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  • 101.
    Berg, Jenny
    et al.
    Karolinska Institute, Sweden; OptumInsight, Sweden.
    Lindgren, Peter
    Karolinska Institute, Sweden; IVBAR, Sweden.
    Mejhert, Marit
    Ersta Hospital, Sweden; Karolinska Institute, Sweden.
    Edner, Magnus
    Karolinska University Hospital, 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.
    Kahan, Thomas
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Determinants of Utility Based on the EuroQol Five-Dimensional Questionnaire in Patients with Chronic Heart Failure and Their Change Over Time: Results from the Swedish Heart Failure Registry2015In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 18, no 4, p. 439-448Article in journal (Refereed)
    Abstract [en]

    Background: There is limited information on drivers of utilities in patients with chronic heart failure (CHF). Objectives: To analyze determinants of utility in CHF and drivers of change over 1 year in a large sample from clinical practice. Methods: We included 5334 patients from the Swedish Heart Failure Registry with EuroQol five-dimensional questionnaire information available following inpatient or outpatient care during 2008 to 2010; 3495 had 1-year follow-up data Utilities based on Swedish and UK value sets were derived. We applied ordinary least squares (OLS) and two-part models for utility at inclusion and OLS regression for change over 1 year, all with robust standard errors. We assessed the predictive accuracy of both models using cross-validation. Results: Patients mean age was 73 years, 65% were men, 19% had a left ventricular ejection fraction of 50% or more, 23% had 40% to 49%, 27% had 30% to 39%, and 31% had less than 30%. For both models and value sets, utility at inclusion was affected by sex, age, New York Heart Association class, ejection fraction, hemoglobin, blood pressure, lung disease, diabetes, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, nitrates, antiplatelets, and diuretics. The OLS model performed slightly better than did the two-part model on a population level and for capturing utility ranges. Change in utility over 1 year was influenced by age, sex, and (measured at inclusion) disease duration, New York Heart Association class, blood pressure, ischemic heart disease, lung disease, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and antiplatelets. Conclusions: Utilities in CHF and their change over time are influenced by diverse demographic and clinical factors. Our findings can be used to target clinical interventions and for economic evaluations of new therapies.

  • 102.
    Berg, Sören
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Akut handläggning av svår sepsis och septisk chock2013In: Sepsis på akuten & IVA: diagnostik och antibiotikaterapi / [ed] Håkan Hanberger, Linköping: Linköpings universitet , 2013, 2, p. 14-25Chapter in book (Other academic)
  • 103.
    Berglund, Elisabeth
    et al.
    Umeå University, Sweden.
    Johansson, Bengt
    Umeå University, Sweden.
    Dellborg, Mikael
    University of Gothenburg, Sweden.
    Sörensson, Peder
    Karolinska Institute, Sweden.
    Christersson, Christina
    Uppsala University, Sweden.
    Nielsen, Niels Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Rinnstrom, Daniel
    Umeå University, Sweden.
    Thilen, Ulf
    Lund University, Sweden; Skåne University Hospital, Sweden.
    High incidence of infective endocarditis in adults with congenital ventricular septal defect2016In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 102, no 22, p. 1835-+Article in journal (Refereed)
    Abstract [en]

    Objective Ventricular septal defects (VSDs), if haemodynamically important, are closed whereas small shunts are left without intervention. The long-term prognosis in congenital VSD is good but patients are still at risk for long-term complications. The aim of this study was to clarify the incidence of infective endocarditis (IE) in adults with VSD. Methods The Swedish registry for congenital heart disease (SWEDCON) was searched for adults with VSD. 779 patients were identified, 531 with small shunts and 248 who had the VSD previously closed. The National Patient Register was then searched for hospitalisations due to IE in adults during a 10-year period. Results Sixteen (2%) patients were treated for IE, 6 men and 10 women, with a mean age of 46.3 +/- 12.2 years. The incidence of IE was 1.7-2.7/1000 years in patients without previous intervention, 20-30 times the risk in the general population. Thirteen had small shunts without previous intervention. There was no mortality in these 13 cases. Two patients had undergone repair of their VSD and also aortic valve replacement before the episode of endocarditis and a third patient with repaired VSD had a bicuspid aortic valve, all of these three patients needed reoperation because of their IE and one patient died. No patient with isolated and operated VSD was diagnosed with IE. Conclusions A small unoperated VSD in adults carries a substantially increased risk of IE but is associated with a low risk of mortality.

  • 104.
    Berglund, Ulf
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, 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 Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Abciximab bolus with optional infusion in intervention for ST-elevation myocardial infarction2013In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 47, no 4, p. 230-235Article in journal (Refereed)
    Abstract [en]

    Objectives. The standard abciximab regimen is a bolus dose followed by a 12-h infusion. Whether the bolus dose alone is sufficient for ST-elevation myocardial infarction patients receiving a high loading dose of clopidogrel is unknown. Design. In an observational study, 693 consecutive patients were treated with abciximab during percutaneous coronary intervention for ST-elevation myocardial infarction. Totally 354 patients received standard strategy of abciximab bolus and infusion followed by 339 patients that recieved abciximab bolus only (271 patients) or bolus and infusion if suboptimal result (68 patients) in combination with a higher loading dose of clopidogrel (600 mg) the modified strategy. Results. The two groups were similar regarding baseline characteristics and in hospital bleeding events. At 30 days, the composite of death, re-infarction or target vessel revascularization was 9.1% in the standard and 7.5% in the modified strategy (p = 0.45). The rate of stent thrombosis was lower in the modified strategy group with 0% and 2.3% in the standard group (pandlt;0.001) and the mean total medical cost was lower in the modified strategy group with 8032 and 8665 in the standard group (pandlt;0.001). Conclusions. In primary percutaneous coronary intervention with a loading dose of 600 mg clopidogrel, it seems safe and cost-saving to give abciximab bolus with optional infusion.

  • 105.
    Bergqvist, D
    et al.
    Uppsala University Hospital.
    Bjorck, M
    Uppsala University Hospital.
    Lundgren, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Troeng, T
    Blekinge Hospital.
    Invasive treatment for renovascular disease. A twenty year experience from a population based registry2008In: JOURNAL OF CARDIOVASCULAR SURGERY, ISSN 0021-9509, Vol. 49, no 5, p. 559-563Article in journal (Refereed)
    Abstract [en]

    Aim. To analyze time trends in invasive treatment of renovascular disease in one country.

    Method Data have been analyzed from registrations in the Swedish Vascular Registry.

    Results. Invasive treatment for renovascular disease contributes around 1% of all vascular surgery within the Swedish Vascular Registry. Over the twenty-year period 1987-2006 the population-based frequency of invasive treatment for renovascular disease has increased; 1597 procedures have been registered with an increase over time. The age of the treated patients has increased over the period (P<0.001). There has been a shift from open to endovascular procedure and from isolated percutaneous transluminal. renal angioplasty (PTRA) to PTRA combined with a stent. Complications and mortality are significantly higher in patients undergoing open reconstruction (P<0.01). One year follow-up is incomplete and long-term results are therefore not possible to evaluate through registry-data only.

    Conclusion Using nation-wide registry data it is possible to analyze time-trends also concerning rare diseases or interventions. The changing pattern toward endovascular treatment of renovascular disease is obvious. Follow-up data at one year are incomplete.

  • 106.
    Bergström, Ida
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Pro- and anti-inflammatory actions in coronary artery disease: with focus on CD56+ T cells and Annexin A12015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    ¨The atherosclerotic process is considered to be driven by an imbalance between proand anti-inflammatory actions. Still, the inflammatory state in patients with coronary artery disease (CAD) remains to be clarified. Annexin A1 (AnxA1) is a glucocorticoidinduced protein which may have a key role in the anti-inflammatory response as a mediator of glucocorticoid effects.

    The general aim of this thesis was to deepen the knowledge of pro- and antiinflammatory mechanisms in CAD via phenotypic assessments of immune cell subsets, in particular CD56+ T cells, and exploration of AnxA1. The long-term goal is to reveal basic mechanisms that will lead to the development of biomarkers, which may be used for individualized treatment and monitoring.

    The AnxA1 protein was constitutively expressed in both neutrophils and peripheral blood mononuclear cells (PBMCs). However, it varied considerably across PBMC subsets, being most abundantly expressed in monocytes. The AnxA1 expression was also higher in CD56+ T cells than in CD56- T cells.

    The expression of total AnxA1 protein in neutrophils was higher in patients with stable angina (SA) compared with controls. However, this was not accompanied by altered neutrophil activation status. Instead, the neutrophils from patients exhibited an enhanced anti-inflammatory response to exogenous AnxA1, emphasizing the potential of AnxA1 as an inhibitor of neutrophil activity. Only patients with acute coronary syndrome (ACS) showed an increase in cell surface-associated AnxA1.

    CAD patients, independent of clinical presentation, had increased proportions of CD56+ T cells compared with controls, a phenomenon likely to represent immunological aging. The CD56+ T cells were found to exhibit a distinct proinflammatory phenotype compared with CD56- T cells. In all T cell subsets, the expression of cell surface-associated AnxA1 was significantly increased in ACS patients, while it tended to be increased in post-ACS patients. In addition, dexamethasone clearly inhibited activation of CD56+ T cells in in vitro assays, whereas AnxA1 did not. The findings highlight the need to clarify whether the role of AnxA1 is different in T cells than in innate immune cells.

    In PBMCs, the mRNA levels of AnxA1 were increased in CAD patients, particularly in ACS patients. Correspondingly, the monocytes in ACS patients exhibited increased AnxA1 protein levels, both totally and on the cell surface. However, only cell surface-associated AnxA1 in monocytes correlated with the glucocorticoid sensitivity of PBMCs ex vivo. We propose the expression of cell surfaceassociated AnxA1 to be a promising candidate marker of glucocorticoid sensitivity, which needs further investigations in larger cohorts and intervention trials. Furthermore, the fact that PBMCs in post-ACS patients exhibited pro-inflammatory activity but no increase in cell surface-associated AnxA1 allow us to speculate that the glucocorticoid action and/or availability might be insufficient in these patients.

    List of papers
    1. Enhanced Neutrophil Expression of Annexin-1 in Coronary Artery Disease
    Open this publication in new window or tab >>Enhanced Neutrophil Expression of Annexin-1 in Coronary Artery Disease
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    2010 (English)In: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 59, no 3, p. 443-440Article in journal (Refereed) Published
    Abstract [en]

    Background: A dysregulated cortisol response in patients with stable coronary artery disease (CAD) is related to systemic inflammatory activity. Moreover, a dysfunctional activation status of neutrophils in CAD has been discussed. The anti-inflammatory actions of glucocorticoids are mediated by annexin-1 (ANXA1), a protein mainly expressed by innate immune cells. An altered expression of glucocorticoid receptors (GR) and ANXA1 has been associated with glucocorticoid resistance.

    Methods and Results: Salivary cortisol levels were measured in the morning and evening during 3 consecutive days in 30 CAD patients and 30 healthy individuals. The neutrophil expression of GR and ANXA1 was determined by flow cytometry. The effect of exogenous ANXA1 was determined in neutrophil stimulation assays. The patients showed a flattened diurnal cortisol pattern compared to healthy subjects, involving higher levels in the evening. The neutrophil expression of GRtotal and GRα, as well as the ratio of GRα:GRβ expression was significantly decreased in patients, whereas the GRβ expression did not differ compared to controls. The neutrophil expression of ANXA1 was significantly increased in patients. Ex vivo, ANXA1 suppressed LTB4-induced ROS production in neutrophils from patients, but not from controls. On the other hand, ANXA1 impaired the LTB4-induced up-regulation of β2-integrins in both patients and controls.

    Conclusion: CAD patients displayed a more flattened diurnal cortisol rhythm caused by higher cortisol levels in the evening compared to healthy subjects. Our findings indicate a chronic overactivation of the hypothalamic-pituitary-adrenal (HPA) axis but give no conclusive evidence for glucocorticoid resistance, as assessed by the neutrophil expression of GR and ANXA1. The data rather point towards an increased anti-inflammatory potential in neutrophils from patients with stable CAD.

    Keywords
    Coronary artery disease, cortisol, neutrophil, glucocorticoid receptor, annexin-1
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-17247 (URN)10.1016/j.metabol.2009.07.044 (DOI)000276761800021 ()
    Note
    Original Publication: Eva Särndahl, Ida Bergström, Johnny Nijm, Tony Forslund, Mauro Perretti and Lena Jonasson, Enhanced Neutrophil Expression of Annexin-1 in Coronary Artery Disease, 2010, Metabolism: Clinical and Experimental, (59), 3, 443-440. http://dx.doi.org/10.1016/j.metabol.2009.07.044 Copyright: Elsevier Science B.V., Amsterdam http://www.elsevier.com/ Available from: 2009-03-12 Created: 2009-03-12 Last updated: 2017-12-13
    2. Persistent accumulation of interferon-gamma-producing CD8(+)CD56(+) T cells in blood from patients with coronary artery disease
    Open this publication in new window or tab >>Persistent accumulation of interferon-gamma-producing CD8(+)CD56(+) T cells in blood from patients with coronary artery disease
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    2012 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 224, no 2, p. 515-520Article in journal (Refereed) Published
    Abstract [en]

    Objective: There is emerging evidence for CD8(+) T cell alterations in blood from patients with coronary artery disease (CAD). We examined whether the distribution and phenotype of CD8(+)CD56(+) T cells differed according to the clinical manifestation of CAD. less thanbrgreater than less thanbrgreater thanMethods: Patients with acute coronary syndrome (ACS, n = 30), stable angina (SA, n = 34) and controls (n = 36) were included. Blood was collected before and up to 12 months after referral for coronary investigation. CD8(+)CD56(+) T cells were assessed by flow cytometry for expression of surface markers, apoptosis, and intracellular expression of cytokines. less thanbrgreater than less thanbrgreater thanResults: The proportions of CD8(+)CD56(+) T cells were significantly higher in both ACS and SA patients compared with controls, and remained so after 3 and 12 months. This was independent of age, sex, systemic inflammation and cytomegalovirus seropositivity. CD8(+)CD56(+) T cells differed from CD8(+)CD56(-) T cells in terms of lower CD28 expression and fewer apoptotic cells. Both CD8(+) T cell subsets were positive for interferon (IFN)-gamma and tumor necrosis factor, although IFN-gamma was significantly more confined to the CD8(+)CD56(+) T cells. less thanbrgreater than less thanbrgreater thanConclusion: The persistent accumulation of CD8(+)CD56(+) T cells in ACS and SA patients share several features with immunological aging. It also contributes to a larger IFN-gamma(+) pool in blood, and may thereby hypothetically drive the atherosclerotic process in a less favorable direction.

