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  • 151.
    Wibault, Johanna
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Activity and Health.
    Öberg, Birgitta
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Dedring, Åsa
    Department of Neurobiology, Care Sciences and Society, Division of Physiotherapy, Karolinska Institutet, Stockholm, Sweden / Department of Physical Therapy, Karolinska University Hospital, Stockholm, Sweden .
    Löfgren, Håkan
    Neuro-Orthopedic Center, Ryhov Hospital, Jönköping, Sweden.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Peolsson, Anneli
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Structured postoperative physiotherapy in patients with cervical radiculopathy: 6-month outcomes of a randomized clinical trial2018In: Journal of Neurosurgery: Spine, ISSN 1547-5654, Vol. 28, no 1, p. 1-9Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the additional benefit of structured postoperative physiotherapy combining neck-specific exercises with a behavioral approach to standard postoperative approach in patients with cervical radiculopathy (CR) at 6 months after surgery.

    Design: A prospective multi-center randomized clinical trial.

    Subjects: Patients with CR (n=202, mean age 50.0, SD 8.4) who were scheduled for surgery.

    Methods: Patients were randomized pre-operatively to structured postoperative physiotherapy (n=101) or standard approach (n=101) which in accordance with Swedish usual care may have included pragmatic physiotherapy after surgery when needed. Outcome measures at baseline and at 3 and 6 months follow-up included the Neck Disability Index (NDI), pain intensity in the neck and arm measured with a visual analogue scale (VAS) and global outcome of treatment. Between-group differences were investigated using complete case and per-protocol approaches.

    Results: No between-group difference was found in NDI, VAS, or global outcome at 6 months after surgery (p> 0.18). The NDI and VAS neck and arm pain were improved in both groups from before surgery to 6 months after surgery (p< 0.001). Sixty-one percent of the patients who received SA reported additional use of postoperative physiotherapy. Global outcome improved during the postoperative period in patients who received structured postoperative physiotherapy only (p< 0.01).

    Conclusions: No additional benefit of structured postoperative physiotherapy compared to standard postoperative approach was found at 6 months of follow-up based on patientreported measures of pain, neck disability and global outcome. However, many patients with CR perceived a need for additional treatments after surgery; and the results may suggest a benefit from combining surgery with structured postoperative physiotherapy in patients with CR. Moreover, the results confirm that neck-specific exercises are tolerated by patients with CR after surgery.

  • 152.
    Wibault, Johanna
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Öberg, Birgitta
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Dedring, Åsa
    Department of Neurobiology, Care Sciences and Society, Division of Physiotherapy, Karolinska Institutet, Stockholm, Sweden / Department of Physical Therapy, Karolinska University Hospital, Stockholm, Sweden .
    Löfgren, Håkan
    Neuro-Orthopedic Center, Ryhov Hospital, Jönköping, Sweden.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Persson, Liselott
    Health Sciences, Division of Physiotherapy, Lund University, Lund, Sweden.
    Jonsson, Margareta R.
    Department of Physical Therapy, Karolinska University Hospital, Stockholm, Sweden.
    Andell, Maria
    Norrahammar Primary Health Care, Norrahammar, Sweden.
    Peolsson, Anneli
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Neck-related physical function, self-efficacy and coping strategies in patients with cervical radiculopathy: a randomized clinical trial of postoperative physiotherapy2017In: Journal of Manipulative and Physiological Therapeutics, ISSN 0161-4754, E-ISSN 1532-6586, Vol. 40, no 5, p. 330-339Article in journal (Refereed)
    Abstract [en]

    Objective: To compare postoperative rehabilitation with structured physiotherapy to standard approach in patients with cervical radiculopathy (CR) based on measures of neck-related physical function, self-efficacy and coping strategies at 6 months follow-up.

    Design: A randomized clinical trial of postoperative physiotherapy in patients with CR.

    Subjects: Patients (n= 202) with persistent CR who were scheduled for surgery.

    Methods: Patients were preoperatively randomized to receive structured postoperative physiotherapy (SPT, n=101) or standard postoperative approach (SA, n=101). SPT combined neck-specific exercises with a behavioral approach. Baseline, 3-month, and 6-month evaluations included questionnaires and clinical examinations. Neck muscle endurance, active cervical range of motion, self-efficacy, pain catastrophizing (CSQ_CAT), perceived control over pain, and ability to decrease pain were analyzed for between-group differences using complete case and per-protocol approaches.

    Results: No between-group difference was reported at the 6-month follow-up (p = 0.05 to 0.99), but all outcomes had improved from baseline (p<0.001). Patients in the SPT group with ≥50% attendance to treatment sessions showed larger improvements in CSQ_CAT (p= 0.04) during the rehabilitation period from 3 to 6 months after surgery compared to the patients who received SA.

    Conclusion: No between-group difference in outcomes was found at 6 months after surgery based on measures of neck-related physical function, self-efficacy and coping strategies. However, the results confirm that neck-specific exercises are tolerated by patients with CR after surgery, and that there may be a benefit from combining surgery with structured postoperative physiotherapy in patients with CR.

  • 153.
    Wibault, Johanna
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Öberg, Birgitta
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Dedring, Åsa
    Karolinska University Hospital, Stockholm, Sweden .
    Löfgren, Håkan
    Ryhov Hospital, Jönköping, Sweden .
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Persson, Liselotte
    Lunds University, Sweden .
    Peolsson, Anneli
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences. University of Queensland, Brisbane, Australia.
    Individual factors associated with neck disability in patients with cervical radiculopathy scheduled for surgery: a study on physical impairments, psychosocial factors, and life style habits2014In: European spine journal, ISSN 0940-6719, E-ISSN 1432-0932, Vol. 23, no 3, p. 599-605Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    The influence of individual factors on patient-reported outcomes is important in the interpretation of disability and treatment effectiveness. The purpose of this study was to assess how physical impairments, psychosocial factors, and life style habits were associated with neck disability based on the Neck Disability Index (NDI), in patients with cervical radiculopathy scheduled for surgery.

    METHODS:

    This cross-sectional study included 201 patients (105 men, 96 women; mean age 50 years). Data included self-reported measures and a clinical examination. Multiple linear regressions were performed to identify significant influencing factors.

    RESULTS:

    Pain, physical impairments in the cervical active range of motion, low self-efficacy, depression, and sickness-related absences explained 73 % of the variance in NDI scores (p < 0.001).

    CONCLUSION:

    Assessments of physical impairments and psychosocial factors in patients with cervical radiculopathy could improve the description of neck disability and the interpretation of treatment outcomes in longitudinal studies.

