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  • 301.
    Flaatten, H.
    et al.
    Gen ICU, Norway; University of Bergen, Norway.
    Walther, Sten
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Activity- or severity-based scoring in the ICU?2017In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, no 1Article in journal (Other academic)
    Abstract [en]

    n/a

  • 302.
    Flodin, Ulf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Paues, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Åkerlind, Britt
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Business support and Development, Department of Communicable Disease and Infection Control.
    Leanderson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Sjögren, Bengt
    Karolinska Institutet, Arbetsmiljötoxikologi, Institutet för miljömedicin Stockholm, Sweden Institutet för miljömedicin, Karolinska Institutet - Arbetsmiljötoxikologi Stockholm, Sweden.
    Svetsare – en riskgrupp för septisk pneumoni [Welders - a risk group for septic pneumonia]: Vaccination mot pneumokocker kan vara motiverat för yrkesgruppen2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, no 6Article in journal (Refereed)
  • 303.
    Flodin, Ulf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Rolander, B.
    Jonkoping Univ, Sweden; Futurum, Sweden.
    Lofgren, H.
    Ryhov Hosp, Sweden.
    Krapi, Blerim
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Nyqvist, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Wåhlin, Charlotte
    Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Unit of Intervention and Implementation Research, Institute for Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Risk factors for neck pain among forklift truck operators: a retrospective cohort study2018In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 19, article id 44Article in journal (Refereed)
    Abstract [en]

    Background

    No previous research has been performed into neck pain among forklift operators. This is a common complaint among these workers, who number around 150,000 in Sweden and six million in Europe. The aim of the study was to examine long-term exposure to unnatural neck positions among forklift operators as a risk factor for neck pain.

    Methods

    A retrospective cohort study was conducted of all eligible employees at a high-level warehouse. Forklift operators and office workers answered an 18-page questionnaire comprising questions about joint pain, work tasks, work postures and year of start for all items. By using person years in the exposed and less-exposed groups before start of neck pain we were able to calculate Incident Rate ratios for various exposures.

    Results

    Forty nine percent of the forklift operators reported having experienced neck pain compared to 30 % of office workers. Being a forklift operator was associated with an increased risk of neck pain (OR = 5.1, 95% CI 1.4–18.2). Holding the head in an unnatural position resulted in significantly increased risks for neck pain, irrespective of type of position. The risks for neck pain remained after taking other ergonomic exposures and psychosocial aspects into consideration.

    Conclusions

    This is the first published study showing that forklift operators have an increased risk of neck pain. The results are therefore of significance for improving work schedules, the adjustment of work tasks for these workers and the design of the vehicles.

  • 304.
    Folkesson, Maggie
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Sadowska, Natalia
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Vikingsson, Svante
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Karlsson, Matts
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Carlhäll, Carl-Johan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Jensen, Lasse
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Differences in cardiovascular toxicities associated with cigarette smoking and snuff use revealed using novel zebrafish models2016In: Biology Open, ISSN 2046-6390, Vol. 5, no 7, p. 970-978Article in journal (Refereed)
    Abstract [en]

    Tobacco use is strongly associated with cardiovascular disease and the only avoidable risk factor associated with development of aortic aneurysm. While smoking is the most common form of tobacco use, snuff and other oral tobacco products are gaining popularity, but research on potentially toxic effects of oral tobacco use has not kept pace with the increase in its use. Here, we demonstrate that cigarette smoke and snuff extracts are highly toxic to developing zebrafish embryos. Exposure to such extracts led to a palette of toxic effects including early embryonic mortality, developmental delay, cerebral hemorrhages, defects in lymphatics development and ventricular function, and aneurysm development. Both cigarette smoke and snuff were more toxic than pure nicotine, indicating that other compounds in these products are also associated with toxicity. While some toxicities were found following exposure to both types of tobacco product, other toxicities, including developmental delay and aneurysm development, were specifically observed in the snuff extract group, whereas cerebral hemorrhages were only found in the group exposed to cigarette smoke extract. These findings deepen our understanding of the pathogenic effects of cigarette smoking and snuff use on the cardiovascular system and illustrate the benefits of using zebrafish to study mechanisms involved in aneurysm development.

  • 305.
    Folkesson, Maggie
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Vorkapic, Emina
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Gulbins, Erich
    University of Duisburg-Essen, University of Cincinnati.
    Japtok, Lukasz
    The department of Toxicology, Institute of Nutritional Science, University of Potsdam.
    Kleuser, Burkhard
    The department of Toxicology, Institute of Nutritional Science, University of Potsdam.
    Welander, Martin
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Inflammatory cells, ceramides, and expression of proteases in perivascular adipose tissue adjacent to human abdominal aortic aneurysms2017In: Journal of Vascular Surgery, ISSN 0741-5214, E-ISSN 1097-6809, Vol. 65, no 4, p. 1171-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Abdominal aortic aneurysm (AAA) is a deadly irreversible weakening and distension of the abdominal aortic wall. The pathogenesis of AAA remains poorly understood. Investigation into the physical and molecular characteristics of perivascular adipose tissue (PVAT) adjacent to AAA has not been done before and is the purpose of this study.

    METHODS AND RESULTS: Human aortae, periaortic PVAT, and fat surrounding peripheral arteries were collected from patients undergoing elective surgical repair of AAA. Control aortas were obtained from recently deceased healthy organ donors with no known arterial disease. Aorta and PVAT was found in AAA to larger extent compared with control aortas. Immunohistochemistry revealed neutrophils, macrophages, mast cells, and T-cells surrounding necrotic adipocytes. Gene expression analysis showed that neutrophils, mast cells, and T-cells were found to be increased in PVAT compared with AAA as well as cathepsin K and S. The concentration of ceramides in PVAT was determined using mass spectrometry and correlated with content of T-cells in the PVAT.

    CONCLUSIONS: Our results suggest a role for abnormal necrotic, inflamed, proteolytic adipose tissue to the adjacent aneurysmal aortic wall in ongoing vascular damage.

  • 306.
    Forsgren, Mikael
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Karlsson, Markus
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dahlström, Nils
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Norén, Bengt
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Romu, Thobias
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ignatova, Simone
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Ekstedt, Mattias
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Cedersund, Gunnar
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Model-inferred mechanisms of liver function from magnetic resonance imaging data: Validation and variation across a clinically relevant cohort2019In: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 15, no 6, article id e1007157Article in journal (Refereed)
    Abstract [en]

    Estimation of liver function is important to monitor progression of chronic liver disease (CLD). A promising method is magnetic resonance imaging (MRI) combined with gadoxetate, a liver-specific contrast agent. For this method, we have previously developed a model for an average healthy human. Herein, we extended this model, by combining it with a patient-specific non-linear mixed-effects modeling framework. We validated the model by recruiting 100 patients with CLD of varying severity and etiologies. The model explained all MRI data and adequately predicted both timepoints saved for validation and gadoxetate concentrations in both plasma and biopsies. The validated model provides a new and deeper look into how the mechanisms of liver function vary across a wide variety of liver diseases. The basic mechanisms remain the same, but increasing fibrosis reduces uptake and increases excretion of gadoxetate. These mechanisms are shared across many liver functions and can now be estimated from standard clinical images.

    Author summary

    Being able to accurately and reliably estimate liver function is important when monitoring the progression of patients with liver disease, as well as when identifying drug-induced liver injury during drug development. A promising method for quantifying liver function is to use magnetic resonance imaging combined with gadoxetate. Gadoxetate is a liver-specific contrast agent, which is taken up by the hepatocytes and excreted into the bile. We have previously developed a mechanistic model for gadoxetate dynamics using averaged data from healthy volunteers. In this work, we extended our model with a non-linear mixed-effects modeling framework to give patient-specific estimates of the gadoxetate transport-rates. We validated the model by recruiting 100 patients with liver disease, covering a range of severity and etiologies. All patients underwent an MRI-examination and provided both blood and liver biopsies. Our validated model provides a new and deeper look into how the mechanisms of liver function varies across a wide variety of liver diseases. The basic mechanisms remain the same, but increasing fibrosis reduces uptake and increases excretion of gadoxetate.

