. 34, no 2, p. 181-191Article in journal (Refereed)
    Abstract [en]

    Purpose Information is scarce on healthcare managers understanding of simulation educators impact on clinical work. Therefore, the aim of this study was to explore healthcare managers perceptions of the significance of clinically active simulation educators for the organisation. Design/methodology/approach Healthcare managers were invited to be interviewed in a semi-structured manner. Inductive thematic analysis was used to identify and analyse patterns of notions describing the managers perceptions of simulation educators impact as co-workers on their healthcare organisations. Findings The identified relevant themes for the healthcare unit were: (1) value for the manager, (2) value for the community and (3) boundaries. Simulation educators were perceived to be valuable gatekeepers of evidence-based knowledge and partners in leadership for educational issues. Their most prominent value for the community was establishing a reflective climate, facilitating open communication and thereby improving the efficacy of teamwork. Local tradition, economy, logistics and staffing of the unit during simulation training were suggested to have possible negative impacts on simulation educators work. Practical implications - The findings might have implications for the implementation and support of simulation training programs. Social implications - Healthcare managers appreciated both the personal value of simulation educators and the effect of their work for their own unit. Local values were prioritised versus global. Simulation training was valued as an educational tool for continual professional development, although during the interviews, the managers did not indicate the importance of employment of pedagogically competent and experienced staff. Originality/value The study provided new insights about how simulation educators as team members affect clinical practice.

    Download full text (pdf)
    fulltext
  • 47.
    Tromp, Jasper
    et al.
    Natl Heart Ctr Singapore, Singapore; Univ Med Ctr Groningen, Netherlands.
    Bamadhaj, Sahiddah
    Natl Heart Ctr Singapore, Singapore.
    Cleland, John G. F.
    Univ Glasgow, Scotland; Imperial Coll, England.
    Angermann, Christiane E.
    Univ Hosp Wurzburg, Germany.
    Dahlström, Ulf
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Ouwerkerk, Wouter
    Natl Heart Ctr Singapore, Singapore; Duke Natl Univ Singapore, Singapore; Univ Amsterdam, Netherlands.
    Tay, Wan Ting
    Natl Heart Ctr Singapore, Singapore.
    Dickstein, Kenneth
    Univ Bergen, Norway.
    Ertl, Georg
    Univ Hosp Wurzburg, Germany; Univ Hosp Wurzburg, Germany.
    Hassanein, Mahmoud
    Alexandria Univ, Egypt.
    Perrone, Sergio V.
    Sanctuary Trinidad Miter, Argentina.
    Ghadanfar, Mathieu
    Novartis Pharmaceut, Switzerland.
    Schweizer, Anja
    Novartis Pharmaceut, Switzerland.
    Obergfell, Achim
    Novartis Pharmaceut, Switzerland.
    Lam, Carolyn S. P.
    Natl Heart Ctr Singapore, Singapore; Duke Natl Univ Singapore, Singapore; Univ Med Ctr Groningen, Netherlands; George Inst Global Hlth, Australia.
    Filippatos, Gerasimos
    Univ Cyprus, Cyprus; Natl and Kapodistrian Univ Athens, Greece.
    Collins, Sean P.
    Vanderbilt Univ, TN 37232 USA.
    Post-discharge prognosis of patients admitted to hospital for heart failure by world region, and national level of income and income disparity (REPORT-HF): a cohort study2020In: The Lancet Global Health, E-ISSN 2214-109X, Vol. 8, no 3, p. E411-E422Article in journal (Refereed)
    Abstract [en]

    Background

    Heart failure is a global public health problem, affecting a large number of individuals from low-income and middle-income countries. REPORT-HF is, to our knowledge, the first prospective global registry collecting information on patient characteristics, management, and prognosis of acute heart failure using a single protocol. The aim of this study was to investigate differences in 1-year post-discharge mortality according to region, country income, and income inequality.

    Methods

    Patients were enrolled during hospitalisation for acute heart failure from 358 centres in 44 countries on six continents. We stratified countries according to a modified WHO regional classification (Latin America, North America, western Europe, eastern Europe, eastern Mediterranean and Africa, southeast Asia, and western Pacific), country income (low, middle, high) and income inequality (according to tertiles of Gini index). Risk factors were identified on the basis of expert opinion and knowledge of the literature.

