Change search
Refine search result
45678910 301 - 350 of 1006
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the 'Create feeds' function.
  • 301.
    Gudjonsson, Sigurdur
    et al.
    Skåne University Hospital, Sweden .
    Blackberg, Mats
    Helsingborg County Hospital, Sweden .
    Chebil, Gunilla
    Helsingborg County Hospital, Sweden .
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Olsson, Hans
    Lund University, Sweden .
    Bendahl, Par-Ola
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Mansson, Wiking
    Skåne University Hospital, Sweden .
    Liedberg, Fredrik
    Skåne University Hospital, Sweden Vaxjo County Hospital, Sweden .
    The value of bladder mapping and prostatic urethra biopsies for detection of carcinoma in situ (CIS)2012In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 110, no 2B, E41-E45 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES To assess the value of bladder mapping and prostatic urethra biopsies for detection of urothelial carcinoma in situ (CIS). CIS of the urinary bladder is a flat high-grade lesion of the mucosa associated with a significant risk of progression to muscle-invasive disease. CIS is difficult to identify on cystoscopy, and definite diagnosis requires histopathology. Traditionally, if CIS is suspected, multiple cold-cup biopsies are taken from the bladder mucosa, and resection biopsies are obtained from the prostatic urethra in males. This approach is often called bladder mapping (BMAP). The accuracy of BMAP as a diagnostic tool is not known. PATIENTS AND METHODS Male patients with bladder cancer scheduled for cystectomy underwent cold-cup bladder biopsies (sidewalls, posterior wall, dome, trigone), and resection biopsies were taken from the prostatic urethra. After cystectomy, the surgical specimen was investigated in a standardised manner and subsequently compared with the BMAP biopsies for the presence of CIS. RESULTS The histopathology reports of 162 patients were analysed. CIS was detected in 46% of the cystoprostatectomy specimens, and multiple (greater than= 2) CIS lesions were found in 30%. BMAP (cold-cup bladder biopsies + resection biopsies from the prostatic urethra) provided sensitivity of 51% for any CIS, and 55% for multiple CIS lesions. The cold-cup biopsies for CIS in the bladder mucosa showed sensitivity and specificity of 46% and 89%, respectively. CONCLUSION Traditional cold-cup biopsies are unreliable for detecting CIS in bladder mucosa and negative findings must be interpreted with caution.

  • 302.
    Gudmundsson, Jens Kristjan
    et al.
    Eskilstuna Hospital, Sweden.
    Ajan, Aida
    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, Maxillofacial Unit.
    Abtahi, Jahan
    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, Maxillofacial Unit.
    The accuracy of fine-needle aspiration cytology for diagnosis of parotid gland masses: a clinicopathological study of 114 patients2016In: Journal of Applied Oral Science, ISSN 1678-7757, E-ISSN 1678-7765, Vol. 24, no 6, 561-567 p.Article in journal (Refereed)
    Abstract [en]

    Objective: Fine-needle aspiration cytology is a valuable method for preoperative assessment of head and neck tumors. However, its accuracy in detection of salivary gland masses is controversial compared with other methods. The aim of this work was to evaluate the effectiveness and accuracy of fine-needle aspiration cytology (FNAC) in the diagnosis of parotid gland masses. Material and Methods: Over a 10-year period, 126 parotid gland masses were resected. Retrospective chart reviews of 114 patients were performed. The results of FNAC and final histological diagnosis were compared and the accuracy of FNAC was determined. Results: Final histological evaluation revealed 11 malignant tumors and 103 benign lesions. Pleomorphic adenoma was the most common neoplasm (63%), followed by Warthins tumor (17.5%). The sensitivity of FNAC in detecting malignant tumors was 73% and the specificity was 97%. Positive predictive value (PPV) was 73% and negative predictive value (NPV) was 97%. The overall accuracy of FNAC in detecting parotid masses was 95%. False-negative diagnosis was found in mucoepidermoid carcinoma, acinic cell carcinoma, and epithelial-myoepithelial carcinoma whereas there was false-positive diagnosis in cases of pleomorphic adenoma and normal parotid gland tissue. Conclusion: FNAC is a reliable minimally invasive diagnostic method with a high sensitivity in diagnosis of lesions in parotid glands. The sensitivity of detection of malignant tumors in parotid glands was low due to the biopsy technique used, and depended on tumor location. Postoperative complications decreased after superficial parotidectomy.

  • 303.
    Gustafsson, Anna
    et al.
    Lund University, Sweden.
    Schilcher, Jörg
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Grassi, Lorenzo
    Lund University, Sweden.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Isaksson, Hanna
    Lund University, Sweden.
    Strains caused by daily loading might be responsible for delayed healing of an incomplete atypical femoral fracture2016In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 88, 125-130 p.Article in journal (Refereed)
    Abstract [en]

    Atypical femoral fractures are insufficiency fractures in the lateral femoral diaphysis or subtrochanteric region that mainly affect older patients on bisphosphonate therapy. Delayed healing is often seen in patients with incomplete fractures (cracks), and histology of bone biopsies shows mainly necrotic material inside the crack. We hypothesized that the magnitude of the strains produced in the soft tissue inside the crack during normal walk exceeds the limit for new bone formation, and thereby inhibit healink. A patient specific finite element model was developed, based on clinical CT images and high resolution CT images of a biopsy from the crack site. Strain distributions in the femur and inside the crack were calculated for load cases representing normal walk. The models predicted large strains inside the crack, with strain levels above 10% in more than three quarters of the crack volume. According to two different tissue differentiation theories, bone would only form in less than 1-5% cif the crack volume. This can explain the impaired healing generally seen in incomplete atypical fractures. Furthermore, the microgeometry of the crack highly influenced the strain distributions. Hence, a realistic microgeometry needs to be considered when modeling the crack. Histology of the biopsy showed signs of remodeling in the bone tissue adjacent to the fracture line, while the crack itself contained mainly necrotic material and signs of healing only in portions that seemed to have been widened by resorption. In conclusion, the poor healing capacity of incomplete atypical femoral fractures can be explained by biomechanical factors, and daily low impact activities are enough to cause strain magnitudes that prohibit bone formation. (C) 2016 Elsevier Inc. All rights reserved.

  • 304.
    Gustafsson, Berit M.
    et al.
    Linköping University, Center for Social and Affective Neuroscience (CSAN). Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Högland Hospital, Sweden; Jönköping University, Sweden.
    Gustafsson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Proczkowska, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Hospital Jönköping, Sweden.
    The Strengths and Difficulties Questionnaire (SDQ) for preschool childrena Swedish validation2016In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 70, no 8, 567-574 p.Article in journal (Refereed)
    Abstract [en]

    Background: In Sweden, 80-90% of children aged 1-5 years attend preschool, and that environment is well suited to identify behaviours that may be signs of mental health problems. The Strengths and Difficulties Questionnaire (SDQ) is a well-known short and structured instrument measuring child behaviours that indicate mental health problems well suited for preschool use.Aim: To investigate whether SDQ is a reliable and valid instrument for identifying behavioural problems in children aged 1-3 years and 4-5 years in a Swedish population, as rated by preschool teachers.Methods: Preschools situated in different sized municipalities in Sweden participated. The preschool teacher rated each individual child. Concurrent validity was tested using the Child-Teacher Report Form (C-TRF) and Child Engagement Questionnaire (CEQ). Exploratory factor analysis was conducted for age groups, 1-3 years and 4-5 years.Results: The preschool teachers considered most of the SDQ items relevant and possible to rate. For the children aged 1-3 years, the subscales Hyperactivity (Cronbach alpha=0.84, split half=0.73) and Conduct (Cronbach alpha=0.76, split half=0.80) were considered to be valid. For the age group 4-5 years, the whole original SDQ scale, 4-factor solution was used and showed reasonable validity (Cronbach alpha=0.83, split half=0.87).Conclusion: SDQ can be used in a preschool setting by preschool teachers as a valid instrument for identifying externalizing behavioural problems (hyperactivity and conduct problems) in young children.Clinical implications: SDQ could be used to identify preschool children at high-risk for mental health problems later in life.