  • 307.
    Forsgren, Mikael
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Wolfram MathCore AB, Linköping, Sweden.
    Norén, Bengt
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Kihlberg, Johan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Comparing hepatic 2D and 3D magnetic resonance elastography methods in a clinical setting – Initial experiences2015In: European Journal of Radiology Open, E-ISSN 2352-0477, Vol. 2, p. 66-70Article in journal (Refereed)
    Abstract [en]

    Purpose

    Continuous monitoring of liver fibrosis progression in patients is not feasible with the current diagnostic golden standard (needle biopsy). Recently, magnetic resonance elastography (MRE) has emerged as a promising method for such continuous monitoring. Since there are different MRE methods that could be used in a clinical setting there is a need to investigate whether measurements produced by these MRE methods are comparable. Hence, the purpose of this pilot study was to evaluate whether the measurements of the viscoelastic properties produced by 2D (stiffness) and 3D (elasticity and ‘Gabs,Elastic’) MRE are comparable.

    Materials and methods

    Seven patients with diffuse or suspect diffuse liver disease were examined in the same day with the two MRE methods. 2D MRE was performed using an acoustic passive transducer, with a 1.5 T GE 450 W MR system. 3D MRE was performed using an electromagnetic active transducer, with a 1.5 T Philips Achieva MR system. Finally, mean viscoelastic values were extracted from the same anatomical region for both methods by an experienced radiologist.

    Results

    Stiffness correlated well with the elasticity, R2 = 0.96 (P < 0.001; slope = 1.08, intercept = 0.61 kPa), as well as with ‘Gabs,ElasticR2 = 0.96 (P < 0.001; slope = 0.95, intercept = 0.28 kPa).

    Conclusion

    This pilot study shows that different MRE methods can produce comparable measurements of the viscoelastic properties of the liver. The existence of such comparable measurements is important, both from a clinical as well as a research perspective, since it allows for equipment-independent monitoring of disease progression.

  • 308.
    Fransen, Jian
    et al.
    Uppsala University, Sweden.
    Huss, Fredrik R. M.
    Uppsala University, Sweden; University of Uppsala Hospital, Sweden.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Rydell, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Surveillance of antibiotic susceptibility in a Swedish Burn Center 1994-20122016In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 42, no 6, p. 1295-1303Article in journal (Refereed)
    Abstract [en]

    Patients with burn trauma are at risk for infections caused by antibiotic resistant bacteria (ABR) with subsequent increase in morbidity and mortality. As part of the Swedish strategic program against antibiotic resistance in intensive care (ICU-Strama), we have surveyed the distribution of species and ABR in isolates from patients admitted to a Swedish burn center at Linkoping University Hospital from 1994 through 2012. In an international comparison Strama has been successful in reducing the antibiotic consumption among animals and humans in primary care. The aim of this study was to investigate the antibiotic consumption pressure and resistance rates in a Swedish burn unit. Methods: Microbiology data, total body surface area (TBSA), patient days, and mortality were collected from a hospital database for all patients admitted to the Burn Center at the University Hospital of Linkoping from April 1994 through December 2012. Results: A total of 1570 patients were admitted with a mean annual admission rate of 83 patients (range: 57-152). 15,006 microbiology cultures (approximately 10 per patient) were collected during the study period and of these 4531 were positive (approximately 3 per patient). The annual mean total body surface area (TBSA) was 13.4% (range 9.5-18.5) with an annual mortality rate of 5.4% (range 1-8%). The MRSA incidence was 1.7% (15/866) which corresponds to an MRSA incidence of 0.34/1000 admission days (TAD). Corresponding figures were for Escherichia coli resistant to 3rd generation cephalosporins (ESBL phenotype) 8% (13/170) and 0.3/TAD, Klebsiella spp. ESBL phenotype 5% (6/134) and 0.14/TAD, carbapenem resistant Pseudomonas aeruginosa 26% (56/209) and 1.28/TAD, and carbapenem resistant Acinetobacter spp. 3% (2/64) and 0.04/TAD. Conclusions: Our results show a sustained low risk for MRSA and high, although not increasing, risk for carbapenem resistant P. aeruginosa. (C) 2016 Elsevier Ltd and ISBI. All rights reserved.

  • 309.
    Fredriksson, Alexandru Grigorescu
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Örebrö University Hospital, Örebro, Sweden.
    Svalbring, Emil
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Eriksson, Jonatan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Dyverfeldt, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Faculty of Science & Engineering. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Carlhäll, Carl-Johan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    4D flow MRI can detect subtle right ventricular dysfunction in primary left ventricular disease.2016In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 43, no 3, p. 558-565Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 310.
    Fredriksson, Alexandru Grigorescu
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Trzebiatowska-Krzynska, Aleksandra
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Dyverfeldt, Petter
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Engvall, Jan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Ebbers, Tino
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Carlhäll, Carljohan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Turbulent kinetic energy in the right ventricle: Potential MR marker for risk stratification of adults with repaired Tetralogy of Fallot2018In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 47, no 4, p. 1043-1053Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 311.
    Fridell, Sara
    et al.
    Region Östergötland, Public Dental Health Care, Center for Oral Rehabilitation Linköping.
    Ström, Edvin
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Agebratt, Christian
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Leanderson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Guldbrand, Hans
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Nyström, Fredrik H.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    A randomised study in young subjects of the effects of eating extra fruit or nuts on periodontal inflammation2018In: BDJ open, ISSN 2056-807X, Vol. 3, article id 17022Article in journal (Refereed)
    Abstract [en]

    Objectives/Aims:

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

    Materials and methods:

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

    Results:

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

    Conclusion:

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

  • 312.
    Frobert, Ole
    et al.
    Örebro University, Sweden.
    Gotberg, Matthias
    University Hospital Lund, Sweden.
    Angeras, Oskar
    Sahlgrens University Hospital, Sweden.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Erlinge, David
    University Hospital Lund, Sweden.
    Engstrom, Thomas
    University of Copenhagen, Denmark.
    Persson, Jonas
    Karolinska Institute, Sweden.
    Jensen, Svend E.
    Aalborg University Hospital, Denmark.
    Omerovic, Elmir
    Sahlgrens University Hospital, Sweden.
    James, Stefan K.
    University Hospital Uppsala, Sweden.
    Lagerqvist, Bo
    University Hospital Uppsala, Sweden.
    Nilsson, Johan
    Umeå University, Sweden.
    Karegren, Amra
    Västerås County Hospital, Sweden.
    Moer, Rasmus
    Feiring Clin, Norway.
    Yang, Cao
    Örebro University, Sweden; Karolinska Institute, Sweden.
    Agus, David B.
    University of Southern Calif, CA 90089 USA.
    Erglis, Andrejs
    Pauls Stradins Clin University Hospital, Latvia.
    Jensen, Lisette O.
    Odense University Hospital, Denmark.
    Jakobsen, Lars
    Aarhus University Hospital, Denmark.
    Christiansen, Evald H.
    Aarhus University Hospital, Denmark.
    Pernow, John
    Karolinska Institute, Sweden.
    Design and rationale for the Influenza vaccination After Myocardial Infarction (IAMI) trial. A registry-based randomized clinical trial2017In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 189, p. 94-102Article in journal (Refereed)
    Abstract [en]

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

  • 313.
    Frodlund, Martina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Reid, S.
    Uppsala Univ, Sweden.
    Wetterö, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Dahlström, Örjan
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research.
    Sjöwall, Christopher
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Leonard, D.
    Uppsala Univ, Sweden.
    The majority of Swedish systemic lupus erythematosus patients are still affected by irreversible organ impairment: factors related to damage accrual in two regional cohorts2019In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, article id UNSP 0961203319860198Article in journal (Refereed)
    Abstract [en]