  • 154.
    Williamson, Adam
    et al.
    Aix Marseille University, France; INSERM, France.
    Rivnay, Jonathan
    Ecole National Super Mines, France.
    Kergoat, Loig
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Jonsson, Amanda
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Inal, Sahika
    Ecole National Super Mines, France.
    Uguz, Ilke
    Ecole National Super Mines, France.
    Ferro, Marc
    Ecole National Super Mines, France.
    Ivanov, Anton
    Aix Marseille University, France; INSERM, France.
    Arbring, Sjöström, Theresia
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Simon, Daniel
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Berggren, Magnus
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Malliaras, George G.
    Ecole National Super Mines, France.
    Bernard, Christophe
    Aix Marseille University, France; INSERM, France.
    Controlling Epileptiform Activity with Organic Electronic Ion Pumps2015In: Advanced Materials, ISSN 0935-9648, E-ISSN 1521-4095, Vol. 27, no 20, p. 3138-3144Article in journal (Refereed)
    Abstract [en]

    In treating epilepsy, the ideal solution is to act at a seizure's onset, but only in the affected regions of the brain. Here, an organic electronic ion pump is demonstrated, which directly delivers on-demand pure molecules to specific brain regions. State-of-the-art organic devices and classical pharmacology are combined to control pathological activity in vitro, and the results are verified with electrophysiological recordings.

  • 155.
    Wirestam, Lina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Biomarkers of disease activity and organ damage in systemic lupus erythematosus2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Systemic lupus erythematosus (SLE) is a systemic inflammatory disease. Clinically, the distinction between ongoing inflammation attributed to SLE, and organ damage due to medication or co-morbidities remains challenging. In addition, SLE is a heterogeneous disease where the various disease phenotypes complicate the search for biomarkers that adequately reflect disease activity and/or signs of increasing organ damage. The aim of the thesis was to investigate and evaluate potential new biomarkers of disease activity and/or organ damage in SLE patients.

    High mobility group box protein-1 (HMGB1) is a nuclear non-histone protein that can shuttle to the cytoplasm, become secreted extracellularly, and participate in systemic inflammation. Administration of monoclonal anti-HMGB1 antibodies has been reported both to attenuate and intensify disease in animal models of arthritis and lupus. In Paper I of the thesis, circulating anti-HMGB1 was found in 23% of the SLE patients and correlated with disease activity variables. The biological role of these autoantibodies remains to be elucidated.

    As a consequence of massive circulating levels of cellular debris and immune complexes, SLE patients have insufficient capacity to remove such material via the reticuloendothelial system. Pentraxin 3 (PTX3) may possibly protect against lupus flares due to classical complement activation, opsonization of apoptotic cells, and cytokine induction. In Paper II, circulating PTX3 was found to be inhibited or exhausted by interferon (IFN)-α, a key cytokine of SLE pathogenesis, and serum levels of PTX3 in SLE patients were inversely related to IFN-α levels. Suppressed PTX3 levels may contribute to a vicious circle resulting in impaired waste clearance, autoantigen exposure and autoantibody production, and sustained disease activity.

    Osteopontin (OPN), a protein known to influence cell signaling and apoptosis, has been proposed as a marker of organ damage in pediatric lupus. In a Swedish cross-sectional study, circulating OPN levels were found to be raised in SLE (Paper III). In patients with recent-onset disease, OPN reflected disease activity, while in established disease, OPN appeared to mirror damage accrual and cardiovascular damage. In Paper IV, OPN was instead analyzed in an international longitudinal multi-center study based on patients with recent-onset SLE and follow-up data. OPN turned out to be a poor predictor of organ damage, but significant associations were observed between OPN and disease activity both at disease onset, as well as over 5 years of follow-up.

    In conclusion, increased anti-HMGB1 antibody and decreased PTX3 levels could potentially sustain the impaired waste-disposal. Of the molecules analyzed in this thesis, OPN seems to be the best marker of disease activity. Further studies of these proteins may help to better understand SLE pathogenesis and to optimize treatment of patients.

    List of papers
    1. Antibodies against High Mobility Group Box protein-1 (HMGB1) versus other anti-nuclear antibody fine-specificities and disease activity in systemic lupus erythematosus
    Open this publication in new window or tab >>Antibodies against High Mobility Group Box protein-1 (HMGB1) versus other anti-nuclear antibody fine-specificities and disease activity in systemic lupus erythematosus
    Show others...
    2015 (English)In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 17, no 338Article in journal (Refereed) Published
    Abstract [en]

    Introduction: The non-histone nuclear protein high mobility group box protein-1 (HMGB1) is typically associated with nucleosomes, but may shuttle between the nucleus and the cytoplasm, and under some conditions also be released extracellularly and participate in systemic inflammation. Monoclonal HMGB1-targeting antibodies can ameliorate murine polyarthritis and lupus-like disease. Interestingly, autoantibodies against HMGB1 have also been described in patients with systemic lupus erythematosus (SLE), but their clinical implications remain elusive. The main aims of this study were to detect serum anti-HMGB1 antibodies in patients with SLE and relate them to other types of antinuclear antibodies (ANA), and to disease activity. Methods: 188 Swedish SLE patients meeting the 1982 American College of Rheumatology classification criteria and/or the 2012 Systemic Lupus International Collaborating Clinics classification criteria participated in the study. Anti-HMGB1 antibody levels were analysed in patient and control (n = 112) sera by an in-house ELISA using recombinant histidine-tagged HMGB1. SLE sera were also analysed for ANA by immunofluorescence (IF) microscopy (IF-ANA) using fixed HEp-2 cells, and by a line-blot assay for antigen fine-specificities. To quantify antibodies to double-stranded DNA, a fluoroenzyme-immunoassay was employed. Results: At inclusion, 23 % of the SLE patients were anti-HMGB1 antibody positive compared to 5 % of the controls. Anti-HMGB1 antibodies occurred in 49 % of the IF-ANA positive SLE patients, and in 34 % of IF-ANA negative cases (p = 0.004). Levels of anti-HMGB1 antibodies correlated with anti-dsDNA antibody levels (r = 0.49; p less than 0.001). Significant, but less pronounced correlations were found regarding anti-HMGB1 and SLE disease activity index (SLEDAI-2K: r = 0.15; p = 0.04), classical complement function (r = -0.24; p = 0.002) and complement protein C4 (r = -0.23; p = 0.002). Average anti-HMGB1 antibody levels were significantly higher among patients with homogenous +/- other IF-ANA staining patterns (median 180 AU) compared to IF-ANA negative cases (median 83 AU) (p = 0.004). Rabbit anti-HMGB1 antibodies gave rise to cytoplasmic, but not nuclear, staining of HEp-2 cells. Conclusions: We confirm that anti-HMGB1 antibodies are common in SLE and correlate with disease activity variables. Although anti-HMGB1 antibodies measured by ELISA often coincide with nuclear IF-ANA staining, our results indicate that anti-HMGB1 antibodies do not give rise to nuclear staining of the predominantly used commercial HEp-2 cell slides.

    Place, publisher, year, edition, pages
    BIOMED CENTRAL LTD, 2015
    Keywords
    HMGB1; Autoantibodies; SLE; Antinuclear antibodies; Inflammation; Clinical phenotype; Complement proteins
    National Category
    Basic Medicine
    Identifiers
    urn:nbn:se:liu:diva-123521 (URN)10.1186/s13075-015-0856-2 (DOI)000365252900001 ()26596890 (PubMedID)
    Note

    Funding Agencies|Swedish Society for Medical Research, Region Ostergotland; Swedish Research Council; Swedish Rheumatism Association; Swedish Society of Medicine; Professor Nanna Svartz foundation; King Gustaf Vs 80-year foundation

    Available from: 2015-12-22 Created: 2015-12-21 Last updated: 2018-01-10
    2. Interferon-α coincides with suppressed levels of pentraxin-3 (PTX3) in systemic lupus erythematosus and regulates leucocyte PTX3 in vitro
    Open this publication in new window or tab >>Interferon-α coincides with suppressed levels of pentraxin-3 (PTX3) in systemic lupus erythematosus and regulates leucocyte PTX3 in vitro
    Show others...
    2017 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 189, no 1, p. 83-91Article in journal (Refereed) Published
    Abstract [en]

    Dysfunctional elimination of cell debris, and the role of opsonins such as pentraxins, is of interest regarding systemic lupus erythematosus (SLE) pathogenesis. Interferon (IFN)- is typically elevated during SLE flares, and inhibits hepatocyte production of the pentraxin C-reactive protein (CRP), partly explaining the poor correlation between CRP levels and SLE disease activity. The extrahepatically produced pentraxin 3 (PTX3) shares waste disposal functions with CRP, but has not been studied extensively in SLE. We analysed serum PTX3 in SLE, and assessed its interference with IFN- in vitro. Serum samples from 243 patients with SLE and 100 blood donors were analysed regarding PTX3. Patient sera were analysed for IFN-, and genotyped for three PTX3 single nucleotide polymorphisms reported previously to associate with PTX3 levels. Stimulated PTX3 release was assessed in the presence or absence of IFN- in blood donor neutrophils and peripheral blood mononuclear cells (PBMC). Serum PTX3 was 44% lower in patients with SLE compared to blood donors (Pamp;lt;00001) and correlated with leucocyte variables. Patients with undetectable IFN- had 29% higher median PTX3 level than patients with detectable IFN- (P=001). PTX3 production by PBMC was inhibited by IFN-, whereas neutrophil degranulation of PTX3 was increased. No differences in PTX3 levels were observed between the SNPs. In conclusion, median serum PTX3 is lower in SLE (especially when IFN- is detectable) compared to blood donors. In addition to its potential consumption during waste disposal, it is plausible that IFN- also attenuates PTX3 by inhibiting synthesis by PBMC and/or exhausting PTX3 storage in neutrophil granules.

    Place, publisher, year, edition, pages
    WILEY, 2017
    Keywords
    biomarkers; interferon-; leucocytes; pentraxin; systemic lupus erythematosus
    National Category
    Immunology
    Identifiers
    urn:nbn:se:liu:diva-138881 (URN)10.1111/cei.12957 (DOI)000402977200008 ()28257596 (PubMedID)
    Note

    Funding Agencies|Swedish Society for Medical Research, Region Ostergotland; Swedish Research Council; Swedish Rheumatism Association; Swedish Society of Medicine; Professor Nanna Svartz Foundation; King Gustaf Vs 80-year foundation

    Available from: 2017-06-27 Created: 2017-06-27 Last updated: 2017-09-08
    3. Osteopontin is associated with disease severity and antiphospholipid syndrome in well characterised Swedish cases of SLE
    Open this publication in new window or tab >>Osteopontin is associated with disease severity and antiphospholipid syndrome in well characterised Swedish cases of SLE
    Show others...
    2017 (English)In: Lupus Science and Medicine, ISSN 2053-8790, E-ISSN 1625-9823, Vol. 4, no 1, p. 7article id 000225Article in journal (Refereed) Published
    Abstract [en]

    Objective The variety of disease phenotypes among patients with SLE challenges the identification of new biomarkers reflecting disease activity and/or organ damage. Osteopontin (OPN) is an extracellular matrix protein with immunomodulating properties. Although raised levels have been reported, the pathogenic implications and clinical utility of OPN as a biomarker in SLE are far from clear. Thus, the aim of this study was to characterise OPN in SLE.

    Methods Sera from 240 well-characterised adult SLE cases classified according to the American College of Rheumatology (ACR) and/or the Systemic Lupus International Collaborating Clinics (SLICC) criteria, and 240 population-based controls were immunoassayed for OPN. The SLE Disease Activity Index 2000 (SLEDAI-2K) was used to evaluate disease activity and the SLICC/ACR Damage Index (SDI) to detect damage accrual.

    Results Serum OPN levels were in average raised fourfold in SLE cases compared with the controls (p<0.0001). OPN correlated with SLEDAI-2K, especially in patients with a disease duration of <12 months (r=0.666, p=0.028). OPN was highly associated with SDI (p<0.0001), especially in the renal (p<0.0001), cardiovascular (p<0.0001) and malignancy (p=0.012) domains. Finally, OPN associated with coherent antiphospholipid syndrome (APS; p=0.009), and both clinical and laboratory criteria of APS had significant positive impact on OPN levels.

    Conclusions In this cross-sectional study, circulating OPN correlates with disease activity in recent-onset SLE, reflects global organ damage and associates with APS. Longitudinal studies to dissect whether serum OPN also precedes and predicts future organ damage are most warranted.

    Place, publisher, year, edition, pages
    BMJ Publishing Group Ltd, 2017. p. 7
    National Category
    Rheumatology and Autoimmunity Neurology Clinical Laboratory Medicine Cardiac and Cardiovascular Systems Gastroenterology and Hepatology
    Identifiers
    urn:nbn:se:liu:diva-140711 (URN)10.1136/lupus-2017-000225 (DOI)
    Available from: 2017-09-08 Created: 2017-09-08 Last updated: 2017-09-08Bibliographically approved
  • 156.
    Wirestam, Lina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Frodlund, Martina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Enocsson, Helena
    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. 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.
    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.
    Osteopontin is associated with disease severity and antiphospholipid syndrome in well characterised Swedish cases of SLE2017In: Lupus Science and Medicine, ISSN 2053-8790, E-ISSN 1625-9823, Vol. 4, no 1, p. 7article id 000225Article in journal (Refereed)
    Abstract [en]

    Objective The variety of disease phenotypes among patients with SLE challenges the identification of new biomarkers reflecting disease activity and/or organ damage. Osteopontin (OPN) is an extracellular matrix protein with immunomodulating properties. Although raised levels have been reported, the pathogenic implications and clinical utility of OPN as a biomarker in SLE are far from clear. Thus, the aim of this study was to characterise OPN in SLE.

    Methods Sera from 240 well-characterised adult SLE cases classified according to the American College of Rheumatology (ACR) and/or the Systemic Lupus International Collaborating Clinics (SLICC) criteria, and 240 population-based controls were immunoassayed for OPN. The SLE Disease Activity Index 2000 (SLEDAI-2K) was used to evaluate disease activity and the SLICC/ACR Damage Index (SDI) to detect damage accrual.

    Results Serum OPN levels were in average raised fourfold in SLE cases compared with the controls (p<0.0001). OPN correlated with SLEDAI-2K, especially in patients with a disease duration of <12 months (r=0.666, p=0.028). OPN was highly associated with SDI (p<0.0001), especially in the renal (p<0.0001), cardiovascular (p<0.0001) and malignancy (p=0.012) domains. Finally, OPN associated with coherent antiphospholipid syndrome (APS; p=0.009), and both clinical and laboratory criteria of APS had significant positive impact on OPN levels.

    Conclusions In this cross-sectional study, circulating OPN correlates with disease activity in recent-onset SLE, reflects global organ damage and associates with APS. Longitudinal studies to dissect whether serum OPN also precedes and predicts future organ damage are most warranted.

  • 157.
    Wårdell, Karin
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Hemm-Ode, Simone
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering. University of Applied Sciences and Arts Northwestern Switzerland, Muttenz , Switzerland.
    Rejmstad, Peter
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    High-Resolution Laser Doppler Measurements of Microcirculation in the Deep Brain Structures: A Method for Potential Vessel Tracking.2016In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 94, no 1, p. 1-9Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Laser Doppler flowmetry (LDF) can be used to measure cerebral microcirculation in relation to stereotactic deep brain stimulation (DBS) implantations.

    OBJECTIVE: To investigate the microcirculation and total light intensity (TLI) corresponding to tissue grayness in DBS target regions with high-resolution LDF recordings, and to define a resolution which enables detection of small vessels.

    METHODS: Stereotactic LDF measurements were made prior to DBS implantation with 0.5-mm steps in the vicinity to 4 deep brain targets (STN, GPi, Vim, Zi) along 20 trajectories. The Mann-Whitney U test was used to compare the microcirculation and TLI between targets, and the measurement resolution (0.5 vs. 1 mm). The numbers of high blood flow spots along the trajectories were calculated.

    RESULTS: There was a significant difference (p < 0.05) in microcirculation between the targets. High blood flow spots were present at 15 out of 510 positions, 7 along Vim and GPi trajectories, respectively. There was no statistical difference between resolutions even though both local blood flow and TLI peaks could appear at 0.5-mm steps.

    CONCLUSIONS: LDF can be used for online tracking of critical regions presenting blood flow and TLI peaks, possibly relating to vessel structures and thin laminas along stereotactic trajectories.

  • 158.
    Yuan, Ximing
    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.
    Ward, Liam
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Forssell, Claes
    Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Siraj, Nabeel
    Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center. Univ Alberta, Dept Internal Med, Edmonton, AB, Canada.
    Li, Wei
    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, Department of Gynaecology and Obstetrics in Linköping.
    Carotid Atheroma From Men Has Significantly Higher Levels of Inflammation and Iron Metabolism Enabled by Macrophages2018In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 49, no 2, p. 419-425Article in journal (Refereed)
    Abstract [en]

    Background and Purpose-Men differ from women in the manifestation of atherosclerosis and iron metabolism. Intraplaque hemorrhage and hemoglobin (Hb) catabolism by macrophages are associated with atherosclerotic lesion instability. The study aims were to investigate sex differences in (1) lesion severity in relation to blood Hb, (2) iron homeostasis in human carotid plaques, and (3) macrophage polarization within atheroma. Methods-The carotid artery samples from 39 men and 23 women were immunostained with cell markers for macrophages, smooth muscle cells, ferritin, and TfR1 (transferrin receptor 1), which were further analyzed according to sex in relation to iron, Hb, and lipids in circulation. Additionally, samples of predefined regions from human carotid atherosclerotic lesions, including internal controls, were used for proteomic analysis by mass spectrometry. Results-Male patients, compared with women, had larger necrotic cores and more plaque rupture, which were associated with higher levels of Hb. Atheroma of male patients had significantly higher levels of Hb in circulation and CD68 macrophages, ferritin, and TfR1 in lesions. CD68 macrophages were significantly correlated with ferritin and TfR1. Plaques from male patients comparatively possessed higher levels of inflammatory macrophage subsets, CD86 (M1) and CD163 (M2), but lower levels of STF (serotransferrin) and HPX (hemopexin). Conclusions-Male patients with carotid atheroma had more advanced and ruptured lesions associated with significantly higher levels of inflammatory macrophage infiltration and high iron stores in the blood and in their plaques. These findings help to understand sex differences and iron metabolism in atherosclerosis and factors related to atheroma progression.

  • 159.
    Zarenoe, Reza
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Tinnitus in Patients with Sensorineural Hearing Loss: Management, Quality of Life and Treatment Strategies2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Approximately 15% of Swedish people experience tinnitus, but only 2.4% experience severe problems. Treatment modalities for tinnitus vary, but the most common treatment is counseling. The majority of patients with tinnitus report some degree of hearing loss, and hearing aids have been used for many years in patients who suffer from both tinnitus and hearing impairment. The aim of the present thesis was to investigate disease management, determine quality of life and identify treatment strategies for patients with tinnitus and sensorineural hearing loss.

    The first two studies described here are retrospective, descriptive studies of patients who sought care for tinnitus and hearing loss at two Ear-Nose-Throat (ENT) clinics in Östergötland County, Sweden, during the years 2004 - 2007. Study I showed that 70% of the cohort had tinnitus; however, many did not initially receive a diagnosis of tinnitus. Information about vertigo, heredity for hearing loss and tinnitus, diabetes history, cardiovascular disease history and other factors related to health was often missing from the patients’ medical records. The results could show that the overall scores using the Tinnitus Handicap Inventory (THI) were higher in female patients than in male patients. Although it is likely that hearing aids would be beneficial for the majority of these patients, 314 (44%) of the 714 total patients had hearing aids. Furthermore, the outcomes from study II demonstrated that a majority of the patients (61%) who were dissatisfied with the care they had obtained had no hearing aids. This finding may indicate that the fitting of hearing aids is an important treatment for patients with both tinnitus and hearing loss.

    Studies III and IV were prospective studies. Data collection was based on patients who sought care for tinnitus and/or hearing loss at the ENT clinic in Linköping during 2012-2013. In study III, 92 patients were divided into two groups: one group contained individuals with both tinnitus and hearing loss, and the other group contained patients with only hearing loss. The patients were assessed using the Reading Span test, the Hearing in Noise Test (HINT) and three questionnaires (the THI, the Hearing Handicap Inventory for Elderly and the Pittsburg Sleep Quality Index) at baseline and follow-up. The results from the age-matched subgroups (n=30+30) generated from the full clinical groups (46+46) showed significantly improved Reading Span test performance and sleep quality in patients with both tinnitus and hearing loss. Similar results were observed in our full clinical population (n=46+46). However, the interpretation of this finding is difficult due to age differences between the groups. In conclusion, hearing aid fitting had a significantly positive impact on working memory capacity and sleep quality in patients with both tinnitus and hearing loss compared with patients with only hearing loss.

    In study IV, a brief Motivational Interviewing (MI) guide was integrated into the hearing rehabilitation process for 23 patients with both tinnitus and hearing loss, and they were compared against a control group (n=23) of patients with both tinnitus and hearing loss who underwent traditional hearing rehabilitation. The results showed that the patients who received the brief MI guide required fewer visits to complete their hearing rehabilitation compared with the patients in the control group. In addition, there was a significant difference in THI scores between the groups, which indicated that the intervention reduced tinnitus annoyance more in the MI group. Furthermore, both groups showed higher scores at follow-up compared with baseline on the International Outcome Inventory for Hearing Aids (IOI-HA) scale, which indicated that both approaches showed a positive effect on hearing aid satisfaction.

    Study V was a retrospective, descriptive study that focused on a part of a Stepped Care model and included patients who participated in half-day tinnitus information meetings from 2004 to 2011 in the audiology clinic at Linköping University Hospital. A total of 426 tinnitus patients with complete questionnaires (the THI and the Hospital Anxiety and Depression Scale, HADS) were included in the study. The results showed significant decreases in scores on the THI and the anxiety module of the HADS before and after the information session. However, there were no statistically significant changes in the depression module of the HADS.

    In conclusion, this thesis underscores the importance of hearing impairment, cognitive variables and motivational procedures in the management of tinnitus. Multidisciplinary group information needs to be further validated.

    List of papers
    1. A cohort study of patients with tinnitus and sensorineural hearing loss in a Swedish population
    Open this publication in new window or tab >>A cohort study of patients with tinnitus and sensorineural hearing loss in a Swedish population
    2013 (English)In: Auris, nasus, larynx, ISSN 0385-8146, E-ISSN 1879-1476, Vol. 40, no 1, p. 41-45Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVE: We aimed to describe a large cohort of patients with tinnitus and sensorineural hearing loss (SNHL) in Sweden, and also to explore the possibility of finding potential possible differences between various diagnoses within SNHL. It is also of great interest to see how a multidisciplinary team was used in the different subgroups and the frequency of hearing aids use in patients with tinnitus.

    METHODS: Medical records of all patients who had received the diagnosis SNHL in Östergötland County, Sweden between 2004 and 2007 were reviewed. Patients between 20 and 80 years with tinnitus and a pure tone average (PTA) lower than 70dB HL were included in the study. Patients were excluded from the analyses if they had a cochlear implantation, middle ear disorders or had a hearing loss since birth or childhood. The investigators completed a form for each included patient, covering background facts, and audiograms taken at the yearly check up.

    RESULTS: Of a total 1672 patients' medical record review, 714 patients were included. The majority of patients (79%) were in the age group over 50 years. In male patients with bilateral tinnitus, the PTA for the left ear was significantly higher than for the right ear. The results regarding the configuration of hearing loss revealed that 555 patients (78%) had symmetric and 159 (22%) asymmetric hearing loss. Retrocochlear examinations were done in 372 patients and MRI was the most common examination. In all patients, 400 had no hearing aids and out of those 220 had unilateral tinnitus and 180 patients had bilateral tinnitus. 219 patients had a PTA>20dB HL and did not have any hearing aid. Results demonstrated that the Stepped Care model was not used widely in the daily practice. In our study, patients with bilateral-, unilateral hearing loss or Mb Ménière were the most common patients included in the Stepped Care model.

    CONCLUSION: In a large cohort of patients with SNHL and tinnitus, despite their hearing loss only 39% had hearing aids. It was observed that the medical record review often showed a lack of information about many background factors, such as; patients' general health condition, which could be a quality factor that needs improvement. Our results show that the Stepped Care model could be an effective option for providing a better access for tinnitus-focused treatment, although the number of patients in this study who were included in the Stepped Care model was low.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-81411 (URN)10.1016/j.anl.2012.05.005 (DOI)22652486 (PubMedID)
    Available from: 2012-09-13 Created: 2012-09-13 Last updated: 2017-12-07Bibliographically approved
    2. Quality of life in patients with tinnitus and sensorineural hearing loss
    Open this publication in new window or tab >>Quality of life in patients with tinnitus and sensorineural hearing loss
    2014 (English)In: B-ENT, ISSN 1781-782X, Vol. 10, no 1, p. 41-51Article in journal (Refereed) Published
    Abstract [en]

    Purpose: The aim of this study was to evaluate the quality of life in patients with tinnitus and SNHL, to investigate patients’ mental and physical health and to measure the level of satisfaction concerning the care experienced by the patients.

    Methods: Three questionnaires related to patients` physical and psychological health, were mailed to 714 Swedish patients with tinnitus and sensorineural hearing loss.

    Results: Female patients had significantly higher Tinnitus Handicap Inventory scores than male patients. Patients who were satisfied with the care they obtained had significantly higher PTA. It was found that the satisfied group had significantly lower THI-scores. In the dissatisfied group, 61% of patients had no hearing aids compared to 42% in the satisfied group.

    Conclusion: Our cohort of patients estimated their life quality and general health at a good level almost 4.5 years after their first report of tinnitus. Another finding was that 47% of patients were not satisfied with the treatment they obtained. In the dissatisfied group, 61% of patients had no hearing aids. Further research is required to find an approach that could motivate patients with both tinnitus and hearing impairment to use hearing aids.

    Place, publisher, year, edition, pages
    ROYAL BELGIAN SOC EAR, NOSE, THROAT, HEAD & NECK SURGERY, 2014
    Keywords
    Tinnitus, Sensorineural hearing loss, Questionnaire, Quality of life
    National Category
    Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-81412 (URN)000334566200007 ()24765828 (PubMedID)
    Available from: 2012-09-13 Created: 2012-09-13 Last updated: 2017-02-20Bibliographically approved
    3. Working Memory, Sleep, and Hearing Problems in Patients with Tinnitus and Hearing Loss Fitted with Hearing Aids
    Open this publication in new window or tab >>Working Memory, Sleep, and Hearing Problems in Patients with Tinnitus and Hearing Loss Fitted with Hearing Aids
    2017 (English)In: Journal of the American Academy of Audiology, ISSN 1050-0545, Vol. 28, no 2, p. 141-151Article in journal (Refereed) Published
    Abstract [en]

    Background: Tinnitus is a common condition and there is a need to evaluate effects of tinnitus management in relation to moderating factors such as degree of hearing loss. As it is possible that tinnitus influences concentration, and thus is likely to disturb cognitive processing, the role of cognitive functioning also needs to be investigated.

    Purpose: To compare a group of patients with sensorineural hearing loss and tinnitus to a control group with only sensorineural hearing loss (and no tinnitus). To investigate working memory, sleep, and hearing problems measured before and after hearing rehabilitation.

    Research Design: A prospective study.

    Study Sample: The sample consisted of 100 patients, 50 with hearing loss and tinnitus, and 50 controls with hearing loss but no tinnitus. All patients were between 40 and 82 yr old and had a pure-tone average (PTA; average of 0.5, 1, 2, and 4 kHz) ,70 dB HL.

    Intervention: Patients were tested before and after rehabilitation with hearing aids with regard to their working memory capacity, sleep quality, hearing problems, speech recognition, and tinnitus annoyance.

    Data Collection and Analysis: Eight patients dropped out of the study. Thus, a total of 92 patients were included for analysis, with 46 in each group. As a consequence of unplanned age and PTA differences between the groups, an age-matched subsample (n 5 30 1 30) was selected for further analysis. Tests including the Reading Span, Hearing-in-Noise Test (HINT), Tinnitus Handicap Inventory (THI), Hearing Handicap Inventory for the Elderly (HHIE), and Pittsburgh Sleep Quality Index (PSQI) were administered before and after hearing aid rehabilitation.

    Results: There were no between-group differences at baseline in the full sample (n 5 92), with the exception of the THI (p , 0.001) and the PSQI (p , 0.002), on which the hearing loss and tinnitus group had significantly higher scores. Pre/post changes were significant for both groups on the Reading Span, and HHIE. However, these improvements were significantly larger for the patients in the hearing loss and tinnitus group on the Reading Span test (p , 0.001) and the PSQI (p , 0.001). Patients with tinnitus and hearing loss also exhibited significantly improved THI scores at follow-up, compared to baseline ( p, 0.001). We conducted the same analyses for the age-matched subsample (n 5 30 1 30). For the baseline data, only the THI (p , 0.001) and the PSQI (p , 0.015) difference remained significant. With regard to the pre/post changes, we found the same differences in improvement in Reading Span ( p , 0.001) and the PSQI (p , 0.015) as in the full sample.

    Conclusions: Patients with tinnitus benefited from hearing aid rehabilitation. The observed differences in cognitive function were unexpected, and there were larger score improvements on the Reading Span test in the hearing loss and tinnitus group than in the hearing loss group. Patients with tinnitus and hearing loss may receive extra benefit in terms of cognitive function following hearing aid rehabilitation.

    Place, publisher, year, edition, pages
    American Academy of Audiology, 2017
    Keywords
    sensorineural hearing loss; hearing aids; tinnitus; working memory capacity
    National Category
    Public Health, Global Health, Social Medicine and Epidemiology Neurology Otorhinolaryngology Psychology
    Identifiers
    urn:nbn:se:liu:diva-132160 (URN)10.3766/jaaa.16023 (DOI)000394478500005 ()28240981 (PubMedID)2-s2.0-85014508703 (Scopus ID)
    Available from: 2016-10-19 Created: 2016-10-19 Last updated: 2018-05-02Bibliographically approved
    4. Motivational Interviewing as an Adjunct to Hearing Rehabilitation for Patients with Tinnitus: A Randomized Controlled Pilot Trial.
    Open this publication in new window or tab >>Motivational Interviewing as an Adjunct to Hearing Rehabilitation for Patients with Tinnitus: A Randomized Controlled Pilot Trial.
    2016 (English)In: Journal of the American Academy of Audiology, ISSN 2157-3107, Vol. 27, no 8, p. 669--676Article in journal (Refereed) Published
    Abstract [en]

    PURPOSE: To test the effects of a brief motivational interviewing (MI) program as an adjunct to hearing aid rehabilitation for patients with tinnitus and sensorineural hearing loss.

    RESEARCH DESIGN: This was a pilot randomized controlled trial.

    STUDY SAMPLE: The sample consisted of 50 patients aged between 40 and 82 yr with both tinnitus and sensorineural hearing loss and a pure-tone average (0.5, 1, 2, and 4 kHz) < 70 dB HL. All patients were first-time hearing aid users.

    INTERVENTION: A brief MI program was used during hearing aid fitting in 25 patients, whereas the remainder received standard practice (SP), with conventional hearing rehabilitation.

    DATA COLLECTION AND ANALYSIS: A total of 46 patients (N = 23 + 23) with tinnitus were included for further analysis. The Tinnitus Handicap Inventory (THI) and the International Outcome Inventory for Hearing Aids (IOI-HA) were administered before and after rehabilitation. THI was used to investigate changes in tinnitus annoyance, and the IOI-HA was used to determine the effect of hearing aid treatment.

    RESULTS: Self-reported tinnitus disability (THI) decreased significantly in the MI group (p < 0.001) and in the SP group (p < 0.006). However, there was greater improvement in the MI group (p < 0.013). Furthermore, the findings showed a significant improvement in patients' satisfaction concerning the hearing aids (IOI-HA, within both groups; MI group, p < 0.038; and SP group, p < 0.026), with no difference between the groups (p < 0.99).

    CONCLUSION: Tinnitus handicap scores decrease to a greater extent following brief MI than following SP. Future research on the value of incorporating MI into audiological rehabilitation using randomized controlled designs is required.

    Place, publisher, year, edition, pages
    Reston: American Academy of Audiology, 2016
    National Category
    Other Medical Sciences
    Identifiers
    urn:nbn:se:liu:diva-131111 (URN)10.3766/jaaa.15126 (DOI)000381957200006 ()27564444 (PubMedID)
    Available from: 2016-09-09 Created: 2016-09-09 Last updated: 2017-05-03Bibliographically approved
  • 160.
    Zarenoe, Reza
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Hällgren, Mathias
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Andersson, Gerhard
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Ledin, Torbjörn
    Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Working Memory, Sleep, and Hearing Problems in Patients with Tinnitus and Hearing Loss Fitted with Hearing Aids2017In: Journal of the American Academy of Audiology, ISSN 1050-0545, Vol. 28, no 2, p. 141-151Article in journal (Refereed)
    Abstract [en]

    Background: Tinnitus is a common condition and there is a need to evaluate effects of tinnitus management in relation to moderating factors such as degree of hearing loss. As it is possible that tinnitus influences concentration, and thus is likely to disturb cognitive processing, the role of cognitive functioning also needs to be investigated.

    Purpose: To compare a group of patients with sensorineural hearing loss and tinnitus to a control group with only sensorineural hearing loss (and no tinnitus). To investigate working memory, sleep, and hearing problems measured before and after hearing rehabilitation.

    Research Design: A prospective study.

    Study Sample: The sample consisted of 100 patients, 50 with hearing loss and tinnitus, and 50 controls with hearing loss but no tinnitus. All patients were between 40 and 82 yr old and had a pure-tone average (PTA; average of 0.5, 1, 2, and 4 kHz) ,70 dB HL.

    Intervention: Patients were tested before and after rehabilitation with hearing aids with regard to their working memory capacity, sleep quality, hearing problems, speech recognition, and tinnitus annoyance.

    Data Collection and Analysis: Eight patients dropped out of the study. Thus, a total of 92 patients were included for analysis, with 46 in each group. As a consequence of unplanned age and PTA differences between the groups, an age-matched subsample (n 5 30 1 30) was selected for further analysis. Tests including the Reading Span, Hearing-in-Noise Test (HINT), Tinnitus Handicap Inventory (THI), Hearing Handicap Inventory for the Elderly (HHIE), and Pittsburgh Sleep Quality Index (PSQI) were administered before and after hearing aid rehabilitation.

    Results: There were no between-group differences at baseline in the full sample (n 5 92), with the exception of the THI (p , 0.001) and the PSQI (p , 0.002), on which the hearing loss and tinnitus group had significantly higher scores. Pre/post changes were significant for both groups on the Reading Span, and HHIE. However, these improvements were significantly larger for the patients in the hearing loss and tinnitus group on the Reading Span test (p , 0.001) and the PSQI (p , 0.001). Patients with tinnitus and hearing loss also exhibited significantly improved THI scores at follow-up, compared to baseline ( p, 0.001). We conducted the same analyses for the age-matched subsample (n 5 30 1 30). For the baseline data, only the THI (p , 0.001) and the PSQI (p , 0.015) difference remained significant. With regard to the pre/post changes, we found the same differences in improvement in Reading Span ( p , 0.001) and the PSQI (p , 0.015) as in the full sample.

    Conclusions: Patients with tinnitus benefited from hearing aid rehabilitation. The observed differences in cognitive function were unexpected, and there were larger score improvements on the Reading Span test in the hearing loss and tinnitus group than in the hearing loss group. Patients with tinnitus and hearing loss may receive extra benefit in terms of cognitive function following hearing aid rehabilitation.

  • 161.
    Zhang, Xueli
    et al.
    Orebro Univ, Sweden; Soochow Univ, Peoples R China.
    Zhang, Hong
    Orebro Univ, Sweden.
    Shen, Bairong
    Soochow Univ, Peoples R China.
    Sun, Xiao-Feng
    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 Oncology.
    Chromogranin-A Expression as a Novel Biomarker for Early Diagnosis of Colon Cancer Patients2019In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 20, no 12, article id 2919Article in journal (Refereed)
    Abstract [en]

    Colon cancer is one of the major causes of cancer death worldwide. The five-year survival rate for the early-stage patients is more than 90%, and only around 10% for the later stages. Moreover, half of the colon cancer patients have been clinically diagnosed at the later stages. It is; therefore, of importance to enhance the ability for the early diagnosis of colon cancer. Taking advantages from our previous studies, there are several potential biomarkers which have been associated with the early diagnosis of the colon cancer. In order to investigate these early diagnostic biomarkers for colon cancer, human chromogranin-A (CHGA) was further analyzed among the most powerful diagnostic biomarkers. In this study, we used a logistic regression-based meta-analysis to clarify associations of CHGA expression with colon cancer diagnosis. Both healthy populations and the normal mucosa from the colon cancer patients were selected as the double normal controls. The results showed decreased expression of CHGA in the early stages of colon cancer as compared to the normal controls. The decline of CHGA expression in the early stages of colon cancer is probably a new diagnostic biomarker for colon cancer diagnosis with high predicting possibility and verification performance. We have also compared the diagnostic powers of CHGA expression with the typical oncogene KRAS, classic tumor suppressor TP53, and well-known cellular proliferation index MKI67, and the CHGA showed stronger ability to predict early diagnosis for colon cancer than these other cancer biomarkers. In the protein-protein interaction (PPI) network, CHGA was revealed to share some common pathways with KRAS and TP53. CHGA might be considered as a novel, promising, and powerful biomarker for early diagnosis of colon cancer.

  • 162.
    Åkerman, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Aspects of the Pre-Diabetic Period in Type 1 Diabetes2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Type 1 diabetes (T1D) is an autoimmune disease characterized by insulin deficiency, due to immune-mediated destruction of beta cells. Current knowledge regarding the period preceding disease onset comes, to a large extent, from studying risk cohorts based on relatives of T1D-patients, as they have an increased disease risk. Among T1D patients in general, however, few have the disease in their immediate family. It is therefore important to study risk cohorts from the general population as well. An ongoing autoimmune reaction can often be seen in the blood long before disease onset, by detection of autoantibodies directed towards beta cell antigens. By autoantibody screening among participants in the ABIS (All Babies in the South-east of Sweden) cohort, we could identify a group of children from the general population with increased risk for T1D, positive for multiple autoantibodies. They were enrolled in a 2-year prospective follow-up aiming to characterize the prediabetic period and to identify factors indicative of progression/non-progression to T1D. We assessed glucose homeostasis and autoantibody titers over time, and searched for risk-biomarkers by analyzing the expression of immune-related genes (Th1-Th2-Th3) in peripheral blood mononuclear cells (PBMC) from these children, in comparison to healthy children and newly diagnosed T1D patients. In the same groups we also compared serum micro RNA (miRNA) profiles, knowing that miRNA molecules have desirable biomarker properties. We found that two specific autoantibodies, IA2A and ZnT8A, were detected at higher concentrations in risk-individuals who progressed to overt T1D during or after the follow-up period, compared to those who still have not. We also observed disturbed glucose homeostasis long before onset in the progressors, but it was seen among those who remain symptom free as well. Further, we found support for the possible role of insulin resistance as an accelerator of the disease process. For gene expression and serum miRNA, few differences were observed between risk-individuals and healthy children overall. However, for PBMC gene expression and serum miRNA both, there were associations to beta cell function and glucose homeostasis, and for miRNA also to islet autoantibodies. Although specific profiles for prediction of disease onset or identification of risk-individuals could not be found, these results are interesting and deserve to be evaluated further. As part of another sub-study within ABIS, the effects of physical activity on glucose homeostasis were assessed in healthy schoolchildren. The level of physical activity, measured by pedometers, was related to insulin resistance and beta cell-stress, and decreased physical activity was associated with increased insulin resistance and load on the insulin-producing beta cells, already at school-age.

    List of papers
    1. Low C-peptide levels and decreased expression of TNF and CD45 in children with high risk of type 1 diabetes
    Open this publication in new window or tab >>Low C-peptide levels and decreased expression of TNF and CD45 in children with high risk of type 1 diabetes
    2013 (English)In: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 148, no 1Article in journal (Refereed) Published
    Abstract [en]

    Type 1 diabetes (T1D) patients have numeral and functional defects in peripheral immune cells, but the pre-diabetic period is fairly uncharacterized. Our aim was to analyze expression of immunological markers in T1D high risk children and relate it to clinical/immunological parameters. Children from ABIS (All Babies in Southeast Sweden) with greater than= 2 diabetes related autoantibodies were considered at high risk. Age-matched controls and new-onset T1D patients were included. Expression of genes related to immune cell function and different arms of the immune system was assessed in peripheral blood mononuclear cells using PCR array. Risk children had lower TNF and CD45, and although there were few differences between the groups, expression of many genes differed when comparing children with regard to residual insulin secretion. Hence, expression of immune related genes seemed related not only to the autoimmune process but rather to residual beta-cell function, which was decreased already during the pre-diabetic phase.

    Place, publisher, year, edition, pages
    Elsevier, 2013
    Keywords
    Type 1 diabetes; Gene expression; PBMC; T1D high risk; T1D autoantibodies; PCR array
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-96458 (URN)10.1016/j.clim.2013.03.011 (DOI)000320427300002 ()
    Available from: 2013-08-23 Created: 2013-08-20 Last updated: 2017-12-06
    2. Physical Activity, Blood Glucose and C-Peptide in Healthy School-Children, a Longitudinal Study
    Open this publication in new window or tab >>Physical Activity, Blood Glucose and C-Peptide in Healthy School-Children, a Longitudinal Study
    2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 6, p. e0156401-Article in journal (Refereed) Published
    Abstract [en]

    Aim To further elucidate the relationship between physical activity and several risk factors for development of diabetes (glucose, C-peptide and obesity) over time. Methods A prospective longitudinal study where physical activity was measured on 199 children from Kalmar and Linkoping at age 8, and the same 107 children from Linkoping again at age 12. Anthropometric data was collected and blood was analyzed for C-peptide and f-glucose. The children in the study were representative for the general Swedish child population, and on an average lean. Results High physical activity was related to lower C-peptide at age 8 and 12. This correlation was especially pronounced in boys, who also were more physically active than girls at both time points. The association seen at 8 years of age was similar at age 12 in most children. Children with higher BMI Z-Score had a higher fasting C-peptide (age 12) but linear regression showed that children with more steps per day were less likely to have a higher fasting C-peptide irrespective of BMI. Longitudinal follow-up showed that a decrease in physical activity increased insulin resistance and beta-cell load. Conclusions Already in young children, physical activity improves insulin sensitivity and decreases the need of C-peptide over time. This seems to become even more pronounced with increasing age when children are followed longitudinally. Low physical activity increases the load on insulin producing beta-cells, might increase the risk for both type 1- and 2 diabetes.

    Place, publisher, year, edition, pages
    PUBLIC LIBRARY SCIENCE, 2016
    National Category
    Pediatrics
    Identifiers
    urn:nbn:se:liu:diva-130132 (URN)10.1371/journal.pone.0156401 (DOI)000377561000012 ()27270732 (PubMedID)
    Note

    Funding Agencies|Swedish Child Diabetes Foundation (Barndiabetesfonden); Novo Nordisk Foundation; Research Council of South-east Sweden (FORSS); Swedish Research Council [K2005-72X-11242-11A]; ALF/County Council of Ostergotland

    Available from: 2016-07-12 Created: 2016-07-11 Last updated: 2017-11-28
  • 163.
    Åström, Mattias
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Medtronic, Sweden; Medtronic, Netherlands.
    Samuelsson, Jennifer
    Umea Univ, Sweden.
    Roothans, Jonas
    Medtronic, Sweden; Medtronic, Netherlands.
    Fytagoridis, Anders
    Umea Univ, Sweden; Karolinska Inst, Sweden.
    Ryzhkov, Maxim
    Medtronic, Sweden; Medtronic, Netherlands.
    Nijlunsing, Rutger
    Medtronic, Sweden; Medtronic, Netherlands.
    Blomstedt, Patric
    Umea Univ, Sweden.
    Prediction of Electrode Contacts for Clinically Effective Deep Brain Stimulation in Essential Tremor2018In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 96, no 5, p. 281-288Article in journal (Refereed)
    Abstract [en]

    Background/Aim: Deep brain stimulation (DBS) is an established neurosurgical treatment that can be used to alleviate symptoms in essential tremor (ET) and other movement disorders. The aim was to develop a method and software tool for the prediction of effective DBS electrode contacts based on probabilistic stimulation maps (PSMs) in patients with ET treated with caudal zona incerta (cZi) DBS. Methods: A total of 33 patients (37 leads) treated with DBS were evaluated with the Essential Tremor Rating Scale (ETRS) 12 months after surgery. In addition, hand tremor and hand function (ETRS items 5/6 and 11-14) were evaluated for every contact during stimulation with best possible outcome without inducing side effects. Prediction of effective DBS electrode contacts was carried out in a retrospective leave-one-out manner based on PSMs, simulated stimulation fields, and a scoring function. Electrode contacts were ranked according to their likelihood of being included in the clinical setting. Ranked electrode contacts were compared to actual clinical settings. Results: Predictions made by the software tool showed that electrode contacts with rank 1 matched the clinically used contacts in 60% of the cases. Contacts with a rank of 1-2 and 1-3 matched the clinical contacts in 83 and 94% of the cases, respectively. Mean improvement of hand tremor and hand function was 79 +/- 21% and 77 +/- 22% for the clinically used and the predicted electrode contacts, respectively. Conclusions: Effective electrode contacts can be predicted based on PSMs in patients treated with cZi DBS for ET. Predictions may in the future be used to reduce the number of clinical assessments that are carried out before a satisfying stimulation setting is defined. (C) 2018 S. Karger AG, Basel

  • 164.
    Österåkeri, A-L
    et al.
    Karolinska Institute, NEUROTEC, Stockholm, Sweden.
    Levi, Richard
    Karolinska Institute, NEUROTEC, Stockholm, Sweden.
    Indicators of psychological distress in postacute spinal cord injured individuals.2005In: Spinal Cord, ISSN 1362-4393, E-ISSN 1476-5624, Vol. 43, no 4, p. 223-229Article in journal (Refereed)
    Abstract [en]

    STUDY DESIGN::Consecutive inclusion of spinal cord injured patients admitted for postacute rehabilitation from June 2000 to January 2002. OBJECTIVE::Assessment of prevalence of indicators of psychological distress in the subacute and early chronic stages after acute-onset spinal cord injury (SCI). SETTING::A Swedish rehabilitation center. METHODS::In all, 36 patients participated. Psychological assessment was obtained at admission, discharge and 6 months follow-up by psychological measures based on the DSM-IV (ie Becks Depression Inventory, SPIFA, SCID-screen, AUDIT) and clinical interview. Ongoing psychotropic medication was noted. RESULTS::Clinical depression was infrequent. However, ongoing psychotropic medication was common, possibly indicating a relatively high incidence of underlying depressive and anxiety disorders. In all, 25%of the sample showed indicators of high alcohol consumption. Few patients had a previously diagnosed personality disorder. By contrast, there was frequent occurrence of personality traits outside normal ranges. CONCLUSION::Medication of psychological problems commonly occurs after SCI, especially for depression and anxiety. There are indications of alcohol overconsumption in a substantial minority of SCI patients. The study raises the question of whether suppression of psychological symptoms by drug therapy is the optimal treatment of such problems in a rehabilitation process. SPONSORSHIP::This study was funded by grants from‘Stiftelsen Tekniska Hjälpmedelåt Handikappade’.Spinal Cord (2005) 43, 223-229. doi:andlt;highlightandgt;10.1038andlt;/highlightandgt;/andlt;highlightandgt;sj.scandlt;/highlightandgt;.andlt;highlightandgt;3101703andlt;/highlightandgt;; Published online 7 December 2004 [ABSTRACT FROM AUTHOR]

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