    Findings

    Of 18 102 patients discharged, 3461 (20%) died within 1 year. Important predictors of 1-year mortality were old age, anaemia, chronic kidney disease, presence of valvular heart disease, left ventricular ejection fraction phenotype (heart failure with reduced ejection fraction [HFrEF] vs preserved ejection fraction [HFpEF]), and being on guideline-directed medical treatment (GDMT) at discharge (p<0·0001 for all). Patients from eastern Europe had the lowest 1-year mortality (16%) and patients from eastern Mediterranean and Africa (22%) and Latin America (22%) the highest. Patients from lower-income countries (ie, ≤US$3955 per capita; hazard ratio 1·58, 95% CI 1·41–1·78), or with greater income inequality (ie, from the highest Gini tertile; 1·25, 1·13–1·38) had a higher 1-year mortality compared with patients from regions with higher income (ie, >$12 235 per capita) or lower income inequality (ie, from the lowest Gini tertile). Compared with patients with HFrEF, patients with HFpEF had a lower 1-year mortality with little variation by income level (pinteraction for HFrEF vs HFpEF <0·0001).

    Interpretation

    Acute heart failure is associated with a high post-discharge mortality, particularly in patients with HFrEF from low-income regions with high income inequality. Regional differences exist in the proportion of eligible patients discharged on GDMT, which was strongly associated with mortality and might reflect lack of access to post-discharge care and prescribing of GDMT.

    Download full text (pdf)
    fulltext
  • 48.
    Törnudd, Mattias
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Ramström, Sofia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Orebro Univ, Sweden.
    Kvitting, John-Peder Escobar
    Oslo Univ Hosp, Norway.
    Alfredsson, Joakim
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Pihl, Richard
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Sci, Linkoping, Sweden; Linkoping Univ, Dept Clin Chem, Linkoping, Sweden; Linkoping Univ, Dept Clin and Expt Med, Linkoping, Sweden.
    Berg, Sören
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Protamine stimulates platelet aggregation in vitro with activation of the fibrinogen receptor and alpha-granule release, but impairs secondary activation via ADP and thrombin receptors2020In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635Article in journal (Refereed)
    Abstract [en]

    Heparin and protamine are fundamental in the management of anticoagulation during cardiac surgery. Excess protamine has been associated with increased bleeding. Interaction between protamine and platelet function has been demonstrated but the mechanism remains unclear. We examined the effect of protamine on platelet function in vitro using impedance aggregometry, flow cytometry, and thrombin generation. Platelets were exposed to protamine at final concentrations of 0, 20, 40, and 80 mu g/mL, alone or together with adenosine diphosphate (ADP) or thrombin PAR1 receptor-activating peptide (TRAP). We found that in the absence of other activators, protamine (80 mu g/mL) increased the proportion of platelets with active fibrinogen receptor (binding of PAC-1) from 3.6% to 97.0% (p amp;lt; .001) measured with flow cytometry. Impedance aggregometry also increased slightly after exposure to protamine alone. When activated with ADP or TRAP protamine at 80 mu g/mL reduced aggregation, from 73.8 +/- 29.4 U to 46.9 +/- 21.1 U (p amp;lt; .001) with ADP and from 126.4 +/- 16.1 U to 94.9 +/- 23.7 U (p amp;lt; .01) with TRAP. P-selectin exposure (a marker of alpha-granule release) measured by median fluorescence intensity (MFI) increased dose dependently with protamine alone, from 0.76 +/- 0.20 (0 mu g/mL) to 10.2 +/- 3.1 (80 mu g/mL), p amp;lt; .001. Protamine 80 mu g/mL by itself resulted in higher MFI (10.16 +/- 3.09) than activation with ADP (2.2 +/- 0.7, p amp;lt; .001) or TRAP (5.7 +/- 2.6, p amp;lt; .01) without protamine. When protamine was combined with ADP or TRAP, there was a concentration-dependent increase in the alpha-granule release. In conclusion, protamine interacts with platelets in vitro having both a direct activating effect and impairment of secondary activation of aggregation by other agonists.