    Background Although the survival of patients with systemic lupus erythematosus (SLE) has improved, irreversible organ damage remains a critical concern. We aimed to characterize damage accrual and its clinical associations and causes of death in Swedish patients. Methods Accumulation of damage was evaluated in 543 consecutively recruited and well-characterized cases during 1998-2017. The Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology damage index (SDI) was used to estimate damage. Results Organ damage (SDI amp;gt;= 1) was observed in 59%, and extensive damage (SDI amp;gt;= 3) in 25% of cases. SDI amp;gt;= 1 was significantly associated with higher age at onset, SLE duration, the number of fulfilled SLICC criteria, neurologic disorder, antiphospholipid antibody syndrome (APS), hypertension, hyperlipidemia, depression and secondary Sjogrens syndrome (SS). In addition, SDI amp;gt;= 3 was associated with serositis, renal and haematological disorders and interstitial lung disease. A multiple regression model identified not only well-known risk factors like APS, antihypertensives and corticosteroids, but pericarditis, haemolytic anaemia, lymphopenia and myositis as being linked to SDI. Malignancy, infection and cardiovascular disease were the leading causes of death. Conclusions After a mean SLE duration of 17 years, the majority of todays Swedish SLE patients have accrued damage. We confirm previous observations and report some novel findings regarding disease phenotypes and damage accrual.

  • 314.
    Frodlund, Martina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Vikerfors, A.
    Karolinska Univ Hosp, Sweden; Swedish Med Prod Agcy, Sweden.
    Grosso, G.
    Karolinska Univ Hosp, Sweden.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Wetterö, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Elvin, K.
    Karolinska Inst, Sweden.
    Gunnarsson, I.
    Karolinska Univ Hosp, Sweden.
    Kastbom, Alf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Dahlström, Örjan
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research.
    Ronnelid, J.
    Uppsala Univ, Sweden.
    Svenungsson, E.
    Karolinska Univ Hosp, Sweden.
    Sjöwall, Christopher
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Immunoglobulin A anti-phospholipid antibodies in Swedish cases of systemic lupus erythematosus: associations with disease phenotypes, vascular events and damage accrual2018In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 194, no 1, p. 27-38Article in journal (Refereed)
    Abstract [en]

    Immunoglobulin (Ig) G- and IgM-class anti-cardiolipin antibodies (aCL) and lupus anti-coagulant (LA) are included in the 1997 update of the American College of Rheumatology (ACR-97) systemic lupus erythematosus (SLE) criteria. Despite limited evidence, IgA-aCL and IgA anti-(2)-glycoprotein-I (anti-(2)GPI) were included in the 2012 Systemic Lupus International Collaborating Clinics criteria. The present study aimed to evaluate IgG-/IgA-/IgM-aCL and anti-(2)GPI occurrence in relation to disease phenotype, smoking habits, pharmacotherapy, anti-phospholipid syndrome (APS) and organ damage among 526 Swedish SLE patients meeting ACR-97. Patients with rheumatoid arthritis (n=100), primary Sjogrens syndrome (n=50) and blood donors (n=507) served as controls. Anti-phospholipid antibodies (aPL) were analysed by fluoroenzyme-immunoassays detecting aCL/anti-(2)GPI. Seventy-six (14%) SLE cases fulfilled the Sydney APS-criteria, and 1 aCL/anti-(2)GPI isotype (IgG/IgA/IgM) occurred in 138 SLE patients (26%). Forty-five (9%) of the SLE cases had IgA-aCL, 20 of whom (4%) lacked IgG-/IgM-aCL. Seventy-four (14%) tested positive for IgA anti-(2)GPI, 34 (6%) being seronegative regarding IgG/IgM anti-(2)GPI. Six (1%) had APS manifestations but were seropositive regarding IgA-aCL and/or IgA anti-(2)GPI in the absence of IgG/IgM-aPL and LA. Positive LA and IgG-aPL tests were associated with most APS-related events and organ damage. Exclusive IgA anti-(2)GPI occurrence associated inversely with Caucasian ethnicity [odds ratio (OR)=021, 95% confidence interval (CI)=006-072) and photosensitivity (OR=019, 95% CI=005-072). Nephritis, smoking, LA-positivity and statin/corticosteroid-medication associated strongly with organ damage, whereas hydroxychloroquine-medication was protective. In conclusion, IgA-aPL is not rare in SLE (16%) and IgA-aPL analysis may have additional value among SLE cases with suspected APS testing negative for other isotypes of aPL and LA.

  • 315.
    Fryk, Emanuel
    et al.
    University of Gothenburg, Sweden.
    Perman Sundelin, Jeanna
    University of Gothenburg, Sweden.
    Strindberg, Lena
    University of Gothenburg, Gothenburg, Sweden.
    Pereira, Maria J.
    Uppsala University, Sweden.
    Federici, Massimo
    University of Roma Tor Vergata, Italy.
    Marx, Nikolaus
    University Hospital RWTH Aachen, Germany.
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Schmelz, Martin
    Heidelberg University, Germany.
    Svensson, Per-Arne
    University of Gothenburg, Sweden.
    Eriksson, Jan W.
    Uppsala University, Sweden.
    Boren, Jan
    University of Gothenburg, Sweden.
    Jansson, Per-Anders
    University of Gothenburg, Sweden.
    Microdialysis and proteomics of subcutaneous interstitial fluid reveals increased galectin-1 in type 2 diabetes patients2016In: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 65, no 7, p. 998-1006Article in journal (Refereed)
    Abstract [en]

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

  • 316.
    Frölund, Maria
    et al.
    Research Unit for Reproductive Microbiology, Statens Serum Institut, Copenhagen S, Denmark.
    Falk, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Ahrens, Peter
    Research Unit for Reproductive Microbiology, Statens Serum Institut, Copenhagen S, Denmark.
    Jensen, Jorgen Skov
    Research Unit for Reproductive Microbiology, Statens Serum Institut, Copenhagen S, Denmark.
    Detection of ureaplasmas and bacterial vaginosis associated bacteria and their association with non-gonococcal urethritis in men2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203Article in journal (Refereed)
    Abstract [en]

    No aetiology is found in up to 40% of men with symptomatic urethritis. Male partners of women with bacterial vaginosis (BV) may be at higher risk of non-gonococcal urethritis (NGU). The aim of this study was to examine the role of BV associated bacteria in first-void urine (FVU) in 97 asymptomatic men without urethritis (controls) and 44 men (cases) with NGU including 20 men with idiopathic urethritis (IU) attending a Swedish STD-clinic between January and October 2010. BV-associated bacteria and ureaplasmas were detected by quantitative PCR assays. All BV associated bacteria, except Megasphaera-like type 1, were strongly positively correlated with Uurealyticum p<0.005 and even stronger with the combined Uurealyticum and Uparvum load (p<0.0005) suggesting that ureaplasma induced elevated pH may stimulate the growth of BV associated bacteria. No statistically significant differences were found between IU cases and controls in the prevalence or load of BV associated bacteria or ureaplasmas. In multiple logistic regression, Megasphaera-like type 1 was associated with IU (p = 0.03), but most positive FVU samples contained very few bacteria and the finding may not be clinically relevant.

  • 317.
    Gabrielson, Marike
    et al.
    Karolinska Institute, Sweden.
    Vorkapic, Emina
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Folkesson, Maggie
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Welander, Martin
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Matussek, Andreas
    University of Coll Health Science, Sweden.
    Dimberg, Jan
    University of Coll Health Science, Sweden.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Skogberg, Josefin
    Karolinska Institute, Sweden.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Altered PPAR gamma Coactivator-1 Alpha Expression in Abdominal Aortic Aneurysm: Possible Effects on Mitochondrial Biogenesis2016In: Journal of Vascular Research, ISSN 1018-1172, E-ISSN 1423-0135, Vol. 53, no 1-2, p. 17-26Article in journal (Refereed)
    Abstract [en]

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

  • 318.
    Gaeta, Stephen
    et al.
    Duke Univ, NC USA.
    Dyverfeldt, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Eriksson, Jonatan
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Carlhäll, Carljohan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Bolger, Ann F
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Univ Calif San Francisco, CA 94143 USA.
    Fixed volume particle trace emission for the analysis of left atrial blood flow using 4D Flow MRI2018In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 47, p. 83-88Article in journal (Refereed)
    Abstract [en]

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

  • 319.
    Gaipov, Abduzhappar
    et al.
    Natl Sci Med Res Ctr, Kazakhstan.
    Molnar, Miklos Z.
    Methodist Univ Hosp, TN USA; Semmelweis Univ, Hungary.
    Potukuchi, Praveen K.
    Natl Sci Med Res Ctr, Kazakhstan.
    Sumida, Keiichi
    Natl Sci Med Res Ctr, Kazakhstan; Toranomon Hosp Kajigaya, Japan.
    Canada, Robert B.
    Natl Sci Med Res Ctr, Kazakhstan.
    Akbilgic, Oguz
    Kazakh Natl Med Univ, Kazakhstan.
    Kabulbayev, Kairat
    Kazakh Natl Med Univ, Kazakhstan.
    Szabo, Zoltán
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Koshy, Santhosh K. G.
    Univ Tennessee, TN 38104 USA.
    Kalantar-Zadeh, Kamyar
    Univ Calif Irvine, CA 92668 USA.
    Kovesdy, Csaba P.
    Natl Sci Med Res Ctr, Kazakhstan; Memphis VA Med Ctr, TN 38104 USA.
    Predialysis coronary revascularization and postdialysis mortality2019In: Journal of Thoracic and Cardiovascular Surgery, ISSN 0022-5223, E-ISSN 1097-685X, Vol. 157, no 3, p. 976-+Article in journal (Refereed)
    Abstract [en]

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

  • 320.
    Gaipov, Abduzhappar
    et al.
    University of Tennessee Health Science Center, Memphis, TN, USA, National Scientific Medical Research Center, Astana, Kazakhstan.
    Molnar, Miklos Z
    University of Tennessee Health Science Center, Memphis, TN, USA, Semmelweis University, Budapest, Hungary.
    Potukuchi, Praveen K
    University of Tennessee Health Science Center, Memphis, TN, USA.
    Sumida, Keiichi
    University of Tennessee Health Science Center, Memphis, TN, USA,Toranomon Hospital Kajigaya, Kanagawa, Japan..
    Szabó, Zoltán
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Akbilgic, Oguz
    University of Tennessee Health Science Center, Memphis, TN, USA.
    Streja, Elani
    University of California, Irvine, Orange, CA, USA..
    Rhee, Connie M
    University of California, Irvine, Orange, CA, USA..
    Koshy, Santhosh K G
    University of Tennessee Health Science Center, Memphis, TN, USA.
    Canada, Robert B
    University of Tennessee Health Science Center, Memphis, TN, USA.
    Kalantar-Zadeh, Kamyar
    University of California, Irvine, Orange, CA, USA..
    Kovesdy, Csaba P
    University of Tennessee Health Science Center, Memphis, TN, USA, Memphis VA Medical Center, Memphis, TN, USA.
    Acute kidney injury following coronary revascularization procedures in patients with advanced CKD.2019In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 34, no 11, p. 1894-1901Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 321.
    Garcia-Etxebarria, Koldo
    et al.
    Biodonostia Hlth Res Inst, Spain; Karolinska Inst, Sweden.
    Zheng, Tenghao
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Bonfiglio, Ferdinando
    Biodonostia Hlth Res Inst, Spain; Karolinska Inst, Sweden.
    Bujanda, Luis
    Biodonostia Hlth Res Inst, Spain; Univ Basque Country, Spain.
    Dlugosz, Aldona
    Karolinska Inst, Sweden.
    Lindberg, Greger
    Karolinska Inst, Sweden.
    Schmidt, Peter T.
    Univ Basque Country, Spain.
    Karling, Pontus
    Umea Univ, Sweden.
    Ohlsson, Bodil
    Lund Univ, Sweden.
    Simren, Magnus
    Univ Gothenburg, Sweden.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Nardone, Gerardo
    University Federico II, Naples, Italy.
    Cuomo, Rosario
    Federico II Univ Hosp, Italy.
    Usai-Satta, Paolo
    Azienda Osped G Brotzu, Italy.
    Galeazzi, Francesca
    Padova Univ Hosp, Italy.
    Neri, Matteo
    G DAnnunzio Univ and Fdn, Italy.
    Portincasa, Piero
    G DAnnunzio Univ and Fdn, Italy.
    Bellini, Massimo
    Univ Bari, Italy.
    Barbara, Giovanni
    Univ Pisa, Italy.
    Jonkers, Daisy
    Univ Bologna, Italy.
    Eswaran, Shanti
    Univ Michigan, MI USA.
    Chey, William D.
    Univ Michigan, MI USA.
    Kashyap, Purna
    Mayo Clin, MN USA.
    Chang, Lin
    Univ Calif Los Angeles, CA 90095 USA.
    Mayer, Emeran A.
    Univ Calif Los Angeles, CA 90095 USA.
    Wouters, Mira M.
    Katholieke Univ Leuven, Belgium.
    Boeckxstaens, Guy
    Katholieke Univ Leuven, Belgium.
    Camilleri, Michael
    Mayo Clin, MN USA; Mayo Clin, MN USA.
    Franke, Andre
    Maastricht Univ, Netherlands; Christian Albrechts Univ Kiel, Germany.
    DAmato, Mauro
    Biodonostia Hlth Res Inst, Spain; Karolinska Inst, Sweden; Karolinska Inst, Sweden; Basque Sci Fdn, Spain.
    Increased Prevalence of Rare Sucrase-isomaltase Pathogenic Variants in Irritable Bowel Syndrome Patients2018In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 16, no 10, p. 1673-1676Article in journal (Refereed)
    Abstract [en]

    n/a

  • 322.
    Garvin, Peter
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Nilsson, Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Falk, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Kristenson, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Plasma Matrix Metalloproteinase-9 Levels Predict First-Time Coronary Heart Disease: An 8-Year Follow-Up of a Community-Based Middle Aged Population2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 9, p. e0138290-Article in journal (Refereed)
    Abstract [en]

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

  • 323.
    Gawel, Danuta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Serra-Musach, Jordi
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Lilja, Sandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Aagesen, Jesper
    Reg Jonkoping Cty, Sweden.
    Arenas, Alex
    Univ Rovira and Virgili, Spain.
    Asking, Bengt
    Reg Jonkoping Cty, Sweden.
    Bengner, Malin
    Reg Jonkoping Cty, Sweden.
    Bjorkander, Janne
    Reg Jonkoping Cty, Sweden.
    Biggs, Sophie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Hjortswang, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Karlsson, Jan-Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Reg Jonkoping Cty, Sweden.
    Köpsén, Mattias
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Jung Lee, Eun Jung
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Yonsei Univ, South Korea.
    Lentini, Antonio
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Li, Xinxiu
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Magnusson, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Martinez, David
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Matussek, Andreas
    Reg Jonkoping Cty, Sweden; Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Schafer, Samuel
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Seifert, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Reg Jonkoping Cty, Sweden.
    Sonmez, Ceylan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Stjernman, Henrik
    Reg Jonkoping Cty, Sweden.
    Tjärnberg, Andreas
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Wu, Simon
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Åkesson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Reg Jonkoping Cty, Sweden.
    Shalek, Alex K.
    MIT, MA 02139 USA; Broad Inst MIT and Harvard, MA 02142 USA; Ragon Inst MGH MIT and Harvard, MA USA.
    Stenmarker, Margaretha
    Reg Jonkoping Cty, Sweden; Inst Clin Sci, Sweden.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Gustafsson, Mika
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases2019In: Genome Medicine, ISSN 1756-994X, E-ISSN 1756-994X, Vol. 11, article id 47Article in journal (Refereed)
    Abstract [en]

    Background

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

    Methods

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

    Results

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

    Conclusions

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

  • 324.
    Ge, Changrong
    et al.
    Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
    Tong, Dongmei
    Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Southern Medical University, Guangzhou, China..
    Liang, Bibo
    Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm,Southern Medical University, Guangzhou, China.
    Lönnblom, Erik
    Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm.
    Schneider, Nadine
    University Hospital Frankfurt Goethe University, Frankfurt, Germany.
    Hagert, Cecilia
    University of Turku, Finland.
    Viljanen, Johan
    Biomedicinskt centrum, Uppsala University, Uppsala, Sweden.
    Ayoglu, Burcu
    KTH Royal Institute of Technology, Stockholm, Sweden.
    Stawikowska, Roma
    Florida Atlantic University, Jupiter, Florida, USA.
    Nilsson, Peter
    KTH Royal Institute of Technology, Stockholm, Sweden.
    Fields, Gregg B
    Florida Atlantic University, Jupiter, Florida, USA.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Kastbom, Alf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Kihlberg, Jan
    Uppsala University, Uppsala, Sweden.
    Burkhardt, Harald
    University Hospital Frankfurt Goethe University, Frankfurt, Germany.
    Dobritzsch, Doreen
    Uppsala University, Uppsala, Sweden.
    Holmdahl, Rikard
    Karolinska Institutet, Stockholm, Sweden; University of Turku, Turku, Finland, Southern Medical University, Guangzhou, China.
    Anti-citrullinated protein antibodies cause arthritis by cross-reactivity to joint cartilage2017In: JCI insight, ISSN 2379-3708, Vol. 2, no 13, article id 93688Article in journal (Refereed)
    Abstract [en]

    Today, it is known that autoimmune diseases start a long time before clinical symptoms appear. Anti-citrullinated protein antibodies (ACPAs) appear many years before the clinical onset of rheumatoid arthritis (RA). However, it is still unclear if and how ACPAs are arthritogenic. To better understand the molecular basis of pathogenicity of ACPAs, we investigated autoantibodies reactive against the C1 epitope of collagen type II (CII) and its citrullinated variants. We found that these antibodies are commonly occurring in RA. A mAb (ACC1) against citrullinated C1 was found to cross-react with several noncitrullinated epitopes on native CII, causing proteoglycan depletion of cartilage and severe arthritis in mice. Structural studies by X-ray crystallography showed that such recognition is governed by a shared structural motif "RG-TG" within all the epitopes, including electrostatic potential-controlled citrulline specificity. Overall, we have demonstrated a molecular mechanism that explains how ACPAs trigger arthritis.

  • 325.
    Ge, Changrong
    et al.
    Karolinska Inst, Sweden.
    Xu, Bingze
    Karolinska Inst, Sweden.
    Liang, Bibo
    Karolinska Inst, Sweden; Southern Med Univ, Peoples R China.
    Lonnblom, Erik
    Karolinska Inst, Sweden.
    Lundstrom, Susanna L.
    Karolinska Inst, Sweden.
    Zubarev, Roman A.
    Karolinska Inst, Sweden.
    Ayoglu, Burcu
    KTH Royal Inst Technol, Sweden.
    Nilsson, Peter
    KTH Royal Inst Technol, Sweden.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Kastbom, Alf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Malmstrom, Vivianne
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Klareskog, Lars
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Toes, Rene E. M.
    Leiden Univ, Netherlands.
    Rispens, Theo
    Univ Amsterdam, Netherlands.
    Dobritzsch, Doreen
    Uppsala Univ, Sweden.
    Holmdahl, Rikard
    Karolinska Inst, Sweden; Southern Med Univ, Peoples R China.
    Structural Basis of Cross-Reactivity of Anti-Citrullinated Protein Antibodies2019In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 71, no 2, p. 210-221Article in journal (Refereed)
    Abstract [en]

    Objective Anti-citrullinated protein antibodies (ACPAs) develop many years before the clinical onset of rheumatoid arthritis (RA). This study was undertaken to address the molecular basis of the specificity and cross-reactivity of ACPAs from patients with RA. Methods Antibodies isolated from RA patients were expressed as monoclonal chimeric antibodies with mouse Fc. These antibodies were characterized for glycosylation using mass spectrometry, and their cross-reactivity was assessed using Biacore and Luminex immunoassays. The crystal structures of the antigen-binding fragment (Fab) of the monoclonal ACPA E4 in complex with 3 different citrullinated peptides were determined using x-ray crystallography. The prevalence of autoantibodies reactive against 3 of the citrullinated peptides that also interacted with E4 was investigated by Luminex immunoassay in 2 Swedish cohorts of RA patients. Results Analysis of the crystal structures of a monoclonal ACPA from human RA serum in complex with citrullinated peptides revealed key residues of several complementarity-determining regions that recognized the citrulline as well as the neighboring peptide backbone, but with limited contact with the side chains of the peptides. The same citrullinated peptides were recognized by high titers of serum autoantibodies in 2 large cohorts of RA patients. Conclusion These data show, for the first time, how ACPAs derived from human RA serum recognize citrulline. The specific citrulline recognition and backbone-mediated interactions provide a structural explanation for the promiscuous recognition of citrullinated peptides by RA-specific ACPAs.

  • 326.
    Geetha, Duvuru
    et al.
    Johns Hopkins University, Baltimore, MD, USA.
    Hruskova, Zdenka
    Charles University, Prague, Czech Republic .
    Segelmark, Mårten
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology.
    Hogan, Jonathan
    Hospital of the University of Pennsylvania, Philadelphia, USA.
    Morgan, Matthew D
    University of Birmingham, UK .
    Cavero, Teresa
    Hospital 12 de Octubre, Madrid, Spain .
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Seo, Philip
    John Hopkins University, Baltimore, USA.
    Manno, Rebecca L
    John Hopkins University, Baltimore, USA.
    Dale, Jessica
    University of Birmingham, Birmingham, UK.
    Harper, Lorraine
    University of Birmingham, UK.
    Tesar, Vladimir
    Charles University, Prague, Czech Republic .
    Jayne, David Rw
    Addenbrooke's Hospital, Cambridge, UK .
    Rituximab for treatment of severe renal disease in ANCA associated vasculitis2016In: JN. Journal of Nephrology (Milano. 1992), ISSN 1121-8428, E-ISSN 1724-6059, Vol. 29, no 2, p. 195-201Article in journal (Refereed)
    Abstract [en]

    Background

    Rituximab (RTX) is approved for remission induction in ANCA associated vasculitis (AAV). However, data on use of RTX in patients with severe renal disease is lacking.

    Methods

    We conducted a retrospective multi-center study to evaluate the efficacy and safety of RTX with glucocorticoids (GC) with and without use of concomitant cyclophosphamide (CYC) for remission induction in patients presenting with e GFR less than 20 ml/min/1.73 m2. We evaluated outcomes of remission at 6 months (6 M), renal recovery after acute dialysis at diagnosis, e-GFR rise at 6 M, patient and renal survival and adverse events.

    Results

    A total 37 patients met the inclusion criteria. The median age was 61 years. (55–73), 62 % were males, 78 % had new diagnosis and 59 % were MPO ANCA positive. The median (IQR) e-GFR at diagnosis was 13 ml/min/1.73 m2 (7–16) and 15 required acute dialysis. Eleven (30 %) had alveolar hemorrhage. Twelve (32 %) received RTX with GC, 25 (68 %) received RTX with GC and CYC and seventeen (46 %) received plasma exchange. The median (IQR) follow up was 973 (200–1656) days. Thirty two of 33 patients (97 %) achieved remission at 6 M and 10 of 15 patients (67 %) requiring dialysis recovered renal function. The median prednisone dose at 6 M was 6 mg/day. The mean (SD) increase in e-GFR at 6 months was 14.5 (22) ml/min/m2. Twelve patients developed ESRD during follow up. There were 3 deaths in the first 6 months. When stratified by use of concomitant CYC, there were no differences in baseline e GFR, use of plasmapheresis, RTX dosing regimen or median follow up days between the groups. No differences in remission, renal recovery ESRD or death were observed.

    Conclusions

    This study of AAV patients with severe renal disease demonstrates that the outcomes appear equivalent when treated with RTX and GC with or without concomitant CYC.

  • 327.
    Gelmi, Amy
    et al.
    Linköping University, Faculty of Science & Engineering. Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Imperial Coll London, England.
    Cieslar-Pobuda, Artur
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Silesian Technical University, Poland.
    de Muinck, Ebo
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Los, Marek Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Pomeranian Medical University, Poland.
    Rafat, Mehrdad
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Jager, Edwin
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Direct Mechanical Stimulation of Stem Cells: A Beating Electromechanically Active Scaffold for Cardiac Tissue Engineering2016In: Advanced Healthcare Materials, ISSN 2192-2640, E-ISSN 2192-2659, Vol. 5, no 12, p. 1471-1480Article in journal (Refereed)
    Abstract [en]

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

  • 328.
    Genaridis, Apostolos
    et al.
    Södersjukhuset, Stockholm, Sweden.
    Engerström, L
    Berkius, Johan
    Västerviks sjukhus, Västervik, Sweden.
    Wickerts, Carl-Johan
    Walther, Sten
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Can we predict who will benefit from non-invasive ventilation in hypoxemic acute respiratory failure?2015Conference paper (Other academic)
  • 329.
    Georg, Carina
    et al.
    Karolinska Inst, Sweden.
    Karlgren, Klas
    Karolinska Inst, Sweden.
    Ulfvarson, Johanna
    Karolinska Inst, Sweden.
    Jirwe, Maria
    Karolinska Inst, Sweden.
    Henriksson Welin, Elisabet
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    A Rubric to Assess Students Clinical Reasoning When Encountering Virtual Patients2018In: Journal of Nursing Education, ISSN 0148-4834, E-ISSN 1938-2421, Vol. 57, no 7, p. 408-+Article in journal (Refereed)
    Abstract [en]

    Background: Training with virtual patients has been proposed as a suitable learning activity to improve clinical reasoning skills for nursing students. However, published instruments with the capacity to assess students reasoning process in the encounter with virtual patients are lacking. Method: Deductive and abductive analyses were used to adapt the Lasater Clinical Judgment Rubric (LCJR) to assess nursing students clinical reasoning skills in the encounter with virtual patients. The new rubrics ability to capture nursing students clinical reasoning processes was tested using deductive analysis and statistical analysis. Results: A grading rubric for virtual patients, the vpLCJR, was developed. Cronbachs alpha showed .892, indicating good internal consistency. Conclusion: The rubric vpLCJR, which deconstructs aspects of clinical reasoning for both students and faculty members, can be used to clarify expectations, assess students clinical reasoning process, and provide feedback for learning when nursing students encounter virtual patients.

  • 330.
    Georgiopoulos, Charalampos
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Davidsson, Anette
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Larsson, Elna-Marie
    Uppsala University, Sweden.
    Zachrisson, Helene
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dizdar (Dizdar Segrell), Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    The diagnostic value of dopamine transporter imaging and olfactory testing in patients with parkinsonian syndromes2015In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 262, no 9, p. 2154-2163Article in journal (Refereed)
    Abstract [en]

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

  • 331.
    Georgiopoulos, Charalampos
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Warntjes, Marcel Jan Bertus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). SyntheticMR AB, Linkoping, Sweden.
    Dizdar Segrell, Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Zachrisson, Helene
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Haller, Sven
    Affidea CDRC Centre Diagnost Radiol Carouge SA, Switzerland; Uppsala University, Sweden.
    Larsson, Elna-Marie
    Uppsala University, Sweden.
    Olfactory Impairment in Parkinsons Disease Studied with Diffusion Tensor and Magnetization Transfer Imaging2017In: Journal of Parkinson's Disease, ISSN 1877-7171, E-ISSN 1877-718X, Vol. 7, no 2, p. 301-311Article in journal (Refereed)
    Abstract [en]

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

  • 332.
    Georgiopoulos, Charalampos
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Witt, Suzanne
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Haller, Sven
    Ctr Imagerie Rive Droite SA, Switzerland; Uppsala Univ, Sweden.
    Dizdar Segrell, Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology in Linköping.
    Zachrisson, Helene
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Larsson, Elna-Marie
    Uppsala Univ, Sweden.
    A study of neural activity and functional connectivity within the olfactory brain network in Parkinsons disease2019In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 23, article id UNSP 101946Article in journal (Refereed)
    Abstract [en]

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

  • 333.
    Georgiopoulos, Charalampos
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Witt, Suzanne Tyson
    Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Haller, Sven
    Affidea CDRC Ctr Diagnost Radiol Carouge SA, Switzerland; Uppsala Univ, Sweden.
    Dizdar Segrell, Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Zachrisson, Helene
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Larsson, Elna-Marie
    Uppsala Univ, Sweden.
    Olfactory fMRI: Implications of Stimulation Length and Repetition Time2018In: Chemical Senses, ISSN 0379-864X, E-ISSN 1464-3553, Vol. 43, no 6, p. 389-398Article in journal (Refereed)
    Abstract [en]

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

  • 334.
    Gerdin, Linda
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Department of Surgery, Höglandssjukhuset, Eksjö, Sweden.
    Eriksson, Anders S.
    Sahlgrens University Hospital, Sweden.
    Olaison, Gunnar
    Northern Hospital Zeeland, Denmark.
    Sjödahl, Rune
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Faculty of Medicine and Health Sciences.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Myrelid, Pär
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    The Swedish Crohn Trial: A Prematurely Terminated Randomized Controlled Trial of Thiopurines or Open Surgery for Primary Treatment of Ileocaecal Crohns Disease2016In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, no 1, p. 50-54Article in journal (Refereed)
    Abstract [en]

    Background and aims: The importance of efficient and safe treatment of Crohns disease is highlighted by its chronicity. Both medical and surgical treatments have shown good results in the symptomatic control of limited ileocaecal Crohns disease. The aim of this study was to compare medical treatment with surgical treatment of ileocaecal Crohns disease. Methods: Thirty-six patients from seven hospitals with primary ileocaecal Crohns disease were randomized to either medical or surgical treatment. The medical treatment was induction of remission with budesonide and thereafter maintenance treatment with azathioprine. The surgical treatment was open ileocaecal resection. Crohns disease activity index over time, expressed as area under the curve at 1, 3 and 5 years, was the primary endpoint. Subjective health measured with the 36-item Short Form Survey Instrument (SF36) and a visual analogue scale (VAS) were secondary endpoints. Results: There were no differences between the treatment groups in Crohns disease activity index over time. General health, measured as SF36 score, was higher in patients receiving surgical treatment than in those receiving medical treatment at 1 year, but there was no corresponding difference in VAS. Due to the slow inclusion rate and changes in clinical practice, the study was t = erminated prematurely. Conclusion: The study ended up being underpowered and should be interpreted with caution, but there was no clinically significant difference between the two treatment arms. Further studies are needed to address this important clinical question.

  • 335.
    Ghafouri, Bijar
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Microdialysis in Profiling Cytokines and Other Macromolecules in the Skin in Health and Disease: A Comment to Falcone et al.2017In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 97, no 10, p. 1269-1269Article in journal (Other academic)
    Abstract [en]

    n/a

  • 336.
    Ghafouri, Bijar
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Carlsson, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Holmberg, Sara
    Department Research and Dev, Sweden.
    Thelin, Anders
    Uppsala University, Sweden.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Biomarkers of lsystemic inflammation in farmers with musculoskeletal disorders; a plasma proteomic study2016In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 17, no 206Article in journal (Refereed)
    Abstract [en]

    Background: Farmers have an increased risk for musculoskeletal disorders (MSD) such as osteoarthritis of the hip, low back pain, and neck and upper limb complaints. The underlying mechanisms are not fully understood. Workrelated exposures and inflammatory responses might be involved. Our objective was to identify plasma proteins that differentiated farmers with MSD from rural referents. Methods: Plasma samples from 13 farmers with MSD and rural referents were included in the investigation. Gel based proteomics was used for protein analysis and proteins that differed significantly between the groups were identified by mass spectrometry. Results: In total, 15 proteins differed significantly between the groups. The levels of leucine-rich alpha-2-glycoprotein, haptoglobin, complement factor B, serotransferrin, one isoform of kininogen, one isoform of alpha-1-antitrypsin, and two isoforms of hemopexin were higher in farmers with MSD than in referents. On the other hand, the levels of alpha-2-HS-glycoprotein, alpha-1B-glycoprotein, vitamin D-binding protein, apolipoprotein A1, antithrombin, one isoform of kininogen, and one isoform of alpha-1-antitrypsin were lower in farmers than in referents. Many of the identified proteins are known to be involved in inflammation. Conclusions: Farmers with MSD had altered plasma levels of protein biomarkers compared to the referents, indicating that farmers with MSD may be subject to a more systemic inflammation. It is possible that the identified differences of proteins may give clues to the biochemical changes occurring during the development and progression of MSD in farmers, and that one or several of these protein biomarkers might eventually be used to identify and prevent work-related MSD.

  • 337.
    Gharehbaghi, Arash
    et al.
    Malardalen University, Sweden.
    Ask, Per
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, Faculty of Science & Engineering.
    Nylander, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Janerot-Sjoberg, Birgitta
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden; KTH Royal Institute Technology, Sweden.
    Ekman, Inger
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Linden, Maria
    Malardalen University, Sweden.
    Babic, Ankica
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. University of Bergen, Norway.
    A Hybrid Model for Diagnosing Sever Aortic Stenosis in Asymptomatic Patients using Phonocardiogram2015In: WORLD CONGRESS ON MEDICAL PHYSICS AND BIOMEDICAL ENGINEERING, 2015, VOLS 1 AND 2, Springer, 2015, Vol. 51, p. 1006-1009Conference paper (Refereed)
    Abstract [en]

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

  • 338.
    Gharehbaghi, Arash
    et al.
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, Faculty of Science & Engineering.
    Ekman, Inger
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Ask, Per
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, Faculty of Science & Engineering.
    Nylander, Eva
    Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Janerot-Sjoberg, Birgitta
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden; Karolinska University Hospital, Sweden; KTH Royal Institute Technology, Sweden.
    Letter: Assessment of aortic valve stenosis severity using intelligent phonocardiography2015In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 198, p. 58-60Article in journal (Other academic)
    Abstract [en]

    n/a

  • 339.
    Gijsberts, Crystel M.
    et al.
    ICIN Netherlands Heart Institute, Netherlands; University of Medical Centre Utrecht, Netherlands.
    Benson, Lina
    Karolinska Institute, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Sim, David
    Singhealth, Singapore.
    Yeo, Daniel P. S.
    Tan Tock Seng Hospital, Singapore.
    Yee Ong, Hean
    Khoo Teck Puat Hospital, Singapore.
    Jaufeerally, Fazlur
    Singapore Gen Hospital, Singapore; Duke NUS, Singapore.
    Leong, Gerard K. T.
    Changi Gen Hospital, Singapore.
    Ling, Lieng H.
    National University of Singapore, Singapore; National University of Health Syst, Singapore.
    Mark Richards, A.
    National University of Singapore, Singapore; National University of Health Syst, Singapore; National University of Singapore, Singapore; University of Otago, New Zealand.
    de Kleijn, Dominique P. V.
    ICIN Netherlands Heart Institute, Netherlands; University of Medical Centre Utrecht, Netherlands; National University of Singapore, Singapore; National University of Singapore, Singapore.
    Lund, Lars H.
    Karolinska Institute, Sweden; Karolinska Institute, Sweden.
    Lam, Carolyn S. P.
    Singhealth, Singapore; National University of Singapore, Singapore; National University of Singapore, Singapore.
    Ethnic differences in the association of QRS duration with ejection fraction and outcome in heart failure2016In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 102, no 18, p. 1464-1471Article in journal (Refereed)
    Abstract [en]

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

  • 340.
    Gilljam, Thomas
    et al.
    University of Gothenburg, Sweden.
    Haugaa, Kristina H.
    Oslo University Hospital, Norway; University of Oslo, Norway.
    Jensen, Henrik K.
    Aarhus University, Denmark; Aarhus University, Denmark.
    Svensson, Anneli
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Bundgaard, Henning
    University of Copenhagen, Denmark.
    Hansen, Jim
    University of Copenhagen, Denmark.
    Dellgren, Goran
    University of Gothenburg, Sweden.
    Gustafsson, Finn
    University of Copenhagen, Denmark.
    Eiskjaer, Hans
    Aarhus University, Denmark; Aarhus University, Denmark.
    Andreassen, Arne K.
    Oslo University Hospital, Norway.
    Sjogren, Johan
    Lund University, Sweden.
    Edvardsen, Thor
    Oslo University Hospital, Norway; University of Oslo, Norway.
    Holst, Anders G.
    University of Copenhagen, Denmark.
    Hastrup Svendsen, Jesper
    University of Copenhagen, Denmark.
    Platonov, Pyotr G.
    Lund University, Sweden; Skåne University Hospital, Sweden.
    Heart transplantation in arrhythmogenic right ventricular cardiomyopathy - Experience from the Nordic ARVC Registry2018In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 250, p. 201-206Article in journal (Refereed)
    Abstract [en]

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

  • 341.
    Glasin, Joakim
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Henricson, Joakim
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Linköping University, Faculty of Medicine and Health Sciences.
    Lindberg, Lars-Göran
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Björk Wilhelms, Daniel
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Wireless vitals: Proof of concept for wireless patient monitoring in an emergency department setting2019In: Journal of Biophotonics, ISSN 1864-063X, E-ISSN 1864-0648, Vol. 12, no 4, article id e201800275Article in journal (Refereed)
    Abstract [en]

    Vital sign assessment is a common task in emergency medicine, but resources for continuous monitoring are restricted, data is often recorded manually, and entangled wires cause frustration. Therefore, we designed a small, wireless photoplethysmographic device capable of continuously assessing pulse, respiratory frequency and oxygen saturation on the sternum and tested the performance and feasibility in an emergency department setting. Fifty (56.3 20.2 years), consenting emergency patients (29 male) were recruited. Heart rate, respiratory rate and oxygen saturation were recorded simultaneously using the device and standard monitoring equipment. Data was compared using Bland-Altman plotting (heart rate, respiratory rate) and mean difference (oxygen saturation). The bias for heart- and respiratory rate was 0.4 (limits of agreements -11.3, 12.2 and -6.1, 7.0). Mean difference for oxygen saturation was -0.21 +/- 2.35%. This may be the first wireless device to use photoplethysmography on the sternum for vital sign assessment. We noted good agreement with standard monitors, but lack of standardization in data processing between monitoring systems may limit the generalizability of these findings. Although further improvements are needed, the feasibility of this approach provides proof of concept for a new paradigm of large scale, wireless patient monitoring.

  • 342.
    Goetze, Jens P.
    et al.
    University of Copenhagen, Denmark; Aarhus University, Denmark.
    Rehfeld, Jens F.
    University of Copenhagen, Denmark.
    Alehagen, Urban
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Cholecystokinin in plasma predicts cardiovascular mortality in elderly females2016In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 209, p. 37-41Article in journal (Refereed)
    Abstract [en]

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

  • 343.
    Gonon, Adrian
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Richter, Arina
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Cederholm, Ingemar
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Khan, Jehangir
    Karolinska Univ Hosp, Sweden.
    Novak, Jacek
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Milovanovic, Micha
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Janerot-Sjoberg, Birgitta
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; Karolinska Univ Hosp, Sweden.
    Effects of thoracic epidural analgesia on exercise-induced myocardial ischaemia in refractory angina pectoris2019In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 63, no 4, p. 515-522Article in journal (Refereed)
    Abstract [en]

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

  • 344.
    Good, Elin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    de Muinck, Ebo
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Editorial Material: Targeting systemic inflammation in atherosclerosis: Who will benefit? in EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY, vol 25, issue 9, pp 921-9222018In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 25, no 9, p. 921-922Article in journal (Other academic)
    Abstract [en]

    n/a

  • 345.
    Good, Elin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Wilhelm, Elisabeth
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Perk, Joep
    3Department of Health and Caring Sciences, Linnaeus University, Sweden.
    Jaarsma, Tiny
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    de Muinck, Ebo
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    High-grade carotid artery stenosis: A forgotten area in cardiovascular risk management2016In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, no 13, p. 1453-1460Article in journal (Refereed)
    Abstract [en]

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

    DESIGN: Cross-sectional retrospective study.

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

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

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

  • 346.
    Gotberg, M.
    et al.
    Lund University, Sweden.
    Christiansen, E. H.
    Aarhus University Hospital, Denmark.
    Gudmundsdottir, I. J.
    Reykjavik University Hospital, Iceland.
    Sandhall, L.
    Helsingborg Hospital, Sweden.
    Danielewicz, M.
    Karlstad Hospital, Sweden.
    Jakobsen, L.
    Aarhus University Hospital, Denmark.
    Olsson, S. -E.
    Helsingborg Hospital, Sweden.
    Ohagen, P.
    Uppsala University, Sweden.
    Olsson, H.
    Karlstad Hospital, Sweden.
    Omerovic, E.
    Sahlgrenska University, Sweden.
    Calais, F.
    Örebro University, Sweden.
    Lindroos, P.
    St Goran Hospital, Sweden.
    Maeng, M.
    Aarhus University Hospital, Denmark.
    Todt, T.
    Lund University, Sweden.
    Venetsanos, Dimitrios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    James, S. K.
    Uppsala University, Sweden.
    Karegren, A.
    Västmanland Hospital Västerås, Sweden.
    Nilsson, M.
    Lund University, Sweden.
    Carlsson, J.
    Kalmar County Hospital, Sweden; Linnaeus University, Sweden.
    Hauer, D.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Jensen, J.
    Karolinska Institute, Sweden; Capio St Gorans Sjukhus, Sweden; Sundsvall Hospital, Sweden.
    Karlsson, A. -C.
    Halmstad County Hospital, Sweden.
    Panayi, G.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Erlinge, D.
    Lund University, Sweden.
    Frobert, O.
    Örebro University, Sweden.
    Instantaneous Wave-free Ratio versus Fractional Flow Reserve to Guide PCI2017In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 376, no 19, p. 1813-1823Article in journal (Refereed)
    Abstract [en]

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

  • 347.
    Graff, Pal
    et al.
    Orebro Univ, Sweden; Natl Inst Occupat Hlth STAMI, Norway.
    Bryngelsson, Ing-Liss
    Orebro Univ, Sweden.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Flodin, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Adult onset asthma in non-allergic women working in dampness damaged buildings: A retrospective cohort study2019In: American Journal of Industrial Medicine, ISSN 0271-3586, E-ISSN 1097-0274, Vol. 62, no 4, p. 357-363Article in journal (Refereed)
    Abstract [en]

    Background There is still no consensus about the association between working in dampness-damaged buildings and new onset of asthma among adults. The purpose of this study was to assess asthma in the staff of two psychiatric clinics where some premises were suffering from dampness. Methods A 20-year retrospective cohort study was performed using questionnaires. Results Incidence rate ratios (IRR) for asthma were non-significantly elevated (IRR = 2.3) among exposed individuals. The risk was greater among females (IRR = 3.5, 95% CI 1.0-16). IRR for non-atopic women was 8.8 (95% CI 1.4-196). Adjusting for smoking habits weakened the risks marginally (IRR = 7.3, 95% CI 1.1-167). The number of male participants was too low to draw conclusion regarding the risk for men. Conclusion The results suggest that working in dampness-damaged buildings might be a possible health hazard. This finding is most pronounced in non-atopic females.

  • 348.
    Graff, Pål
    et al.
    Örebro University, Örebro , Sweden.
    Ståhlbom, Bengt
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center. Linköping University, Faculty of Medicine and Health Sciences.
    Nordenberg, Eva
    Siemens Industrial Turbomachinery, Finspång, Sweden.
    Graichen, Andreas
    Siemens Industrial Turbomachinery, Finspång, Sweden.
    Johansson, Pontus
    Siemens Industrial Turbomachinery, Finspång, Sweden.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center. Linköping University, Faculty of Medicine and Health Sciences.
    Evaluating Measuring Techniques for Occupational Exposure during Additive Manufacturing of Metals: A Pilot Study2017In: Journal of Industrial Ecology, ISSN 1088-1980, E-ISSN 1530-9290, Vol. 21, p. 120-129Article in journal (Refereed)
    Abstract [en]

    Additive manufacturing that creates three-dimensional objects by adding layer uponlayer of material is a new technique that has proven to be an excellent tool for themanufacturing of complex structures for a variety of industrial sectors. Today, knowl-edge regarding particle emissions and potential exposure-related health hazards forthe operators is limited. The current study has focused on particle numbers, masses,sizes, and identities present in the air during additive manufacturing of metals. Mea-surements were performed during manufacturing with metal powder consisting es-sentially of chromium, nickel, and cobalt. Instruments used were Nanotracer (10 to300 nanometers [nm]), Lighthouse (300 nm to 10 micrometers), and traditional filter-basedparticle mass estimation followed by inductively coupled plasma mass spectrometry. Resultsshowed that there is a risk of particle exposure at certain operations and that particle sizestended to be smaller in recycled metal powder compared to new. In summary, nanosizedparticles were present in the additive manufacturing environment and the operators wereexposed specifically while handling the metal powder. For the workers’ safety, improvedpowder handling systems and measurement techniques for nanosized particles will possiblyhave to be developed and then translated into work environment regulations. Until then,relevant protective equipment and regular metal analyses of urine is recommended

  • 349.
    Grams, Morgan E
    et al.
    Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
    Sang, Yingying
    Departments of Epidemiology, Baltimore, Maryland, USA.
    Coresh, Josef
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
    Ballew, Shoshana H
    Departments of Epidemiology, Baltimore, Maryland, USA.
    Matsushita, Kunihiro
    Departments of Epidemiology, Baltimore, Maryland, USA.
    Levey, Andrew S
    Departments of Epidemiology, Baltimore, Maryland, USA.
    Greene, Tom H
    5Division of Clinical Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah, USA.
    Molnar, Miklos Z
    6Division of Nephrology, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
    Szabó, Zoltán
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Kalantar-Zadeh, Kamyar
    University of California Irvine Medical Center, Irvine, California, USA.
    Kovesdy, Csaba P
    University of Tennessee Health Science Center, Memphis, Tennessee, USA.
    Candidate Surrogate End Points for ESRD after AKI2016In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 27, no 9, p. 2851-2859Article in journal (Refereed)
    Abstract [en]

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

  • 350.
    Grams, Morgan E
    et al.
    Johns Hopkins University School of Medicine, Baltimore, MD.
    Sang, Yingying
    Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
    Coresh, Josef
    Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
    Ballew, Shoshana
    Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
    Matsushita, Kunihiro
    Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
    Molnar, Miklos Z
    Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
    Szabó, Zoltán
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Kalantar-Zadeh, Kamyar
    Harold Simmons Center for Chronic Disease Research & Epidemiology, University of California Irvine Medical Center, Irvine.
    Kovesdy, Csaba P
    Nephrology Section, Memphis Veterans Affairs Medical Center, Memphis, TN.
    Acute Kidney Injury After Major Surgery: A Retrospective Analysis of Veterans Health Administration Data.2016In: American Journal of Kidney Diseases, ISSN 0272-6386, E-ISSN 1523-6838, Vol. 67, no 6, p. 872-880Article in journal (Refereed)
    Abstract [en]

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

    STUDY DESIGN: Observational cohort study.

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

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

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

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

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

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

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