    Place, publisher, year, edition, pages
    Elsevier, 2012
    Keywords
    Acute coronary syndrome, Coronary artery disease, Cytokines, Immune system, Leukocytes
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-84895 (URN)10.1016/j.atherosclerosis.2012.07.033 (DOI)000309261400039 ()
    Note

    Funding Agencies|Swedish Research Council||Swedish Heart-Lung Foundation||County Council of Ostergotland, Sweden||Eleanora Demeroutis Foundation, Linkoping, Sweden||Heart Foundation at Linkoping University, Linkoping, Sweden||

    Available from: 2012-10-26 Created: 2012-10-26 Last updated: 2017-12-07
    3. Higher expression of annexin A1 in 1 CD56+ than in CD56-T cells: Potential implications for coronary artery disease
    Open this publication in new window or tab >>Higher expression of annexin A1 in 1 CD56+ than in CD56-T cells: Potential implications for coronary artery disease
    Show others...
    2014 (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Increased proportions of circulating proinflammatory CD56+ T cells have been reported in patients with coronary artery disease (CAD). Yet, little is known about regulation of these cells. In the present study, we investigated the expression and potential role of the glucocorticoid-mediated protein annexin A1 (AnxA1) in CD56+ and CD56-T cell subsets, with focus on CAD.

    Methods and Results: We included totally 52 healthy individuals, 28 patients with acute coronary syndrome (ACS) and 57 patients with a history of ACS. AnxA1 mRNA expression was assessed in peripheral blood mononuclear cells. AnxA1 protein expression (total and cell surface-associated) was measured by whole blood flow cytometry in circulating CD56+ and CD56- T cell subsets. Furthermore, inhibitory effects of dexamethasone and/or recombinant AnxA1 on cytokine secretion by CD56+ and CD56- T cells were explored in vitro. We found that CD56+ T cells (the majority CD8+), expressed higher levels of AnxA1 mRNA and protein than did CD56- T cells. When comparing CAD patients with healthy controls, significantly higher levels of cell surface-associated AnxA1 expression were seen in patients, most pronounced in ACS patients. In vitro, dexamethasone reduced cytokine secretion by CD56+ T cells, whereas AnxA1 alone had no effect, and AnxA1 combined with dexamethasone abolished the dexamethasone-induced suppressive effects.

    Conclusion: AnxA1 was expressed more abundantly in proinflammatory CD56+ T cells. Patients with ACS exhibited increased levels of cell surface-associated AnxA1, thus indicating increased activation of the AnxA1 pathway. Our data further suggested that AnxA1 might counteract glucocorticoid mediated anti-inflammatory effects in T cells.

    Keywords
    Annexin A1, T cell, CD56, coronary artery disease, acute coronary syndrome
    National Category
    Cardiac and Cardiovascular Systems Cell and Molecular Biology
    Identifiers
    urn:nbn:se:liu:diva-114121 (URN)
    Available from: 2015-02-10 Created: 2015-02-10 Last updated: 2018-01-11Bibliographically approved
    4. Annexin A1 expression in blood mononuclear cells: a potential marker of glucocorticoid activity in patients with coronary artery disease
    Open this publication in new window or tab >>Annexin A1 expression in blood mononuclear cells: a potential marker of glucocorticoid activity in patients with coronary artery disease
    Show others...
    2014 (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    An imbalance between pro- and anti-inflammatory actions is believed to drive progression of atherosclerosis. Annexin A1 (AnxA1) is a key player in resolution of inflammation and a mediator of anti-inflammatory effects of glucocorticoids. Here, we investigated whether expression of AnxA1 in peripheral blood mononuclear cells (PBMCs) was altered in patients with coronary artery disease (CAD) and also related findings to glucocorticoid sensitivity ex vivo.

    We included 57 patients 6-12 months after acute coronary syndrome (ACS), 10 patients with ACS, and healthy controls. AnxA1 mRNA was measured in PBMCs and AnxA1 protein was assessed in monocytes and lymphocyte subsets by flow cytometry. In post-ACS patients and controls, glucocorticoid sensitivity was determined by measuring inhibitory effects of dexamethasone on LPS46 induced cytokine secretion.

    AnxA1 mRNA levels in PBMCs were higher in patients compared with controls, although most pronounced in ACS patients. AnxA1 protein was most abundant in the monocyte fraction. ACS patients exhibited the highest levels of cell surface-associated AnxA1 protein while levels in post-ACS patients and controls were similar. Ex vivo assays showed that PBMCs from post-ACS patients were more prone to release IL-6. Glucocorticoid sensitivity correlated with cell surface-associated AnxA1 protein in peripheral monocytes. Dexamethasone also induced upregulation of AnxA1 mRNA.

    AnxA1 expression in PBMCs is closely associated with glucocorticoid actions and cell surface associated AnxA1 appears to be a marker of glucocorticoid sensitivity. Although still speculative, a “normal” expression of cell surface-associated AnxA1 in post-ACS patients may suggest that glucocorticoid actions in vivo are insufficient to provide adequate anti-inflammatory effects in these patients.

    Keywords
    Annexin A1, monocytes, glucocorticoids, coronary artery disease, acute coronary syndrome
    National Category
    Cardiac and Cardiovascular Systems Cell and Molecular Biology
    Identifiers
    urn:nbn:se:liu:diva-114122 (URN)
    Available from: 2015-02-10 Created: 2015-02-10 Last updated: 2018-01-11Bibliographically approved
  • 107.
    Bergström, Ida
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Lundberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Jönsson, Simon
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Särndahl, Eva
    Department of Clinical Medicine, School of Health and Medical Sciences, and iRiSC - Inflammatory 18 Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Annexin A1 expression in blood mononuclear cells: a potential marker of glucocorticoid activity in patients with coronary artery disease2014Manuscript (preprint) (Other academic)
    Abstract [en]

    An imbalance between pro- and anti-inflammatory actions is believed to drive progression of atherosclerosis. Annexin A1 (AnxA1) is a key player in resolution of inflammation and a mediator of anti-inflammatory effects of glucocorticoids. Here, we investigated whether expression of AnxA1 in peripheral blood mononuclear cells (PBMCs) was altered in patients with coronary artery disease (CAD) and also related findings to glucocorticoid sensitivity ex vivo.

    We included 57 patients 6-12 months after acute coronary syndrome (ACS), 10 patients with ACS, and healthy controls. AnxA1 mRNA was measured in PBMCs and AnxA1 protein was assessed in monocytes and lymphocyte subsets by flow cytometry. In post-ACS patients and controls, glucocorticoid sensitivity was determined by measuring inhibitory effects of dexamethasone on LPS46 induced cytokine secretion.

    AnxA1 mRNA levels in PBMCs were higher in patients compared with controls, although most pronounced in ACS patients. AnxA1 protein was most abundant in the monocyte fraction. ACS patients exhibited the highest levels of cell surface-associated AnxA1 protein while levels in post-ACS patients and controls were similar. Ex vivo assays showed that PBMCs from post-ACS patients were more prone to release IL-6. Glucocorticoid sensitivity correlated with cell surface-associated AnxA1 protein in peripheral monocytes. Dexamethasone also induced upregulation of AnxA1 mRNA.

    AnxA1 expression in PBMCs is closely associated with glucocorticoid actions and cell surface associated AnxA1 appears to be a marker of glucocorticoid sensitivity. Although still speculative, a “normal” expression of cell surface-associated AnxA1 in post-ACS patients may suggest that glucocorticoid actions in vivo are insufficient to provide adequate anti-inflammatory effects in these patients.

  • 108.
    Bergström, Ida
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Lundberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Jönsson, Simon
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Sarndahl, Eva
    Örebro University, Sweden.
    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.
    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.
    Annexin A1 in blood mononuclear cells from patients with coronary artery disease: Its association with inflammatory status and glucocorticoid sensitivity2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 3, article id e0174177Article in journal (Refereed)
    Abstract [en]

    Annexin A1 (AnxA1) is a key player in resolution of inflammation and a mediator of glucocorticoid actions. In atherosclerotic tissue, increased expression of AnxA1 has been associated with protective plaque-stabilizing effects. Here, we investigated the expression of AnxA1 in peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease (CAD). Blood was collected from 57 patients with stable CAD (SCAD) and 41 healthy controls. We also included a minor group (n = 10) with acute coronary syndrome (ACS). AnxA1 mRNA was measured in PBMCs. Expression of AnxA1 protein (total and surface-bound) and glucocorticoid receptors (GR) were detected in PBMC subsets by flow cytometry. Also, salivary cortisol, interleukin(IL)-6 and IL-10 in plasma, and LPS-induced cytokine secretion from PBMCs, with or without dexamethasone, were assessed. AnxA1 mRNA was found to be slightly increased in PBMCs from SCAD patients compared with controls. However, protein expression of AnxA1 or GRs in PBMC subsets did not differ between SCAD patients and controls, despite SCAD patients showing a more proinflammatory cytokine profile ex vivo. Only surface expression of AnxA1 on monocytes correlated with dexamethasone-mediated suppression of cytokines. In ACS patients, a marked activation of AnxA1 was seen involving both gene expression and translocation of protein to cell surface probably reflecting a rapid glucocorticoid action modulating the acute inflammatory response in ACS. To conclude, surface expression of AnxA1 on monocytes may reflect the degree of glucocorticoid sensitivity. Speculatively, "normal" surface expression of AnxA1 indicates that anti-inflammatory capacity is impaired in SCAD patients.

  • 109.
    Bergström, Ida
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Lundberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Reutelingsperger, Chris
    Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Särndahl, Eva
    Department of Clinical Medicine, School of Health and Medical Sciences, and iRiSC - Inflammatory 18 Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Higher expression of annexin A1 in 1 CD56+ than in CD56-T cells: Potential implications for coronary artery disease2014Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Increased proportions of circulating proinflammatory CD56+ T cells have been reported in patients with coronary artery disease (CAD). Yet, little is known about regulation of these cells. In the present study, we investigated the expression and potential role of the glucocorticoid-mediated protein annexin A1 (AnxA1) in CD56+ and CD56-T cell subsets, with focus on CAD.

    Methods and Results: We included totally 52 healthy individuals, 28 patients with acute coronary syndrome (ACS) and 57 patients with a history of ACS. AnxA1 mRNA expression was assessed in peripheral blood mononuclear cells. AnxA1 protein expression (total and cell surface-associated) was measured by whole blood flow cytometry in circulating CD56+ and CD56- T cell subsets. Furthermore, inhibitory effects of dexamethasone and/or recombinant AnxA1 on cytokine secretion by CD56+ and CD56- T cells were explored in vitro. We found that CD56+ T cells (the majority CD8+), expressed higher levels of AnxA1 mRNA and protein than did CD56- T cells. When comparing CAD patients with healthy controls, significantly higher levels of cell surface-associated AnxA1 expression were seen in patients, most pronounced in ACS patients. In vitro, dexamethasone reduced cytokine secretion by CD56+ T cells, whereas AnxA1 alone had no effect, and AnxA1 combined with dexamethasone abolished the dexamethasone-induced suppressive effects.

    Conclusion: AnxA1 was expressed more abundantly in proinflammatory CD56+ T cells. Patients with ACS exhibited increased levels of cell surface-associated AnxA1, thus indicating increased activation of the AnxA1 pathway. Our data further suggested that AnxA1 might counteract glucocorticoid mediated anti-inflammatory effects in T cells.

  • 110.
    Bergthorsdottir, R
    et al.
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Nilsson, A G
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Gillberg, P
    Shire, Danderyd, Sweden.
    Ekman, Bertil
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Wahlberg, Jeanette
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Health-Related Quality of Life In Patients With Adrenal Insufficiency Receiving Plenadren Compared With Immediate-Release Hydrocortisone.2015In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 18, no 7, p. A616-Article in journal (Refereed)
    Abstract [en]

    Background

    Previous studies in patients with primary adrenal insufficiency (PAI) on conventional replacement therapy suggest decreased health-related quality of life (HRQoL), and that patients report more frequently fatigue, increased anxiety and inability to work compared to background population.

    Objectives

    To study self-reported health status with EQ-5D in patients with PAI. Patients treated with Plenadren (modified-release hydrocortisone) were compared with patients treated with immediate release hydrocortisone (IRHC) replacement therapy.

    Methods

    This was a cross-sectional, multi-centre, non-interventional survey of patients with PAI receiving Plenadren or immediate release hydrocortisone (IRHC) replacement.

    Subjects

    One hundred thirty-four adult patients with PAI of whom 36 (19 females [53%]) were treated with Plenadren and 98 (77 females [79%]) were treated with IRHC, were included.

    MAIN OUTCOME MEASURE

    HRQoL described by the EQ-5D, a generic preference-based measure of health.

    RESULTS

    Patients on Plenadren and on IRHC had a mean ± SD age of 53.1 ± 12.7 years and 48.0 ± 13.1 years, respectively (P=0.043). The majority of the patients were diagnosed more than 5 years ago (69%). The mean ± SD daily Plenadren and IRHC doses were 27.0 ± 6.8 mg and 26.6 ± 10.9 mg, respectively (P=0.807). 47% of the Plenadren patients had been receiving Plenadren and 82% of the IRHC patients had been receiving IRHC for more than 3 years. Patients receiving Plenadren had better HRQoL measured by the EQ-5D questionnaire compared to patients replaced with IRHC (0.76 ± 0.18 vs 0.68 ± 0.18, respectively [P=0.040]).

    CONCLUSIONS

    Replacement therapy with Plenadren in patients with PAI confers measurable benefit on HRQoL relative to IRHC as estimated by the EQ-5D questionnaire, and may therefore be advantageous when compared to IRHC substitution.

  • 111.
    Berkius, Johan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Intensive care in chronic obstructive pulmonary disease: treatment with non-invasive ventilation and long-term outcome2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality throughout the world. When we began this project our knowledge about the outcome of COPD patients admitted to the ICU in Sweden was scarce.

    Aims: To investigate the characteristics, survival and health-related quality of life (HRQL) of COPD patients admitted to Swedish ICUs. To investigate how ICU personnel decide whether to use invasive or non-invasive ventilatory treatment (NIV) of the newly admitted COPD patient in need of ventilatory support. To investigate outcome according to mode of ventilation.

    Material and methods: Detailed data, including HRQL during recovery, from COPD patients admitted to ICUs that participated in the Swedish intensive care registry were analysed. A questionnaire was distributed to personnel in 6 of the participating ICUs in order to define factors deemed important in making the choice between invasive and non-invasive ventilation immediately after admission. The answers were analysed.

    Results: The proportion of COPD patients admitted to Swedish ICUs in need of ventilatory support is 1.3-1.6 % of all admissions. The patients are around 70 years-old and are severely ill on admission, with high respiratory rates and most have life-threatening disturbances in their acid-base balance and blood gases. There are more women than men. The short- and long-term mortality is high despite intensive care treatment. The majority of patients are treated with NIV. The length of stay on the ICU is shorter when NIV is used. The choice between NIV and invasive ventilation in these patients may be irrational. It is guided by current guidelines, but other non-patient-related factors seem to influence this decision. NIV seems to be preferable to invasive ventilation at admission, not only according to short-term benefits but also to long-term survival. Failure of NIV followed by invasive ventilation does not have a poorer prognosis than directly employing invasive ventilation. The health-related quality of life of COPD patients after treatment on Swedish ICUs is lower than in the general population. However it does not decline between 6 and 24 months after ICU discharge. After 24 months the HRQL is quite similar to that of COPD patients not treated on the ICU.

    Conclusions: COPD patients in need of ventilatory support admitted to Swedish ICUs are severely ill on admission, and their short- and long-term mortality is high despite ICU care and ventilatory treatment. Non-invasive ventilation should be the first line treatment on admission. NIV has short- and long-term benefits compared to invasive ventilation, without increasing mortality risk in case of failure. After discharge from the ICU and recovery, the HRQL of COPD patients is lower than in the general population, but comparable to COPD patients not treated on the ICU.

    List of papers
    1. Characteristics and long-term outcome of acute exacerbations in chronic obstructive pulmonary disease: An analysis of cases in the Swedish Intensive Care Registry during 2002-2006
    Open this publication in new window or tab >>Characteristics and long-term outcome of acute exacerbations in chronic obstructive pulmonary disease: An analysis of cases in the Swedish Intensive Care Registry during 2002-2006
    2008 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 52, no 6, p. 759-765Article in journal (Refereed) Published
    Abstract [en]

    Background: Chronic obstructive pulmonary disease (COPD) represents a major and growing health problem. The purpose of this work was to examine characteristics, resource use and long-term survival in patients with an acute exacerbation of COPD that were admitted to Swedish intensive care units (ICU). Methods: Patient characteristics at admission, length of stay (LOS), resource use and outcome were collected for admissions due to COPD during 2002-2006 in the database of the Swedish Intensive Care Registry. Vital status was secured for 99.6% of the patients. Kaplan-Meier survival estimates were computed for index admissions only. Results: We identified 1009 patients with 1199 admissions due to COPD (1.3% of all intensive care admissions). The mean (SD) age was 70.2 (9.1) years and the proportion of women were 61.5%. Mean (SD) Acute Physiology and Chronic Health Evaluation II probability of hospital death was 0.31 (0.19). Median LOS was 28 (interquartile range 52) h. The number of readmissions was 190 during the 5-year study. Older patients had fewer readmissions (OR 0.96, 95% CI: 0.95-0.98/year increase in age). ICU mortality was 7.3% (87 of 1199 admissions) and 30-day mortality was 26.0% (262 of 1009 index admissions). Median survival was 14.5 months and 31% of patients survived 3 years after the index admission. Conclusions: Short (30 days) and long-term survival is poor in acute COPD. Readmissions are frequent reflecting the severity of this chronic illness. Patients are less likely to be readmitted with increasing age which may be due to withholding of further intensive care. © 2008 The Authors.

    Keywords
    chronic obstructive pulmonary disease; critical care; survival analysis
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-44985 (URN)10.1111/j.1399-6576.2008.01632.x (DOI)78991 (Local ID)78991 (Archive number)78991 (OAI)
    Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13Bibliographically approved
    2. Long-term survival according to ventilation mode in acute respiratory failure secondary to chronic obstructive pulmonary disease: A multicenter, inception cohort study
    Open this publication in new window or tab >>Long-term survival according to ventilation mode in acute respiratory failure secondary to chronic obstructive pulmonary disease: A multicenter, inception cohort study
    Show others...
    2010 (English)In: JOURNAL OF CRITICAL CARE, ISSN 0883-9441, Vol. 25, no 3Article in journal (Refereed) Published
    Abstract [en]

    Purpose: The aim of the study was to investigate 5-year survival stratified by mechanical ventilation modality in chronic obstructive pulmonary disease (COPD) patients treated in the ICU. Materials and Methods: Prospective, observational study of COPD patients with acute respiratory failure admitted to 9 multidisciplinary ICUs in Sweden. Characteristics on admission, including illness severity scores and the first blood gas, and survival were analyzed stratified by ventilation modality (noninvasive [NIV] vs invasive mechanical ventilation). Results: Ninety-three patients, mean age of 70.6 (SD, 9.6) years, were included. Sixteen patients were intubated immediately, whereas 77 were started on NIV. Patients who were started on NIV had a lower median body mass index (BMI) (21.9 vs 27.0; P andlt; .01) and were younger compared to those who were intubated immediately (median age, 70 vs 74.5 years; P andlt; .05). There were no differences in the initial blood gas results between the groups. Long-term survival was greater in patients with NIV (P andlt; .05, log rank). The effect of NIV on survival remained after including age, Acute Physiology and Chronic Health Evaluation II score, and BMI in a multivariate Cox regression model (NIV hazard ratio, 0.44; 95% confidence interval, 0.21-0.92). Fifteen patients with failed NIV were intubated and mechanically ventilated. Long-term survival in patients with failed NIV was not significantly different from patients who were intubated immediately. Conclusion: The short-term survival benefit of NIV previously found in randomized controlled trials still applies after 5 years of observation.

    Place, publisher, year, edition, pages
    Elsevier Science B. V., Amsterdam, 2010
    Keywords
    Intensive care, Mechanical ventilation, Noninvasive ventilation, Endotracheal intubation, Long-term outcome
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-62148 (URN)10.1016/j.jcrc.2010.02.006 (DOI)000283719800028 ()
    Available from: 2010-11-19 Created: 2010-11-19 Last updated: 2013-11-11
    3. What determines immediate use of invasive ventilation in patients with COPD?
    Open this publication in new window or tab >>What determines immediate use of invasive ventilation in patients with COPD?
    Show others...
    2013 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 57, no 3, p. 312-319Article in journal (Refereed) Published
    Abstract [en]

    Background The choice between non-invasive ventilation (NIV) and invasive ventilation in patients with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) may be irrational. The aim of this study was to examine those patient characteristics, and circumstances deemed important in the choice made between NIV and invasive ventilation in the intensive care unit (ICU). Methods We first examined 95 admissions of AECOPD patients on nine ICUs and identified variables associated with invasive ventilation. Thereafter, a questionnaire was sent to ICU personnel to study the relative importance of different factors with a possible influence on the decision to use invasive ventilation at once. Results Univariable analysis showed that increasing age [odds ratio (OR) 1.06 per year] and increasing body mass index (BMI) (OR 1.11 per kg/m2) were associated with immediate invasive ventilation, while there was no such association with arterial blood gases or breath rate. BMI was the only factor that remained associated with immediate invasive ventilation in the multivariable analysis [OR 1.12 (95% confidence interval 1.031.23) kg/m2]. Ranking of responses to the questionnaire showed that consciousness, respiratory symptoms and blood gases were powerful factors determining invasive ventilation, whereas high BMI and age were ranked low. Non-patient-related factors were also deemed important (physician in charge, presence of guidelines, ICU workload). Conclusion Factors other than those deemed most important in guidelines appear to have an inappropriate influence on the choice between NIV and immediate intubation in AECOPD in the ICU. These factors must be identified to further increase the appropriate use of NIV.

    Place, publisher, year, edition, pages
    Wiley-Blackwell, 2013
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-89802 (URN)10.1111/aas.12049 (DOI)000314652400007 ()
    Note

    Funding Agencies|Health Research Council in the southeast of Sweden (FORSS)||

    Available from: 2013-03-07 Created: 2013-03-07 Last updated: 2017-12-06
    4. A prospective longitudinal multicentre study of health related quality of life in ICU survivors with COPD
    Open this publication in new window or tab >>A prospective longitudinal multicentre study of health related quality of life in ICU survivors with COPD
    Show others...
    2013 (English)In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 17, no 5, p. R211-Article in journal (Refereed) Published
    Abstract [en]

    INTRODUCTION: Mortality amongst COPD patients treated on the ICU is high. Health-related quality of life (HRQL) after intensive care is a relevant concern for COPD patients, their families and providers of health care. Still, there are few HRQL studies after intensive care of this patient group. Our hypothesis was that HRQL of COPD patients treated on the ICU declines rapidly with time.

    METHODS: Fifty-one COPD patients (COPD-ICU group) with an ICU stay longer than 24 hours received a questionnaire at 6, 12 and 24 months after discharge from ICU. HRQL was measured using two generic instruments: the EuroQoL instrument (EQ-5D and EQ-VAS) and the Short Form 36 Health Survey (SF-36). The results were compared to HRQL of two reference groups from the general population; an age- and sex-adjusted reference population (Non-COPD reference) and a reference group with COPD (COPD reference).

    RESULTS: HRQL of the COPD-ICU group at 6 months after discharge from ICU was lower compared to the COPD reference group: Median EQ-5D was 0.66 vs. 0.73, P=0.08 and median EQ-VAS was 50 vs.55, P<0.05. There were no significant differences in the SF-36 dimensions between the COPD-ICU and COPD-reference groups, although the difference in physical functioning (PF) approached statistical significance (P=0.059). Patients in the COPD-ICU group who were lost to follow-up after 6 months had low HRQL scores at 6 months. Scores for patients who died were generally lower compared to patients who failed to respond to the questionnaire. The PF and social functioning (SF) scores in those who died were significantly lower compared to patients with a complete follow up. HRQL of patients in the COPD-ICU group that survived a complete 24 months follow up was low but stable with no statistically significant decline from 6 to 24 months after ICU discharge. Their HRQL at 24 months was not significantly different from HRQL in the COPD reference group.

    CONCLUSIONS: HRQL in COPD survivors after intensive care was low but did not decline from 6 to 24 months after discharge from ICU. Furthermore, HRQL at 24 months was similar to patients with COPD who had not received ICU treatment.

    Place, publisher, year, edition, pages
    BioMed Central, 2013
    National Category
    Clinical Medicine Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-100737 (URN)10.1186/cc13019 (DOI)000331540900132 ()24063309 (PubMedID)
    Available from: 2013-11-11 Created: 2013-11-11 Last updated: 2017-12-06Bibliographically approved
  • 112.
    Berkius, Johan
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Department of Anaesthesia and Intensive Care, Västervik County Hospital, Västervik, Sweden.
    Engerström, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping.
    Orwelius, Lotti
    Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Nordlund, Peter
    Department of Anaesthesia and Intensive Care, Ryhov Hospital, Jönköping,.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Walther, Sten M
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences.
    A prospective longitudinal multicentre study of health related quality of life in ICU survivors with COPD2013In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 17, no 5, p. R211-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Mortality amongst COPD patients treated on the ICU is high. Health-related quality of life (HRQL) after intensive care is a relevant concern for COPD patients, their families and providers of health care. Still, there are few HRQL studies after intensive care of this patient group. Our hypothesis was that HRQL of COPD patients treated on the ICU declines rapidly with time.

    METHODS: Fifty-one COPD patients (COPD-ICU group) with an ICU stay longer than 24 hours received a questionnaire at 6, 12 and 24 months after discharge from ICU. HRQL was measured using two generic instruments: the EuroQoL instrument (EQ-5D and EQ-VAS) and the Short Form 36 Health Survey (SF-36). The results were compared to HRQL of two reference groups from the general population; an age- and sex-adjusted reference population (Non-COPD reference) and a reference group with COPD (COPD reference).

    RESULTS: HRQL of the COPD-ICU group at 6 months after discharge from ICU was lower compared to the COPD reference group: Median EQ-5D was 0.66 vs. 0.73, P=0.08 and median EQ-VAS was 50 vs.55, P<0.05. There were no significant differences in the SF-36 dimensions between the COPD-ICU and COPD-reference groups, although the difference in physical functioning (PF) approached statistical significance (P=0.059). Patients in the COPD-ICU group who were lost to follow-up after 6 months had low HRQL scores at 6 months. Scores for patients who died were generally lower compared to patients who failed to respond to the questionnaire. The PF and social functioning (SF) scores in those who died were significantly lower compared to patients with a complete follow up. HRQL of patients in the COPD-ICU group that survived a complete 24 months follow up was low but stable with no statistically significant decline from 6 to 24 months after ICU discharge. Their HRQL at 24 months was not significantly different from HRQL in the COPD reference group.

    CONCLUSIONS: HRQL in COPD survivors after intensive care was low but did not decline from 6 to 24 months after discharge from ICU. Furthermore, HRQL at 24 months was similar to patients with COPD who had not received ICU treatment.

  • 113.
    Bertus Warntjes, Marcel Jan
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Blystad, Ida
    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). Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Tisell, Anders
    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). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Lundberg, Peter
    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). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Obtaining Double Inversion Recovery and Phase Sensitive Inversion Recovery Images without additional Scan Time2014Conference paper (Other academic)
  • 114.
    Beygui, Farzin
    et al.
    Caen University Hospital, France.
    Castren, Maaret
    Helsinki University Hospital and Helsinki University, Finland; Karolinska Institutet, Stockholm, Sweden.
    Brunetti, Natale Daniele
    University of Foggia, Italy.
    Rosell-Ortiz, Fernando
    Empresa Pública de Emergencias Sanitarias de Andalucía, Spain.
    Christ, Michael
    Paracelsus Medical University, Nuremberg, Germany.
    Zeymer, Uwe
    Klinikum der Stadt Ludwigshafen am Rhein gGmbH, Germany.
    Huber, Kurt
    Cardiology and Emergency Medicine, Wilhelminenhospital, Vienna, Austria.
    Folke, Fredrik
    Copenhagen University Hospital, Gentofte, Denmark.
    Svensson, Leif
    Karolinska Institutet, Solna, Sweden.
    Bueno, Hector
    Hospital 12 de Octubre, Madrid, Spain.
    Van't Hof, Arnoud
    Interventional Cardiology, Zwolle, The Netherlands.
    Nikolaou, Nikolaos
    Konstantopouleio General Hospital, Athens, Greece.
    Nibbe, Lutz
    Medizinische Klinik m.S. Intensivmedizin und Nephrologie, Berlin, Germany.
    Charpentier, Sandrine
    University Hospital of Rangueil, Toulouse, France.
    Swahn, 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 Cardiology in Linköping.
    Tubaro, Marco
    San Filippo Neri Hospital, Rome, Italy.
    Goldstein, Patrick
    Lille University Hospital, France.
    Gestione pre-ospedaliera dei pazienti con dolore toracico e/o dispnea di origine cardiaca[Pre-hospital management of patients with chest pain and/or dyspnoea of cardiac origin]2017In: Recenti progressi in medicina, ISSN 2038-1840, Vol. 108, no 1, p. 27-51Article in journal (Refereed)
    Abstract [en]

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

  • 115.
    Bilchick, Kenneth C.
    et al.
    University of Virginia Health Syst, VA USA.
    Wang, Yongfei
    Yale New Haven Medical Centre, CT 06504 USA; Yale University, CT USA.
    Cheng, Alan
    Johns Hopkins Medical Institute, MD 21205 USA.
    Curtis, Jeptha P.
    Yale New Haven Medical Centre, CT 06504 USA; Yale University, CT USA.
    Dharmarajan, Kumar
    Yale New Haven Medical Centre, CT 06504 USA; Yale University, CT USA.
    Stukenborg, George J.
    University of Virginia, VA USA.
    Shadman, Ramin
    Southern Calif Permanente Medical Grp, CA USA.
    Anand, Inder
    University of Minnesota, MN USA.
    Lund, Lars H.
    Karolinska University Hospital, 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.
    Sartipy, Ulrik
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Maggioni, Aldo
    Italian Assoc Hospital Cardiologists, Italy.
    Swedberg, Karl
    University of Gothenburg, Sweden; Imperial Coll, England.
    OConner, Chris
    Inova Healthcare Syst, VA USA.
    Levy, Wayne C.
    University of Washington, WA USA.
    Seattle Heart Failure and Proportional Risk Models Predict Benefit From Implantable Cardioverter-Defibrillators2017In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 69, no 21, p. 2606-2618Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Recent clinical trials highlight the need for better models to identify patients at higher risk of sudden death. OBJECTIVES The authors hypothesized that the Seattle Heart Failure Model (SHFM) for overall survival and the Seattle Proportional Risk Model (SPRM) for proportional risk of sudden death, including death from ventricular arrhythmias, would predict the survival benefit with an implantable cardioverter-defibrillator (ICD). METHODS Patients with primary prevention ICDs from the National Cardiovascular Data Registry (NCDR) were compared with control patients with heart failure (HF) without ICDs with respect to 5-year survival using multivariable Cox proportional hazards regression. RESULTS Among 98,846 patients with HF (87,914 with ICDs and 10,932 without ICDs), the SHFM was strongly associated with all-cause mortality (p amp;lt; 0.0001). The ICD-SPRM interaction was significant (p amp;lt; 0.0001), such that SPRM quintile 5 patients had approximately twice the reduction in mortality with the ICD versus SPRM quintile 1 patients (adjusted hazard ratios [HR]: 0.602; 95% confidence interval [CI]: 0.537 to 0.675 vs. 0.793; 95% CI: 0.736 to 0.855, respectively). Among patients with SHFM-predicted annual mortality amp;lt;= 5.7%, those with a SPRM-predicted risk of sudden death below the median had no reduction in mortality with the ICD (adjusted ICD HR: 0.921; 95% CI: 0.787 to 1.08; p = 0.31), whereas those with SPRM above the median derived the greatest benefit (adjusted HR: 0.599; 95% CI: 0.530 to 0.677; p amp;lt; 0.0001). CONCLUSIONS The SHFM predicted all-cause mortality in a large cohort with and without ICDs, and the SPRM discriminated and calibrated the potential ICD benefit. Together, the models identified patients less likely to derive a survival benefit from primary prevention ICDs. (J Am Coll Cardiol 2017;69:2606-18) (C) 2017 by the American College of Cardiology Foundation.

  • 116.
    Bjarnegård, Niclas
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Jonsson, Anders
    Jönköping Hospital.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Long-term hyperglycaemia impairs vascular smooth muscle cell function in women with type 1 diabetes mellitus2009In: DIABETES and VASCULAR DISEASE RESEARCH, ISSN 1479-1641, Vol. 6, no 1, p. 25-31Article in journal (Refereed)
    Abstract [en]

    Observations of increased stiffness in the elastic aorta in women with diabetes, but not men, emphasise the need for further analysis regarding early abnormalities in arterial wall properties of women with type 1 diabetes mellitus (DM).

    Ultrasound was used to study the wall properties of the distal brachial artery (BA) in 37 type 1 diabetic women (aged 22-45 years) without evident complications and in 53 controls (C). Blood samples were drawn for later analysis.

    Flow-mediated dilatation (FMD) was slightly lower in DM than C, 8.1 +/- 4.3% vs. 10.3 +/- 4.9% (p&lt;0.05), and nitrate-mediated dilatation (NMD) was markedly lower, 21.7 +/- 6.6% vs. 31.4 +/- 5.7% (p&lt;0.001). Lumen diameter, intima-media thickness and distensibility were similar in DM and C. Insulin-like growth factor (IGF-1) was lower in DM than C, 231 +/- 65 vs. 349 +/- 68 ng/ml (p&lt;0.001). Glycosylated haemoglobin (HbA(1C)) and matrix metalloproteinase (MMP-9) were independent predictors of the reduced NMD in the DM.

    Brachial artery responsiveness to an exogenous donor of nitric oxide (NO) was markedly reduced in type 1 diabetic women despite only limited reduction in endothelium-dependent dilatation. The negative association between NMD and HbA(1C) suggests that long-term hyperglycaemia impairs vascular smooth muscle cell function in DM.

  • 117.
    Bjarnegård, Niclas
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.
    Hedman, Kristofer
    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.
    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).
    Vascular Adaptation to Indoor Cycling Exercise in Premenopausal Women2019In: International Journal of Sports Medicine, ISSN 0172-4622, E-ISSN 1439-3964, Vol. 40, no 4, p. 245-252Article in journal (Refereed)
    Abstract [en]

    The early vascular adaptation to indoor cycling, a popular activity at many fitness centres, is incompletely evaluated. Forty two healthy women (21-45 years) underwent measurements of arterial wall properties and geometry as well as a maximal bicycle exercise test before and after a 3 months period during which 21 of the women joined indoor cycling classes at a gym 2-3 times per week, while 21 women served as time controls. Peak work load increased by in average 16% (pamp;lt;0.001) and ascending aortic diameter by 4% (pamp;lt;0.01) in the exercise group, while unchanged in control group. The exercise intervention had no significant influence on the local intima-media thickness, blood pressure or the pulse pressure wave configuration while the carotid artery distensibility (pamp;lt;0.05) was higher after the intervention. There was a positive correlation between change in () peak work load and -diameter of tubular ascending aorta (r=0.42, pamp;lt;0.01) in the exercise group. In conclusion, after only 3 months of bicycle exercise training, signs of central arterial remodelling were seen in premenopausal women, which was associated to improvement in exercise capacity.

    The full text will be freely available from 2020-06-01 11:54
  • 118.
    Bjarnegård, Niclas
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Arterial properties along the upper arm in humans: age-related effects and the consequence of anatomical location2010In: JOURNAL OF APPLIED PHYSIOLOGY, ISSN 8750-7587, Vol. 108, no 1, p. 34-38Article in journal (Refereed)
    Abstract [en]

    The normal aging process of the brachial artery (BA) wall is of specific interest since it is often selected as a model artery in studies of vascular function. With echo-tracking ultrasound, diameter, absolute diameter change, and intima-media thickness (IMT) were registered in 60 healthy subjects, 21-86 yr (30 men), at a proximal, upper third, and distal arterial site along the upper arm. Blood pressure was recorded noninvasively, and the distensibility coefficient (DC) was calculated. The diameter at the proximal site increased with age from 5.5 +/- 0.2 mm in the young subjects to 6.9 +/- 0.3 mm (P andlt; 0.01) in the elderly subjects, concomitantly as IMT increased from 0.40 +/- 0.01 to 0.65 +/- 0.03 mm (P andlt; 0.001). The diameter at the other sites was similar in the young and elderly subjects, whereas IMT increased slightly with age. At the proximal site, DC decreased dramatically from 40.7 +/- 2.2 to 10.1 +/- 0.8 10(-3)/kPa (P andlt; 0.001) with age, whereas hardly no change was seen in the distal upper arm. The principal transit zone between elastic to predominantly muscular artery behavior seems to be located within the proximal part of the brachial artery, emphasizing the importance of carefully defining the arterial examination site.

  • 119.
    Bjarnegård, Niclas
    et al.
    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. Reg Jonkoping Cty, 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.
    Cinthio, M.
    Lund Univ, Sweden.
    Ekstrand, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hedman, Kristofer
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    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.
    Henriksson, J.
    Karolinska Inst, Sweden.
    Vascular characteristics in young women: Effect of extensive endurance training or a sedentary lifestyle2018In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 223, no 2, article id UNSP e13041Article in journal (Refereed)
    Abstract [en]

    AimTo explore whether high-level endurance training in early age has an influence on the arterial wall properties in young women. MethodsForty-seven athletes (ATH) and 52 controls (CTR), all 17-25 years of age, were further divided into runners (RUN), whole-body endurance athletes (WBA), sedentary controls (SC) and normally active controls (AC). Two-dimensional ultrasound scanning of the carotid arteries was conducted to determine local common carotid artery (CCA) geometry and wall distensibility. Pulse waves were recorded with a tonometer to determine regional pulse wave velocity (PWV) and pulse pressure waveform. ResultsCarotid-radial PWV was lower in WBA than in RUN (P amp;lt; .05), indicating higher arterial distensibility along the arm. Mean arterial pressure was lower in ATH than in CTR and in RUN than in WBA (P amp;lt; .05). Synthesized aortic augmentation index (AI@75) was lower among ATH than among CTR (-12.8 1.6 vs -2.6 +/- 1.2%, P amp;lt; .001) and in WBA than in RUN (-16.4 +/- 2.5 vs -10.7 +/- 2.0%, P amp;lt; .05), suggesting a diminished return of reflection waves to the aorta during systole. Carotid-femoral PWV and intima-media thickness (IMT), lumen diameter and radial distensibility of the CCA were similar in ATH and CTR. ConclusionElastic artery distensibility and carotid artery IMT are not different in young women with extensive endurance training over several years and in those with sedentary lifestyle. On the other hand, our data suggest that long-term endurance training is associated with potentially favourable peripheral artery adaptation, especially in sports where upper body work is added. This adaptation, if persisting later in life, could contribute to lower cardiovascular risk.

  • 120.
    Bjarnegård, Niclas
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Morsing, E
    Lund University, Sweden .
    Cinthio, M
    Lund University, Sweden .
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Brodszki, J
    Lund University, Sweden .
    Cardiovascular function in adulthood following intrauterine growth restriction with abnormal fetal blood flow2013In: Ultrasound in Obstetrics and Gynecology, ISSN 0960-7692, E-ISSN 1469-0705, Vol. 41, no 2, p. 177-184Article in journal (Refereed)
    Abstract [en]

    Objectives To examine whether intrauterine growth restriction (IUGR) is associated with increased cardiovascular risk later in life. Methods We examined 19 young adults (aged 2225 years) who were born at term after IUGR, along with 18 controls. All had been examined previously with fetal Doppler, and in the present follow-up with echocardiography, carotid echo-tracking ultrasound, applanation tonometry, blood pressure and laser Doppler, in order to characterize their cardiac and vascular geometry and/or function. Results The diameter of the ascending aorta and the left ventricular diameter were smaller in the IUGR group, but only ascending aortic diameter remained significantly smaller after adjustment for body surface area (Pandlt;0.05). The aortic pressure augmentation index was higher in the IUGR group (Pandlt;0.05). The common carotid artery diameter, intimamedia thickness and distensibility as well as left ventricular mass and function were similar in the two groups. IUGR status was found to be an independent predictor of ascending aortic diameter. Conclusions IUGR due to placental dysfunction seems to contribute to the higher systolic blood pressure augmentation and the smaller aortic dimensions that are observed in adults more than 20 years later, with possible negative consequences for future left ventricular performance due to increased aortic impedance.

  • 121.
    Block, Keith I.
    et al.
    Block Centre Integrat Cancer Treatment, IL 60077 USA.
    Gyllenhaal, Charlotte
    Block Centre Integrat Cancer Treatment, IL 60077 USA; National Cancer Centre, South Korea.
    Lowe, Leroy
    Getting Know Canc, Canada; University of Lancaster, England.
    Amedei, Amedeo
    University of Florence, Italy.
    Ruhul Amin, A. R. M.
    University of Florence, Italy.
    Amin, Amr
    University of Florence, Italy.
    Aquilano, Katia
    United Arab Emirates University, U Arab Emirates.
    Arbiser, Jack
    Atlanta Vet Adm Medical Centre, GA USA; Emory University, GA USA.
    Arreola, Alexandra
    University of Roma Tor Vergata, Italy.
    Arzumanyan, Alla
    University of N Carolina, NC 27599 USA.
    Salman Ashraf, S.
    Temple University, PA 19122 USA.
    Azmi, Asfar S.
    United Arab Emirates University, U Arab Emirates.
    Benencia, Fabian
    Wayne State University, MI USA.
    Bhakta, Dipita
    Ohio University, OH 45701 USA.
    Bilsland, Alan
    SASTRA University, India.
    Bishayeen, Anupam
    University of Glasgow, Scotland.
    Blain, Stacy W.
    Larkin Health Science Institute, FL USA.
    Block, Penny B.
    Block Centre Integrat Cancer Treatment, IL 60077 USA.
    Boosani, Chandra S.
    Suny Downstate Medical Centre, NY USA.
    Carey, Thomas E.
    Creighton University, NE 68178 USA.
    Carnero, Amancio
    University of Michigan, MI USA.
    Carotenuto, Marianeve
    CSIC, Spain; Centre Ingn Genet and Biotecnol Avanzate, Italy.
    Casey, Stephanie C.
    University of Naples Federico II, Italy.
    Chakrabarti, Mrinmay
    Stanford University, CA 94305 USA.
    Chaturvedi, Rupesh
    University of S Carolina, SC USA.
    Zhuo Chen, Georgia
    Winship Cancer Institute of Emory University, Atlanta, GA, United States.
    Chenx, Helen
    Jawaharlal Nehru University, India.
    Chen, Sophie
    University of British Columbia, Canada.
    Charlie Chen, Yi
    Ovarian and Prostate Cancer Research Lab, England; Alderson Broaddus University, PA USA.
    Choi, Beom K.
    National Cancer Centre, South Korea.
    Rosa Ciriolo, Maria
    United Arab Emirates University, U Arab Emirates.
    Coley, Helen M.
    University of Surrey, England.
    Collins, Andrew R.
    University of Oslo, Norway.
    Connell, Marisa
    Jawaharlal Nehru University, India.
    Crawford, Sarah
    So Connecticut State University, CT 06515 USA.
    Curran, Colleen S.
    University of Wisconsin, WI USA.
    Dabrosin, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Damia, Giovanna
    Ist Ric Farmacol Mario Negri, Italy.
    Dasgupta, Santanu
    University of Texas Health Science Centre Tyler, TX USA.
    DeBerardinis, Ralph J.
    University of Texas SW Medical Centre Dallas, TX 75390 USA.
    Decker, William K.
    Baylor Coll Med, TX 77030 USA.
    Dhawan, Punita
    Vanderbilt University, TN 37212 USA.
    Diehl, Anna Mae E.
    Duke University, NC 27710 USA.
    Dong, Jin-Tang
    Winship Cancer Institute of Emory University, Atlanta, GA, United States.
    Ping Dou, Q.
    United Arab Emirates University, U Arab Emirates.
    Drew, Janice E.
    University of Aberdeen, Scotland.
    Elkord, Eyad
    United Arab Emirates University, U Arab Emirates.
    El-Rayes, Bassel
    Emory University, GA 30322 USA.
    Feitelson, Mark A.
    University of N Carolina, NC 27599 USA.
    Felsher, Dean W.
    University of Naples Federico II, Italy.
    Ferguson, Lynnette R.
    University of Auckland, New Zealand.
    Fimognari, Carmela
    University of Auckland, New Zealand.
    Firestone, Gary L.
    University of Bologna, Italy.
    Frezza, Christian
    University of Calif Berkeley, CA 94720 USA.
    Fujii, Hiromasa
    University of Cambridge, England.
    Fuster, Mark M.
    Nara Medical University, Japan.
    Generali, Daniele
    University of Calif San Diego, CA 92103 USA; University of Calif San Diego, CA 92103 USA.
    Georgakilas, Alexandros G.
    University of Trieste, Italy.
    Gieseler, Frank
    Azienda Osped Ist Ospitalieri Cremona, Italy.
    Gilbertson, Michael
    National Technical University of Athens, Greece.
    Green, Michelle F.
    University Hospital Schleswig Holstein, Germany.
    Grue, Brendan
    Getting Know Canc, Canada.
    Guha, Gunjan
    Ohio University, OH 45701 USA.
    Halicka, Dorota
    Duke University, NC USA.
    Helferich, William G.
    Dalhousie University, Canada.
    Heneberg, Petr
    New York Medical Coll, NY 10595 USA.
    Hentosh, Patricia
    University of Illinois, IL 61820 USA.
    Hirschey, Matthew D.
    University Hospital Schleswig Holstein, Germany.
    Hofseth, Lorne J.
    Charles University of Prague, Czech Republic.
    Holcombe, Randall F.
    Old Domin University, VA USA.
    Honoki, Kanya
    Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, Japan.
    Hsu, Hsue-Yin
    University of S Carolina, SC 29208 USA.
    Huang, Gloria S.
    Mt Sinai School Med, NY USA.
    Jensen, Lasse D.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Jiang, Wen G.
    Cardiff University, Wales.
    Jones, Lee W.
    Mem Sloan Kettering Cancer Centre, NY 10021 USA.
    Karpowicz, Phillip A.
    University of Windsor, Canada.
    Nicol Keith, W.
    SASTRA University, India.
    Kerkar, Sid P.
    Mayo Clin, MN USA.
    Khan, Gazala N.
    Henry Ford Hospital, MI 48202 USA.
    Khatami, Mahin
    National Institute Heatlh, MD USA.
    Ko, Young H.
    University of Maryland BioPark, MD USA.
    Kucuk, Omer
    Winship Cancer Institute of Emory University, Atlanta, GA, United States.
    Kulathinal, Rob J.
    University of N Carolina, NC 27599 USA.
    Kumar, Nagi B.
    University of S Florida, FL USA.
    Kwon, Byoung S.
    National Cancer Centre, South Korea; Tulane University, LA 70118 USA.
    Le, Anne
    Johns Hopkins University, MD USA.
    Lea, Michael A.
    Rutgers State University, NJ USA.
    Lee, Ho-Young
    Seoul National University, South Korea.
    Lichtor, Terry
    Rush University, IL 60612 USA.
    Lin, Liang-Tzung
    Taipei Medical University, Taiwan.
    Locasale, Jason W.
    Cornell University, NY 14853 USA.
    Lokeshwar, Bal L.
    Georgia Regents University, GA USA.
    Longo, Valter D.
    University of So Calif, CA USA.
    Lyssiotis, Costas A.
    University of Michigan, MI USA; University of Michigan, MI USA.
    MacKenzie, Karen L.
    Childrens Cancer Institute Australia, Australia.
    Malhotra, Meenakshi
    McGill University, Canada.
    Marino, Maria
    University of Rome Tre, Italy.
    Martinez-Chantar, Maria L.
    Technology Pk Bizkaia, Spain.
    Matheu, Ander
    Biodonostia Institute, Spain.
    Maxwell, Christopher
    Jawaharlal Nehru University, India.
    McDonnell, Eoin
    University Hospital Schleswig Holstein, Germany.
    Meeker, Alan K.
    Johns Hopkins University, MD 21205 USA.
    Mehrmohamadi, Mahya
    Cornell University, NY USA.
    Mehta, Kapil
    University of Texas MD Anderson Cancer Centre, TX 77030 USA.
    Michelotti, Gregory A.
    Duke University, NC 27710 USA.
    Mohammad, Ramzi M.
    United Arab Emirates University, U Arab Emirates.
    Mohammed, Sulma I.
    Purdue University, IN 47907 USA.
    James Morre, D.
    Mor NuCo Inc, IN USA.
    Muqbil, Irfana
    United Arab Emirates University, U Arab Emirates.
    Muralidhar, Vinayak
    Harvard University, MA USA; MIT, MA 02139 USA.
    Murphy, Michael P.
    MRC Mitochondrial Biol Unit, England.
    Purnachandra Nagaraju, Ganji
    Emory University, GA 30322 USA.
    Nahta, Rita
    Winship Cancer Institute of Emory University, Atlanta, GA, United States.
    Niccolai, Elena
    University of Florence, Italy.
    Nowsheen, Somaira
    Mayo Clin, MN USA.
    Panis, Carolina
    State University of West Parana, Brazil.
    Pantano, Francesco
    University of Campus Bio Med, Italy.
    Parslow, Virginia R.
    University of Auckland, New Zealand.
    Pawelec, Graham
    University of Tubingen, Germany.
    Pedersen, Peter L.
    Johns Hopkins University, MD USA.
    Poore, Brad
    Johns Hopkins University, MD USA.
    Poudyal, Deepak
    Charles University of Prague, Czech Republic.
    Prakash, Satya
    McGill University, Canada.
    Prince, Mark
    University of Michigan, MI USA.
    Raffaghello, Lizzia
    Ist Giannina Gaslini, Italy.
    Rathmell, Jeffrey C.
    University Hospital Schleswig Holstein, Germany.
    Kimryn Rathmell, W.
    University of Roma Tor Vergata, Italy.
    Ray, Swapan K.
    Stanford University, CA 94305 USA.
    Reichrath, Joerg
    Saarland University Hospital, Germany.
    Rezazadeh, Sarallah
    University of Rochester, NY 14627 USA.
    Ribatti, Domenico
    University of Bari, Italy.
    Ricciardiello, Luigi
    National Cancer Institute Giovanni Paolo II, Italy.
    Brooks Robey, R.
    University of Bologna, Italy; White River Junct Vet Affairs Medical Centre, VT USA.
    Rodier, Francis
    Geisel School Medical Dartmouth, NH USA; University of Montreal, Canada.
    Vasantha Rupasinghe, H. P.
    Institute Cancer Montreal, Canada.
    Luigi Russo, Gian
    University of Montreal, Canada.
    Ryan, Elizabeth P.
    Dalhousie University, Canada.
    Samadi, Abbas K.
    Sanus Biosciences, San Diego, CA, United States.
    Sanchez-Garcia, Isidro
    CNR, Italy.
    Sanders, Andrew J.
    Cardiff University, Wales.
    Santini, Daniele
    University of Campus Bio Med, Italy.
    Sarkar, Malancha
    Colorado State University, CO 80523 USA.
    Sasada, Tetsuro
    Department of Immunology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
    Saxena, Neeraj K.
    University of Salamanca, Spain.
    Shackelford, Rodney E.
    University of Miami, FL USA.
    Shantha Kumara, H. M. C.
    St Lukes Roosevelt Hospital, NY 10025 USA.
    Sharma, Dipali
    Kurume University, Japan.
    Shin, Dong M.
    Winship Cancer Institute of Emory University, Atlanta, GA, United States.
    Sidransky, David
    University of Maryland, MD 21201 USA.
    David Siegelin, Markus
    Louisiana State University, LA 71105 USA.
    Signori, Emanuela
    Johns Hopkins University, MD 21205 USA; Johns Hopkins University, MD USA.
    Singh, Neetu
    Johns Hopkins University, MD USA; King Georges Medical University, India.
    Sivanand, Sharanya
    Columbia University, NY USA; University of Penn, PA 19104 USA.
    Sliva, Daniel
    Institute Translat Pharmacol, Italy; Purdue Research Pk, IN USA.
    Smythe, Carl
    University of Sheffield, England.
    Spagnuolo, Carmela
    University of Montreal, Canada.
    Stafforini, Diana M.
    University of Utah, UT USA.
    Stagg, John
    University of Utah, UT USA.
    Subbarayan, Pochi R.
    University of Montreal, Canada.
    Sundin, Tabetha
    University of Miami, FL USA.
    Talib, Wamidh H.
    Sentara Healthcare, VA USA.
    Thompson, Sarah K.
    Appl Science University, Jordan.
    Tran, Phuoc T.
    Royal Adelaide Hospital, Australia.
    Ungefroren, Hendrik
    Azienda Osped Ist Ospitalieri Cremona, Italy.
    Vander Heiden, Matthew G.
    MIT, MA 02139 USA.
    Venkateswaran, Vasundara
    Johns Hopkins University, MD USA; University of Toronto, Canada.
    Vinay, Dass S.
    Tulane University, LA USA.
    Vlachostergios, Panagiotis J.
    Johns Hopkins University, MD USA; New York University, NY USA.
    Wang, Zongwei
    Johns Hopkins University, MD USA; Harvard University, MA USA.
    Wellendx, Kathryn E.
    Columbia University, NY USA; University of Penn, PA 19104 USA.
    Whelan, Richard L.
    St Lukes Roosevelt Hospital, NY 10025 USA.
    Yang, Eddy S.
    University of Alabama Birmingham, AL USA.
    Yang, Huanjie
    Harbin Institute Technology, Peoples R China.
    Yang, Xujuan
    Dalhousie University, Canada.
    Yaswen, Paul
    Lawrence Berkeley National Lab, CA USA.
    Yedjou, Clement
    Jackson State University, MS USA.
    Yin, Xin
    Nara Medical University, Japan.
    Zhu, Jiyue
    Washington State University, WA USA.
    Zollo, Massimo
    CSIC, Spain; Centre Ingn Genet and Biotecnol Avanzate, Italy.
    Designing a broad-spectrum integrative approach for cancer prevention and treatment2015In: Seminars in Cancer Biology, ISSN 1044-579X, E-ISSN 1096-3650, Vol. 35, p. S276-S304Article, review/survey (Refereed)
    Abstract [en]

    Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. (C) 2015 The Authors. Published by Elsevier Ltd.

  • 122.
    Blomstrand, Peter
    et al.
    County Hospital Ryhov, Jönköping, Sweden.
    Engvall, Martin
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Festin, Karin
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Maret, Eva
    Karolinska University Hospital, Stockholm.
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Maret-Ouda, John
    Karolinska University Hospital, Stockholm.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Primary Health Care in Motala.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Left ventricular diastolic function, assessed by echocardiography and tissue Doppler imaging, is a strong predictor of cardiovascular events, superior to global left ventricular longitudinal strain, in patients with type 2 diabetes.2015In: European heart journal cardiovascular Imaging, ISSN 2047-2412, Vol. 16, no 9, p. 1000-1007Article in journal (Refereed)
    Abstract [en]

    AIMS: The aim of the study was to determine whether left ventricular systolic function, in terms of global left ventricular longitudinal strain (GLS), and diastolic function, expressed as the ratio between early diastolic transmitral flow and mitral annular motion velocities (E/e'), can predict cardiovascular events in patients with diabetes mellitus type 2.

    METHODS AND RESULTS: We prospectively investigated 406 consecutive patients, aged 55-65 years, with diabetes mellitus, who participated in the CARDIPP study. Echocardiography, pulse pressure (pp), and glycosylated haemoglobin (HbA1c) were analysed. Twelve cases of myocardial infarction and seven cases of stroke were identified during the follow-up period of 67 ± 17 months. Univariate Cox regression analysis showed that E/e' was a strong predictor of cardiovascular events (hazards ratio 1.12; 95% confidence interval 1.06-1.18, P < 0.001). E/e' was prospectively associated with cardiovascular events independent of age, sex, GLS, left ventricular ejection fraction (LVEF), pp, and HbA1c in multivariate analysis. Receiver operating characteristic curves showed that E/e' and HbA1c were the strongest predictors for cardiovascular events, both having an area under the curve (AUC) of 0.71 followed by LVEF with an AUC of 0.65 and GLS of 0.61. In a Kaplan-Meyer analysis, the cumulative probability of an event during the follow-up period was 8.6% for patients with an E/e' ratio >15 compared with 2.6% for patients with E/e' ≤15, P = 0.011.

    CONCLUSION: In middle-aged patients with type 2 diabetes, E/e' is a strong predictor of myocardial infarction and stroke, comparable with HbA1c and superior to GLS and LVEF.

  • 123.
    Blomstrand, Peter
    et al.
    Cty Hosp Ryhov, Sweden; Jonkoping Univ, Sweden.
    Sjöblom, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Mats
    Acad Hlth and Care, Sweden.
    Wijkman, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Engvall, Martin
    Linköping University, Department of Medical and Health Sciences. 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.
    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.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Overweight and obesity impair left ventricular systolic function as measured by left ventricular ejection fraction and global longitudinal strain2018In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 17, article id 113Article in journal (Refereed)
    Abstract [en]

    Aims: Obesity is associated with type 2 diabetes mellitus, left ventricular diastolic dysfunction and heart failure but it is unclear to which extent it is related to left ventricular systolic dysfunction. The aim of the study was to explore the effects of overweight and obesity on left ventricular systolic function in patients with type 2 diabetes mellitus and a control group of non-diabetic persons. Methods: We prospectively investigated 384 patients with type 2 diabetes mellitus, and 184 controls who participated in the CARDIPP and CAREFUL studies. The participants were grouped according to body mass index (normal weight amp;lt; 25 kg/m(2), overweight 25-29 kg/m(2), and obesity amp;gt;= 30 kg/m(2) ). Echocardiography was performed at the beginning of the study and after 4-years in the patient group. Results: Univariable and multivariable regression analysis revealed that variations in left ventricular ejection fraction, global longitudinal strain, left ventricular mass and diastolic function expressed as E/e (the ratio between early diastolic mitral flow and annular motion velocities) all are related to body mass index. The mean and standard deviation of left ventricular ejection fraction and global longitudinal strain values were 57% (8%) vs. - 18.6% (2.3%) for normal weight patients, 53% (8%) vs. - 17.5% (2.3%) for overweight, and 49% (9%) vs. - 16.2% (3.0%) for obese (p amp;lt; 0.05 vs. p amp;lt;0.05). Corresponding results in the control group were 58% (6%) vs. -22.3% (3.0%), 55% (7%) vs. - 20.8% (3.1%) and 54% (8%) - 19.6% (4.0%) (p amp;lt;0.05 vs. p amp;lt;0.05). Patients who gained weight from baseline to follow-up changed left ventricular ejection fraction (median and interquartile range) by - 1.0 (9.0) % (n =187) and patients who lost weight changed left ventricular ejection fraction by 1.0 (10.0) % (n =179) (p amp;lt;0.05). Conclusion: Overweight and obesity impair left ventricular ejection fraction and global longitudinal strain in both patients with type 2 diabetes mellitus and non-diabetic persons.

  • 124.
    Blystad, Ida
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    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).
    Smedby, Örjan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). KTH Royal Institute Technology, Sweden.
    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 Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Larsson, Elna-Marie
    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). Uppsala University, Sweden.
    Tisell, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Quantitative MRI for analysis of peritumoral edema in malignant gliomas2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 5, article id e0177135Article in journal (Refereed)
    Abstract [en]

    Background and purpose Damage to the blood-brain barrier with subsequent contrast enhancement is a hallmark of glioblastoma. Non-enhancing tumor invasion into the peritumoral edema is, however, not usually visible on conventional magnetic resonance imaging. New quantitative techniques using relaxometry offer additional information about tissue properties. The aim of this study was to evaluate longitudinal relaxation R-1, transverse relaxation R-2, and proton density in the peritumoral edema in a group of patients with malignant glioma before surgery to assess whether relaxometry can detect changes not visible on conventional images. Methods In a prospective study, 24 patients with suspected malignant glioma were examined before surgery. A standard MRI protocol was used with the addition of a quantitative MR method (MAGIC), which measured R-1, R-2, and proton density. The diagnosis of malignant glioma was confirmed after biopsy/surgery. In 19 patients synthetic MR images were then created from the MAGIC scan, and ROIs were placed in the peritumoral edema to obtain the quantitative values. Dynamic susceptibility contrast perfusion was used to obtain cerebral blood volume (rCBV) data of the peritumoral edema. Voxel-based statistical analysis was performed using a mixed linear model. Results R-1, R-2, and rCBV decrease with increasing distance from the contrast-enhancing part of the tumor. There is a significant increase in R1 gradient after contrast agent injection (Pamp;lt;.0001). There is a heterogeneous pattern of relaxation values in the peritumoral edema adjacent to the contrast-enhancing part of the tumor. Conclusion Quantitative analysis with relaxometry of peritumoral edema in malignant gliomas detects tissue changes not visualized on conventional MR images. The finding of decreasing R-1 and R-2 means shorter relaxation times closer to the tumor, which could reflect tumor invasion into the peritumoral edema. However, these findings need to be validated in the future.

  • 125.
    Boano, Gabriella
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Linköping University, Faculty of Medicine and Health Sciences.
    Åström Aneq, Meriam
    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.
    Kemppi, Jennie
    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.
    Vánky, Farkas
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Linköping University, Faculty of Medicine and Health Sciences.
    Cox-maze IV cryoablation and postoperative heart failure in mitral valve surgery patients2017In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 51, no 1, p. 15-20Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The indications for and the risk and benefit of concomitant surgical ablation for atrial fibrillation (AF) have not been fully delineated. Our aim was to survey whether the Cox-maze IV procedure is associated with postoperative heart failure (PHF) or other adverse short-term outcomes after mitral valve surgery (MVS).

    DESIGN: Consecutive patients with AF undergoing MVS with (n = 50) or without (n = 66) concomitant Cox-maze IV cryoablation were analysed regarding perioperative data and one-year mortality.

    RESULTS: The patients in the Maze group were younger, were in lower NYHA classes, had better right ventricular function and had lower pulmonary artery pressure. The Maze group had 30 min longer median cross-clamp time (CCT) and 50% had PHF compared with 33% in the No-maze group, p = 0.09. Two patients in the No-maze group died within one year of surgery. Congestive heart failure (OR 4.3 [CI 95%: 1.8-10], p < 0.0001) and CCT (OR 1.03 [CI 95%: 1.01-1.04], p = 0.001) were associated with PHF.

    CONCLUSION: The current data cannot exclude that concomitant cryoablation increases the risk for PHF, possibly by increasing the cross clamp time.

  • 126.
    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 USA.
    Preventing Endocarditis No Rest for the Worrier2018In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 72, no 20, p. 2455-2456Article in journal (Other academic)
    Abstract [en]

    n/a

  • 127.
    Bolger, Ann F
    et al.
    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.
    Eidenvall, Lars
    Ask, Per
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Loyd, Dan
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, The Institute of Technology.
    Wranne, Bengt
    Linköping University, Department of Medicine and Care, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    THE MULTIPLE DETERMINANTS OF CONTINUOUS WAVE SIGNAL INTENSITY1992In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 86, no 4, SArticle in journal (Refereed)
  • 128.
    Borg, Sabina
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Öberg, Birgitta
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Leosdottir, Margret
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Lindholm, Daniel
    Uppsala Univ, Sweden; Uppsala Clin Res Ctr, Sweden.
    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.
    Bäck, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. Sahlgrens Univ Hosp, Sweden.
    Factors associated with non-attendance at exercise-based cardiac rehabilitation (vol 11, 13, 2019)2019In: BMC SPORTS SCIENCE MEDICINE AND REHABILITATION, ISSN 2052-1847, Vol. 11, no 1, article id 24Article in journal (Refereed)
    Abstract [en]

    n/a

  • 129.
    Borg, Sabina
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Öberg, Birgitta
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Leosdottir, Margret
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Lindolm, Daniel
    Uppsala Univ, Sweden; Uppsala Clin Res Ctr, Sweden.
    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.
    Bäck, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. Sahlgrens Univ Hosp, Sweden.
    Factors associated with non-attendance at exercise-based cardiac rehabilitation2019In: BMC SPORTS SCIENCE MEDICINE AND REHABILITATION, ISSN 2052-1847, Vol. 11, article id 13Article in journal (Refereed)
    Abstract [en]

    BackgroundDespite its well-established positive effects, exercise-based cardiac rehabilitation (exCR) is underused in patients following an acute myocardial infarction (AMI). The aim of the study was to identify factors associated with non-attendance at exCR in patients post-AMI in a large Swedish cohort.MethodsA total of 31,297 patients who have suffered an AMI, mean age 62.44years, were included from the SWEDEHEART registry during the years 2010-2016. Comparisons between attenders and non-attenders at exCR were done at baseline for the following variables: age, sex, body mass index, occupational status, smoking, previous diseases, type of index cardiac event and intervention, and left ventricular function. Distance of residence from the hospital and type of hospital were added as structural variables in logistic regression analyses, with non-attendance at exCR at one-year follow-up as dependent, and with individual and structural variables as independent variables.ResultsIn total, 16,214 (52%) of the patients did not attend exCR. The strongest predictor for non-attendance was distance to the exCR centre (OR 1.75 [95% CI: 1.64-1.86]). Other predictors for non-attendance included smoking, history of stroke, percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), AMI or diabetes, male sex, being retired vs. being employed, and being followed-up at a county hospital. Patients with ST-elevation myocardial infarction (STEMI) and those intervened with PCI or CABG were more likely to attend exCR.Conclusions A distance greater than 16km was associated with increased probability of non-attendance at exCR, as were smoking, a higher burden of comorbidities, and male sex. A better understanding of individual and structural factors can support the development of future rehabilitation services.

  • 130.
    Borg, Sabina
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Öberg, Birgitta
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    Söderlund, Anne
    Mälardalen University, Sweden.
    Bäck, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    The role of a behavioural medicine intervention in physiotherapy for the effects of rehabilitation outcomes in exercise-based cardiac rehabilitation (ECRA) - the study protocol of a randomised, controlled trial2017In: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 17, article id 134Article in journal (Refereed)
    Abstract [en]

    Background: To help patients with coronary artery disease (CAD) benefit from the positive health effects attained by exercise-based cardiac rehabilitation (CR), adherence to these programmes according to international guidelines is important. Strategies to increase adherence to exercise-based CR are mainly an unexplored area. The objective of this study is to investigate the effects of a behavioural medicine intervention in physiotherapy, containing goal-setting, self-monitoring and feedback, with the aim of improving rehabilitation outcomes for exercise-based CR, compared with usual care. Methods: This is a randomised, controlled trial. A total of 160 patients with CAD will be included consecutively at the Coronary Care Unit at a university hospital in Sweden. Patients are randomised 1:1 using sealed envelopes to usual care or a behavioural medicine intervention in physiotherapy, in addition to usual care for 4 months. Outcome assessment at baseline, 4 and 12 months includes submaximal aerobic capacity (primary outcome), exercise adherence, muscle endurance, level of physical activity, biomarkers, anxiety and depression, health-related quality of life, patient enablement and self-efficacy (secondary outcomes). Discussion: This is the first study to evaluate the role of an integrated behavioural medicine intervention in exercise-based CR in the effects of rehabilitation outcomes. The results of this study will provide valuable information about the effect of these interventions in exercise-based CR and it has the potential to inform and assist in further treatment in secondary prevention for patients with CAD.

  • 131.
    Borssen, Åsa D.
    et al.
    Umeå University, Sweden.
    Palmqvist, Richard
    Umeå University, Sweden.
    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.
    Marschall, Hanns-Ulrich
    University of Gothenburg, Sweden.
    Bergquist, Annika
    Karolinska University, Sweden.
    Rorsman, Fredrik
    Uppsala University, Sweden.
    Weiland, Ola
    Karolinska University, Sweden.
    Verbaan, Hans
    Lund University, Sweden.
    Nyhlin, Nils
    Örebro University, Sweden.
    Nilsson, Emma
    Lund University, Sweden.
    Werner, Marten
    Umeå University, Sweden.
    Histological improvement of liver fibrosis in well-treated patients with autoimmune hepatitis A cohort study2017In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 96, no 34, article id e7708Article in journal (Refereed)
    Abstract [en]

    Autoimmune hepatitis (AIH) is a chronic autoimmune liver disease that if left untreated may lead to the development of cirrhosis. Previous studies on AIH patients have suggested that fibrosis and even cirrhosis can be reversed by medical treatment. The aim of this study was to evaluate the efficacy of medical treatment for protection of developing fibrosis and cirrhosis. A total of 258 liver biopsies from 101 patients (72 women, 29 men) were analyzed by a single pathologist and classified according to the Ishak grading (inflammation) and staging (fibrosis) system. Liver histology was stratified according to the temporal changes of fibrosis stage (increased, decreased, or stable), and groups were compared. Complete or partial response to medical treatment was 94.9%. Reduction of fibrosis stage from the first to the last biopsy was seen in 63 patients (62.4%). We found an association between a reduction in the fibrosis stage and continuous glucocorticoid medication, as well as lowered scores of inflammation at last biopsy. Twenty-one patients had cirrhosis (Ishak stage 6) at least in one of the previous biopsies, but only 5 patients at the last biopsy. Histological improvement is common in AIH patients that respond to medical treatment, and a reduction or stabilization of fibrosis stage occurs in about 2/3 of such patients.

  • 132.
    Bothe, Wolfgang
    et al.
    Stanford University School of Medicine, USA.
    Ennis, Daniel
    Stanford University School of Medicine, USA.
    Carlhäll, Carl Johan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Stanford University School of Medicine, USA.
    Nguyen, Tom
    Stanford University School of Medicine, USA.
    Timek, Tomasz
    Stanford University School of Medicine, USA.
    Lai, David
    Stanford University School of Medicine, USA.
    Itoh, Akinobu
    Stanford University School of Medicine, USA.
    Ingels, Neil
    Stanford University School of Medicine & Research Institute of the Palo Alto Medical Foundation, California, USA.
    Miller, Craig
    Stanford University School of Medicine, USA.
    Regional Mitral Leaflet Opening During Acute Ischemic Mitral Regurgitation2009In: Journal of Heart Valve Disease, ISSN 0966-8519, E-ISSN 2053-2644, Vol. 18, no 6, p. 586-597Article in journal (Refereed)
    Abstract [en]

    Background and aim of the study

    Diastolic mitral valve (MV) opening characteristics during ischemic mitral regurgitation (IMR) are poorly characterized. The diastolic MV opening dynamics was quantified along the entire valvular coaptation line in an ovine model of acute IMR.

    Methods

    Ten radiopaque markers were sutured in pairs on the anterior (A1-E1) and corresponding posterior (A2-E2) leaflet edges from the anterior (A1/A2) to the posterior (E1/E2) commissure in 11 adult sheep. Immediately after surgery, 4-D marker coordinates were obtained before and during occlusion of the proximal left circumflex coronary artery. Distances between marker pairs were calculated throughout the cardiac cycle every 16.7 ms. Leaflet opening was defined as the time after end-systole (ES) when the first derivative of the distance between marker pairs was greater than a threshold value of 3 cm/s. Valve opening velocity was defined as the maximum slope of marker pair tracings.

    Results

    Hemodynamics were consistent with acute ischemia, as reflected by increased MR grade (0.5 ± 0.3 versus 2.3 ± 0.7, p <0.05), decreased contractility (dP/dtmax: 1,948 ± 598 versus 1,119 ± 293 mmHg/s, p <0.05), and slower left ventricular relaxation rate (dP/dtmin: −1,079 ± 188 versus −538 ± 147 mmHg/s, p <0.05). During ischemia, valve opening occurred earlier (A1/A2: 112 ± 28 versus 83 ± 43 ms, B1/B2: 105 ± 32 versus 68 ± 35 ms, C1/C2: 126 ± 25 versus 74 ± 37 ms, D1/D2: 114 ± 28 versus 71 ± 34 ms, E1/E2: 125 ± 29 versus 105 ± 33 ms; all p <0.05) and was slower (A1/A2: 16.8 ± 9.6 versus 14.2 ± 9.4 cm/s, B1/B2: 40.4 ± 9.9 versus 32.2 ± 10.0 cm/s, C1/C2: 59.0 ± 14.9 versus 50.4 ± 18.1 cm/s, D1/D2: 34.4 ± 10.4 versus 25.5 ± 10.9 cm/s; all p <0.05), except at the posterior edge (E1/E2: 13.3 ± 8.7 versus 10.6 ± 7.2 cm/s). The sequence of regional mitral leaflet separation along the line of coaptation did not change with ischemia.

    Conclusion

    Acute posterolateral left ventricular ischemia causes earlier leaflet opening, probably due to a MR-related elevation in left-atrial pressure; reduces leaflet opening velocity, potentially reflecting an impaired left ventricular relaxation rate; and does not perturb the homogeneous temporal pattern of regional valve opening along the line of coaptation. Future studies will confirm whether these findings are apparent in patients with chronic IMR, and may help to refine the current strategies used to treat IMR.

  • 133.
    Bothe, Wolfgang
    et al.
    Stanford University.
    Nguyen, Tom C
    Stanford University.
    Ennis, Daniel B
    Stanford University.
    Itoh, Akinobu
    Stanford University.
    Carlhäll, Carljohan
    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. Stanford University School of Medicine.
    Lai, David T
    Stanford University.
    Ingels, Neil B
    Stanford University.
    Miller, D. Craig
    Stanford University.
    Effects of acute ischemic mitral regurgitation on three-dimensional mitral leaflet edge geometry2008In: European Journal of Cardio-Thoracic Surgery, ISSN 1010-7940, E-ISSN 1873-734X, Vol. 33, p. 191-197Article in journal (Refereed)
    Abstract [en]

    Background: Improved quantitative understanding of in vivo leaflet geometry in ischemic mitral regurgitation (IMR) is needed to improve reparative techniques, yet few data are available due to current imaging limitations. Using marker technology we tested the hypotheses that IMR (1) occurs chiefly during early systole; (2) affects primarily the valve region contiguous with the myocardial ischemic insult; and (3) results in systolic leaflet edge restriction. Methods: Eleven sheep had radiopaque markers sutured as five opposing pairs along the anterior (A1–E1) and posterior (A2–E2) mitral leaflet free edges from the anterior commissure (A1–A2) to the posterior commissure (E1–E2). Immediately postoperatively, biplane videofluoroscopy was used to obtain 4D marker coordinates before and during acute proximal left circumflex artery occlusion. Regional mitral orifice area (MOA) was calculated in the anterior (Ant-MOA), middle (Mid-MOA), and posterior (Post-MOA) mitral orifice segments during early systole (EarlyS), mid systole (MidS), and end systole (EndS). MOA was normalized to zero (minimum orifice opening) at baseline EndS. Tenting height was the distance of the midpoint of paired markers to the mitral annular plane at EndS. Results: Acute ischemia increased echocardiographic MR grade (0.5 ± 0.3 vs 2.3 ± 0.7, p < 0.01) and MOA in all regions at EarlyS, MidS, and EndS: Ant-MOA (7 ± 10 vs 22 ± 19 mm2, 1 ± 2 vs18 ± 16 mm2, 0 vs 17 ± 15 mm2); Mid-MOA (9 ± 13 vs 25 ± 17 mm2, 3 ± 6 vs 21 ± 19 mm2, 0 vs 25 ± 17 mm2); and Post-MOA (8 ± 10 vs 25 ± 16, 2 ± 4 vs 22 ± 13 mm2, 0 vs 23 ± 13 mm2), all p < 0.05. There was no change in MOA throughout systole (EarlyS vs MidS vs EndS) during baseline conditions or ischemia. Tenting height increased with ischemia near the central and the anterior commissure leaflet edges (B1–B2: 7.1 ± 1.8 mm vs 7.9 ± 1.7 mm, C1–C2: 6.9 ± 1.3 mm vs 8.0 ± 1.5 mm, both p < 0.05). Conclusions: MOA during ischemia was larger throughout systole, indicating that acute IMR in this setting is a holosystolic phenomenon. Despite discrete postero-lateral myocardial ischemia, Post-MOA was not disproportionately larger. Acute ovine IMR was associated with leaflet restriction near the central and the anterior commissure leaflet edges. This entire constellation of annular, valvular, and subvalvular ischemic alterations should be considered in the approach to mitral repair for IMR.

  • 134.
    Braun, Oscar O.
    et al.
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Nilsson, Johan
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Gustafsson, Finn
    Rigshosp, Denmark.
    Dellgren, Goran
    Sahlgrens Univ Hosp, Sweden.
    Fiane, Arnt E.
    Oslo Univ Hosp, Norway; Univ Oslo, Norway.
    Lemstrom, Karl
    Helsinki Univ Hosp, Finland.
    Hübbert, Laila
    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.
    Hellgren, Laila
    Uppsala Univ Hosp, Sweden.
    Lund, Lars H.
    Karolinska Univ Hosp, Sweden; Karolinska Univ Hosp, Sweden.
    Continuous-flow LVADs in the Nordic countries: complications and mortality and its predictors2019In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 53, no 1, p. 14-20Article in journal (Refereed)
    Abstract [en]

    Objectives: The purpose of this study was to assess complications and mortality and its predictors, with continuous-flow left ventricular assist devices (CF-LVADs) in the Nordic Countries. Design: This was a retrospective, international, multicenter cohort study. Results: Between 1993 and 2013, 442 surgically implanted long-term mechanical assist devices were used among 8 centers in the Nordic countries. Of those, 238 were CF-LVADs (HVAD or HeartMate II) implanted in patients amp;gt;18 years with complete data. Postoperative complications and survival were compared and Cox proportion hazard regression analysis was used to identify predictors of mortality. The overall Kaplan-Meier survival rate was 75% at 1 year, 69% at 2 years and 63% at 3 years. A planned strategy of destination therapy had poorer survival compared to a strategy of bridge to transplantation or decision (2-year survival of 41% vs. 76%, p amp;lt; .001). The most common complications were non-driveline infections (excluding sepsis) (44%), driveline infection (27%), need for continuous renal replacement therapy (25%) and right heart failure (24%). In a multivariate model age and left ventricular diastolic dimension was left as independent risk factors for mortality with a hazard ratio of 1.35 (95% confidence interval (CI) [1.01-1.80], p = .046) per 10 years and 0.88 (95% CI [0.72-0.99], p = .044) per 5 mm, respectively. Conclusion: Outcome with CF LVAD in the Nordic countries was comparable to other cohorts. Higher age and destination therapy require particularly stringent selection.

  • 135.
    Braunschweig, Frieder
    et al.
    Karolinska Institutet, Stockholm, Karolinska University Hospital, Stockholm.
    Linde, Cecilia
    Karolinska Institutet, Stockholm, Karolinska University Hospital, Stockholm.
    Benson, Lina
    Karolinska Institutet, Department of Clinical Science and Education, South Hospital, Stockholm, Sweden.
    Ståhlberg, Marcus
    Karolinska Institutet, Stockholm, Karolinska University Hospital, Stockholm.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lund, Lars H
    Karolinska Institutet, Stockholm, Karolinska University Hospital, Stockholm.
    New York Heart Association functional class, QRS duration, and survival in heart failure with reduced ejection fraction: implications for cardiac resychronization therapy.2017In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 19, no 3, p. 366-376Article in journal (Refereed)
    Abstract [en]

    AIMS: Symptom severity assessed by NYHA functional class and QRS duration are essential criteria for selection of heart failure (HF) patients for CRT. This study assessed the relationship between NYHA class, QRS duration, and survival in a nationwide HF registry.

    METHODS AND RESULTS: We studied 13 423 patients with HF in NYHA class II-IV and LVEF <40% in the Swedish Heart Failure Registry. Survival was followed via the Swedish Population Registry. Of 12 534 patients without CRT (age 71 ± 12 years, 29% women), 51% and 49% were in NYHA class II and III-IV, respectively. Patients in NYHA class II compared with class III-IV were younger (69 vs. 73 years), and had a better systolic function (49% vs. 58% with LVEF <30%), P <0.001 for all, and a favourable co-morbidity profile. QRS duration was 116 ± 29 ms in NYHA class II and 119 ± 29 ms in NYHA class III-IV with QRS ≥120 ms found in 37% vs. 44%, and an LBBB in 23% vs. 28% (P < 0.001 for all). Upon multivariable Cox regression adjusting for 40 clinically relevant variables, mortality risk was higher in NYHA class III-IV vs. class II, with a hazard ratio (HR) of 1.31, 95% confidence interval (CI) 1.23-1.40. Mortality was also higher with QRS prolongation ≥120 ms vs. narrow QRS. The HR in NYHA class II patients with non-LBBB was 1.19 (95% CI 1.05 - 1.36) and in those with LBBB it was 1.16 (95% CI 1.03-1.41). The corresponding HRs in NYHA class III-IV were 1.33 (95% CI 1.21-1.47) and 1.12 (95% CI 1.02-1.22). There was no significant interaction between the effects of NYHA class and QRS duration or morphology on mortality. Applying different scenarios to estimate guideline adherence, fewer patients with NYHA class II (range 14.4-42.6%) compared with NYHA class III-IV (18.0-45.4%) had received a CRT device when indicated.

    CONCLUSIONS: In HF with reduced LVEF, QRS prolongation is common and independently linked to worse survival. The increase in mortality risk associated with QRS prolongation of both LBBB and non-LBBB morphology is similar in NYHA class II and III-IV.

  • 136.
    Brautigam, Lars
    et al.
    Karolinska Institute, Sweden .
    Dahl Ejby Jensen, Lasse
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Karolinska Institute, Sweden .
    Poschmann, Gereon
    University of Dusseldorf, Germany .
    Nystrom, Staffan
    Karolinska Institute, Sweden .
    Bannenberg, Sarah
    Karolinska Institute, Sweden .
    Dreij, Kristian
    Karolinska Institute, Sweden .
    Lepka, Klaudia
    University of Dusseldorf, Germany .
    Prozorovski, Timour
    University of Dusseldorf, Germany .
    Montano, Sergio J
    Karolinska Institute, Sweden .
    Aktas, Orhan
    University of Dusseldorf, Germany .
    Uhlen, Per
    Karolinska Institute, Sweden .
    Stuehler, Kai
    University of Dusseldorf, Germany .
    Cao, Yihai
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Karolinska Institute, Sweden .
    Holmgren, Arne
    Karolinska Institute, Sweden .
    Berndt, Carsten
    Karolinska Institute, Sweden .
    Glutaredoxin regulates vascular development by reversible glutathionylation of sirtuin 12013In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 110, no 50, p. 20057-20062Article in journal (Refereed)
    Abstract [en]

    Embryonic development depends on complex and precisely orchestrated signaling pathways including specific reduction/oxidation cascades. Oxidoreductases of the thioredoxin family are key players conveying redox signals through reversible posttranslational modifications of protein thiols. The importance of this protein family during embryogenesis has recently been exemplified for glutaredoxin 2, a vertebrate-specific glutathione-disulfide oxidoreductase with a critical role for embryonic brain development. Here, we discovered an essential function of glutaredoxin 2 during vascular development. Confocal microscopy and time-lapse studies based on two-photon microscopy revealed that morpholino-based knockdown of glutaredoxin 2 in zebrafish, a model organism to study vertebrate embryogenesis, resulted in a delayed and disordered blood vessel network. We were able to show that formation of a functional vascular system requires glutaredoxin 2-dependent reversible S-glutathionylation of the NAD(+)-dependent protein deacetylase sirtuin 1. Using mass spectrometry, we identified a cysteine residue in the conserved catalytic region of sirtuin 1 as target for glutaredoxin 2-specific deglutathionylation. Thereby, glutaredoxin 2-mediated redox regulation controls enzymatic activity of sirtuin 1, a mechanism we found to be conserved between zebrafish and humans. These results link S-glutathionylation to vertebrate development and successful embryonic angiogenesis.

  • 137.
    Brolin, Gustav
    et al.
    Lund University, Sweden.
    Edenbrandt, Lars
    EQUALIS AB, Sweden; Lund University, Sweden.
    Granerus, Göran
    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.
    Olsson, Anna
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences.
    Afzelius, David
    EQUALIS AB, Sweden.
    Gustafsson, Agneta
    EQUALIS AB, Sweden; Karolinska University Hospital, Sweden.
    Jonsson, Cathrine
    EQUALIS AB, Sweden; Karolinska University Hospital, Sweden.
    Hagerman, Jessica
    EQUALIS AB, Sweden; Skåne University Hospital, Sweden.
    Johansson, Lena
    EQUALIS AB, Sweden; Central Hospital Karlstad, Sweden.
    Riklund, Katrine
    EQUALIS AB, Sweden; Umeå University, Sweden.
    Ljungberg, Michael
    Lund University, Sweden.
    The accuracy of quantitative parameters in Tc-99m-MAG3 dynamic renography: a national audit based on virtual image data2016In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 36, no 2, p. 146-154Article in journal (Refereed)
    Abstract [en]

    Assessment of image analysis methods and computer software used in Tc-99m-MAG3 dynamic renography is important to ensure reliable study results and ultimately the best possible care for patients. In this work, we present a national multicentre study of the quantification accuracy in Tc-99m-MAG3 renography, utilizing virtual dynamic scintigraphic data obtained by Monte Carlo-simulated scintillation camera imaging of digital phantoms with time-varying activity distributions. Three digital phantom studies were distributed to the participating departments, and quantitative evaluation was performed with standard clinical software according to local routines. The differential renal function (DRF) and time to maximum renal activity (T-max) were reported by 21 of the 28 Swedish departments performing Tc-99m-MAG3 studies as of 2012. The reported DRF estimates showed a significantly lower precision for the phantom with impaired renal uptake than for the phantom with normal uptake. The T-max estimates showed a similar trend, but the difference was only significant for the right kidney. There was a significant bias in the measured DRF for all phantoms caused by different positions of the left and right kidney in the anterior-posterior direction. In conclusion, this study shows that virtual scintigraphic studies are applicable for quality assurance and that there is a considerable uncertainty associated with standard quantitative parameters in dynamic Tc-99m-MAG3 renography, especially for patients with impaired renal function.

  • 138.
    Broström, Anders
    et al.
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology. Department of Nursing, School of Health and Welfare, Jönköping University, Sweden.
    Wahlin, Ake
    Institute of Gerontology, School of Health and Welfare, Jönköping University, Sweden.
    Alehagen, Urban
    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.
    Ulander, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Johansson, Peter
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Sex-Specific Associations Between Self-reported Sleep Duration, Cardiovascular Disease, Hypertension, and Mortality in an Elderly Population.2018In: Journal of Cardiovascular Nursing, ISSN 0889-4655, E-ISSN 1550-5049, Vol. 33, no 5, p. 422-428Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Both short and long sleep durations have been associated to increased mortality. Knowledge about sex-specific differences among elderly regarding associations between sleep duration, cardiovascular health, and mortality is sparse.

    OBJECTIVE: The aims of this study are to examine the association between self-reported sleep duration and mortality and to investigate whether this association is sex specific and/or moderated by cardiovascular morbidity, and also to explore potential mediators of sleep duration effects on mortality.

    METHODS: A population-based, observational, cross-sectional design with 6-year follow-up with mortality as primary outcome was conducted. Self-rated sleep duration, clinical examinations, echocardiography, and blood samples (N-terminal fragment of proBNP) were collected. A total of 675 persons (50% women; mean age, 78 years) were divided into short sleepers (≤6 hours; n = 231), normal sleepers (7-8 hours; n = 338), and long sleepers (≥9 hours; n = 61). Data were subjected to principal component analyses. Cardiovascular disease (CVD) and hypertension factors were extracted and used as moderators and as mediators in the regression analyses.

    RESULTS: During follow-up, 55 short sleepers (24%), 68 normal sleepers (20%), and 21 long sleepers (34%) died. Mediator analyses showed that long sleep was associated with mortality in men (hazard ratio [HR], 1.8; P = .049), independently of CVD and hypertension. In men with short sleep, CVD acted as a moderator of the association with mortality (HR, 4.1; P = .025). However, when using N-terminal fragment of proBNP, this effect became nonsignificant (HR, 3.1; P = .06). In woman, a trend to moderation involving the hypertension factor and short sleep was found (HR, 4.6; P = .09).

    CONCLUSION: Short and long sleep duration may be seen as risk markers, particularly among older men with cardiovascular morbidity.

  • 139.
    Broström, Anders
    et al.
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology. Jonkoping Univ, Sweden.
    Wahlin, Ake
    Jonkoping Univ, Sweden.
    Alehagen, Urban
    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.
    Ulander, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Johansson, Peter
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Sex-specific associations between self-reported sleep duration, depression, anxiety, fatigue and daytime sleepiness in an older community-dwelling population2018In: Scandinavian Journal of Caring Sciences, ISSN 0283-9318, E-ISSN 1471-6712, Vol. 32, no 1, p. 290-298Article in journal (Refereed)
    Abstract [en]

    PurposeThe purpose of this study was to explore whether associations between self-reported sleep duration, depressive symptoms, anxiety, fatigue and daytime sleepiness differed in older community-dwelling men and women. DesignCross-sectional. MethodsA community-dwelling sample of 675 older men and women (mean age 77.7years, SD 3.8years) was used. All participants underwent a clinical examination by a cardiologist. Validated questionnaires were used to investigate sleep duration, depressive symptoms, anxiety, fatigue and daytime sleepiness. Subjects were divided into short sleepers (6hours), n=231; normal sleepers (7-8hours), n=338; and long sleepers (9hours), n=61. ancovas were used to explore sex-specific effects. ResultsDepressive symptoms were associated with short sleep in men, but not in women. Fatigue was associated with both short and long sleep duration in men. No sex-specific associations of sleep duration with daytime sleepiness or anxiety were found. ConclusionNurses investigating sleep duration and its correlates, or effects, in clinical practice need to take sex into account, as some associations may be sex specific. Depressive symptoms and fatigue can be used as indicators to identify older men with sleep complaints.

  • 140.
    Brudin, Lars
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Jorfeldt, L.
    Karolinska Institute, Sweden Karolinska University Hospital, Sweden .
    Pahlm, O.
    Skåne University Hospital, Sweden .
    Comparison of two commonly used reference materials for exercise bicycle tests with a Swedish clinical database of patients with normal outcome2014In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 34, no 4, p. 297-307Article in journal (Refereed)
    Abstract [en]

    Background: Reference values for working capacity, blood pressure, heart rate, perceived exertion, etc. during bicycle exercise tests have been sought after for many years. This is because earlier commonly used reference values for physical work capacity have been either too low or too high when compared to the clinical experience of several Swedish departments of clinical physiology. The aim of the study was to compare two commonly used reference materials with normal outcomes from a clinical database. Methods: Data from a clinical database of standardized exercise tests in Kalmar, Sweden, between 2004 and 2012, and having been judged as normal, were divided into 5-year categories of 5-10 to 75-80 years of age covering people from 7 to 80 years of age. Results: Maximal working capacity (W-max), maximal heart rate, maximal systolic blood pressure and maximal perceived exertion are presented for each of the 15 age categories. Regression equations are also presented for each sex with age and height as independent predictors. Quantitative comparisons of W-max are calculated for the three materials and possible explanations discussed. Conclusions: Values of W-max lie between the two reference materials most commonly used in Sweden. In addition, the present material covers subjects aged 7-19 years.

  • 141.
    Brunner-La Rocca, Hans-Peter
    et al.
    Maastricht University Medical Centre, Maastricht, the Netherlands.
    Eurlings, Luc
    Maastricht University Medical Centre, Maastricht, the Netherlands.
    Richards, A Mark
    National University Heart Centre, Singapore.
    Januzzi, James L
    Massachusetts General Hospital, Boston, MA, USA.
    Pfisterer, Matthias E
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Pinto, Yigal M
    Academic Medical Centre, Amsterdam, the Netherlands.
    Karlström, Patric
    County Hospital Ryhov, Jonkoping, Sweden.
    Erntell, Hans
    Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Berger, Rudolf
    Medical University of Vienna, Vienna, Austria.
    Persson, Hans
    11Duke Clinical Research Institute, Duke University, NC, USA.
    O'Connor, Christopher M
    LKH, St Poelten, Austria..
    Moertl, Deddo
    Massachusetts General Hospital, Boston, MA, USA.
    Gaggin, Hanna K
    Massachusetts General Hospital, Boston, MA, USA.
    Frampton, Christopher M
    University of Otago Christchurch, Christchurch Hospital, Christchurch, New Zealand..
    Nicholls, M Gary
    University of Otago Christchurch, Christchurch Hospital, Christchurch, New Zealand..
    Troughton, Richard W
    University of Otago Christchurch, Christchurch Hospital, Christchurch, New Zealand..
    Which heart failure patients profit from natriuretic peptide guided therapy? A meta-analysis from individual patient data of randomized trials.2015In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 17, no 12, p. 1252-1261Article in journal (Refereed)
    Abstract [en]

    AIMS: Previous analyses suggest that heart failure (HF) therapy guided by (N-terminal pro-)brain natriuretic peptide (NT-proBNP) might be dependent on left ventricular ejection fraction, age and co-morbidities, but the reasons remain unclear.

    METHODS AND RESULTS: To determine interactions between (NT-pro)BNP-guided therapy and HF with reduced [ejection fraction (EF) ≤45%; HF with reduced EF (HFrEF), n = 1731] vs. preserved EF [EF > 45%; HF with preserved EF (HFpEF), n = 301] and co-morbidities (hypertension, renal failure, chronic obstructive pulmonary disease, diabetes, cerebrovascular insult, peripheral vascular disease) on outcome, individual patient data (n = 2137) from eight NT-proBNP guidance trials were analysed using Cox-regression with multiplicative interaction terms. Endpoints were mortality and admission because of HF. Whereas in HFrEF patients (NT-pro)BNP-guided compared with symptom-guided therapy resulted in lower mortality [hazard ratio (HR) = 0.78, 95% confidence interval (CI) 0.62-0.97, P = 0.03] and fewer HF admissions (HR = 0.80, 95% CI 0.67-0.97, P = 0.02), no such effect was seen in HFpEF (mortality: HR = 1.22, 95% CI 0.76-1.96, P = 0.41; HF admissions HR = 1.01, 95% CI 0.67-1.53, P = 0.97; interactions P < 0.02). Age (74 ± 11 years) interacted with treatment strategy allocation independently of EF regarding mortality (P = 0.02), but not HF admission (P = 0.54). The interaction of age and mortality was explained by the interaction of treatment strategy allocation with co-morbidities. In HFpEF, renal failure provided strongest interaction (P < 0.01; increased risk of (NT-pro)BNP-guided therapy if renal failure present), whereas in HFrEF patients, the presence of at least two of the following co-morbidities provided strongest interaction (P < 0.01; (NT-pro)BNP-guided therapy beneficial only if none or one of chronic obstructive pulmonary disease, diabetes, cardiovascular insult, or peripheral vascular disease present). (NT-pro)BNP-guided therapy was harmful in HFpEF patients without hypertension (P = 0.02).

    CONCLUSION: The benefits of therapy guided by (NT-pro)BNP were present in HFrEF only. Co-morbidities seem to influence the response to (NT-pro)BNP-guided therapy and may explain the lower efficacy of this approach in elderly patients.

  • 142.
    Brynhildsen, Jan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Sydsjö, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Blomberg, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Claesson, Ing-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Nyström, Fredrik H.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Sydsjö, Adam
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Josefsson, Ann
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Leptin and adiponectin in cord blood from children of normal weight, overweight and obese mothers2013In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 102, no 6, p. 620-624Article in journal (Refereed)
    Abstract [en]

    Aim To study cord blood concentrations of adiponectin and leptin in children born by normal weight, overweight and obese mothers and to study these parameters in relation to a weight gain intervention programme for obese mothers. Methods Ten millilitre cord blood was collected and analysed for leptin and adiponectin concentrations in children with gestational age andgt;37weeks born by 60 normal weight, 45 overweight and 145 obese mothers. 82 obese mothers took part in a weight gain intervention programme. Results Concentrations of leptin and adiponectin were higher in cord blood from children of overweight and obese mothers compared with children of normal weight mothers (leptin: Md 13.2, 30, 3 and 90.2ng/mL respectively, pandlt;0.001; adiponectin 35.9, 205.4, 213.8ng/L pandlt;0.001). No differences were found between overweight and obese mothers. The weight gain intervention programme for obese pregnant women had significant effects on the weight gain during pregnancy but had no effects on cord blood serum concentrations of leptin and adiponectin. Conclusion Cord blood leptin and adiponectin concentrations were higher in children born by overweight or obese women compared with children of normal weight mothers. A weight gain intervention programme for obese pregnant women did not affect these results. Intrauterine exposition to high concentrations of leptin and adiponectin may play a role in weight development later in life.

  • 143.
    Burman, P
    et al.
    Skånes University Hospital Malmö Lund, Sweden .
    Mattsson, A F
    Pfizer Health AB, Sweden .
    Johannsson, G
    University of Gothenburg, Sweden .
    Hoybye, C
    Karolinska University Hospital, Sweden .
    Holmer, H
    Central Hospital Kristianstad, Sweden .
    Dahlqvist, P
    Umeå University, Sweden .
    Berinder, K
    Karolinska University Hospital, Sweden .
    Engstrom, B E
    Uppsala University, Sweden .
    Ekman, Bertil
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Erfurth, E M.
    Skånes University Hospital Malmö Lund, Sweden .
    Svensson, J
    University of Gothenburg, Sweden .
    Wahlberg, J
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Karlsson, F A
    Uppsala University, Sweden .
    Deaths Among Adult Patients With Hypopituitarism: Hypocortisolism During Acute Stress, and De Novo Malignant Brain Tumors Contribute to an Increased Mortality2013In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 98, no 4, p. 1466-1475Article in journal (Refereed)
    Abstract [en]

    Context: Patients with hypopituitarism have an increased standardized mortality rate. The basis for this has not been fully clarified. less thanbrgreater than less thanbrgreater thanObjective: To investigate in detail the cause of death in a large cohort of patients with hypopituitarism subjected to long-term follow-up. less thanbrgreater than less thanbrgreater thanDesign and Methods: All-cause and cause-specific mortality in 1286 Swedish patients with hypopituitarism prospectively monitored in KIMS (Pfizer International Metabolic Database) 1995-2009 were compared to general population data in the Swedish National Cause of Death Registry. In addition, events reported in KIMS, medical records, and postmortem reports were reviewed. less thanbrgreater than less thanbrgreater thanMain Outcome Measures: Standardized mortality ratios (SMR) were calculated, with stratification for gender, attained age, and calendar year during follow-up. less thanbrgreater than less thanbrgreater thanResults: An excess mortality was found, 120 deaths vs 84.3 expected, SMR 1.42 (95% confidence interval: 1.18-1.70). Infections, brain cancer, and sudden death were associated with significantly increased SMRs (6.32, 9.40, and 4.10, respectively). Fifteen patients, all ACTH-deficient, died from infections. Eight of these patients were considered to be in a state of adrenal crisis in connection with death (medical reports and post-mortem examinations). Another 8 patients died from de novo malignant brain tumors, 6 of which had had a benign pituitary lesion at baseline. Six of these 8 subjects had received prior radiation therapy. less thanbrgreater than less thanbrgreater thanConclusion: Two important causes of excess mortality were identified: first, adrenal crisis in response to acute stress and intercurrent illness; second, increased risk of a late appearance of de novo malignant brain tumors in patients who previously received radiotherapy. Both of these causes may be in part preventable by changes in the management of pituitary disease. (J Clin Endocrinol Metab 98: 1466-1475, 2013)

  • 144.
    Burman, Pia
    et al.
    Lund University, Sweden.
    Eden-Engstrom, Britt
    Uppsala University, Sweden.
    Ekman, Bertil
    Region Östergötland, Heart and Medicine Center, Department of Endocrinology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Anders Karlsson, F.
    Uppsala University, Sweden.
    Schwarcz, Erik
    University of Örebro, Sweden.
    Wahlberg Topp, Jeanette
    Region Östergötland, Heart and Medicine Center, Department of Endocrinology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Limited value of cabergoline in Cushings disease: a prospective study of a 6-week treatment in 20 patients2016In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 174, no 1, p. 17-24Article in journal (Refereed)
    Abstract [en]

    Context and objective: The role of cabergoline in Cushings disease (CD) remains controversial. The experience is limited to case reports and few open studies that report the effects determined after &gt;= 1 month of treatment. In prolactinomas and dopamine-responsive GH-secreting tumours, effects of cabergoline are seen within days or weeks. Here, we searched for short-term effects of cabergoline in CD. Design: Twenty patients (19 naive and one recurrent) were included in a prospective study. Cabergoline was administered in increasing doses of 0.5-5 mg/week over 6 weeks. Methods: Urinary free cortisol (UFC) 24 h, morning cortisol and ACTH, and salivary cortisol at 0800, 1600 and 2300 h were determined once weekly throughout. Diurnal curves (six samples) of serum cortisol were measured at start and end. Results: At study end, the median cabergoline dose was 5 mg, range 2.5-5 mg/week. The prolactin levels, markers of compliance, were suppressed in all patients. During the treatment, hypercortisolism varied, gradual and dose-dependent reductions were not seen. Five patients had a &gt;50% decrease of UFC, three had a &gt;50% rise of UFC. Salivary cortisol at 2300 h showed a congruent &gt;50% change with UFC in two of the five cases with decreased UFC, and in one of the three cases with increased UFC. One patient with decreases in both UFC and 2300 h salivary cortisol also had a reduction in diurnal serum cortisol during the course of the study. Conclusions: Cabergoline seems to be of little value in the management of CD. Only one patient had a response-like pattern. Given the known variability of disease activity in CD, this might represent a chance finding.

  • 145.
    Bustamante, Mariana
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Automated Assessment of Blood Flow in the Cardiovascular System Using 4D Flow MRI2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Medical image analysis focuses on the extraction of meaningful information from medical images in order to facilitate clinical assessment, diagnostics and treatment. Image processing techniques have gradually become an essential part of the modern health care system, a consequence of the continuous technological improvements and the availability of a variety of medical imaging techniques.

    Magnetic Resonance Imaging (MRI) is an imaging technique that stands out as non-invasive, highly versatile, and capable of generating high quality images without the use of ionizing radiation. MRI is frequently performed in the clinical setting to assess the morphology and function of the heart and vessels. When focusing on the cardiovascular system, blood flow visualization and quantification is essential in order to fully understand and identify related pathologies. Among the variety of MR techniques available for cardiac imaging, 4D Flow MRI allows for full three-dimensional spatial coverage over time, also including three-directional velocity information. It is a very powerful technique that can be used for retrospective analysis of blood flow dynamics at any location in the acquired volume.

    In the clinical routine, however, flow analysis is typically done using two-dimensional imaging methods. This can be explained by their shorter acquisition times, higher in-plane spatial resolution and signal-to-noise ratio, and their relatively simpler post-processing requirements when compared to 4D Flow MRI. The extraction of useful knowledge from 4D Flow MR data is especially challenging due to the large amount of information included in these images, and typically requires substantial user interaction.

    This thesis aims to develop and evaluate techniques that facilitate the post-processing of thoracic 4D Flow MRI by automating the steps necessary to obtain hemodynamic parameters of interest from the data. The proposed methods require little to no user interaction, are fairly quick, make effective use of the information available in the four-dimensional images, and can easily be applied to sizable groups of data.The addition of the proposed techniques to the current pipeline of 4D Flow MRI analysis simplifies and expedites the assessment of these images, thus bringing them closer to the clinical routine.

    List of papers
    1. Improving left ventricular segmentation in four-dimensional flow MRI using intramodality image registration for cardiac blood flow analysis
    Open this publication in new window or tab >>Improving left ventricular segmentation in four-dimensional flow MRI using intramodality image registration for cardiac blood flow analysis
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    2018 (English)In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 79, no 1, p. 554-560Article in journal (Refereed) Published
    Abstract [en]

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

    Place, publisher, year, edition, pages
    WILEY, 2018
    Keywords
    four-dimensional flow MRI; image registration; blood flow analysis; cardiology; MRI; 4D flow MRI; image registration; blood flow analysis; cardiology; MRI
    National Category
    Medical Image Processing
    Identifiers
    urn:nbn:se:liu:diva-143887 (URN)10.1002/mrm.26674 (DOI)000417926300054 ()28303611 (PubMedID)
    Note

    Funding Agencies|ERC [310612]; 310612; Grant sponsor: Vetenskapsradet [621-2014-6191]; Hjart-Lungfonden [20140398]; Knut och Alice Wallenbergs Stiftelse [KAW 2013.0076]

    Available from: 2017-12-29 Created: 2017-12-29 Last updated: 2018-03-22
    2. Atlas-based analysis of 4D flow CMR: Automated vessel segmentation and flow quantification
    Open this publication in new window or tab >>Atlas-based analysis of 4D flow CMR: Automated vessel segmentation and flow quantification
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    2015 (English)In: Journal of Cardiovascular Magnetic Resonance, ISSN 1097-6647, E-ISSN 1532-429X, Vol. 17, no 87Article in journal (Refereed) Published
    Abstract [en]

    Background: Flow volume quantification in the great thoracic vessels is used in the assessment of several cardiovascular diseases. Clinically, it is often based on semi-automatic segmentation of a vessel throughout the cardiac cycle in 2D cine phase-contrast Cardiovascular Magnetic Resonance (CMR) images. Three-dimensional (3D), time-resolved phase-contrast CMR with three-directional velocity encoding (4D flow CMR) permits assessment of net flow volumes and flow patterns retrospectively at any location in a time-resolved 3D volume. However, analysis of these datasets can be demanding. The aim of this study is to develop and evaluate a fully automatic method for segmentation and analysis of 4D flow CMR data of the great thoracic vessels. Methods: The proposed method utilizes atlas-based segmentation to segment the great thoracic vessels in systole, and registration between different time frames of the cardiac cycle in order to segment these vessels over time. Additionally, net flow volumes are calculated automatically at location