  • 49.
    Ward, Rebecca
    et al.
    Univ Coll Dublin, Ireland.
    Ali, Zaheer
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Slater, Kayleigh
    Univ Coll Dublin, Ireland.
    Reynolds, Alison L.
    Univ Coll Dublin, Ireland; Univ Coll Dublin, Ireland.
    Jensen, Lasse
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Kennedy, Breandan N.
    Univ Coll Dublin, Ireland.
    Pharmacological restoration of visual function in a zebrafish model of von-Hippel Lindau disease2020In: Developmental Biology, ISSN 0012-1606, E-ISSN 1095-564X, Vol. 457, no 2, p. 226-234Article in journal (Refereed)
    Abstract [en]

    Von Hippel-Lindau (VHL) syndrome is a rare, autosomal dominant disorder, characterised by hypervascularised tumour formation in multiple organ systems. Vision loss associated with retinal capillary hemangioblastomas remains one of the earliest complications of VHL disease. The mortality of Vhl(-/-) mice in utero restricted modelling of VHL disease in this mammalian model. Zebrafish harbouring a recessive germline mutation in the vhl gene represent a viable, alternative vertebrate model to investigate associated ocular loss-of-function phenotypes. Previous studies reported neovascularisation of the brain, eye and trunk together with oedema in the vhl(-/-) zebrafish eye. In this study, we demonstrate vhl(-/-) zebrafish almost entirely lack visual function. Furthermore, hyaloid vasculature networks in the vhl(-/-) eye are improperly formed and this phenotype is concomitant with development of an ectopic intraretinal vasculature. Sunitinib malate, a multi tyrosine kinase inhibitor, market authorised for cancer, reversed the ocular behavioural and morphological phenotypes observed in vhl(-/-) zebrafish. We conclude that the zebrafish yid gene contributes to an endogenous molecular barrier that prevents development of intraretinal vasculature, and that pharmacological intervention with sunitinib can improve visual function and hyaloid vessel patterning while reducing abnormally formed ectopic intraretinal vessels in vhl(-/-) zebrafish.

  • 50.
    Wiik, Anna
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Lundberg, Tommy R.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Rullman, Eric
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Andersson, Daniel P.
    Karolinska Inst, Sweden.
    Holmberg, Mats
    Karolinska Univ Hosp, Sweden.
    Mandic, Mirko
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Brismar, Torkel B.
    Karolinska Inst, Sweden.
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. AMRA Med AB, Linkoping, Sweden.
    Chanpen, Setareh
    Karolinska Univ Hosp, Sweden.
    Flanagan, John N.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Arver, Stefan
    Karolinska Univ Hosp, Sweden.
    Gustafsson, Thomas
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Muscle Strength, Size, and Composition Following 12 Months of Gender-affirming Treatment in Transgender Individuals2020In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 105, no 3, p. E805-E813Article in journal (Refereed)
    Abstract [en]

    Context. As many sports are divided in male/female categories, governing bodies have formed regulations on the eligibility for transgender individuals to compete in these categories. Yet, the magnitude of change in muscle mass and strength with gender-affirming treatment remains insufficiently explored. Objective. This study explored the effects of gender-affirming treatment on muscle function, size, and composition during 12 months of therapy. Design, settings, participants. In this single-center observational cohort study, untrained transgender women (TW, n = 11) and transgender men (TM, n = 12), approved to start gender-affirming medical interventions, underwent assessments at baseline, 4 weeks after gonadal suppression of endogenous hormones but before hormone replacement, and 4 and 12 months after treatment initiation. Main outcome measures. Knee extensor and flexor strength were assessed at all examination time points, and muscle size and radiological density (using magnetic resonance imaging and computed tomography) at baseline and 12 months after treatment initiation. Results. Thigh muscle volume increased (15%) in TM, which was paralleled by increased quadriceps cross-sectional area (CSA) (15%) and radiological density (6%). In TW, the corresponding parameters decreased by -5% (muscle volume) and -4% (CSA), while density remained unaltered. The TM increased strength over the assessment period, while the TW generally maintained their strength levels. Conclusions. One year of gender-affirming treatment resulted in robust increases in muscle mass and strength in TM, but modest changes in TW. These findings add new knowledge on the magnitude of changes in muscle function, size, and composition with cross-hormone therapy, which could be relevant when evaluating the transgender eligibility rules for athletic competitions.

12 1 - 50 of 55
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf