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  • 251.
    Ekman, Anna-Karin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Bivik Eding, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Rundquist, Ingemar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Enerbäck, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    IL-17 and IL-22 Promote Keratinocyte Stemness in the Germinative Compartment in Psoriasis2019In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 139, no 7, p. 1564-+Article in journal (Refereed)
    Abstract [en]

    Psoriasis is an inflammatory skin disorder characterized by the hyperproliferation of basal epidermal cells. It is regarded as T-cell mediated, but the role of keratinocytes (KCs) in the disease pathogenesis has reemerged, with genetic studies identifying KC-associated genes. We applied flow cytometry on KCs from lesional and nonlesional epidermis to characterize the phenotype in the germinative compartment in psoriasis, and we observed an overall increase in the stemness markers CD29 (2.4-fold), CD44 (2.9-fold), CD49f (2.8-fold), and p63 (1.4-fold). We found a reduced percentage of cells positive for the early differentiation marker cytokeratin 10 and a greater fraction of CD29(+) and involucrin thorn cells in the psoriasis KCs than in nonlesional KCs. The up-regulation of stemness markers was more pronounced in the K10(+) cells. Furthermore, the psoriasis cells were smaller, indicating increased proliferation. Treatment with IL-17 and IL-22 induced a similar expression pattern of an up-regulation of p63, CD44, and CD29 in normal KCs and increased the colony-forming efficiency and long-term proliferative capacity, reflecting increased stem cell-like characteristics in the KC population. These data suggest that IL-17 and IL-22 link the inflammatory response to the immature differentiation and epithelial regeneration by acting directly on KCs to promote cell stemness.

    The full text will be freely available from 2020-01-23 08:00
  • 252.
    Ekman, Anna-Karin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Ingrid Asp Psoriasis Research Center.
    Enerbäck, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Ingrid Asp Psoriasis Research Center.
    Lack of preclinical support for the efficacy of histone deacetylase inhibitors in the treatment of psoriasis.2016In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 174, no 2, p. 424-426Article in journal (Refereed)
  • 253.
    Ekman, Anna-Karin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Vegfors, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Bivik, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Enerbäck, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Overexpression of Psoriasin (S100A7) Contributes to Dysregulated Differentiation in Psoriasis.2017In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 97, no 4, p. 441-448Article in journal (Refereed)
    Abstract [en]

    Psoriasin, which is highly expressed in psoriasis, is encoded by a gene located within the epidermal differentiation complex. The aim of this study was to investigate the effect of endogenous psoriasin on disturbed keratinocyte differentiation in psoriasis. Immunohistochemical staining revealed a gradient of psoriasin expression in the psoriatic epidermis with highest expression in the suprabasal, differentiated layers. Induction of keratinocyte differentiation caused concurrent expression of psoriasin and the differentiation marker involucrin. The differentiation-induced psoriasin expression was found to be mediated by the protein kinase C pathway. The downregulation of psoriasin expression by small interfering RNA revealed that psoriasin mediates the expression of involucrin, desmoglein 1, transglutaminase 1 and CD24 in normal differentiation. The lentivirus-mediated overexpression of psoriasin, mimicking the psoriatic milieu, gave rise to an altered regulation of differentiation genes and an expression pattern reminiscent of that in psoriatic epidermis. These findings suggest that psoriasin contributes to the dysregulated differentiation process in the psoriasis epidermis.

  • 254.
    Ekman, Bertil
    et al.
    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.
    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.
    Landberg, Eva
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences.
    Urine oligosaccharide pattern in patients with hyperprolactinaemia2015In: Glycoconjugate Journal, ISSN 0282-0080, E-ISSN 1573-4986, Vol. 32, no 8, p. 635-641Article in journal (Refereed)
    Abstract [en]

    Free milk-type oligosaccharides are produced during pregnancy and lactation and may have an impact on several cells in the immune system. Our aim was to investigate if patients with isolated hyperprolactinaemia, not related to pregnancy, also have increased synthesis and urinary excretion of milk-type oligosaccharides and to compare the excretion pattern with that found during pregnancy. Urine samples were collected as morning sample from 18 patients with hyperprolactinaemia, 13 healthy controls with normal prolactin levels and four pregnant women. After purification, lactose and free oligosaccharides were analysed and quantified by high-performance anion-exchange chromatography with pulsed amperometric detection. The identity of peaks was confirmed by exoglycosidase treatment and comparison with oligosaccharide standards. Prolactin was measured in serum collected between 09 and 11 a.m. by a standardized immunochemical method. Patients with hyperprolactinaemia had higher urinary excretion of lactose than normoprolactinemic controls and urinary lactose correlated positively to prolactin levels (r = 0.51, p less than 0.05). Increased levels of the fucosylated oligosaccharides 2-fucosyl lactose and lacto-di-fucotetraose were found in urine from three and two patients, respectively. The acidic oligosaccharide 3-sialyl lactose was found in high amount in urine from two patients with prolactin of greater than 10,000 mU/l. However, pregnant women in their third trimester had the highest concentration of all these oligosaccharides and excretion increased during pregnancy. This study is first to show that both lactose and certain fucosylated and sialylated milk-type oligosaccharides are increased in some patients with hyperprolactinaemia. It remains to elucidate the functional importance of these findings.

  • 255.
    Ekstedt, Mattias
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Hagström, Hannes
    Unit of Gastroenterology and Hepatology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm .
    Nasr, Patrik
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Stal, Per
    Unit of Gastroenterology and Hepatology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm .
    Kechagias, Stergios
    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 Gastroentorology.
    Hultcrantz, Rolf
    Unit of Gastroenterology and Hepatology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm.
    Nonalcoholic Fatty Liver Disease Activity Score and Mortality: Imperfect But Not Insignificant REPLY2016In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 64, no 1, p. 310-311Article in journal (Refereed)
  • 256.
    Ekstedt, Mattias
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Hagström, Hannes
    Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Nasr, Patrik
    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.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Stål, Per
    Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Hultcrantz, Rolf
    Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up2015In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 61, no 5, p. 1547-1554Article in journal (Refereed)
    Abstract [en]

    Background and rationale for the study: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, strongly associated with insulin resistance and the metabolic syndrome. Nonalcoholic steatohepatitis, i.e. fatty liver accompanied by necroinflammatory changes, is mostly defined by the NAFLD activity score (NAS). The aim of the current study was to determine disease-specific mortality in NAFLD, and evaluate the NAS and fibrosis stage as prognostic markers for overall and disease-specific mortality. Methods: In a cohort study, data from 229 well-characterized patients with biopsy-proven NAFLD were collected. Mean follow-up was 26.4 (± 5.6, range 6-33) years. A reference population was obtained from the National Registry of Population, and information on time and cause of death were obtained from the Registry of Causes of Death. Main results: NAFLD patients had an increased mortality compared with the reference population (HR 1.29, CI 1.04-1.59, p=0.020), with increased risk of cardiovascular disease (HR 1.55, CI 1.11-2.15, p=0.01), hepatocellular carcinoma (HR 6.55, CI 2.14-20.03, p=0.001), infectious disease (HR 2.71, CI 1.02-7.26, p=0.046), and cirrhosis (HR 3.2, CI 1.05-9.81, p=0.041). Overall mortality was not increased in patients with NAS 5-8 and fibrosis stage 0-2 (HR 1.41, CI 0.97-2.06, p=0.07), whereas patients with fibrosis stage 3-4, irrespective of NAS, had increased mortality (HR 3.3, CI 2.27-4.76, p<0.001). Conclusions: NAFLD patients have increased risk of death, with a high risk of death from cardiovascular disease and liver-related disease. The NAS was not able to predict overall mortality, whereas fibrosis stage predicted both overall and disease-specific mortality.

  • 257.
    Ekstrom, Magnus Pär
    et al.
    Lund Univ, Sweden.
    Blomberg, Anders
    Umea Univ, Sweden.
    Bergström, Göran
    Univ Gothenburg, Sweden.
    Brandberg, John
    Univ Gothenburg, Sweden.
    Caidahl, Kenneth
    Univ Gothenburg, Sweden.
    Engström, Gunnar
    Lund Univ, Sweden.
    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.
    Eriksson, Maria
    Karolinska Inst, Sweden.
    Gränsbo, Klas
    Lund Univ, Sweden.
    Hansen, Tomas
    Uppsala Univ, Sweden.
    Jernberg, Tomas
    Karolinska Inst, Sweden.
    Nilsson, Lars
    Umea Univ, Sweden.
    Nilsson, Ulf
    Umea Univ, Sweden.
    Olin, Anna-Carin
    Univ Gothenburg, Sweden.
    Persson, Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Rosengren, Annika
    Univ Gothenburg, Sweden.
    Sandelin, Martin
    Uppsala Univ, Sweden.
    Sköld, Magnus
    Karolinska Inst, Sweden; Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Sundström, Johan
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    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.
    Söderberg, Stefan
    Umea Univ, Sweden.
    Tanash, Hanan A.
    Lund Univ, Sweden.
    Torén, Kjell
    Sahlgrens Univ Hosp, Sweden.
    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, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Lindberg, Eva
    Uppsala Univ, Sweden.
    The association of body mass index, weight gain and central obesity with activity-related breathlessness: the Swedish Cardiopulmonary Bioimage Study2019In: Thorax, ISSN 0040-6376, E-ISSN 1468-3296, Vol. 74, no 10, p. 958-964Article in journal (Refereed)
    Abstract [en]

    Introduction Breathlessness is common in the population, especially in women and associated with adverse health outcomes. Obesity (body mass index (BMI) amp;gt;30 kg/m(2)) is rapidly increasing globally and its impact on breathlessness is unclear. Methods This population-based study aimed primarily to evaluate the association of current BMI and self-reported change in BMI since age 20 with breathlessness (modified Research Council score amp;gt;= 1) in the middle-aged population. Secondary aims were to evaluate factors that contribute to breathlessness in obesity, including the interaction with spirometric lung volume and sex. Results We included 13 437 individuals; mean age 57.5 years; 52.5% women; mean BMI 26.8 (SD 4.3); mean BMI increase since age 20 was 5.0 kg/m(2); and 1283 (9.6%) reported breathlessness. Obesity was strongly associated with increased breathlessness, OR 3.54 (95% CI, 3.03 to 4.13) independent of age, sex, smoking, airflow obstruction, exercise level and the presence of comorbidities. The association between BMI and breathlessness was modified by lung volume; the increase in breathlessness prevalence with higher BMI was steeper for individuals with lower forced vital capacity (FVC). The higher breathlessness prevalence in obese women than men (27.4% vs 12.5%; pamp;lt;0.001) was related to their lower FVC. Irrespective of current BMI and confounders, individuals who had increased in BMI since age 20 had more breathlessness. Conclusion Breathlessness is independently associated with obesity and with weight gain in adult life, and the association is stronger for individuals with lower lung volumes.

  • 258.
    Enerbäck, Charlotta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Univ Michigan, MI 48109 USA.
    Sandin, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Lambert, S.
    Univ Michigan, MI 48109 USA.
    Zawistowski, M.
    Univ Michigan, MI 48109 USA.
    Stuart, P. E.
    Univ Michigan, MI 48109 USA.
    Verma, Deepti
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Tsoi, L. C.
    Univ Michigan, MI 48109 USA.
    Nair, R. P.
    Univ Michigan, MI 48109 USA.
    Johnston, A.
    Univ Michigan, MI 48109 USA.
    Elder, J. T.
    Univ Michigan, MI 48109 USA; Ann Arbor Vet Affairs Hlth Syst, MI USA.
    The psoriasis-protective TYK2 I684S variant impairs IL-12 stimulated pSTAT4 response in skin-homing CD4+and CD8+memory T-cells2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 7043Article in journal (Refereed)
    Abstract [en]

    Tyrosine kinase 2 (TYK2) belongs to the Janus kinase (JAK) family of tyrosine kinases, which transmit signals from activated cytokine receptors. GWAS have consistently implicated TYK2 in psoriasis susceptibility. We performed an in-depth association analysis of TYK2 using GWAS and resequencing data. Strong genetic association of three nonsynonymous variants in the exonic regions of the TYK2 gene (rs34536443, rs12720356, and rs2304256) were found. rs12720356 encoding I684S is predicted to be deleterious based on its location in the pseudokinase domain. We analyzed PBMCs from 29 individuals representing the haplotypes containing each of the significantly associated signals. STAT4 phosphorylation was evaluated by phospho-flow cytometry after CD3/CD28 activation of cells followed by IL-12 stimulation. Individuals carrying the protective I684S variant manifested significantly reduced p-STAT4 levels in CD4 + CD25 + CD45RO + (mean Stimulation Index (S.I.) 48.08, n = 10) and CD8 + CD25 + CD45RO + cells (S.I. 55.71, n = 10), compared to controls homozygous for the ancestral haplotype (S.I. 68.19, n = 10 (p = 0.002) and 76.76 n = 10 (p = 0.0008) respectively). Reduced p-STAT4 levels were also observed in skin-homing, cutaneous lymphocyte associated antigen (CLA)-positive CD4 and CD8 cells from I684S carriers. No significant changes in p-STAT4 for the psoriasis-associated variant rs34536443 was found. These data establish the functional significance of the TYK2 I684S variant in psoriasis susceptibility.

  • 259.
    Engerström, Lars
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping.
    Kramer, Andrew A.
    Prescient Healthcare Consulting, Charlottesville, VA.
    Nolin, Thomas
    The Swedish Intensive Care Registry, Karlstad, Sweden.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Karlström, Göran
    The Swedish Intensive Care Registry, Karlstad, Sweden.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Academic Research Center, Linköping University, Linköping, Sweden.
    Walther, Sten M
    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.
    Comparing Time-Fixed Mortality Prediction Models and Their Effect on ICU Performance Metrics Using the Simplified Acute Physiology Score 3.2016In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 44, no 11Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To examine ICU performance based on the Simplified Acute Physiology Score 3 using 30-day, 90-day, or 180-day mortality as outcome measures and compare results with 30-day mortality as reference.

    DESIGN: Retrospective cohort study of ICU admissions from 2010 to 2014.

    SETTING: Sixty-three Swedish ICUs that submitted data to the Swedish Intensive Care Registry.

    PATIENTS: The development cohort was first admissions to ICU during 2011-2012 (n = 53,546), and the validation cohort was first admissions to ICU during 2013-2014 (n = 57,729).

    INTERVENTIONS: None.

    MEASUREMENTS AND MAIN RESULTS: Logistic regression was used to develop predictive models based on a first level recalibration of the original Simplified Acute Physiology Score 3 model but with 30-day, 90-day, or 180-day mortality as measures of outcome. Discrimination and calibration were excellent for the development dataset. Validation in the more recent 2013-2014 database showed good discrimination (C-statistic: 0.85, 0.84, and 0.83 for the 30-, 90-, and 180-d models, respectively), and good calibration (standardized mortality ratio: 0.99, 0.99, and 1.00; Hosmer-Lemeshow goodness of fit H-statistic: 66.4, 63.7, and 81.4 for the 30-, 90-, and 180-d models, respectively). There were modest changes in an ICU's standardized mortality ratio grouping (< 1.00, not significant, > 1.00) when follow-up was extended from 30 to 90 days and 180 days, respectively; about 11-13% of all ICUs.

    CONCLUSIONS: The recalibrated Simplified Acute Physiology Score 3 hospital outcome prediction model performed well on long-term outcomes. Evaluation of ICU performance using standardized mortality ratio was only modestly sensitive to the follow-up time. Our results suggest that 30-day mortality may be a good benchmark of ICU performance. However, the duration of follow-up must balance between what is most relevant for patients, most affected by ICU care, least affected by administrative policies and practically feasible for caregivers.

  • 260.
    Engerström, Lars
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Nolin, Thomas
    Central Hospital Kristianstad, Sweden.
    Mårdh, Caroline
    Landstinget Värmland, Sweden.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Karlström, Göran
    Landstinget Varmland, Sweden.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences, Forum Östergötland.
    Walther, Sten
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Impact of Missing Physiologic Data on Performance of the Simplified Acute Physiology Score 3 Risk-Prediction Model*2017In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 45, no 12, p. 2006-2013Article in journal (Refereed)
    Abstract [en]

    Objectives: The Simplified Acute Physiology 3 outcome prediction model has a narrow time window for recording physiologic measurements. Our objective was to examine the prevalence and impact of missing physiologic data on the Simplified Acute Physiology 3 models performance. Design: Retrospective analysis of prospectively collected data. Setting: Sixty-three ICUs in the Swedish Intensive Care Registry. Patients: Patients admitted during 2011-2014 (n = 107,310). Interventions: None. Measurements and Main Results: Model performance was analyzed using the area under the receiver operating curve, scaled Briers score, and standardized mortality rate. We used a recalibrated Simplified Acute Physiology 3 model and examined model performance in the original dataset and in a dataset of complete records where missing data were generated (simulated dataset). One or more data were missing in 40.9% of the admissions, more common in survivors and low-risk admissions than in nonsurvivors and high-risk admissions. Discrimination did not decrease with one to two missing variables, but accuracy was highest with no missing data. Calibration was best in the original dataset with a mix of full records and records with some missing values (area under the receiver operating curve was 0.85, scaled Brier 27%, and standardized mortality rate 0.99). With zero, one, and two data missing, the scaled Brier was 31%, 26%, and 21%; area under the receiver operating curve was 0.84, 0.87, and 0.89; and standardized mortality rate was 0.92, 1.05 and 1.10, respectively. Datasets where the missing data were simulated for oxygenation or oxygenation and hydrogen ion concentration together performed worse than datasets with these data originally missing. Conclusions: There is a coupling between missing physiologic data, admission type, low risk, and survival. Increased loss of physiologic data reduced model performance and will deflate mortality risk, resulting in falsely high standardized mortality rates.

  • 261.
    Englund, Anders
    et al.
    Arytmicenter Stockholm, Sweden.
    Walfridsson, Håkan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Kateterburen ablation - bättre än läkemedel.2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112Article in journal (Other academic)
    Abstract [sv]

    Randomiserade studier har visat att ablation av förmaksflimmer har bättre effekt än antiarytmisk medicinering. 

    Enligt europeiska och ameri­kanska riktlinjer kan alla typer av förmaksflimmer komma ifråga för ablation. 

    Hos patienter med paroxysmalt förmaksflimmer är lyckandefrekvensen ca 70–80 procent, medan den är något lägre vid persisterande och långvarigt flimmer. 

    Risken för allvarliga komplikationer är låg, <1,0 procent.

  • 262.
    Englund, Martin
    et al.
    Lund University, Sweden; Boston University, MA 02215 USA.
    Merkel, Peter A.
    University of Penn, PA 19104 USA.
    Tomasson, Gunnar
    University of Iceland, Iceland.
    Segelmark, Mårten
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology.
    Mohammad, Aladdin J.
    Lund University, Sweden; Addenbrookes Hospital, England.
    Comorbidities in Patients with Antineutrophil Cytoplasmic Antibody-associated Vasculitis versus the General Population2016In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 43, no 8, p. 1553-1558Article in journal (Refereed)
    Abstract [en]

    Objective. To evaluate the consultation rates of selected comorbidities in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) compared with the general population in southern Sweden. Methods. We used data from a population-based cohort of patients with AAV diagnosed between 1998 and 2010 in Southern Sweden (701,000 inhabitants). For each patient we identified 4 reference subjects randomly sampled from the general population and matched for year of birth, sex, area of residence, and index year. Using the population-based Skane Healthcare Register, we identified relevant diagnostic codes, registered between 1998 and 2011, for selected comorbidities assigned after the date of diagnosis of AAV or the index date for the reference subjects. We calculated rate ratios for comorbidities (AAV: reference subjects). Results. There were 186 patients with AAV (95 women, mean age 64.5 yrs) and 744 reference persons included in the analysis. The highest rate ratios (AAV: reference) were obtained for osteoporosis (4.6, 95% CI 3.0-7.0), followed by venous thromboembolism (4.0, 95% CI 1.9-8.3), thyroid diseases (2.1, 95% CI 1.3-3.3), and diabetes mellitus (2.0, 95% CI 1.3-2.9). For ischemic heart disease, the rate ratio of 1.5 (95% CI 1.0-2.3) did not reach statistical significance. No statistically significant differences were found for cerebrovascular accidents. Conclusion. AAV is associated with increased consultation rates of several comorbidities including osteoporosis and thromboembolic and endocrine disorders. Comorbid conditions should be taken into consideration when planning and providing care for patients with AAV.

  • 263.
    Enocsson, Helena
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöwall, Christoffer
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Wetterö, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Soluble urokinase plasminogen activator receptor: A valuable biomarker in systemic lupus erythematosus?2015In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 444, p. 234-241Article, review/survey (Refereed)
    Abstract [en]

    Systemic lupus erythematosus (SLE) is a potentially severe autoimmune condition with an unpredictable disease course, often with fluctuations in disease activity over time. Long term inflammation and drug-related side-effects may subsequently lead to permanent organ damage, a consequence which is intimately connected to decreased quality of life and mortality. New lupus biomarkers that convey information regarding inflammation and/or organ damage are thus warranted. Today, there is no clinical biomarker that indicates the risk of damage accrual. Herein we highlight the urokinase plasminogen activator receptor (uPAR) and especially its soluble form (suPAR) that besides having biological functions in e.g. proteolysis, cell migration and tissue homeostasis, recently has emerged as a promising biomarker of inflammation and prognosis of several disorders. A strong association between suPAR and organ damage in SLE was recently demonstrated, and preliminary data (presented in this review) suggests the possibility of a predictive value of suPAR blood levels. The involvement of suPAR in the pathogenesis of SLE remains obscure, but its effects in leukocyte recruitment, phagocytic uptake of dying cells (efferocytosis) and complement regulation suggests that the central parts of the SLE pathogenesis could be regulated by suPAR, and vice versa.

  • 264.
    Enocsson, Helena
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöwall, Christoffer
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Department of Rheumatology. Linköping University, Faculty of Medicine and Health Sciences.
    Wirestam, Lina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Kastbom, Alf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Department of Rheumatology. Linköping University, Faculty of Medicine and Health Sciences.
    Ronnelid, Johan
    Uppsala University, Sweden.
    Wetterö, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Department of Rheumatology. Linköping University, Faculty of Medicine and Health Sciences.
    Four Anti-dsDNA Antibody Assays in Relation to Systemic Lupus Erythematosus Disease Specificity and Activity2015In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 42, no 5, p. 817-825Article in journal (Refereed)
    Abstract [en]

    Objective. Analysis of antibodies against dsDNA is an important diagnostic tool for systemic lupus erythematosus (SLE), and changes in anti-dsDNA antibody levels are also used to assess disease activity. Herein, 4 assays were compared with regard to SLE specificity, sensitivity, and association with disease activity variables. Methods. Cross-sectional sera from 178 patients with SLE, of which 11 were followed consecutively, from a regional Swedish SLE register were analyzed for immunoglobulin G (IgG) anti-dsDNA by bead-based multiplex assay (FIDIS; Theradig), fluoroenzyme-immunoassay (EliA; Phadia/Thermo Fisher Scientific), Crithidia luciliae immunofluorescence test (CLIFT; ImmunoConcepts), and line blot (EUROLINE; Euroimmun). All patients with SLE fulfilled the 1982 American College of Rheumatology and/or the 2012 Systemic Lupus International Collaborating Clinics (SLICC-12) classification criteria. Healthy individuals (n = 100), patients with rheumatoid arthritis (n = 95), and patients with primary Sjogren syndrome (n = 54) served as controls. Results. CLIFT had the highest SLE specificity (98%) whereas EliA had the highest sensitivity (35%). When cutoff levels for FIDIS, EliA, and EUROLINE were adjusted according to SLICC-12 (i.e., double the reference limit when using ELISA), the specificity and sensitivity of FIDIS was comparable to CLIFT. FIDIS and CLIFT also showed the highest concordance (84%). FIDIS performed best regarding association with disease activity in cross-sectional and consecutive samples. Fishers exact test revealed striking differences between methods regarding associations with certain disease phenotypes. Conclusion. CLIFT remains a good choice for diagnostic purposes, but FIDIS performs equally well when the cutoff is adjusted according to SLICC-12. Based on results from cross-sectional and consecutive analyses, FIDIS can also be recommended to monitor disease activity.

  • 265.
    Erdbrügger, Uta
    et al.
    Division of Nephrology, Department of Medicine, University of Virginia Health System, Virginia, USA.
    Kielstein, Jan T
    Department of Hypertension and Nephrology, Medical Clinic V, Klinikum Braunschweig, Braunschweig, Germany.
    Westman, Kerstin
    Department of Nephrology, Lund University, Lund, Sweden.
    Ma, Jennie Z
    Department of Biostatistics, University of Virginia Health System, Virginia, USA.
    Xin, Wenjun
    Department of Biostatistics, University of Virginia Health System, Virginia, USA.
    Bode-Böger, Stephanie M
    Otto-von-Guericke University, Institute of Clinical Pharmacology, Magdeburg, Germany.
    Segelmark, Mårten
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology.
    Rasmussen, Niels
    Department of Biochemistry and Immunology, Statens Seruminstitut, Copenhagen, Denmark.
    De Groot, Kirsten
    Department of Nephrology and Rheumatology, Medical Clinic III, Sana Klinikum, Offenbach, Germany.
    Higher levels of SDMA and not ADMA are associated with poorer survival of trial patients with systemic ANCA-associated vasculitis2018In: European journal of rheumatology, ISSN 2147-9720, Vol. 5, no 3, p. 153-159Article in journal (Refereed)
    Abstract [en]

    Endothelial dysfunction, increased cardiovascular events (CVE), and accelerated atherosclerosis have been described in patients with small vessel vasculitis and collagen vascular disease. Identifying predictors of cardiovascular risk will help to optimize short- and long-term care of patients with vasculitis. The present study investigates the predictive role of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) and its stereoisomer symmetric dimethylarginine (SDMA) for cardiovascular risk, all-cause mortality, and renal function in patients with anti-neutrophil-cytoplasmic antibodies-associated small vessel vasculitis (AASV) subjected to standardized treatment regimens in four European Vasculitis Study Group trials representing all stages of renal disease.

  • 266.
    Ergatoudes, Constantinos
    et al.
    Univ Gothenburg, Sweden.
    Schaufelberger, Maria
    Univ Gothenburg, Sweden.
    Andersson, Bert
    Univ Gothenburg, Sweden.
    Pivodic, Aldina
    Statistiska Konsultgruppen, 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.
    Fu, Michael
    Univ Gothenburg, Sweden.
    Non-cardiac comorbidities and mortality in patients with heart failure with reduced vs. preserved ejection fraction: a study using the Swedish Heart Failure Registry2019In: Clinical Research in Cardiology, ISSN 1861-0684, E-ISSN 1861-0692, Vol. 108, no 9, p. 1025-1033Article in journal (Refereed)
    Abstract [en]

    Background Heart failure (HF) and non-cardiac comorbidities often coexist and are known to have an adverse effect on outcome. However, the prevalence and prognostic impact of non-cardiac comorbidities in patients with HF with reduced ejection fraction (HFrEF) vs. those with preserved (HFpEF) remain inadequately studied. Methods and results We used data from the Swedish Heart Failure Registry from 2000 to 2012. HFrEF was defined as EF amp;lt; 50% and HFpEF as EF amp;gt;= 50%. Of 31 344 patients available for analysis, 79.3% (n = 24 856) had HFrEF and 20.7% (n = 6 488) HFpEF. The outcome was all-cause mortality. We examined the association between ten non-cardiac comorbidities and mortality and its interaction with EF using adjusted hazard ratio (HR). Stroke, anemia, gout and cancer had a similar impact on mortality in both phenotypes, whereas diabetes (HR 1.57, 95% confidence interval [CI] [1.50-1.65] vs. HR 1.39 95% CI [1.27-1.51], p = 0.0002), renal failure (HR 1.65, 95% CI [1.57-1.73] vs. HR 1.44, 95% CI [1.32-1.57], p = 0.003) and liver disease (HR 2.13, 95% CI [1.83-2.47] vs. HR 1.42, 95% CI [1.09-1.85] p = 0.02) had a higher impact in the HFrEF patients. Moreover, pulmonary disease (HR 1.46, 95% CI [1.40-1.53] vs. HR 1.66 95% CI [1.54-1.80], p = 0.007) was more prominent in the HFpEF patients. Sleep apnea was not associated with worse prognosis in either group. No significant variation was found in the impact over the 12-year study period. Conclusions Non-cardiac comorbidities contribute significantly but differently to mortality, both in HFrEF and HFpEF. No significant variation was found in the impact over the 12-year study period. These results emphasize the importance of including the management of comorbidities as a part of a standardized heart failure care in both HF phenotypes.

  • 267.
    Ericsson, Maria
    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 Cardiology in Linköping.
    Angerud, Karin H.
    Umea Univ, Sweden; Umea Univ, Sweden.
    Brannstrom, Margareta
    Umea Univ, Sweden.
    Sederholm Lawesson, Sofia
    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.
    Strömberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Thylén, Ingela
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Interaction between tele-nurses and callers with an evolving myocardial infarction: Consequences for level of directed care2019In: European Journal of Cardiovascular Nursing, ISSN 1474-5151, E-ISSN 1873-1953, Vol. 18, no 7, p. 545-553Article in journal (Refereed)
    Abstract [en]

    Background: Rapid contact with emergency medical services is imperative to save the lives of acute myocardial infarction patients. However, many patients turn to a telehealth advisory nurse instead, where the delivery of urgent and safe care largely depends on how the interaction in the call is established. Purpose: The purpose of this study was to explore the interaction between tele-nurses and callers with an evolving myocardial infarction after contacting a national telehealth advisory service number as their first medical contact. Method: Twenty men and 10 women (aged 46-89 years) were included. Authentic calls were analysed using inductive content analysis. Findings: One overall category, Movement towards directed level of care, labelled the whole interaction between the tele-nurse and the caller. Four categories conceptualised the different interactions: a distinct, reasoning, indecisive or irrational interaction. The interactions described how tele-nurses and callers assessed and elaborated on symptoms, context and actions. The interaction was pivotal for progress in the dialogue and affected the achievement of mutual understanding in the communicative process. An indecisive or irrational interaction could increase the risk of failing to recommend or call for acute care. Conclusion: The interaction in the communication could either lead or mislead the level of care directed in the call. This study adds new perspectives to the communicative process in the acute setting in order to identify a myocardial infarction and the level of urgency from both individuals experiencing myocardial infarction and professionals in the health system.

  • 268.
    Eriksson, B.
    et al.
    Karolinska Inst, Sweden.
    Wandell, P.
    Karolinska Inst, 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.
    Nasman, P.
    KTH Royal Inst Technol, Sweden.
    Lund, L. H.
    Karolinska Univ Hosp, Sweden.
    Edner, M.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Comorbidities, risk factors and outcomes in patients with heart failure and an ejection fraction of more than or equal to 40% in primary care- and hospital care-based outpatient clinics2018In: Scandinavian Journal of Primary Health Care, ISSN 0281-3432, E-ISSN 1502-7724, Vol. 36, no 2, p. 207-215Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study is to describe patients with heart failure and an ejection fraction (EF) of more than or equal to 40%, managed in both Primary- and Hospital based outpatient clinks separately with their prognosis, comorbidities and risk factors. Further to compare the heart failure medication in the two groups. Design: We used the prospective Swedish Heart Failure Registry to include 9654 out-patients who had HF and EF amp;gt;= 40%, 1802 patients were registered in primary care and 7852 in hospital care. Descriptive statistical tests were used to analyze base line characteristics in the two groups and multivariate logistic regression analysis to assess mortality rate in the groups separately. Setting: The prospective Swedish Heart Failure Registry. Setting: The prospective Swedish Heart Failure Registry. Subjects: Patients with heart failure and an ejection fraction (EF) of more than or equal to 40%. Main outcome measures: Comorbidities, risk factors and mortality. Results: Mean-age was 77.5 (primary care) and 70.3 years (hospital care) p amp;lt; 0.0001, 46.7 vs. 36.3% women respectively (p amp;lt; 0.0001) and EF amp;gt;= 50% 26.1 vs. 13.4% (p amp;lt; 0.0001). Co-morbidities were common in both groups (97.2% vs. 92.3%), the primary care group having more atrial fibrillation, hypertension, ischemic heart disease and COPD. According to the multivariate logistic regression analysis smoking, COPD and diabetes were the most important independent risk factors in the primary care group and valvular disease in the hospital care group. All-cause mortality during mean follow-up of almost 4 years was 315% in primary care and 27.8% in hospital care. One year-mortality rates were 7.8%, and 7.0% respectively. Conclusion: Any co-morbidity was noted in 97% of the HF-patients with an EF of more than or equal to 40% managed at primary care based out-patient clinics and these patients had partly other independent risk factors than those patients managed in hospital care based outpatients clinics. Our results indicate that more attention should be payed to manage COPD in the primary care group.

  • 269.
    Eriksson, D.
    et al.
    Karolinska Institute, Sweden; Metab and Diabet Karolinska University Hospital, Sweden.
    Bianchi, M.
    Uppsala University, Sweden.
    Landegren, N.
    Karolinska Institute, Sweden; Uppsala University, Sweden.
    Nordin, J.
    Uppsala University, Sweden.
    Dalin, F.
    Karolinska Institute, Sweden; Uppsala University, Sweden.
    Mathioudaki, A.
    Uppsala University, Sweden.
    Eriksson, G. N.
    Karolinska Institute, Sweden.
    Hultin-Rosenberg, L.
    Uppsala University, Sweden.
    Dahlqvist, J.
    Uppsala University, Sweden.
    Zetterqvist, H.
    Uppsala University, Sweden; Uppsala University, Sweden.
    Karlsson, A.
    Uppsala University, Sweden.
    Hallgren, A.
    Karolinska Institute, Sweden; Uppsala University, Sweden.
    Farias, F. H. G.
    Uppsala University, Sweden.
    Muren, E.
    Uppsala University, Sweden.
    Ahlgren, K. M.
    Uppsala University, Sweden.
    Lobell, A.
    Uppsala University, Sweden.
    Andersson, G.
    Swedish University of Agriculture Science, Sweden.
    Tandre, K.
    Uppsala University, Sweden.
    Dahlqvist, S. R.
    Umeå University, Sweden.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Rönnblom, L.
    Uppsala University, Sweden.
    Hulting, A. -L.
    Karolinska Institute, Sweden.
    Wahlberg Topp, Jeanette
    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.
    Ekwall, O.
    University of Gothenburg, Sweden.
    Dahlqvist, P.
    Umeå University, Sweden.
    Meadows, J. R. S.
    Uppsala University, Sweden.
    Bensing, S.
    Metab and Diabet Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Lindblad-Toh, K.
    Uppsala University, Sweden; Broad Institute MIT and Harvard, MA USA.
    Kampe, O.
    Karolinska Institute, Sweden; Metab and Diabet Karolinska University Hospital, Sweden; Uppsala University, Sweden.
    Pielberg, G. R.
    Uppsala University, Sweden.
    Extended exome sequencing identifies BACH2 as a novel major risk locus for Addisons disease2016In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 286, no 6, p. 595-608Article in journal (Refereed)
    Abstract [en]

    BackgroundAutoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addisons disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology. MethodsTo understand the genetic background of Addisons disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addisons disease and 1394 controls. ResultsWe identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 x 10(-15), MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addisons disease development. We also confirmed the previously known associations with the HLA complex. ConclusionWhilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addisons disease, we have identified BACH2 as a major risk locus in Addisons disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.

  • 270.
    Eriksson, Daniel
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Bianchi, Matteo
    Uppsala Univ, Sweden.
    Landegren, Nils
    Karolinska Inst, Sweden; Uppsala Univ, Sweden.
    Dalin, Frida
    Karolinska Inst, Sweden; Uppsala Univ, Sweden.
    Skov, Jakob
    Karolinska Inst, Sweden.
    Hultin-Rosenberg, Lina
    Uppsala Univ, Sweden.
    Mathioudaki, Argyri
    Uppsala Univ, Sweden.
    Nordin, Jessika
    Uppsala Univ, Sweden.
    Hallgren, Asa
    Karolinska Inst, Sweden.
    Andersson, Goran
    Swedish Univ Agr Sci, Sweden.
    Tandre, Karolina
    Uppsala Univ, Sweden.
    Rantapaa Dahlqvist, Solbritt
    Umea Univ, Sweden.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Ronnblom, Lars
    Uppsala Univ, Sweden.
    Hulting, Anna-Lena
    Not Found:[Eriksson, Daniel; Landegren, Nils; Dalin, Frida; Hallgren, Asa; Kampe, Olle] Karolinska Inst, Dept Med Solna, Ctr Mol Med, Stockholm, Sweden; [Eriksson, Daniel; Bensing, Sophie; Kampe, Olle] Karolinska Univ Hosp, Dept Endocrinol Metab and Diabet, Stockholm, Sweden; [Bianchi, Matteo; Hultin-Rosenberg, Lina; Mathioudaki, Argyri; Nordin, Jessika; Meadows, Jennifer R. S.; Lindblad-Toh, Kerstin; Pielberg, Gerli Rosengren] Uppsala Univ, Dept Med Biochem and Microbiol, Sci Life Lab, Uppsala, Sweden; [Landegren, Nils; Dalin, Frida; Tandre, Karolina; Ronnblom, Lars] Uppsala Univ, Dept Med Sci, Sci Life Lab, Uppsala, Sweden; [Skov, Jakob; Bensing, Sophie] Karolinska Inst, Dept Mol Med and Surg, Stockholm, Sweden; [Andersson, Goran] Swedish Univ Agr Sci, Dept Anim Breeding and Genet, Uppsala, Sweden; [Dahlqvist, Solbritt Rantapaa; Dahlqvist, Per] Umea Univ, Dept Publ Hlth and Clin Med, Umea, Sweden; [Soderkvist, Peter; Wahlberg, Jeanette] Linkoping Univ, Dept Clin and Expt Med, Linkoping, Sweden; [Wahlberg, Jeanette] Linkoping Univ, Dept Endocrinol, Linkoping, Sweden; [Wahlberg, Jeanette] Linkoping Univ, Dept Med and Hlth Sci, Linkoping, Sweden; [Ekwall, Olov] Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Pediat, Gothenburg, Sweden; [Ekwall, Olov] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol and Inflammat Res, Gothenburg, Sweden; [Lindblad-Toh, Kerstin] Broad Inst MIT and Harvard, Cambridge, MA USA; [Kampe, Olle] KG Jebsen Ctr Autoimmune Dis, Bergen, Norway;.
    Wahlberg, Jeanette
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Dahlqvist, Per
    Umea Univ, Sweden.
    Ekwall, Olov
    Univ Gothenburg, Sweden; Univ Gothenburg, Sweden.
    Meadows, Jennifer R. S.
    Uppsala Univ, Sweden.
    Lindblad-Toh, Kerstin
    Uppsala Univ, Sweden; Broad Inst MIT and Harvard, MA USA.
    Bensing, Sophie
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Pielberg, Gerli Rosengren
    Uppsala Univ, Sweden.
    Kampe, Olle
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; KG Jebsen Ctr Autoimmune Dis, Norway.
    Common genetic variation in the autoimmune regulator (AIRE) locus is associated with autoimmune Addisons disease in Sweden2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 8395Article in journal (Refereed)
    Abstract [en]

    Autoimmune Addisons disease (AAD) is the predominating cause of primary adrenal failure. Despite its high heritability, the rarity of disease has long made candidate-gene studies the only feasible methodology for genetic studies. Here we conducted a comprehensive reinvestigation of suggested AAD risk loci and more than 1800 candidate genes with associated regulatory elements in 479 patients with AAD and 2394 controls. Our analysis enabled us to replicate many risk variants, but several other previously suggested risk variants failed confirmation. By exploring the full set of 1800 candidate genes, we further identified common variation in the autoimmune regulator (AIRE) as a novel risk locus associated to sporadic AAD in our study. Our findings not only confirm that multiple loci are associated with disease risk, but also show to what extent the multiple risk loci jointly associate to AAD. In total, risk loci discovered to date only explain about 7% of variance in liability to AAD in our study population.

  • 271.
    Eriksson, Daniel
    et al.
    Karolinska Institutet, Stockholm, Karolinska University Hospital, Stockholm, Sweden.
    Dalin, Frida
    Karolinska Institutet, Stockholm, Uppsala University, Uppsala, Sweden.
    Eriksson, Gabriel Nordling
    Karolinska Institutet, Stockholm, Sweden.
    Landegren, Nils
    Karolinska Institutet, Stockholm, Sweden, Uppsala University, Uppsala, Sweden.
    Bianchi, Matteo
    Uppsala University, Uppsala, Sweden.
    Hallgren, Åsa
    Karolinska Institutet, Stockholm, Uppsala University, Uppsala, Sweden.
    Dahlqvist, Per
    Umeå University, Umeå, Sweden.
    Wahlberg, Jeanette
    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. Linköping University, Department of Clinical and Experimental Medicine.
    Ekwall, Olov
    Sahlgrenska Academy, University of Gothenburg, Gothenburg.
    Winqvist, Ola
    Karolinska Institutet, Stockholm, Sweden.
    Catrina, Sergiu-Bogdan
    Karolinska Institutet, Stockholm, Sweden.
    Rönnelid, Johan
    Uppsala University, Uppsala, Sweden.
    Hulting, Anna-Lena
    Karolinska Institutet, Stockholm, Sweden.
    Lindblad-Toh, Kerstin
    Uppsala University, Uppsala, Sweden, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts.
    Alimohammadi, Mohammad
    Uppsala University, Uppsala, Sweden.
    Husebye, Eystein S
    Karolinska Institutet, Stockholm, University of Bergen, Bergen, K.G. Jebsen Center for Autoimmune Disorders, Bergen, Norway.
    Knappskog, Per Morten
    University of Bergen, Bergen, Haukeland University Hospital, Bergen, Norway.
    Rosengren Pielberg, Gerli
    Uppsala University, Uppsala, Sweden.
    Bensing, Sophie
    Karolinska University Hospital, Stockholm, Karolinska Institutet, Stockholm, Sweden.
    Kämpe, Olle
    Karolinska Institutet, Stockholm, Karolinska University Hospital, Stockholm, Uppsala University, Uppsala, Sweden, K.G. Jebsen Center for Autoimmune Disorders, Bergen, Norway.
    Cytokine Autoantibody Screening in the Swedish Addison Registry Identifies Patients With Undiagnosed APS1.2018In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 103, no 1, p. 179-186Article in journal (Refereed)
    Abstract [en]

    Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features autoimmune Addison disease as a major component. Although APS1 accounts for only a small fraction of all patients with Addison disease, early identification of these individuals is vital to prevent the potentially lethal complications of APS1.

    Objective: To determine whether available serological and genetic markers are valuable screening tools for the identification of APS1 among patients diagnosed with Addison disease.

    Design: We systematically screened 677 patients with Addison disease enrolled in the Swedish Addison Registry for autoantibodies against interleukin-22 and interferon-α4. Autoantibody-positive patients were investigated for clinical manifestations of APS1, additional APS1-specific autoantibodies, and DNA sequence and copy number variations of AIRE.

    Results: In total, 17 patients (2.5%) displayed autoantibodies against interleukin-22 and/or interferon-α4, of which nine were known APS1 cases. Four patients previously undiagnosed with APS1 fulfilled clinical, genetic, and serological criteria. Hence, we identified four patients with undiagnosed APS1 with this screening procedure.

    Conclusion: We propose that patients with Addison disease should be routinely screened for cytokine autoantibodies. Clinical or serological support for APS1 should warrant DNA sequencing and copy number analysis of AIRE to enable early diagnosis and prevention of lethal complications.

  • 272.
    Eriksson, Elisabet
    et al.
    Univ Gavle, Sweden.
    Berg, Sören
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Engstrom, Maria
    Univ Gavle, Sweden; Uppsala Univ, Sweden; Lishui Univ, Peoples R China.
    Internationally educated nurses and medical graduates experiences of getting a license and practicing in Sweden - a qualitative interview study2018In: BMC Medical Education, ISSN 1472-6920, E-ISSN 1472-6920, Vol. 18, article id 296Article in journal (Refereed)
    Abstract [en]

    Background: The Swedish healthcare system has an increased need for nurses and physicians, and the number of International Educated Nurses (IENs) and International Medical Graduates (IMGs) seeking job opportunities and a license to practice in Sweden is rising. This study explored how IENs and IMGs describe their experience of getting a license to practice, their perceptions of working in Sweden and of how their intercultural competence is utilized. Method: A qualitative study based on semi-structured interviews with 11 IENs and 11 IMGs. The interviews were conducted between 2015 and 2017. The data were analyzed using qualitative content analysis. Results: Three main themes were identified: Getting a license - a different story, The work is familiar, yet a lot is new, Trying to master a new language. The time to obtain a license to practice and finding a job was shorter for IENs and IMGs coming from European countries than for those from non-European countries. Some of the experiences of getting a license to practice and of entering a new workplace in another country were the same for nurses and physicians. In general, both IENs and IMGs felt welcomed and used their intercultural competence at work. Lack of language skills was regarded as the main problem for both professions, while workplace introduction was shorter for IMGs than for IENs. Conclusions: Problems related to language and culture are often underestimated, therefore organizations and managers employing IENs and IMGs should provide longer workplace introduction to facilitate the acculturation process. More time-efficient language courses specifically adapted to IENs and IMGs could make the transition easier and shorten the time to obtain a license to practice for both professions.

  • 273.
    Eriksson, Jonatan
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    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. University of Calif San Francisco, CA USA.
    Carlhäll, Carljohan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Spatial Heterogeneity of Four-Dimensional Relative Pressure Fields in the Human Left Ventricle2015In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 74, no 6, p. 1716-1725Article in journal (Refereed)
    Abstract [en]

    Purpose: To assess the spatial heterogeneity of the four-dimensional (4D) relative pressure fields in the healthy human left ventricle (LV) and provide reference data for normal LV relative pressure. Methods: Twelve healthy subjects underwent a cardiac MRI examination where 4D flow and morphological data were acquired. The latter data were segmented and used to define the borders of the LV for computation of relative pressure fields using the pressure Poisson equation. The LV lumen was divided into 17 pie-shaped segments. Results: In the normal left ventricle, the relative pressure in the apical segments was significantly higher relative to the basal segments (P &lt; 0.0005) along both the anteroseptal and inferolateral sides after the peaks of early (E-wave) and late (A-wave) diastolic filling. The basal anteroseptal segment showed significantly lower median pressure than the opposite basal inferolateral segment during both E-wave (P &lt; 0.0005) and A-wave (P = 0.0024). Conclusion: Relative pressure in the left ventricle is heterogeneous. During diastole, the main pressure differences in the LV occur along the basal-apical axis. However, pressure differences were also found in the short axis direction and may reflect important aspects of atrioventricular coupling. Additionally, this study provides reference data on LV pressure dynamics for a group of healthy subjects. (C) 2014 Wiley Periodicals, Inc.

  • 274.
    Eriksson, Jonatan
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Zajac, Jakub
    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).
    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.
    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. University of Calif San Francisco, CA USA.
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Carlhäll, Carljohan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Left ventricular hemodynamic forces as a marker of mechanical dyssynchrony in heart failure patients with left bundle branch block2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 2971Article in journal (Refereed)
    Abstract [en]

    Left bundle branch block (LBBB) causes left ventricular (LV) dyssynchrony which is often associated with heart failure. A significant proportion of heart failure patients do not demonstrate clinical improvement despite cardiac resynchronization therapy (CRT). How LBBB-related effects on LV diastolic function may contribute to those therapeutic failures has not been clarified. We hypothesized that LV hemodynamic forces calculated from 4D flow MRI could serve as a marker of diastolic mechanical dyssynchrony in LBBB hearts. MRI data were acquired in heart failure patients with LBBB or matched patients without LBBB. LV pressure gradients were calculated from the Navier-Stokes equations. Integration of the pressure gradients over the LV volume rendered the hemodynamic forces. The findings demonstrate that the LV filling forces are more orthogonal to the main LV flow direction in heart failure patients with LBBB compared to those without LBBB during early but not late diastole. The greater the conduction abnormality the greater the discordance of LV filling force with the predominant LV flow direction (r(2) = 0.49). Such unique flow-specific measures of mechanical dyssynchrony may serve as an additional tool for considering the risks imposed by conduction abnormalities in heart failure patients and prove to be useful in predicting response to CRT.

  • 275.
    Eriksson, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Andersson, Carina
    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.
    Cassel, Petra
    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.
    Nyström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    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.
    Letter: Increase in Th17-associated CCL20 and decrease in Th2-associated CCL22 plasma chemokines in active ANCA-associated vasculitis2015In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 44, no 1, p. 80-83Article in journal (Other academic)
    Abstract [en]

    n/a

  • 276.
    Eriksson, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Wallin, Philip
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Sjöwall, Christopher
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Clinical Experience of Sirolimus Regarding Efficacy and Safety in Systemic Lupus Erythematosus2019In: Frontiers in Pharmacology, ISSN 1663-9812, E-ISSN 1663-9812, Vol. 10, article id 82Article in journal (Refereed)
    Abstract [en]

    New treatment options constitute unmet needs for patients diagnosed with systemic lupus erythematosus (SLE). Inhibition of the mammalian target of rapamycin (mTOR) pathway by sirolimus, a drug approved and in clinical use to prevent transplant rejection, has shown promising effects in lupus animal models as well as in patients with both antiphospholipid syndrome and SLE. Sirolimus inhibits antigen-induced T cell proliferation and increases the number of circulating regulatory T cells. Recently, sirolimus was tested in an open label phase 1/2 trial, including 43 patients with active SLE, resistant or intolerant to conventional medications. The results were encouraging showing a progressive improvement, including mucocutaneous and musculoskeletal manifestations. At our university unit, we have more than 16 years experience of sirolimus as treatment for non-renal manifestations of SLE. Herein, we retrospectively evaluated data on tolerance, dosage, affected organ systems, disease activity measures, corticosteroid reduction, concomitant immunosuppressive therapies, and patient-reported outcome measures (PROMs) such as pain intensity, fatigue, well-being and quality-of-life (QoL) in 27 Caucasian patients with mildly active SLE. Musculoskeletal manifestation was the main reason for sirolimus treatment followed by skin involvement and leukocytopenia. Mean time on sirolimus was 47.1 (range 2-140) months. Decreasing global disease activity was observed, as measured by the clinical SLE disease activity index-2000, with a mean reduction of 2.5 points (range -10 to 0) and a corresponding mean reduction of the physicians global assessment (0-4) of 0.64 (range -2 to 0). The mean daily dose of corticosteroids (prednisolone) was reduced by 3.3 mg (-12.5 to 0). Non-significant trends toward improvements of QoL and pain intensity were found. Serious side-effects were not seen during sirolimus treatment, but early withdrawal due to nausea (n = 4) and non-serious infections (n = 2) appeared. This observational study, including longtime real-life use of sirolimus in SLE, is the largest to date and it essentially confirms the results of the recent phase 1/2 trial. Our data indicate that sirolimus is efficient in patients with musculoskeletal SLE manifestations, particularly arthritis and tendinitis. Further randomized controlled trials evaluating the potential benefits of sirolimus in SLE are warranted, but should aim to enroll patients with shorter disease duration, less accrued damage, and more diverse ethnicities.

  • 277.
    Eriksson, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Segelmark, Mårten
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology.
    Hallböök, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Frequency, Diagnosis, Treatment, and Outcome of Gastrointestinal Disease in Granulomatosis with Polyangiitis and Microscopic Polyangiitis2018In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 45, no 4, p. 529-537Article in journal (Refereed)
    Abstract [en]

    Objective. Involvement of the gastrointestinal (GI) tract is a rare complication of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). The aim was to describe frequency, diagnosis, treatment, and outcome of GI disease in a large series of patients in a single center. Methods. A database that includes all patients with GPA and MPA diagnosed since 1997 in a defined area of southeastern Sweden as well as prevalent older cases and tertiary referral patients was screened for patients with GI disease. Data were retrieved from the patients medical records, and GI manifestations of vasculitis were defined as proposed by Pagnoux, et al in 2005. Results. Fourteen (6.5%) of 216 consecutive patients with GPA/MPA had GI manifestations. Abdominal pain and GI bleeding were the most common symptoms. Radiology was important for detection of GI disease, while endoscopy failed to support the diagnosis in many patients. Because of perforation, 5 patients underwent hemicolectomy or small intestine resection. Primary anastomosis was created in 2/5 and enterostomy in 3/5 patients. One patient had a hemicolectomy because of lower GI bleeding. One sigmoid abscess was treated with drainage, and 1 intraabdominal bleeding condition with arterial coiling. Two patients died from GI disease. GPA and MPA patients with and without GI disease exhibited a similar overall survival. Conclusion. GI disease was found in 6.5% among 216 patients with GPA or MPA. Surgery was judged necessary only in cases with GI perforation or severe bleeding. Multidisciplinary engagement is strongly recommended.

  • 278.
    Erlinge, D.
    et al.
    Lund University, Sweden.
    Omerovic, E.
    Sahlgrens University Hospital, Sweden.
    Frobert, O.
    Örebro University, Sweden.
    Linder, R.
    Danderyd Hospital, Sweden.
    Danielewicz, M.
    Karlstad Hospital, Sweden.
    Hamid, M.
    Mälarsjukhuset, Sweden.
    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.
    Henareh, L.
    Karolinska University Hospital, Sweden.
    Wagner, H.
    Helsingborg Lasarett, Sweden.
    Hardhammar, P.
    Halmstad County Hospital, Sweden.
    Sjogren, I.
    Falun Central Hospital, Sweden.
    Stewart, J.
    Skaraborgs Hospital, Sweden.
    Grimfjard, P.
    Västmanlands Sjukhus, Sweden.
    Jensen, J.
    Karolinska Institute, Sweden.
    Aasa, M.
    Södersjukhuset AB, Sweden.
    Robertsson, L.
    Södra Älvsborgs Sjukhus, Sweden.
    Lindroos, P.
    Karolinska Institute, Sweden.
    Haupt, J.
    Sunderby Sjukhus, Sweden.
    Wikstrom, H.
    Kristianstad Hospital, Sweden.
    Ulvenstam, A.
    Östersund Hospital, Sweden.
    Bhiladvala, P.
    Lund University, Sweden.
    Lindvall, B.
    Sundsvall Hospital, Sweden.
    Lundin, A.
    Lund University, Sweden.
    Todt, T.
    Lund University, Sweden.
    Ioanes, D.
    Sahlgrens University Hospital, Sweden.
    Ramunddal, T.
    Sahlgrens University Hospital, Sweden.
    Kellerth, T.
    Örebro University, Sweden.
    Zagozdzon, L.
    Örebro University, Sweden.
    Gotberg, M.
    Lund University, Sweden.
    Andersson, J.
    Umeå University, Sweden.
    Angeras, O.
    Sahlgrens University Hospital, Sweden.
    Ostlund, O.
    Uppsala University, Sweden.
    Lagerqvist, B.
    Uppsala University, Sweden.
    Held, C.
    Uppsala University, Sweden.
    Wallentin, L.
    Uppsala University, Sweden.
    Schersten, F.
    Lund University, Sweden.
    Eriksson, P.
    Umeå University, Sweden.
    Koul, S.
    Lund University, Sweden.
    James, S.
    Uppsala University, Sweden.
    Bivalirudin versus Heparin Monotherapy in Myocardial Infarction2017In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 377, no 12, p. 1132-1142Article in journal (Refereed)
    Abstract [en]

    BACKGROUND The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y 12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors. METHODS In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y(12) inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The patients were randomly assigned to receive bivalirudin or heparin during PCI, which was performed predominantly with the use of radial-artery access. The primary end point was a composite of death from any cause, myocardial infarction, or major bleeding during 180 days of follow-up. RESULTS A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end-point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P = 0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P = 0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P = 0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P = 0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P = 0.76). CONCLUSIONS Among patients undergoing PCI for myocardial infarction, the rate of the composite of death from any cause, myocardial infarction, or major bleeding was not lower among those who received bivalirudin than among those who received heparin monotherapy. (Funded by the Swedish Heart-Lung Foundation and others;

  • 279.
    Escaned, Javier
    et al.
    Hosp Clin San Carlos, Spain; Univ Complutense Madrid, Spain.
    Ryan, Nicola
    Hosp Clin San Carlos, Spain; Univ Complutense Madrid, Spain.
    Mejia-Renteria, Hernan
    Hosp Clin San Carlos, Spain; Univ Complutense Madrid, Spain.
    Cook, Christopher M.
    Imperial Coll London, England.
    Dehbi, Hakim-Moulay
    UCL, England.
    Alegria-Barrero, Eduardo
    Hosp Univ Torrejon, Spain; Univ Francisco de Vitoria, Spain.
    Alghamdi, Ali
    King Abdulaziz Med City Cardiac Ctr, Saudi Arabia.
    Al-Lamee, Rasha
    Imperial Coll London, England.
    Altman, John
    Colorado Heart and Vasc, CO USA.
    Ambrosia, Alphonse
    Mesa, Arizona, USA.
    Baptista, Sergio B.
    Hosp Prof Doutor Fernando Fonseca, Portugal.
    Bertilsson, Maria
    Uppsala Univ, Sweden.
    Bhindi, Ravinay
    Royal North Shore Hosp, Australia.
    Birgander, Mats
    Lund Univ, Sweden.
    Bojara, Waldemar
    Kemperhof Koblenz, Germany.
    Brugaletta, Salvatore
    Inst Invest Biomed August Pi and Sunyer, Spain.
    Buller, Christopher
    St Michaels Hosp, Canada.
    Calais, Fredrik
    Orebro Univ, Sweden.
    Silva, Pedro Canas
    Hosp Santa Maria, Portugal.
    Carlsson, Jorg
    Kalmar Cty Hosp, Sweden; Linnaeus Univ, Sweden.
    Christiansen, Evald H.
    Aarhus Univ Hosp, Denmark.
    Danielewicz, Mikael
    Karlstad Hosp, Sweden.
    Di Mario, Carlo
    Imperial Coll London, England; Univ Florence, Italy.
    Doh, Joon-Hyung
    Inje Univ, South Korea.
    Erglis, Andrejs
    Pauls Stradins Clin Univ Hosp, Latvia.
    Erlinge, David
    Lund Univ, Sweden.
    Gerber, Robert T.
    Conquest Hosp, England.
    Going, Olaf
    Sana Klinikum Lichtenberg, Germany.
    Gudmundsdottir, Ingibjorg
    Reykjavik Univ Hosp, Iceland.
    Haerle, Tobias
    Carl von Ossietzky Univ Oldenburg, Germany.
    Hauer, Dario
    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.
    Hellig, Farrel
    Sunninghill Hosp, South Africa.
    Indolfi, Ciro
    Magna Graecia Univ Catanzaro, Italy.
    Jakobsen, Lars
    Aarhus Univ Hosp, Denmark.
    Janssens, Luc
    Imelda Hosp, Belgium.
    Jensen, Jens
    Karolinska Inst, Sweden; Capio St Gorans Sjukhus, Sweden; Sundsvall Hosp, Sweden.
    Jeremias, Allen
    SUNY Stony Brook, NY 11794 USA.
    Karegren, Amra
    Vastmanland Hosp Vasteras, Sweden.
    Karlsson, Ann-Charlotte
    Halmstad Cty Hosp, Sweden.
    Kharbanda, Rajesh K.
    Oxford Univ Hosp Fdn Trust, England.
    Khashaba, Ahmed
    Ain Shams Univ, Egypt.
    Kikuta, Yuetsu
    Fukuyama Cardiovasc Hosp, Japan.
    Krackhardt, Florian
    Univ Med, Germany.
    Koo, Bon-Kwon
    Seoul Natl Univ Hosp, South Korea.
    Koul, Sasha
    Lund Univ, Sweden.
    Laine, Mika
    Helsinki Univ Hosp, Finland.
    Lehman, Sam J.
    Flinders Univ S Australia, Australia.
    Lindroos, Pontus
    St Goran Hosp, Sweden.
    Malik, Iqbal S.
    Imperial Coll London, England.
    Maeng, Michael
    Aarhus Univ Hosp, Denmark.
    Matsuo, Hitoshi
    Gifu Heart Ctr, Japan.
    Meuwissen, Martijn
    Amphia Hosp, Netherlands.
    Nam, Chang-Wook
    Keimyung Univ, South Korea.
    Niccoli, Giampaolo
    Univ Cattolica Sacro Cuore, Italy.
    Nijjer, Sukhjinder S.
    Imperial Coll London, England.
    Olsson, Hans
    Karlstad Hosp, Sweden.
    Olsson, Sven-Erik
    Helsingborg Hosp, Sweden; Helsingborg Hosp, Sweden.
    Omerovic, Elmir
    Sahlgrenska Univ Gothenburg, Sweden.
    Panayi, Georgios
    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.
    Petraco, Ricardo
    Imperial Coll London, England.
    Piek, Jan J.
    Acad Med Ctr, Netherlands.
    Ribichini, Flavo
    Univ Hosp Verona, Italy.
    Samady, Habib
    Emory Univ, GA 30322 USA.
    Samuels, Bruce
    Cedars Sinai Heart Inst, CA USA.
    Sandhall, Lennart
    Helsingborg Hosp, Sweden; Helsingborg Hosp, Sweden.
    Sapontis, James
    MonashHeart, Australia; Monash Univ, Australia.
    Sen, Sayan
    Imperial Coll London, England.
    Seto, Arnold H.
    Vet Affairs Long Beach Healthcare Syst, CA USA.
    Sezer, Murat
    Istanbul Univ, Turkey.
    Sharp, Andrew S. P.
    Royal Devon and Exeter Hosp, England; Univ Exeter, England.
    Shin, Eun-Seok
    Univ Ulsan, South Korea.
    Singh, Jasvindar
    Washington Univ, MO USA.
    Takashima, Hiroaki
    Aichi Med Univ Hosp, Japan.
    Talwar, Suneel
    Royal Bournemouth Gen Hosp, England.
    Tanaka, Nobuhiro
    Tokyo Med Univ, Japan.
    Tang, Kare
    Essex Cardiothorac Ctr, England; Anglia Ruskin Univ, England.
    Van Belle, Eric
    Lille Univ Hosp, France; INSERM, France.
    van Royen, Niels
    Vrije Univ Amsterdam Med Ctr, Netherlands.
    Varenhorst, Christoph
    Uppsala Univ, Sweden.
    Vinhas, Hugo
    Hosp Garcia de Horta, Portugal.
    Vrints, Christiaan J.
    Antwerp Univ Hosp, Belgium.
    Walters, Darren
    Prince Charles Hosp, Australia.
    Yokoi, Hiroyoshi
    Fukuoka Sannou Hosp, Japan.
    Frobert, Ole
    Orebro Univ, Sweden.
    Patel, Manesh R.
    Duke Univ, NC USA.
    Serruys, Patrick
    Imperial Coll London, England.
    Davies, Justin E.
    Imperial Coll London, England.
    Gotberg, Matthias
    Lund Univ, Sweden.
    Safety of the Deferral of Coronary Revascularization on the Basis of Instantaneous Wave-Free Ratio and Fractional Flow Reserve Measurements in Stable Coronary Artery Disease and Acute Coronary Syndromes2018In: JACC: Cardiovascular Interventions, ISSN 1936-8798, E-ISSN 1876-7605, Vol. 11, no 15, p. 1437-1449Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES The aim of this study was to investigate the clinical outcomes of patients deferred from coronary revascularization on the basis of instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable angina pectoris (SAP) and acute coronary syndromes (ACS). BACKGROUND Assessment of coronary stenosis severity with pressure guidewires is recommended to determine the need for myocardial revascularization. METHODS The safety of deferral of coronary revascularization in the pooled per-protocol population (n = 4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trials was investigated. Patients were stratified according to revascularization decision making on the basis of iFR or FFR and to clinical presentation (SAP or ACS). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. RESULTS Coronary revascularization was deferred in 2,130 patients. Deferral was performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in the FFR group (p amp;lt; 0.01). At 1 year, the MACE rate in the deferred population was similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical presentation with ACS was associated with a higher MACE rate compared with SAP in deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p = 0.04). CONCLUSIONS Overall, deferral of revascularization is equally safe with both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently deferred when iFR was used to assess physiological significance. In deferred patients presenting with ACS, the event rate was significantly increased compared with SAP at 1 year. (C) 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

  • 280.
    Escobar Kvitting, John-Peder
    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 Thoracic and Vascular Surgery. Oslo Univ Hosp, Norway.
    Hermansson, Ulf
    Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Vanhanen, Ingemar
    Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Resection of a plasma cell granuloma combining a conventional posterolateral left-sided thoracotomy with a minimally invasive valve approach2019In: GENERAL THORACIC AND CARDIOVASCULAR SURGERY, ISSN 1863-6705, Vol. 67, no 10, p. 894-896Article in journal (Refereed)
    Abstract [en]

    Plasma cell granuloma (PCG) is a rare benign tumor that is difficult to differentiate from malignancy. Depending on the location of the PCG, surgical management can be challenging. We describe a patient with a PCG involving the left lower lobe extending into the left atrium, that was resected en bloc using a conventional posterolateral thoracotomy combined with a surgical approach predominantly used for minimally invasive mitral valve surgery. This case illustrates how it is possible to utilize a technique used for cardiac surgery for tumors of pulmonary origin involving the heart.

  • 281.
    Escobar Kvitting, John-Peder
    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 Thoracic and Vascular Surgery. Department of Cardiothoracic Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
    Nielsen, Niels Erik
    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.
    Vanhanen, Ingemar
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Baranowski, Jacek
    Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Surgical management of outflow tract obstruction after transapical mitral valve implantation2018In: Journal of cardiac surgery, ISSN 0886-0440, E-ISSN 1540-8191, Vol. 33, no 9, p. 545-547Article in journal (Refereed)
    Abstract [en]

    Left ventricular outflow tract (LVOT) obstruction due to systolic anterior motion of the anterior mitral valve leaflet (AML) is a known complication after mitral valve repair or transfemoral/transapical mitral valve implantation (TMVI). We present a patient with a previous mitral valve repair who developed LVOT obstruction after TMVI in whom the AML was surgically resected using a transaortic approach.

  • 282.
    Evangelista, Lorraine S.
    et al.
    Univ Calif Irvine, CA 92717 USA.
    Cacciata, Marysol
    Univ Calif Irvine, CA 92717 USA.
    Strömberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Dracup, Kathleen
    Univ Calif San Francisco, CA 94143 USA.
    Dose-Response Relationship Between Exercise Intensity, Mood States, and Quality of Life in Patients With Heart Failure2017In: Journal of Cardiovascular Nursing, ISSN 0889-4655, E-ISSN 1550-5049, Vol. 32, no 6, p. 530-537Article in journal (Refereed)
    Abstract [en]

    Background: We conducted a secondary analysis to (1) compare changes in mood disorders and quality of life (QOL) among 4 groups of patients with heart failure in a home-based exercise program who had varying degrees of change in their exercise capacity and (2) determine whether there was an association between exercise capacity, mood disorders, and QOL. Methods: Seventy-one patients were divided into 4 groups based on changes in exercise capacity from baseline to 6 months: group 1showed improvements of greater than 10% (n = 19), group 2 showed improvements of 10% or less (n = 16), group 3 showed reductions of 10% or less (n = 9), and group 4 showed reductions of greater than 10% (n = 27). Results: Over time, patients in all 4 groups demonstrated significantly lower levels of depression and hostility (P amp;lt; .001) and higher levels of physical and overall quality of life (P = .046). Group differences over time were noted in anxiety (P = .009), depression (P = .015), physical quality of life (P amp;lt; .001), and overall quality of life (P = .002). Greater improvement in exercise capacity was strongly associated with lower depression scores (r = -0.49, P = .01). Conclusions: An improvement in exercise capacity with exercise training was associated with a decrease in depression and anxiety and an increase in QOL in patients with heart failure.

  • 283.
    Evangelista, Lorraine S.
    et al.
    University of Calif Irvine, CA 92697 USA.
    Strömberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Nicholas Dionne-Odom, J.
    University of Alabama Birmingham, AL USA.
    An integrated review of interventions to improve psychological outcomes in caregivers of patients with heart failure2016In: CURRENT OPINION IN SUPPORTIVE AND PALLIATIVE CARE, ISSN 1751-4258, Vol. 10, no 1, p. 24-31Article, review/survey (Refereed)
    Abstract [en]

    Purpose of reviewThis article examines interventions aimed at improving psychological outcomes (e.g., caregiver burden, quality of life, anxiety, depression, perceived control, stress mastery, caregiver confidence and preparedness, and caregiver mastery) in family caregivers of patients with heart failure.Recent findingsEight studies meeting the inclusion criteria were included in the review. The most common intervention involved psychoeducation facilitated by a nurse (6/8) and supplemented with a combination of follow-up face-to-face sessions (2/6), home visits (2/6), telephone calls (3/6), and telemonitoring (3/6). Two studies used a support group intervention of four to six sessions. Half of the interventions reported a significant effect on one or more primary outcomes, including caregiver burden (n=4), depressive symptoms (n=1), stress mastery (n=1), caregiver confidence and preparedness (n=1), and caregiver mastery (n=1).SummaryCompared with dementia and cancer family caregiving, few interventions have been evaluated in caregivers of patients with heart failure. Of the existing interventions identified in this review, considerable variability was observed in aims, intervention content, delivery methods, duration, intensity, methodological rigor, outcomes, and effects. Given this current state of the science, direct comparison of heart failure caregiver interventions and recommendations for clinical practice are premature. Thus, research priority is strongly warranted for intervention development and testing to enhance heart failure caregiver support and education.

  • 284.
    Fabris, Enrico
    et al.
    Cardiology Department, Isala Heart Center, the Netherlands, Cardiovascular Department, University of Trieste, Italy.
    van 't Hof, Arnoud
    Isala Heart Center, Maastricht University Medical Center, Zuyderland Hospital, the Netherlands,.
    Hamm, Christian W
    Kerckhoff Heart and Thorax Center, Germany.
    Lapostolle, Frédéric
    Hôpital Avicenne, France.
    Lassen, Jens F
    Aarhus University Hospital, Denmark.
    Goodman, Shaun G
    Canadian Heart Research Centre, University of Toronto, Canada.
    Ten Berg, Jurriën M
    St Antonius Hospital Nieuwegein, the Netherlands.
    Bolognese, Leonardo
    Cardiovascular and Neurological Department, Azienda Ospedaliera Arezzo, Italy.
    Cequier, Angel
    Heart Disease Institute, University of Barcelona, Spain.
    Chettibi, Mohamed
    Centre Hospito-universitaire Frantz Fanon, Algeria.
    Hammett, Christopher J
    Royal Brisbane and Women's Hospital, Australia.
    Huber, Kurt
    Wilhelminen Hospital, Austria, Sigmund Freud Private University, Austria.
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Merkely, Béla
    Heart and Vascular Center, Semmelweis University, Hungary.
    Storey, Robert F
    Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, UK.
    Zeymer, Uwe
    Klinikum Ludwigshafen and Institut für Herzinfarktforschung, Germany.
    Cantor, Warren J
    Southlake Regional Health Centre, University of Toronto, Canada.
    Tsatsaris, Anne
    Astra Zeneca, UK.
    Kerneis, Mathieu
    ACTION Study Group, Sorbonne Université Paris 6, France.
    Diallo, Abdourahmane
    ACTION Study Group, Hospital Lariboisiere, France..
    Vicaut, Eric
    ACTION Study Group, Hospital Lariboisiere, France..
    Montalescot, Gilles
    ACTION Study Group, Sorbonne Université Paris 6, France.
    Clinical impact and predictors of complete ST segment resolution after primary percutaneous coronary intervention: A subanalysis of the ATLANTIC Trial2019In: European heart journal. Acute cardiovascular care., ISSN 2048-8726, Vol. 8, no 3, p. 208-217Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In the ATLANTIC (Administration of Ticagrelor in the catheterization laboratory or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery) trial the early use of aspirin, anticoagulation, and ticagrelor coupled with very short medical contact-to-balloon times represent good indicators of optimal treatment of ST-elevation myocardial infarction and an ideal setting to explore which factors may influence coronary reperfusion beyond a well-established pre-hospital system.

    METHODS: This study sought to evaluate predictors of complete ST-segment resolution after percutaneous coronary intervention in ST-elevation myocardial infarction patients enrolled in the ATLANTIC trial. ST-segment analysis was performed on electrocardiograms recorded at the time of inclusion (pre-hospital electrocardiogram), and one hour after percutaneous coronary intervention (post-percutaneous coronary intervention electrocardiogram) by an independent core laboratory. Complete ST-segment resolution was defined as ≥70% ST-segment resolution.

    RESULTS: Complete ST-segment resolution occurred post-percutaneous coronary intervention in 54.9% ( n=800/1456) of patients and predicted lower 30-day composite major adverse cardiovascular and cerebrovascular events (odds ratio 0.35, 95% confidence interval 0.19-0.65; p<0.01), definite stent thrombosis (odds ratio 0.18, 95% confidence interval 0.02-0.88; p=0.03), and total mortality (odds ratio 0.43, 95% confidence interval 0.19-0.97; p=0.04). In multivariate analysis, independent negative predictors of complete ST-segment resolution were the time from symptoms to pre-hospital electrocardiogram (odds ratio 0.91, 95% confidence interval 0.85-0.98; p<0.01) and diabetes mellitus (odds ratio 0.6, 95% confidence interval 0.44-0.83; p<0.01); pre-hospital ticagrelor treatment showed a favorable trend for complete ST-segment resolution (odds ratio 1.22, 95% confidence interval 0.99-1.51; p=0.06).

    CONCLUSIONS: This study confirmed that post-percutaneous coronary intervention complete ST-segment resolution is a valid surrogate marker for cardiovascular clinical outcomes. In the current era of ST-elevation myocardial infarction reperfusion, patients' delay and diabetes mellitus are independent predictors of poor reperfusion and need specific attention in the future.

  • 285.
    Fabris, Enrico
    et al.
    Isala Clinics, Zwolle, the Netherlands, University of Trieste, Trieste, Italy.
    Van't Hof, Arnoud
    Isala Clinics, Zwolle, the Netherlands.
    Hamm, Christian W
    Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany.
    Lapostolle, Frédéric
    Hôpital Avicenne, Bobigny, France.
    Lassen, Jens Flensted
    Aarhus University Hospital, Aarhus N, Denmark.
    Goodman, Shaun G
    St. Michael’s Hospital, University of Toronto, Toronto, Canada.
    Ten Berg, Jurriën M
    Antonius Hospital Nieuwegein, Nieuwegein, the Netherlands.
    Bolognese, Leonardo
    Cardiovascular and Neurological Department, Azienda Ospedaliera Arezzo, Arezzo, Italy.
    Cequier, Angel
    University of Barcelona, Barcelona, Spain.
    Chettibi, Mohamed
    Centre Hospitalo Universitaire Frantz Fanon, Blida, Algeria.
    Hammett, Christopher H
    Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia.
    Huber, Kurt
    Wilhelminen Hospital and Sigmund Freud Private University, Medical School, Vienna, Austria.
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Merkely, Béla
    Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
    Storey, Robert F
    University of Sheffield, Sheffield, United Kingdom.
    Zeymer, Uwe
    Klinikum Ludwigshafen and Institut für Herzinfarktforschung, Ludwigshafen, Germany.
    Cantor, Warren J
    University of Toronto, Newmarket, Ontario, Canada;.
    Rousseau, Hélène
    Hospital Lariboisiere, ACTION Study Group, Paris, France.
    Vicaut, Eric
    Hospital Lariboisiere, ACTION Study Group, Paris, France.
    Montalescot, Gilles
    Sorbonne Université Paris 6, ACTION Study Group, Hospital Pitie-Salpetriere (AP-HP), Paris, France.
    Impact of presentation and transfer delays on complete ST-segment resolution before primary percutaneous coronary intervention: insights from the ATLANTIC trial.2017In: EuroIntervention, ISSN 1774-024X, E-ISSN 1969-6213, Vol. 13, no 1, p. 69-77, article id EIJ-D-16-00965Article in journal (Refereed)
    Abstract [en]

    AIMS: The aim of this study was to identify predictors of complete ST-segment resolution (STR) pre-primary percutaneous coronary intervention (PCI) in patients enrolled in the ATLANTIC trial.

    METHODS AND RESULTS: ECGs recorded at the time of inclusion (pre-hospital [pre-H]-ECG) and in the catheterisation laboratory before angiography (pre-PCI-ECG) were analysed by an independent core laboratory. Complete STR was defined as ≥70%. Complete STR occurred pre-PCI in 12.8% (204/1,598) of patients and predicted lower 30-day composite MACCE (OR=0.10, 95% CI: 0.002-0.57, p=0.001) and total mortality (OR=0.16, 95% CI: 0.004-0.95, p=0.035). Independent predictors of complete STR included the time from index event to pre-H-ECG (OR=0.94, 95% CI: 0.89-1.00, p=0.035), use of heparins before pre-PCI-ECG (OR=1.75, 95% CI: 1.25-2.45, p=0.001) and time from pre-H-ECG to pre-PCI-ECG (OR=1.09, 95% CI: 1.03-1.16, p=0.005). In the pre-H ticagrelor group, patients with complete STR had a significantly longer delay between pre-H-ECG and pre-PCI-ECG compared to patients without complete STR (median 53 [44-73] vs. 49 [38.5-61] mins, p=0.001); however, this was not observed in the control group (in-hospital ticagrelor) (50 [40-67] vs. 49 [39-61] mins, p=0.258).

    CONCLUSIONS: Short patient delay, early administration of anticoagulant and ticagrelor if a long transfer delay is expected may help to achieve reperfusion prior to PCI. Pre-H treatment may be beneficial in patients with longer transfer delays, allowing the drug to become biologically active.

  • 286.
    Fabris, Enrico
    et al.
    Cardiology Department, Isala Heart Center, Zwolle, the Netherlands, , Cardiovascular Department, University of Trieste, Trieste, Italy.
    Van't Hof, Arnoud
    Cardiology Department, Isala Heart Center, Zwolle, the Netherlands, Maastricht University Medical Center, Maastricht, the Netherlands, Zuyderland Hospital, Heerlen, the Netherlands.
    Hamm, Christian W
    Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany.
    Lapostolle, Frédéric
    SAMU 93 Hôpital Avicenne, Bobigny, France.
    Lassen, Jens Flensted
    Department of Cardiology B, Aarhus University Hospital, Aarhus, Denmark.
    Goodman, Shaun G
    Canadian Heart Research Centre, Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Canada.
    Ten Berg, Jurriën M
    Department of Cardiology, St. Antonius Hospital Nieuwegein, Nieuwegein, the Netherlands.
    Bolognese, Leonardo
    Cardiovascular and Neurological Department, Azienda Ospedaliera Arezzo, Arezzo, Italy.
    Cequier, Angel
    Heart Disease Institute, Hospital Universitario de Bellvitge, University of Barcelona, Spain.
    Chettibi, Mohamed
    Centre Hospito-universitaire Frantz Fanon, Blida, Algeria.
    Hammett, Christopher J
    Department of Cardiology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
    Huber, Kurt
    3rd Department of Medicine, Cardiology and Intensive Care Medicine, Wilhelminen hospital and Sigmund Freud University, Medical School, Vienna, Austria..
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Merkely, Béla
    Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
    Storey, Robert F
    Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom.
    Zeymer, Uwe
    Klinikum Ludwigshafen and Institut für Herzinfarktforschung, Ludwigshafen, Germany.
    Cantor, Warren J
    Southlake Regional Health Centre, University of Toronto, Ontario, Canada.
    Kerneis, Mathieu
    Sorbonne Université, ACTION Study Group, Hospital Pitie-Salpetriere (AP-HP), Paris, France.
    Diallo, Abdourahmane
    Hospital Lariboisiere, ACTION Study Group, Paris, France.
    Vicaut, Eric
    Hospital Lariboisiere, ACTION Study Group, Paris, France.
    Montalescot, Gilles
    Sorbonne Université, ACTION Study Group, Hospital Pitie-Salpetriere (AP-HP), Paris, France.
    Pre-hospital administration of ticagrelor in diabetic patients with ST-elevation myocardial infarction undergoing primary angioplasty: A sub-analysis of the ATLANTIC trial2019In: Catheterization and cardiovascular interventions, ISSN 1522-1946, E-ISSN 1522-726X, Vol. 93, no 7, p. E369-E377Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: We investigated, in the contemporary era of ST-elevation myocardial infarction (STEMI) treatment, the influence of diabetes mellitus (DM) on cardiovascular outcomes, and whether pre-hospital administration of ticagrelor may affect these outcomes in a subgroup of STEMI patients with DM.

    BACKGROUND: DM patients have high platelet reactivity and a prothrombotic condition which highlight the importance of an effective antithrombotic regimen in this high-risk population.

    METHODS: In toal 1,630 STEMI patients enrolled in the ATLANTIC trial who underwent primary percutaneous coronary intervention (PCI) were included. Multivariate analysis was used to explore the association of DM with outcomes and potential treatment-by-diabetes interaction was tested.

    RESULTS: A total of 214/1,630 (13.1%) patients had DM. DM was an independent predictor of poor myocardial reperfusion as reflected by less frequent ST-segment elevation resolution (≥70%) after PCI (OR 0.59, 95% CI 0.43-0.82, P < 0.01) and was an independent predictor of the composite 30-day outcomes of death/new myocardial infarction (MI)/urgent revascularization/definite stent thrombosis (ST) (OR 2.80, 95% CI 1.62-4.85, P < 0.01), new MI or definite acute ST (OR 2.46, 95% CI 1.08-5.61, P = 0.03), and definite ST (OR 10.00, 95% CI 3.54-28.22, P < 0.01). No significant interaction between pre-hospital ticagrelor vs in-hospital ticagrelor administration and DM was present for the clinical, electrocardiographic and angiographic outcomes as well as for thrombolysis in myocardial infarction major bleeding.

    CONCLUSIONS: DM remains independently associated with poor myocardial reperfusion and worse 30-day clinical outcomes. No significant interaction was found between pre-hospital vs in-hospital ticagrelor administration and DM status. Further approaches for the treatment of DM patients are needed.

    CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01347580.

  • 287.
    Fagerström, Carola
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Hollman Frisman, Gunilla
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Living With Liver Cirrhosis A Vulnerable Life2017In: Gastroenterology Nursing, ISSN 1042-895X, E-ISSN 1538-9766, Vol. 40, no 1, p. 38-46Article in journal (Refereed)
    Abstract [en]

    Liver cirrhosis is a chronic liver disease. Patients with liver cirrhosis need to manage the symptoms of the disease and possible complications. Symptoms due to ascites, encephalopathy, and/ or varices are hard to manage and live with. Self-care is necessary for coping with the symptoms and for improving the patients life situation. The aim of this study was to explore the areas of life situation and self-care among patients suffering from liver cirrhosis with complications. Interviews with patients with liver cirrhosis (n = 13), seven women and six men (46-70 years), were performed. Data were analyzed using inductive content analysis. The experience of the patients life situation was described from two aspects: vulnerability and reflection on life. Vulnerability was expressed as symptom experience, feelings of loneliness, preconceptions, and limits in daily life. In reflection on life, the patients expressed acceptance and sadness. Self-care dealt with (a) being responsible by observing symptoms and signs; (b) adhering to treatment, prescription, and advice; and (c) the need for more understanding of and information about the disease. When caring for patients with liver cirrhosis, it is important to identify symptoms and feelings and help patients individually to maintain health through self-care.

  • 288.
    Falk, Lars
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Skov Jensen, Jorgen
    Microbiology and Infection Control, Sexually Transmitted Infections, Research and Development, Statens Serum Institut, Copenhagen, Denmark.
    Successful outcome of macrolide-resistant Mycoplasma genitalium urethritis after spectinomycin treatment: a case report2017In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 72, no 2, p. 624-625Article in journal (Refereed)
  • 289.
    Feldt, Kari
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    De Palma, Rodney
    Buckinghamshire NHS Trust, England; Karolinska Inst, Sweden.
    Bjursten, Henrik
    Lund Univ, Sweden.
    Petursson, Petur
    Gothenburg Univ, Sweden.
    Nielsen, Niels Erik
    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 Cardiology in Linköping.
    Kellerth, Thomas
    Orebro Univ Hosp, Sweden.
    Jonsson, Anders
    Univ Hosp, Sweden.
    Nilsson, Johan
    Umea Univ Hosp, Sweden.
    Ruck, Andreas
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Settergren, Magnus
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Change in mitral regurgitation severity impacts survival after transcatheter aortic valve replacement2019In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 294, p. 32-36Article in journal (Refereed)
    Abstract [en]

    Background: The impact of a change in mitral regurgitation (MR) following TAVR is unknown. We studied the impact of baseline MR and early post-procedural change in MR on survival following TAVR. Methods: The SWEDEHEART registry included all TAVRs performed in Sweden. Patients were dichotomized into no/mild and moderate/severe MR groups. Vital status, echocardiographic data at baseline and within 7 days after TAVR were analyzed. Results: 1712 patients were included. 1404 (82%) had no/mild MR and 308 (18%) had moderate/severe MR. Baseline moderate/severe MR conferred a higher mortality rate at 5-year follow-up (adjusted HR 1.29, CI 1.01-1.65, p = 0.04). Using persistent amp;lt;= mild MR as the reference, when moderate/severe MR persisted or if MR worsened from amp;lt;= mild at baseline to moderate/severe after TAVR, higher 5-year mortality rates were seen (adjusted HR 1.66, CI 1.17-2.34, p = 0.04; adjusted HR 1.97, CI 1.29-3.00, p = 0.002, respectively). If baseline moderate/severe MR improved to = mild after TAVR no excess mortality was seen (HR 1.09, CI 0.75-1.58, p = 0.67). Paravalvular aortic regurgitation (PVL) was inversely associated with MR improvement after TAVR (OR 0.4, 95%: CI 0.17-0.94; p = 0.034). Atrial fibrillation (OR 2.1, 95% CI: 1.27-3.39, p = 0.004), self-expanding valve (OR 3.8, 95% CI: 2.08-7.14, p amp;lt; 0.0001), and PVL (4.3, 95% CI 2.32-7.78. p amp;lt; 0.0001) were associated with MR worsening. Conclusions: Moderate/severe baseline MR in patients undergoing TAVR is associated with a mortality increase during 5 years of follow-up. This risk is offset if MR improves to amp;lt;= mild, whereas worsening of MR after TAVR is associated with a 2-fold mortality increase. (C) 2019 Elsevier B.V. All rights reserved.

  • 290.
    Fernando, Germain J. P.
    et al.
    Vaxxas Pty Ltd, Australia.
    Hickling, Julian
    Working Tandem Ltd, England.
    Flores, Cesar M. Jayashi
    Vaxxas Pty Ltd, Australia.
    Griffin, Paul
    QIMR Berghofer Med Res Inst, Australia; Q Pharm Pry Ltd, Australia; Mater Hosp, Australia; Mater Res Inst, Australia; Univ Queensland, Australia.
    Anderson, Chris D
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Skinner, S. Rachel
    Univ Sydney, Australia; Childrens Hosp Westmead, Australia.
    Davies, Cristyn
    Univ Sydney, Australia; Childrens Hosp Westmead, Australia.
    Witham, Katey
    Vaxxas Pty Ltd, Australia.
    Pryor, Melinda
    360Biolabs Pry Ltd, Australia.
    Bodle, Jesse
    Seqirus Pty Ltd, Australia.
    Rockman, Steve
    Seqirus Pty Ltd, Australia; Univ Melbourne, Australia.
    Frazer, Ian H.
    Not Found:[Fernando, Germain J. P.; Flores, Cesar M. Jayashi; Witham, Katey; Forster, Angus H.] Vaxxas Pty Ltd, Translat Res Inst, 37 Kent St, Brisbane, Qld 4102, Australia; [Hickling, Julian] Working Tandem Ltd, Cambridge, England; [Griffin, Paul] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia; [Griffin, Paul] Q Pharm Pry Ltd, Brisbane, Qld, Australia; [Griffin, Paul] Mater Hosp, Dept Med and Infect Dieases, Brisbane, Qld, Australia; [Griffin, Paul] Mater Res Inst, Brisbane, Qld, Australia; [Griffin, Paul] Univ Queensland, Brisbane, Qld, Australia; [Anderson, Christopher D.] Linkoping Univ, Dept Clin and Expt Med, Fac Hlth Sci, Linkoping, Sweden; [Anderson, Christopher D.] Heart and Med Ctr, Dept Dermatol and Venereol, Region Ostergotland, Sweden; [Skinner, S. Rachel; Davies, Cristyn] Univ Sydney, Sydney Med Sch, Discipline Child and Adolescent Hlth, Sydney, NSW, Australia; [Skinner, S. Rachel; Davies, Cristyn] Childrens Hosp Westmead, Sydney, NSW, Australia; [Pryor, Melinda] 360Biolabs Pry Ltd, Burnet Inst, Melbourne, Vic, Australia; [Bodle, Jesse; Rockman, Steve] Seqirus Pty Ltd, Melbourne, Vic, Australia; [Rockman, Steve] Univ Melbourne, Melbourne, Vic, Australia;.
    Forster, Angus H.
    Vaxxas Pty Ltd, Australia.
    Safety, tolerability, acceptability and immunogenicity of an influenza vaccine delivered to human skin by a novel high-density microprojection array patch (Nanopatch (TM))2018In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 36, no 26, p. 3779-3788Article in journal (Refereed)
    Abstract [en]

    Background: Injection using needle and syringe (Namp;S) is the most widely used method for vaccination, but requires trained healthcare workers. Fear of needles, risk of needle-stick injury, and the need to reconstitute lyophilised vaccines, are also drawbacks. The Nanopatch (NP) is a microarray skin patch comprised of a high-density array of microprojections dry-coated with vaccine that is being developed to address these shortcomings. Here we report a randomised, partly-blinded, placebo-controlled trial that represents the first use in humans of the NP to deliver a vaccine. Methods: Healthy volunteers were vaccinated once with one of the following: (1) NPs coated with split inactivated influenza virus (A/California/07/2009 [H1N1], 15 mu g haemagglutinin (HA) per dose), applied to the volar forearm (NP-HAIFA), n = 15; (2) NPs coated with split inactivated influenza virus (A/California/07/2009 11-11N1 I, 15 mu g HA per dose), applied to the upper arm (NP-HA/UA), n = 15; (3) Fluvaxe (R) 2016 containing 15 mu g of the same H1N1 HA antigen injected intramuscularly (IM) into the deltoid (IM-HA/D), n = 15; (4) NPs coated with excipients only, applied to the volar forearm (NP-placebo/FA), n = 5; (5) NPs coated with excipients only applied to the upper arm (NP-placebo/UA), n = 5; or (6) Saline injected IM into the deltoid (IM-placebo/D), n = 5. Antibody responses at days 0, 7, and 21 were measured by haemagglutination inhibition (HAI) and microneutralisation (MN) assays. Findings: NP vaccination was safe and acceptable; all adverse events were mild or moderate. Most subjects (55%) receiving patch vaccinations (HA or placebo) preferred the NP compared with their past experience of IM injection with Namp;S (preferred by 24%). The antigen-vaccinated groups had statistically higher HAI titres at day 7 and 21 compared with baseline (p amp;lt; 0.0001), with no statistical differences between the treatment groups (p amp;gt; 0.05), although the group sizes were small. The geometric mean HAI titres at day 21 for the NP-HA/FA, NP-HA/UA and IM-HA/D groups were: 335 (189-593 95% CI), 160 (74-345 95% CI), and 221 (129-380 95% CI) respectively. A similar pattern of responses was seen with the MN assays. Application site reactions were mild or moderate, and more marked with the influenza vaccine NPs than with the placebo or IM injection. Interpretation: Influenza vaccination using the NP appeared to be safe, and acceptable in this first time in humans study, and induced similar immune responses to vaccination by IM injection. (C) 2018 The Author(s). Published by Elsevier Ltd.

  • 291.
    Fernlund, Eva
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus. Lund University, Sweden.
    Wålinder Österberg, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Kuchinskaya, Ekaterina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Gustafsson, Mikael
    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.
    Jansson, Kjell
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Gunnarsson, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics. Region Östergötland, Center for Business support and Development.
    Novel Genetic Variants in BAG3 and TNNT2 in a Swedish Family with a History of Dilated Cardiomyopathy and Sudden Cardiac Death2017In: Pediatric Cardiology, ISSN 0172-0643, E-ISSN 1432-1971, Vol. 38, no 6, p. 1262-1268Article in journal (Refereed)
    Abstract [en]

    Familial dilated cardiomyopathy is a rare cause of dilated cardiomyopathy (DCM), especially in childhood. Our aim was to describe the clinical course and the genetic variants in a family where the proband was a four-month-old infant presenting with respiratory problems due to DCM. In the family, there was a strong family history of DCM and sudden cardiac death in four generations. DNA was analyzed initially from the deceased girl using next-generation sequencing including 50 genes involved in cardiomyopathy. A cascade family screening was performed in the family after identification of the TNNT2 and the BAG3 variants in the proband. The first-degree relatives underwent clinical examination including biochemistry panel, cardiac ultrasound, Holter ECG, exercise stress test, and targeted genetic testing. The index patient presented with advanced DCM. After a severe clinical course, the baby had external left ventricular assist as a bridge to heart transplantation. 1.5 months after transplantation, the baby suffered sudden cardiac death (SCD) despite maximal treatment in the pediatric intensive care unit. The patient was shown to carry two heterozygous genetic variants in the TNNT2 gene [TNNT2 c.518G amp;gt; A(p.Arg173Gln)] and BAG3 [BAG3 c.785C amp;gt; T(p.Ala262Val)]. Two of the screened individuals (two females) appeared to carry both the familial variants. All the individuals carrying the TNNT2 variant presented with DCM, the two adult patients had mild or moderate symptoms of heart failure and reported palpitations but no syncope or presyncopal attacks prior to the genetic diagnosis. The female carriers of TNNT2 and BAG3 variants had more advanced DCM. In the family history, there were three additional cases of SCD due to DCM, diagnosed by autopsy, but no genetic analysis was possible in these cases. Our findings suggest that the variants in TNNT2 and BAG3 are associated with a high propensity to life-threatening cardiomyopathy presenting from childhood and young adulthood.

  • 292.
    Fernström, Anders
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Region Östergötland, Heart and Medicine Center, Department of Nephrology. Linköping University, Faculty of Medicine and Health Sciences.
    Hylander Rössner, Britta
    Njurmedicinska kliniken, Karolinska universitetssjukhuset, Solna .
    Polycystisk njursjukdom (ADPKD)2015Other (Other academic)
    Abstract [sv]
    • Polycystisk njursjukdom (ADPKD) innebär att man i njurarna bildar ett fåtal till hundratals cystor i njurarna som slår ut den normala njurfunktionen och ökar buktrycket.
    • Orsakas av mutationer på PKD-1 och PKD-2-generna.
    • Ärvs autosomalt dominant.
    • Vanliga symtom är:- Tryckkänsla/smärta i buken- Njursten- Nedsatt urinkoncentrationsförmåga- Hypertoni- UVI- Hematuri- Uremiska symtom
    • Kan ge manifestationer extrarenalt- Levercystor- Pankreascystor- Intracerebrala aneurysm- Klaffvitium- Divertikulos- Bukväggsbråck
    • Diagnos sätts antingen på förekomst av cystor och ärftlighet för ADPKD eller enbart på förekomst av cystor (dock krävs då fler cystor).
    • Botande behandling annan än transplantation saknas.
    • Symtomlindrande behandling syftar till att minska mortalitet och morbiditet på grund av sjunkande njurfunktion.
    • Transplantation är indicerat om patienten är uremisk.
    • Nya behandlingar är under utveckling.
  • 293.
    Filippatos, Gerasimos
    et al.
    University of Athens, Greece.
    Sana Khan, Sadiya
    Northwestern University, IL 60611 USA.
    Ambrosy, Andrew P.
    Duke University, NC USA.
    Cleland, John G. F.
    University of London Imperial Coll Science Technology and Med, England; University of London Imperial Coll Science Technology and Med, England.
    Collins, Sean P.
    Vanderbilt University, TN 37235 USA.
    Lam, Carolyn S. P.
    National Heart Centre, Singapore.
    Angermann, Christiane E.
    University of Wurzburg, Germany; University of Wurzburg, Germany.
    Ertl, Georg
    University of Wurzburg, Germany; University of Wurzburg, Germany.
    Dahlström, Ulf
    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 Health Sciences.
    Hu, Dayi
    Peking University, Peoples R China.
    Dickstein, Kenneth
    University of Bergen, Norway.
    Perrone, Sergio V.
    Institute Fleni, Argentina.
    Ghadanfar, Mathieu
    Novartis Pharma AG, Switzerland.
    Bermann, Georgina
    Novartis Pharma AG, Switzerland.
    Noe, Adele
    Novartis Pharma AG, Switzerland.
    Schweizer, Anja
    Novartis Pharma AG, Switzerland.
    Maier, Thomas
    Novartis Pharma AG, Switzerland.
    Gheorghiade, Mihai
    Northwestern University, IL 60611 USA.
    International REgistry to assess medical Practice with lOngitudinal obseRvation for Treatment of Heart Failure (REPORT-HF): rationale for and design of a global registry2015In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 17, no 5, p. 527-533Article in journal (Refereed)
    Abstract [en]

    AimsThe clinical characteristics, initial presentation, management, and outcomes of patients hospitalized with new-onset (first diagnosis) heart failure (HF) or decompensation of chronic HF are poorly understood worldwide. REPORT-HF (International REgistry to assess medical Practice with lOngitudinal obseRvation for Treatment of Heart Failure) is a global, prospective, and observational study designed to characterize patient trajectories longitudinally during and following an index hospitalization for HF. MethodsData collection for the registry will be conducted at approximate to 300 sites located in approximate to 40 countries. Comprehensive data including demographics, clinical presentation, co-morbidities, treatment patterns, quality of life, in-hospital and post-discharge outcomes, and health utilization and costs will be collected. Enrolment of approximate to 20 000 adult patients hospitalized with new-onset (first diagnosis) HF or decompensation of chronic HF over a 3-year period is planned with subsequent 3 years follow-up. PerspectiveThe REPORT-HF registry will explore the clinical characteristics, management, and outcomes of HF worldwide. This global research programme may have implications for the formulation of public health policy and the design and conduct of international clinical trials.

  • 294.
    Fjalldal, S.
    et al.
    Skane Univ Hosp, Sweden.
    Follin, C.
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Svärd, Daniel
    Lund University, Lund, Sweden.
    Rylander, L.
    Lund Univ, Sweden.
    Gabery, S.
    Lund Univ, Sweden.
    Petersen, A.
    Lund Univ, Sweden.
    van Westen, D.
    Lund Univ, Sweden.
    Sundgren, P. C.
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Bjorkman-Burtscher, I. M.
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Latt, J.
    Skane Univ Hosp, Sweden.
    Ekman, Bertil
    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.
    Johanson, A.
    Skane Univ Hosp, Sweden.
    Erfurth, E. M.
    Skane Univ Hosp, Sweden.
    Microstructural white matter alterations and hippocampal volumes are associated with cognitive deficits in craniopharyngioma2018In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 178, no 6, p. 577-587Article in journal (Refereed)
    Abstract [en]

    Context: Patients with craniopharyngioma (CP) and hypothalamic lesions (HL) have cognitive deficits. Which neural pathways are affected is unknown. Objective: To determine whether there is a relationship between microstructural white matter (WM) alterations detected with diffusion tensor imaging (DTI) and cognition in adults with childhood-onset CP. Design: A cross-sectional study with a median follow-up time of 22 (6-49) years after operation. Setting: The South Medical Region of Sweden (2.5 million inhabitants). Participants: Included were 41 patients (24 women, amp;gt;= 17 years) surgically treated for childhood-onset CP between 1958-2010 and 32 controls with similar age and gender distributions. HI was found in 23 patients. Main outcome measures: Subjects performed cognitive tests and magnetic resonance imaging, and images were analyzed using DTI of uncinate fasciculus, fornix, cingulum, hippocampus and hypothalamus as well as hippocampal volumetry. Results: Right uncinate fasciculus was significantly altered (P amp;lt;= 0.01) Microstructural WM alterations in left ventral cingulum were significantly associated with worse performance in visual episodic memory, explaining approximately 50% of the variation. Alterations in dorsal cingulum were associated with worse performance in immediate, delayed recall and recognition, explaining 26-38% of the variation, and with visuospatial ability and executive function, explaining 19-29%. Patients who had smaller hippocampal volume had worse general knowledge (P = 0.028), and microstructural WM alterations in hippocampus were associated with a decline in general knowledge and episodic visual memory. Conclusions: A structure to function relationship is suggested between microstructural WM alterations in cingulum and in hippocampus with cognitive deficits in CP.

  • 295.
    Fjälldal, S.
    et al.
    Skåne Univ Hosp, Sweden.
    Follin, C.
    Skane Univ Hosp, Sweden.
    Gabery, S.
    Lund Univ, Sweden.
    Sundgren, P. C.
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Bjorkman-Burtscher, I. M.
    Skane Univ Hosp, Sweden; Lund Univ, Sweden; Lund Univ, Sweden.
    Latt, J.
    Skane Univ Hosp, Sweden.
    Mannfolk, P.
    Skane Univ Hosp, Sweden.
    Nordstrom, C. H.
    Skane Univ Hosp, Sweden.
    Rylander, L.
    Lund Univ, Sweden.
    Ekman, Bertil
    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.
    Cheong, R.
    Lund Univ, Sweden.
    Palsson, A.
    Skane Univ Hosp, Sweden.
    Petersen, A.
    Lund Univ, Sweden.
    Erfurth, E. M.
    Skane Univ Hosp, Sweden.
    Detailed assessment of hypothalamic damage in craniopharyngioma patients with obesity2019In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 43, no 3, p. 533-544Article in journal (Refereed)
    Abstract [en]

    Background/objectives Hypothalamic obesity (HO) occurs in 50% of patients with the pituitary tumor craniopharyngioma (CP). Attempts have been made to predict the risk of HO based on hypothalamic (HT) damage on magnetic resonance imaging (MRI), but none have included volumetry. We performed qualitative and quantitative volumetric analyses of HT damage. The results were explored in relation to feeding related peptides and body fat. Subjects/methods A cross-sectional study of childhood onset CPs involving 3 Tesla MRI, was performed at median 22 years after first operation; 41 CPs, median age 35 (range: 17-56), of whom 23 had HT damage, were compared to 32 controls. After exclusions, 35 patients and 31 controls remained in the MRI study. Main outcome measures were the relation of metabolic parameters to HT volume and qualitative analyses of HT damage. Results Metabolic parameters scored persistently very high in vascular risk particularly among HT damaged patients. Patients had smaller HT volumes compared to controls 769 (35-1168) mm(3) vs. 879 (775-1086) mm(3); P amp;lt; 0.001. HT volume correlated negatively with fat mass and leptin among CP patients (r(s) = -0.67; P amp;lt; .001; r(s) = -0.53; P = 0.001), and explained 39% of the variation in fat mass. For every 100 mm(3) increase in HT volume fat mass decreased by 2.7 kg (95% CI: 1.5-3.9; P amp;lt; 0.001). Qualitative assessments revealed HT damage in three out of six patients with normal volumetry, but HT damage according to operation records. Conclusions A decrease in HT volume was associated with an increase in fat mass and leptin. We present a method with a high inter-rater reliability (0.94) that can be applied by nonradiologists for the assessment of HT damage. The method may be valuable in the risk assessment of diseases involving the HT.

  • 296.
    Flaatten, H.
    et al.
    Gen ICU, Norway; University of Bergen, Norway.
    Walther, Sten
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Activity- or severity-based scoring in the ICU?2017In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, no 1Article in journal (Other academic)
    Abstract [en]

    n/a

  • 297.
    Flodin, Ulf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Paues, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Åkerlind, Britt
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Business support and Development, Department of Communicable Disease and Infection Control.
    Leanderson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Sjögren, Bengt
    Karolinska Institutet, Arbetsmiljötoxikologi, Institutet för miljömedicin Stockholm, Sweden Institutet för miljömedicin, Karolinska Institutet - Arbetsmiljötoxikologi Stockholm, Sweden.
    Svetsare – en riskgrupp för septisk pneumoni [Welders - a risk group for septic pneumonia]: Vaccination mot pneumokocker kan vara motiverat för yrkesgruppen2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, no 6Article in journal (Refereed)
  • 298.
    Flodin, Ulf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Rolander, B.
    Jonkoping Univ, Sweden; Futurum, Sweden.
    Lofgren, H.
    Ryhov Hosp, Sweden.
    Krapi, Blerim
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Nyqvist, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Wåhlin, Charlotte
    Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Unit of Intervention and Implementation Research, Institute for Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Risk factors for neck pain among forklift truck operators: a retrospective cohort study2018In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 19, article id 44Article in journal (Refereed)
    Abstract [en]

    Background

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

    Methods

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

    Results

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

    Conclusions

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

  • 299.
    Folkesson, Maggie
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Sadowska, Natalia
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Vikingsson, Svante
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Karlsson, Matts
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Carlhäll, Carl-Johan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Jensen, Lasse
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Differences in cardiovascular toxicities associated with cigarette smoking and snuff use revealed using novel zebrafish models2016In: Biology Open, ISSN 2046-6390, Vol. 5, no 7, p. 970-978Article in journal (Refereed)
    Abstract [en]

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

  • 300.
    Folkesson, Maggie
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Vorkapic, Emina
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Gulbins, Erich
    University of Duisburg-Essen, University of Cincinnati.
    Japtok, Lukasz
    The department of Toxicology, Institute of Nutritional Science, University of Potsdam.
    Kleuser, Burkhard
    The department of Toxicology, Institute of Nutritional Science, University of Potsdam.
    Welander, Martin
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Inflammatory cells, ceramides, and expression of proteases in perivascular adipose tissue adjacent to human abdominal aortic aneurysms2017In: Journal of Vascular Surgery, ISSN 0741-5214, E-ISSN 1097-6809, Vol. 65, no 4, p. 1171-Article in journal (Refereed)
    Abstract [en]

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

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

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

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