  • 305.
    Gustafsson, Berit
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Högland Hospital, Sweden; Jonköping University, Sweden; Hogland Hospital, Sweden.
    Proczkowska-Björklund, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Hospital Jonköping, Sweden.
    Gustafsson, Per A.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Emotional and behavioural problems in Swedish preschool children rated by preschool teachers with the Strengths and Difficulties Questionnaire (SDQ)2017In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 17, no 110Article in journal (Refereed)
    Abstract [en]

    Background: There is a high risk that young children who show early signs of mental health problems develop symptoms in the same or overlapping areas some years later. The Strengths and Difficulties Questionnaire (SDQ) is widely used to screen externalizing and internalizing problems early in life. In Sweden 80-90% of all children aged 1-5 years go to preschool and preschool is thus an appropriate context for finding early signs of mental health problems among children. Methods: This study is part of a longitudinal project too investigate the frequency of emotional and behavioural problems for children between 1 and 5 years of age in Sweden. The SDQ including the impairment supplement questions were rated by preschool teachers too establish Swedish norms for SDQ in preschool children. Results: The sample involved 815 children with a mean age of 42 months (SD = 16, range 13-71 months). 195 children were followed longitudinally for three years. There were significant differences between boys and girls on all subscales except for the Emotional subscale. The prevalence of behavioural problems was similar to other that in European countries, except for Prosocial behaviour, which was rated lower, and Conduct problems, rated higher. Swedish children were estimated to have more problems in the preschool setting, scored by preschool teachers. The development of behaviour over time differed for the different subscales of SDQ. Conclusions: The teacher version of the SDQ, for 2-4 year-olds, can be used as a screening instrument to identify early signs of emotional distress/behavioural problems in young children. Preschool teachers seem to be able to identify children with problematic behaviour with the use of SDQ at an early age. The development of behaviour over time differs for the different subscales of SDQ. The Swedish norms for SDQ are to a large extent, similar to findings from other European countries.

  • 306.
    Gustafsson, Mika
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Edström, Måns
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Gawel, Danuta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Wang, Hui
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Barrenäs, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Tojo, James
    Karolinska Institute, Sweden Centre Molecular Med, Sweden .
    Kockum, Ingrid
    Karolinska Institute, Sweden Centre Molecular Med, Sweden .
    Olsson, Tomas
    Karolinska Institute, Sweden Centre Molecular Med, Sweden .
    Serra-Musach, Jordi
    IDIBELL, Spain .
    Bonifaci, Nuria
    IDIBELL, Spain .
    Angel Pujana, Miguel
    IDIBELL, Spain .
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Integrated genomic and prospective clinical studies show the importance of modular pleiotropy for disease susceptibility, diagnosis and treatment2014In: Genome Medicine, ISSN 1756-994X, Vol. 6, no 17Article in journal (Refereed)
    Abstract [en]

    Background: Translational research typically aims to identify and functionally validate individual, disease-specific genes. However, reaching this aim is complicated by the involvement of thousands of genes in common diseases, and that many of those genes are pleiotropic, that is, shared by several diseases. Methods: We integrated genomic meta-analyses with prospective clinical studies to systematically investigate the pathogenic, diagnostic and therapeutic roles of pleiotropic genes. In a novel approach, we first used pathway analysis of all published genome-wide association studies (GWAS) to find a cell type common to many diseases. Results: The analysis showed over-representation of the T helper cell differentiation pathway, which is expressed in T cells. This led us to focus on expression profiling of CD4(+) T cells from highly diverse inflammatory and malignant diseases. We found that pleiotropic genes were highly interconnected and formed a pleiotropic module, which was enriched for inflammatory, metabolic and proliferative pathways. The general relevance of this module was supported by highly significant enrichment of genetic variants identified by all GWAS and cancer studies, as well as known diagnostic and therapeutic targets. Prospective clinical studies of multiple sclerosis and allergy showed the importance of both pleiotropic and disease specific modules for clinical stratification. Conclusions: In summary, this translational genomics study identified a pleiotropic module, which has key pathogenic, diagnostic and therapeutic roles.

  • 307.
    Gustafsson, Mika
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Gawel, Danuta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Alfredsson, Lars
    Karolinska Institute, Sweden.
    Baranzini, Sergio
    University of Calif San Francisco, CA, USA.
    Bjorkander, Janne
    County Council Jonköping, Sweden.
    Blomgran, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hellberg, Sandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Eklund, Daniel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Kockum, Ingrid
    Karolinska Institute, Sweden; Centre Molecular Med, Sweden.
    Konstantinell, Aelita
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Arctic University of Norway, Norway.
    Lahesmaa, Riita
    University of Turku, Finland; Abo Akad University, Finland.
    Lentini, Antonio
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Liljenström, H. Robert I.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Mattson, Lina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Matussek, Andreas
    County Council Jonköping, Sweden.
    Mellergård, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Mendez, Melissa
    University of Peruana Cayetano Heredia, Peru.
    Olsson, Tomas
    Karolinska Institute, Sweden; Centre Molecular Med, Sweden.
    Pujana, Miguel A.
    Catalan Institute Oncol, Spain.
    Rasool, Omid
    University of Turku, Finland; Abo Akad University, Finland.
    Serra-Musach, Jordi
    Catalan Institute Oncol, Spain.
    Stenmarker, Margaretha
    County Council Jonköping, Sweden.
    Tripathi, Subhash
    University of Turku, Finland; Abo Akad University, Finland.
    Viitala, Miro
    University of Turku, Finland; Abo Akad University, Finland.
    Wang, Hui
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. University of Texas MD Anderson Cancer Centre, TX 77030 USA.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    A validated gene regulatory network and GWAS identifies early regulators of T cell-associated diseases2015In: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 7, no 313, 313ra178Article in journal (Refereed)
    Abstract [en]

    Early regulators of disease may increase understanding of disease mechanisms and serve as markers for presymptomatic diagnosis and treatment. However, early regulators are difficult to identify because patients generally present after they are symptomatic. We hypothesized that early regulators of T cell-associated diseases could be found by identifying upstream transcription factors (TFs) in T cell differentiation and by prioritizing hub TFs that were enriched for disease-associated polymorphisms. A gene regulatory network (GRN) was constructed by time series profiling of the transcriptomes and methylomes of human CD4(+) T cells during in vitro differentiation into four helper T cell lineages, in combination with sequence-based TF binding predictions. The TFs GATA3, MAF, and MYB were identified as early regulators and validated by ChIP-seq (chromatin immunoprecipitation sequencing) and small interfering RNA knockdowns. Differential mRNA expression of the TFs and their targets in T cell-associated diseases supports their clinical relevance. To directly test if the TFs were altered early in disease, T cells from patients with two T cell-mediated diseases, multiple sclerosis and seasonal allergic rhinitis, were analyzed. Strikingly, the TFs were differentially expressed during asymptomatic stages of both diseases, whereas their targets showed altered expression during symptomatic stages. This analytical strategy to identify early regulators of disease by combining GRNs with genome-wide association studies may be generally applicable for functional and clinical studies of early disease development.

  • 308.
    Gustafsson, Mika
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Barabasi, Albert-Laszlo
    Northeastern University, MA 02115 USA.
    Baranzini, Sergio
    University of Calif San Francisco, CA 94143 USA.
    Brunak, Soeren
    Technical University of Denmark, Denmark; University of Copenhagen, Denmark.
    Fan Chung, Kian
    University of London Imperial Coll Science Technology and Med, England.
    Federoff, Howard J.
    Georgetown University, DC 20057 USA.
    Gavin, Anne-Claude
    European Molecular Biol Lab, Germany.
    Meehan, Richard R.
    University of Edinburgh, Scotland.
    Picotti, Paola
    University of Zurich, Switzerland.
    Angel Pujana, Miguel
    Bellvitge Biomed Research Institute IDIBELL, Spain.
    Rajewsky, Nikolaus
    Max Delbruck Centre Molecular Med, Germany.
    Smith, Kenneth G. C.
    University of Cambridge, England; University of Cambridge, England.
    Sterk, Peter J.
    University of Amsterdam, Netherlands.
    Villoslada, Pablo
    Hospital Clin Barcelona, Spain; Hospital Clin Barcelona, Spain.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Modules, networks and systems medicine for understanding disease and aiding diagnosis2014In: Genome Medicine, ISSN 1756-994X, Vol. 6, no 82Article, review/survey (Refereed)
    Abstract [en]

    Many common diseases, such as asthma, diabetes or obesity, involve altered interactions between thousands of genes. High-throughput techniques (omics) allow identification of such genes and their products, but functional understanding is a formidable challenge. Network-based analyses of omics data have identified modules of disease-associated genes that have been used to obtain both a systems level and a molecular understanding of disease mechanisms. For example, in allergy a module was used to find a novel candidate gene that was validated by functional and clinical studies. Such analyses play important roles in systems medicine. This is an emerging discipline that aims to gain a translational understanding of the complex mechanisms underlying common diseases. In this review, we will explain and provide examples of how network-based analyses of omics data, in combination with functional and clinical studies, are aiding our understanding of disease, as well as helping to prioritize diagnostic markers or therapeutic candidate genes. Such analyses involve significant problems and limitations, which will be discussed. We also highlight the steps needed for clinical implementation.

  • 309.
    Göranson, Emma
    et al.
    Östergötlands Läns Landsting, Public Dental Health Care.
    Lundström, Fredrik
    Östergötlands Läns Landsting, Public Dental Health Care.
    Bågesund, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Public Dental Health Care.
    Outcome of orthodontic care and residual treatment need in Swedish 19-year-olds2014In: Swedish Dental Journal, ISSN 0347-9994, Vol. 38, no 3, 133-142 p.Article in journal (Refereed)
    Abstract [en]

    The purpose of the study was to assess the outcome of orthodontic care in Linkoping, Sweden. The dental records of 207 (107 M,100 F) 19-year-olds registered at one public dental health clinic were studied. A clinical examination was performed where malocclusions were registered, where after residual orthodontic treatment need was measured using the Index of Complexity, Outcome and Need (ICON). The 19-year-olds also filled in a questionnaire regarding residual subjective orthodontic treatment demand. Differences between genders were analysed. One hundred and ten (47 M, 63 F) individuals (53.1%) had partaken in orthodontic consultations. Orthodontic appliance treatment had been received by 86 (38 M, 48 F) individuals (41.6%). A residual orthodontic treatment need was registered in 28 (22 M, 6 F) individuals (13.5%). Residual subjective orthodontic treatment demand was expressed by 9 (3 M, 6 F) individuals (4.3%). Eight (2 M, 6 F) of those had no residual treatment need. A higher (p=0.006) rate of females (63.0%) than males (44.0%) had participated in orthodontic consultations. The proportion of males (35.5%) who had experienced orthodontic treatment was not significantly lower (p=0.069) than among the females (48.0%). However, a lower (p=0.009) proportion of treated males (55.3%; n=21 out of 38) than of treated females (81.3%; n=39 out of 48) had received their treatment by orthodontic specialists. At 19 years of age, the proportion of males with residual treatment need (20.6%) was higher (p=0.002) than among the females (6.0%). Every patient with orthodontic treatment need and -demand at 19 years of age had previously been offered orthodontic treatment. The conclusion was drawn that the orthodontic care scheme had successfully diagnosed and treated orthodontic problems in the population. However, notable differences between genders regarding treatment modalities and the amount of residual treatment need at age 19 were found.

  • 310.
    Hagg, Mary
    et al.
    Hudiksvall Hospital, Sweden; Uppsala University, Sweden.
    Tibbling, Lita
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Franzen, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Esophageal dysphagia and reflux symptoms before and after oral IQoro(R) training2015In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 21, no 24, 7558-7562 p.Article in journal (Refereed)
    Abstract [en]

    AIM: To examine whether muscle training with an oral IQoro(R) screen (IQS) improves esophageal dysphagia and reflux symptoms. METHODS: A total of 43 adult patients (21 women and 22 men) were consecutively referred to a swallowing center for the treatment and investigation of long-lasting nonstenotic esophageal dysphagia. Hiatal hernia was confirmed by radiologic examination in 21 patients before enrollment in the study (group A; median age 52 years, range: 19-85 years). No hiatal hernia was detected by radiologic examination in the remaining 22 patients (group B; median age 57 years, range: 22-85 years). Before and after training with an oral IQS for 6-8 mo, the patients were evaluated using a symptom questionnaire (esophageal dysphagia and acid chest symptoms; score 0-3), visual analogue scale (ability to swallow food: score 0-100), lip force test (greater than= 15 N), velopharyngeal closure test (greater than= 10 s), orofacial motor tests, and an oral sensory test. Another twelve patients (median age 53 years, range: 22-68 years) with hiatal hernia were evaluated using oral IQS traction maneuvers with pressure recordings of the upper esophageal sphincter and hiatus canal as assessed by high-resolution manometry. RESULTS: Esophageal dysphagia was present in all 43 patients at entry, and 98% of patients showed improvement after IQS training [mean score (range): 2.5 (1-3) vs 0.9 (0-2), P less than 0.001]. Symptoms of reflux were reported before training in 86% of the patients who showed improvement at follow-up [1.7 (0-3) vs 0.5 (0-2), P less than 0.001). The visual analogue scale scores were classified as pathologic in all 43 patients, and 100% showed improvement after IQS training [71 (30-100) vs 22 (0-50), P less than 0.001]. No significant difference in symptom frequency was found between groups A and B before or after IQS training. The lip force test [31 N (12-80 N) vs 54 N (27-116), P less than 0.001] and velopharyngeal closure test values [28 s (5-74 s) vs 34 s (13-80 s), P less than 0.001] were significantly higher after IQS training. The oral IQS traction results showed an increase in mean pressure in the diaphragmatic hiatus region from 0 mmHg at rest (range: 0-0 mmHG) to 65 mmHg (range: 20-100 mmHg). CONCLUSION: Oral IQS training can relieve/improve esophageal dysphagia and reflux symptoms in adults, likely due to improved hiatal competence.

  • 311.
    Hagman, H.
    et al.
    County Hospital Ryhov, Sweden.
    Frodin, J. -E.
    Karolinska University Hospital, Sweden.
    Berglund, A.
    University of Uppsala Hospital, Sweden.
    Sundberg, J.
    Skåne University Hospital, Sweden.
    Vestermark, L. W.
    Odense University Hospital, Denmark.
    Albertsson, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Fernebro, E.
    Vaxjo Hospital, Sweden.
    Johnsson, A.
    Skåne University Hospital, Sweden.
    A randomized study of KRAS-guided maintenance therapy with bevacizumab, erlotinib or metronomic capecitabine after first-line induction treatment of metastatic colorectal cancer: the Nordic ACT2 trial2016In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 27, no 1, 140-147 p.Article in journal (Refereed)
    Abstract [en]

    Maintenance treatment (mt) with bevacizumab (bev) +/- erlotinib (erlo) has modest effect after induction chemotherapy in metastatic colorectal cancer (mCRC). We hypothesized the efficacy of erlo to be dependent on KRAS mutational status and investigated this by exploring mt strategies with bev +/- erlo and low-dose capecitabine (cap). Included patients had mCRC scheduled for first-line therapy, Eastern Cooperative Oncology Group (ECOG) 0-1 and no major comorbidities. Treatment with XELOX/FOLFOX or XELIRI/FOLFIRI + bev was given for 18 weeks. After induction, patients without progression were eligible for randomization to mt; KRAS wild-type (wt) patients were randomized to bev +/- erlo (arms wt-BE, N = 36 versus wt-B, N = 35), KRAS mutated (mut) patients were randomized to bev or metronomic cap (arms mut-B, N = 34 versus mut-C, N = 33). Primary end point was progression-free survival (PFS) rate (PFSr) at 3 months after start of mt. A pooled analysis of KRAS wt patients from the previous ACT study was performed. We included 233 patients. Median age was 64 years, 62% male, 68% ECOG 0, 52% with primary tumor in situ. A total of 138 patients started mt after randomization. PFSr was 64.7% versus 63.6% in wt-B versus wt-BE, P = 1.000; and 75% versus 66.7% in mut-B versus mut-C, P = 0.579, with no significant difference in median PFS and overall survival (OS). In the pooled cohort, median PFS was 3.7 months in wt-B (N = 64) and 5.7 months in wt-BE (N = 62) (hazard ratios 1.03, 95% confidence interval 0.70-1.50, P = 0.867). The frequency of any grade 3/4 toxicities during mt was: 28%/58%/18%/15% (wt-B/wt-BE/mut-B/mut-C). Addition of erlo to bev as mt in KRAS wt mCRC did not significantly improve PFS or OS, but it did increase toxicity. KRAS status does not seem to influence the outcome of treatment with erlotinib. Metronomic cap warrants further investigation in mt strategies, given our explorative results. NCT01229813.

  • 312.
    Hagopian, William
    et al.
    Pacific Northwest Diabet Research Institute, WA USA .
    Ferry, Robert J Jr.
    Le Bonheur Childrens Hospital, TN USA .
    Sherry, Nicole
    Massachusetts Gen Hospital, MA USA .
    Carlin, David
    MacroGenics, MD USA .
    Bonvini, Ezio
    MacroGenics, MD USA .
    Johnson, Syd
    MacroGenics, MD USA .
    Stein, Kathryn E.
    MacroGenics, MD USA .
    Koenig, Scott
    MacroGenics, MD USA .
    Daifotis, Anastasia G.
    MacroGenics, MD USA .
    Herold, Kevan C.
    Yale University, CT USA .
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Teplizumab Preserves C-Peptide in Recent-Onset Type 1 Diabetes2013In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 62, no 11, 3901-3908 p.Article in journal (Refereed)
    Abstract [en]

    Protege was a phase 3, randomized, double-blind, parallel, placebo-controlled 2-year study of three intravenous teplizumab dosing regimens, administered daily for 14 days at baseline and again after 26 weeks, in new-onset type 1 diabetes. We sought to determine efficacy and safety of teplizumab immunotherapy at 2 years and to identify characteristics associated with therapeutic response. Of 516 randomized patients, 513 were treated, and 462 completed 2 years of follow-up. Teplizumab (14-day full-dose) reduced the loss of C-peptide mean area under the curve (AUC), a prespecified secondary end point, at 2 years versus placebo. In analyses of prespecified and post hoc subsets at entry, U.S. residents, patients with C-peptide mean AUC andgt;0.2 nmol/L, those randomized 6 weeks after diagnosis, HbA(1c) andlt;7.5% (58 mmol/mol), insulin use andlt;0.4 units/kg/day, and 8-17 years of age each had greater teplizumab-associated C-peptide preservation than their counterparts. Exogenous insulin needs tended to be reduced versus placebo. Antidrug antibodies developed in some patients, without apparent change in drug efficacy. No new safety or tolerability issues were observed during year 2. In summary, anti-CD3 therapy reduced C-peptide loss 2 years after diagnosis using a tolerable dose.

  • 313.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Behm, Pascal
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology. University of Applied Sciences in Northwest Switzerland.
    Shabo, Ivan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Fluorescence spectroscopy using indocyanine green for lymph node mapping2014In: Proceedings of SPIE, the International Society for Optical Engineering, ISSN 0277-786X, E-ISSN 1996-756X, ISSN 0277-786X, Vol. 8935, no 893504, 1-6 p.Article in journal (Refereed)
    Abstract [en]

    The principles of cancer treatment has for years been radical resection of the primary tumor. In the oncologic surgeries where the affected cancer site is close to the lymphatic system, it is as important to detect the draining lymph nodes for metastasis (lymph node mapping). As a replacement for conventional radioactive labeling, indocyanine green (ICG) has shown successful results in lymph node mapping; however, most of the ICG fluorescence detection techniques developed are based on camera imaging. In this work, fluorescence spectroscopy using a fiber-optical probe was evaluated on a tissue-like ICG phantom with ICG concentrations of 6-64 μM and on breast tissue from five patients. Fiber-optical based spectroscopy was able to detect ICG fluorescence at low intensities; therefore, it is expected to increase the detection threshold of the conventional imaging systems when used intraoperatively. The probe allows spectral characterization of the fluorescence and navigation in the tissue as opposed to camera imaging which is limited to the view on the surface of the tissue

  • 314.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Milos, 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.
    Hildesjö, Camilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Fluorescence spectroscopy and optical coherence tomography for brain tumor detection2016Conference paper (Refereed)
    Abstract [en]

    Resection of brain tumor is a challenging task as the tumor does not have clear borders and the malignant types specifically have often a diffuse and infiltrative pattern of growth. Recently, neurosurgical microscopes have been modified to incorporate fluorescence modules for detection of tumor when 5-aminolevulinic acid (5-ALA) is used as a contrast. We have in combination with the fluorescence microscopes implemented and evaluated a fluorescence spectroscopy based handheld probe for detecting the 5-aminolevulinic acid (ALA) induced protoporphyrin IX (PpIX) in the gliomas in 50 patients intraoperatively. The results show a significantly high sensitivity for differentiating tumor from the healthy tissue and distinguished fluorescence intensity levels in the tumor cell infiltration zone around the tumor. However, knowledge on association of the quantified fluorescence signals specifically in the intermediate inflammatory zone with the infiltrative tumor cells can be complemented with volumetric tissue imaging and a higher precision histopathological analysis. In this work, a spectral domain optical coherence tomography (OCT) system with central wavelength of 1325nm has been used to image the tissue volume that the fluorescence is collected from and is evaluated against histopathological analysis for a higher precision slicing. The results show that although healthy brain has a homogenous microstructure in the OCT images, the brain tumor shows a distinguished texture in the images correlated with the PpIX fluorescence intensity and histopathology.

  • 315.
    Haj-Hosseini, Neda
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Milos, Peter
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Hildesjö, Camilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Detection of brain tumor using fluorescence and optical coherence tomography2015Conference paper (Refereed)
    Abstract [en]

    Resection of brain tumor is a challenging task as the tumor does not have clear borders and the malignant types specifically have often a diffuse and infiltrative pattern of growth. We have previously implemented and evaluated a fluorescence spectroscopy based handheld probe for detecting the 5-aminolevulinic acid induced protoporphyrin IX (PpIX) in the gliomas. To add another dimension to the brain tumor detection and volumetric analysis of the tissue that exhibits fluorescence, optical coherence tomography was investigated on tumor specimens.

    Material and Methods:

    A fluorescence microscopy and a spectroscopy system as reported previously were used for detecting the fluorescence signals [1, 2]. A total of 50 patients have been included for intraoperative assessment of the tumor borders using the fluorescence techniques. A spectral domain OCT imaging system (TELESTO II, Thorlabs, Inc., NJ, USA) with central wavelength of 1325 nm was used to study the tissue microstructure post operatively. The system has a resolution of 13 and 5.5 μm in the lateral and axial directions, respectively. Tissue specimens from three patients undergoing brain tumor surgery were studied using the OCT system.

    Results and Conclusion:

    Using fluorescence spectroscopy the tumor could be detected with a sensitivity of 0.84 which was significantly higher than that of the surgical microscope (0.30). Brain tissue appeared rather homogeneous in the OCT images however the highly malignant tissue showed a clear structural difference from the non-malignant or low malignant brain tumor tissue which could be related to the fluorescence signal intensities.

  • 316.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Medicine and Health Sciences.
    Petersson, Pernilla
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Shabo, Ivan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Optical Coherence Tomography for Pathological Analysis of Thyroid2016Conference paper (Refereed)
  • 317.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Stepp, Herbert
    Ludwig Maximilians Universitet, München.
    Markwardt, Niklas
    Ludwig Maximilians Universitet, München.
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Shabo, Ivan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Optical biopsy during thyroid and parathyroid surgery2015Conference paper (Refereed)
  • 318.
    Hammar, Mats
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Finspång, Primary Health Care in Finspång.
    Healthy aging and age-adjusted nutrition and physical fitness2013In: Baillière's Best Practice & Research: Clinical Obstetrics & Gynaecology, ISSN 1521-6934, Vol. 27, no 5, 741-752 p.Article in journal (Refereed)
    Abstract [en]

    Expected life span is gradually increasing worldwide. Healthy dietary and exercise habits contribute to healthy ageing. Certain types of diet can prevent or reduce obesity, and may reduce the risk of diseases (e.g. cardiovascular disease). Exercise also reduces the risk of diseases (e.g. cardiovascular disease, osteoporosis, some cancers and some mental disturbances). A less sedentary life style seems at least as important as regular exercise. Exercise can probably be tailored to reduce the risk of cardiovascular disease and extent of bone loss. To ensure adherence, it is important to increase slowly the frequency, duration and intensity of exercise, and to find activities that suit the individual. More research is needed to find ideal modes and doses of exercise, and to increase long-term adherence. Dietary and exercise modification seem to be strong promoters of healthy ageing.

  • 319.
    Hammerman, Malin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Blomgran, Parmis
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Ramstedt, Sandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Linköping University, Faculty of Health Sciences.
    COX-2 inhibition impairs mechanical stimulation of early tendon healing in rats by reducing the response to microdamage2015In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 119, no 5, 534-540 p.Article in journal (Refereed)
    Abstract [en]

    Early tendon healing can be stimulated by mechanical loading and inhibited by cyclooxygenase (COX) inhibitors (nonsteroidal anti-inflammatory drugs). Therefore, we investigated if impairment of tendon healing by a COX-2 inhibitor (parecoxib) is related to loading. Because loading might infer microdamage, which also stimulates healing, we also investigated if this effect is inhibited by parecoxib. The Achilles tendon was transected in 114 rats. Three degrees of loading were used: full loading, partial unloading, and unloading (no unloading, Botox injections in the plantar flexor muscles, or Botox in combination with tail suspension). For each loading condition, the rats received either parecoxib or saline. In a second experiment, rats were unloaded with Botox, and the tendon was subjected to microdamage by needling combined with either saline or parecoxib. Mechanical testing day 7 showed that there was a significant interaction between loading and parecoxib for peak force at failure (P less than 0.01). However, logarithmic values showed no significant interaction, meaning that we could not exclude that the inhibitory effect of parecoxib was proportionate to the degree of loading. Microbleeding was common in the healing tissue, suggesting that loading caused microdamage. Needling increased peak force at failure (P less than 0.01), and this effect of microdamage was almost abolished by parecoxib (P less than 0.01). Taken together, this suggests that COX-2 inhibition impairs the positive effects of mechanical loading during tendon healing, mainly by reducing the response to microdamage.

  • 320.
    Hanberger, Håkan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Antonelli, Massimo
    Policlinico University of A. Gemelli, Rome, Italy.
    Holmbom, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Lipman, Jeffrey
    University of Queensland, Herston, Australia.
    Pickkers, Peter
    Radboud University Medical Centre, Nijmegen, The Netherlands.
    Leone, Marc
    Aix Marseille University, France.
    Rello, Jordi
    University Autonoma of Barcelona, Spain.
    Sakr, Yasser
    Friedrich-Schiller University, Jena, Germany.
    Walther, Sten
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Vanhems, Philippe
    University of Lyon 1, France.
    Vincent, Jean-Louis
    University Libre Bruxelles, Belgium.
    Infections, antibiotic treatment and mortality in patients admitted to ICUs in countries considered to have high levels of antibiotic resistance compared to those with low levels2014In: BMC Infectious Diseases, ISSN 1471-2334, Vol. 14, no 513Article in journal (Refereed)
    Abstract [en]

    Background: Antimicrobial resistance is an increasing concern in ICUs worldwide. Infection with an antibiotic resistant (ABR) strain of an organism is associated with greater mortality than infection with the non-resistant strain, but there are few data assessing whether being admitted to an intensive care unit (ICU) with high levels of antimicrobial resistance is associated with a worse outcome than being admitted to an ICU with low rates of resistance. The aim of this study was, therefore, to compare the characteristics of infections and antibiotic treatments and patient outcomes in patients admitted to ICUs in countries considered as having high levels of antibiotic resistance and those admitted to ICUs in countries considered as having low levels of antibiotic resistance. Methods: Data from the large, international EPIC II one-day point prevalence study on infections in patients hospitalized in ICUs were used. For the current study, we compared the data obtained from patients from two groups of countries: countries with reported MRSA rates of greater than= 25% (highABR: Greece, Israel, Italy, Malta, Portugal, Spain, and Turkey) and countries with MRSA rates of less than 5% (lowABR: Denmark, Finland, Netherlands, Norway, and Sweden). Results: On the study day, 1187/2204 (53.9%) patients in the HighABR ICUs were infected and 255/558 (45.7%) in the LowABR ICUs (P less than 0.01). Patients in the HighABR ICUs were more severely ill than those in the LowABR ICUs, as reflected by a higher SAPS II score (35.6 vs 32.7, P less than 0.05) and had longer median ICU (12 days vs 5 days) and hospital (24 days vs 16 days) lengths of stay. They also had higher crude ICU (20.0% vs 15.4%) and hospital (27.0% vs 21.5%) mortality rates (both P less than 0.05). However, after multivariable adjustment and matched pair analysis there were no differences in ICU or hospital mortality rates between High or LowABR ICU patients overall or among those with infections. Conclusions: Being hospitalized in an ICU in a region with high levels of antimicrobial resistance is not associated per se with a worse outcome.

  • 321.
    Hanberger, Lena
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Akesson, K.
    County Hospital Ryhov, Sweden Jonköping University, Sweden Jonköping University, Sweden .
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Glycated haemoglobin variations in paediatric type 1 diabetes: the impact of season, gender and age2014In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 103, no 4, 398-403 p.Article in journal (Refereed)
    Abstract [en]

    AimTo study whether monthly variations in type 1 diabetes incidence are related to monthly glycated haemoglobin (HbA1c) levels at diagnosis and if high HbA1c at diagnosis is related to certain clinical variables at diagnosis and during the clinical course of the disease. MethodsData from 4430 boys and 3590 girls registered in the Swedish paediatric diabetes quality registry, Swedish paediatric diabetes quality registry, from 2000 to 2010 were analysed. ResultsMonth of onset varied (pless than0.001), with 53% diagnosed during September to February, and mean HbA1c at diagnosis was highest in May (10.9%, 96mmol/mol) and lowest in (October 9.4%, 88mmol/mol) (pless than0.001). Girls showed higher HbA1c at onset than boys (pless than0.001). More than half (53%) with an annual mean HbA1c of greater than9.3% (78mmol/mol) and 4% of those with an annual mean of less than7.4% (57mmol/mol) in 2007 had greater than9.3% (78mmol/mol) in 2010. ConclusionPatients with high HbA1c levels during a certain period have the same high levels several years later. This group, perhaps including those with high HbA1c level at diagnosis, may need more intensive care, including extra support from the diabetes teams and other forms of medical treatment.

  • 322.
    Hanberger, Lena
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Birkebaek, Niels
    Department of Paediatrics, Aarhus, Aarhus University Hospital, Skejby, Denmark.
    Bjarnason, Ragnar
    Children’s Medical Center, Landspítali University Hospital and Faculty of Medicine, University of Iceland, Reykjavík, Iceland.
    Drivvoll, Ann Kristin
    Woman and Children’s Division, Department of Paediatric Medicine, Norwegian Childhood Diabetes Registry, Oslo University Hospital, Oslo, Norway.
    Johansen, Anders
    Department of Paediatrics, Herlev University Hospital, Herlev, Denmark.
    Skrivarhaug, Torild
    Woman and Children’s Division, Department of Paediatric Medicine, Norwegian Childhood Diabetes Registry, Oslo University Hospital, Oslo, Norway / Woman and Children’s Division, Department of Paediatric Medicine, Oslo University Hospital, Oslo, Norway.
    Thorsson, Arni V
    Children’s Medical Center, Landspítali University Hospital and Faculty of Medicine, University of Iceland, Reykjavík, Iceland.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Childhood diabetes in the nordic countries: a comparison of quality registries.2014In: Journal of diabetes science and technology, ISSN 1932-2968, Vol. 8, no 4, 738-44 p.Article in journal (Refereed)
    Abstract [en]

    In 2008 a Nordic collaboration was established between the quality registries in Denmark, Iceland, Norway, and Sweden to improve quality of care for children with diabetes. This study aimed to describe those registries and confirm that the registry variables are comparable. Selected variables were used to demonstrate outcome measurements. The organization of the registries and methodology are described. Cross-sectional data for patients between birth and 14.9 years with type 1 diabetes mellitus in 2009 (n = 6523) from 89 centers were analyzed. Variables were age, gender, and diabetic ketoacidosis at onset, together with age, gender, HbA1c, insulin regimen, and severe hypoglycemia at follow-up in 2009. All 4 registries use a standardized registration at the onset of diabetes and at follow-up, conducted at the local pediatric diabetes centers. Methods for measuring HbA1c varied as did methods of registration for factors such as hypoglycemia. No differences were found between the outcomes of the clinical variables at onset. Significant variations were found at follow-up for mean HbA1c, the proportion of children with HbA1c < 57 mmol/mol (NGSP/DCCT 7.4%), (range 15-31%), the proportion with insulin pumps (range 34-55%), and the numbers with severe hypoglycemia (range 5.6-8.3/100 patient years). In this large unselected population from 4 Nordic countries, a high proportion did not reach their treatment target, indicating a need to improve the quality of pediatric diabetes care. International collaboration is needed to develop and harmonize quality indicators and offers possibilities to study large geographic populations, identify problems, and share knowledge.

  • 323.
    Hanberger, Lena
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Nordfeldt, Sam
    Linköping University, Department of Medical and Health Sciences, Health Technology Assessment. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Use of a Web 2.0 Portal to Improve Education and Communication in Young Patients With Families: Randomized Controlled Trial2013In: Journal of Medical Internet Research, ISSN 1438-8871, Vol. 15, no 8Article in journal (Refereed)
    Abstract [en]

    Background: Diabetes requires extensive self-care and comprehensive knowledge, making patient education central to diabetes self-management. Web 2.0 systems have great potential to enhance health information and open new ways for patients and practitioners to communicate. less thanbrgreater than less thanbrgreater thanObjective: To develop a Web portal designed to facilitate self-management, including diabetes-related information and social networking functions, and to study its use and effects in pediatric patients with diabetes. less thanbrgreater than less thanbrgreater thanMethods: A Web 2.0 portal was developed in collaboration with patients, parents, and practitioners. It offered communication with local practitioners, interaction with peers, and access to relevant information and services. Children and adolescents with diabetes in a geographic population of two pediatric clinics in Sweden were randomized to a group receiving passwords for access to the portal or a control group with no access (n=230) for 1 year. All subjects had access during a second study year. Users activity was logged by site and page visits. Health-related quality of life (HRQOL), empowerment (DES), and quality of information (QPP) questionnaires were given at baseline and after 1 and 2 study years. Clinical data came from the Swedish pediatric diabetes quality registry SWEDIABKIDS. less thanbrgreater than less thanbrgreater thanResults: There was a continuous flow of site visits, decreasing in summer and Christmas periods. In 119/233 families (51%), someone visited the portal the first study year and 169/484 (35%) the second study year. The outcome variables did not differ between intervention and control group. No adverse treatment or self-care effects were identified. A higher proportion of mothers compared to fathers visited once or more the first year (Pandlt;.001) and the second year (Pandlt;.001). The patients who had someone in the family visiting the portal 5 times or more, had shorter diabetes duration (P=.006), were younger (P=.008), had lower HbA1c after 1 year of access (P=.010), and were more often girls (Pandlt;.001). Peer interaction seems to be a valued aspect. less thanbrgreater than less thanbrgreater thanConclusions: The Web 2.0 portal may be useful as a complement to traditional care for this target group. Widespread use of a portal would need integration in routine care and promotion by diabetes team members.

  • 324.
    Harle, Karolina
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Lindgren, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Hallböök, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Experience of living with an enterocutaneous fistula2015In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 24, no 15-16, 2175-2183 p.Article in journal (Refereed)
    Abstract [en]

    Aims and objectives. The purpose of this study was to describe patients experiences of living with an enterocutaneous fistula. Background. An enterocutaneous fistula is a complex and serious illness that usually occurs as a complication from surgery or spontaneously as a result of an underlying disease. The illness is demanding both physically and mentally and causes substantial medical and nursing problems for the afflicted individual. Design. A descriptive design with a qualitative approach. Methods. In-depth interviews were performed with nine participants who had experiences of living with an enterocutaneous fistula. The analysis was conducted using descriptive phenomenology according to Giorgi. Results. The essence of this study was that living with an enterocutaneous fistula is about handling an illness that causes several limitations in daily life and the following five themes emerged from the data: restrictions in daily life, approaches to illness, emotions, dependence and need of support. A constant fear of leakage from the fistula appliance, being dependent on intravenous fluids and being dependent on health care professionals caused isolation and social restriction. Conclusions. The participants had many strategies for handling their illness. By being well trained, engaged and having a positive and understanding approach, health care professionals can encourage hope, motivation and self-care. This can lead to decreased dependence and help the patient to better handle their illness. Relevance to clinical practice. The competence of health care professionals is essential in the care of patients with an enterocutaneous fistula.

  • 325.
    Hasselgren, Kristina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Halldestam, Ingvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Fraser, M. P.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Benjaminsson Nyberg, Pernilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Gasslander, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Björnsson, Bergthor
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Does the Introduction of Laparoscopic Distal Pancreatectomy Jeopardize Patient Safety and Well-Being?2016In: Scandinavian Journal of Surgery, ISSN 1457-4969, E-ISSN 1799-7267, Vol. 105, no 4, 223-227 p.Article in journal (Refereed)
    Abstract [en]

    Background/Purpose: Despite retrospective data indicating short-term superiority for laparoscopic distal pancreatectomy compared to open distal pancreatectomy, the implementation of the procedure has been slow. The aim of this study was to investigate whether patients operated with laparoscopic distal pancreatectomy during the early phase of introduction are at higher risk for complications than patients operated with open distal pancreatectomy.

    Methods: A retrospective single-center analysis of patients operated with laparoscopic distal pancreatectomy (n=37) from the introduction of the procedure and comparison regarding demographic data, preoperative data, operative factors, and postoperative outcomes to patients operated with open distal pancreatectomy was done.

    Results: Operation duration shortened (195 vs 143min, p=0.04) and severe complications reduced (37% vs 6%, p=0.02) significantly in the laparoscopic distal pancreatectomy group between the first half of the study and the second half. Blood loss was significantly (pamp;lt;0.001) lower in the laparoscopic distal pancreatectomy group (75mL) than in the open distal pancreatectomy group (550mL), while complication rate and hospital stay as well as the percentage of radical resections were the same.

    Conclusion: Laparoscopic distal pancreatectomy can be introduced without jeopardizing patient safety and well-being during the early learning curve. The procedures should be compared in a prospective randomized manner.

  • 326.
    Hasselgren, Kristina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Björnsson, Bergthor
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Role of associating liver partition and portal vein ligation for staged hepatectomy in colorectal liver metastases: A review2015In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 21, no 15, 4491-4498 p.Article, review/survey (Refereed)
    Abstract [en]

    Colorectal cancer is the third most common cancer in the Western world. Approximately half of patients will develop liver metastases, which is the most common cause of death. The only potentially curative treatment is surgical resection. However, many patients retain a to small future liver remnant (FLR) to allow for resection directly. There are therefore strategies to decrease the tumor with neoadjuvant chemotherapy and to increase the FLR. An accepted strategy to increase the FLR is portal vein occlusion (PVO). A concern with this strategy is that a large proportion of patients will never be operated because of progression during the interval between PVO and resection. ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) is a new procedure with a high resection rate. A concern with this approach is the rather high frequency of complications and high mortality, compared to PVO. In this review, it is shown that with ALPPS the resection rate was 97.1% for CRLM and the mortality rate for all diagnoses was 9.6%. The mortality rate was likely lower for patients with CRLM, but some data were lacking in the reports. Due to the novelty of ALPPS, the indications and technique are not yet established but there are arguments for ALPPS in the context of CRLM and a small FLR.

  • 327.
    Hasselgren, Kristina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Gasslander, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Björnsson, Bergthor
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Multivisceral Resection in Patients with Advanced Abdominal Tumors2016In: Scandinavian Journal of Surgery, ISSN 1457-4969, E-ISSN 1799-7267, Vol. 105, no 3, 147-152 p.Article in journal (Refereed)
    Abstract [en]

    Background/Aim: Multivisceral resection for advanced tumors can result in prolonged survival but may also increase the risk of postoperative morbidity and mortality. The primary aim of this study was to investigate whether extensive resections increase the severity of postoperative complications. Materials and Methods: A retrospective study was conducted between 2009 and 2014 at the Linkoping University Hospital surgical department. All patients with a confirmed or presumed malignant disease who underwent a non-standardized surgical procedure requiring a multivisceral resection were included. The primary endpoint was 90-day complications according to the Clavien-Dindo score. Results: Forty-eight patients were included, with an age range of 17-77years. A median of three organs was resected. The most common diagnoses were neuroendocrine tumor (n=8), gastric cancer (n=7), and gastrointestinal stromal tumor (n=6). One patient died during surgery. Complications grade 3b according to Clavien-Dindo score occurred in 10 patients. R0 resection was achieved in 32 patients. No correlation was observed between the number of anastomoses, perioperative blood loss, operative time, and complications. Only postoperative blood transfusion was correlated with severe complications (p=0.046); however, a tendency toward more complications with an increasing number of resected organs was observed (p=0.06). Conclusion: Multivisceral resection can result in R0, potentially curing patients with advanced tumors. Here, no correlation between extensive resections and complications was observed. Only postoperative blood transfusion was correlated with severe complications.

  • 328.
    Hedelin, Maria
    et al.
    University of Gothenburg, Sweden; Karolinska Institute, Sweden.
    Löf, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    Sandin, Sven
    Karolinska Institute, Sweden.
    Adami, Hans-Olov
    Karolinska Institute, Sweden; Harvard University, MA 02115 USA.
    Weiderpass, Elisabete
    Karolinska Institute, Sweden; Cancer Registry Norway, Norway; Arctic University of Norway, Norway; Folkhalsan Research Centre, Finland.
    Prospective Study of Dietary Phytoestrogen Intake and the Risk of Colorectal Cancer2016In: Nutrition and Cancer, ISSN 0163-5581, E-ISSN 1532-7914, Vol. 68, no 3, 388-395 p.Article in journal (Refereed)
    Abstract [en]

    Dietary phytoestrogen intake has been inversely associated with the risk of prostate and breast cancer and might also affect the risk of colorectal cancer. We evaluated the associations between dietary lignan intake, dietary isoflavonoid intake, dietary coumestrol intake, and dietary enterolignans and equol intake, and risk of colorectal cancer. Data from the Womens Lifestyle and Health (WLH) Cohort study was used. The WLH study is a prospective population-based cohort study including 48,268 Swedish women aged 30-49years at the time of enrolment in 1991-92. Follow-up for colorectal cancer incidence, death, and emigration until the end of 2010 was performed through record linkage to the Swedish Cancer Registry and Total Population Register. During follow-up 206 incident colorectal cancer cases were identified. Cox proportional hazards models were fitted to estimate adjusted risk ratios with 95% confidence intervals. We found no statistically significant association between the intake of dietary lignans, dietary isoflavonoids, coumestrol, or enterolignans and equol, and risk of colorectal cancer. We found no association between dietary phytoestrogen intake and the risk of colorectal cancer. However, since the number of cancer cases was small, our results need to be confirmed. Future studies should investigate colon and rectal cancer separately.

  • 329.
    Heedman, P. A.
    et al.
    Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden. Palliat Educ and Research Centre, Sweden.
    Canslatt, E.
    Lanssjukhuset Kalmar, Sweden.
    Henriks, G.
    Jonköping County Council, Sweden.
    Starkhammar, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Fomichov, Victoria
    Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Sjödahl, Rune
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Variation at presentation among colon cancer patients with metastases: a population-based study2015In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 17, no 5, 403-408 p.Article in journal (Refereed)
    Abstract [en]

    AimThe study aimed to describe and follow a 2year cohort of colon cancer patients with Stage IV disease from presentation to long-term outcome. MethodThe records of 177 colon cancer patients diagnosed in southeast Sweden during 2009-2010 with disseminated disease at presentation were reviewed retrospectively. ResultsThe patients were heterogeneous with respect to age, performance status and survival. Despite metastatic disease, local symptoms from the primary tumour dominated the initial clinical picture. Forty-one per cent had anaemia. The time from suspicion of colon cancer to established diagnosis of disseminated disease varied from 0 to 231days (emergency cases included, median 12days). The majority (77%) were diagnosed in hospital. In 53% the primary tumour and the metastases were not diagnosed on the same occasion which may increase the risk for misinformation or delays in the care process. The possibility of simultaneous diagnosis was doubled when the patient was investigated as an inpatient. Patients were seen by one to 12 physicians (median three) in the investigation phase, and one to 47 (median 11) from diagnosis until the last record in the hospital notes. The 1-year survival was 46%. ConclusionPatients with metastatic colon cancer at presentation are heterogeneous and warrant an adapted multidisciplinary approach to achieve the goal of individualized treatment for each patient in accordance with the Swedish national cancer strategy.

  • 330.
    Hellberg, Sandra
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Eklund, Daniel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Gawel, Danuta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Köpsén, Mattias
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Kockum, Ingrid
    Karolinska Institute, Department Clin Neurosci, Neuroimmunol Unit, S-17177 Linkoping, Sweden.
    Olsson, Tomas
    Karolinska Institute, Department Clin Neurosci, Neuroimmunol Unit, S-17177 Linkoping, Sweden.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Kastbom, Alf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    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.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Håkansson, Irene
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Gustafsson, Mika
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    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.
    Dynamic Response Genes in CD4+T Cells Reveal a Network of Interactive Proteins that Classifies Disease Activity in Multiple Sclerosis2016In: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 16, no 11, 2928-2939 p.Article in journal (Refereed)
    Abstract [en]

    Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS and has a varying disease course as well as variable response to treatment. Biomarkers may therefore aid personalized treatment. We tested whether in vitro activation of MS patient-derived CD4+ T cells could reveal potential biomarkers. The dynamic gene expression response to activation was dysregulated in patient-derived CD4+ T cells. By integrating our findings with genome-wide association studies, we constructed a highly connected MS gene module, disclosing cell activation and chemotaxis as central components. Changes in several module genes were associated with differences in protein levels, which were measurable in cerebrospinal fluid and were used to classify patients from control individuals. In addition, these measurements could predict disease activity after 2 years and distinguish low and high responders to treatment in two additional, independent cohorts. While further validation is needed in larger cohorts prior to clinical implementation, we have uncovered a set of potentially promising biomarkers.

  • 331.
    Hemdan, Tammer
    et al.
    University Hospital Uppsala, Sweden.
    Johansson, Robert
    Umeå University Hospital, Sweden.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Hellström, Pekka
    University Central Hospital, Oulu, Finland.
    Tasdemir, Ilker
    Central Hospital of Rogaland, Stavanger, Norway.
    Malmström, Per-Uno
    University Hospital Uppsala, Sweden.
    5-Year Outcome of a Randomized Prospective Study Comparing bacillus Calmette-Guerin with Epirubicin and Interferon-alpha 2b in Patients with T1 Bladder Cancer2014In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 191, no 5, 1244-1249 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: In a multicenter, prospectively randomized study we evaluated the 5-year outcomes of bacillus Calmette-Guerin alone compared to a combination of epirubicin and interferon-alpha 2b in the treatment of patients with T1 bladder cancer. Materials and Methods: Transurethral resection was followed by a second resection and bladder mapping. Stratification was for grade and carcinoma in situ. Followup entailed regular cystoscopy and cytology during the first 5 years. The end points assessed in this analysis were recurrence-free survival, time to treatment failure and progression, cancer specific survival and prognostic factors. Results: The study recruited 250 eligible patients. The 5-year recurrence-free survival rate was 38% in the combination arm and 59% in the bacillus Calmette-Guerin arm (p = 0.001). The corresponding rates for the other end points were not significantly different, as free of progression 78% and 77%, treatment failure 75% and 75%, and cancer specific survival 90% and 92%, respectively. The type of treatment, tumor size and tumor status at second resection were independent variables associated with recurrence. Concomitant carcinoma in situ was not predictive of failure of bacillus Calmette-Guerin therapy. An independent factor for treatment failure was remaining T1 stage at second resection. Conclusions: Bacillus Calmette-Guerin was more effective than the tested combination therapy. The currently recommended management with second resection and 3-week maintenance bacillus Calmette-Guerin entails a low risk of cancer specific death. More aggressive treatment in patients with infiltrative tumors at second resection might improve these results. In particular, concomitant carcinoma in situ was not a predictive factor for poor outcome after bacillus Calmette-Guerin therapy.

  • 332.
    Hemdan, Tammer
    et al.
    Department of Surgical Sciences, Uppsala University, Uppsala.
    Malmström, Per-Uno
    Department of Surgical Sciences, Uppsala University, Uppsala.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland. Department of Surgical Sciences, Uppsala University, Uppsala.
    Segersten, Ulrika
    Department of Surgical Sciences, Uppsala University, Uppsala.
    Emmprin expression predicts response and survival following cisplatin containing chemotherapy for bladder cancer: A validation study2015In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 194, no 6, 1575-1581 p.Article in journal (Refereed)
    Abstract [en]

    Purpose Neoadjuvant chemotherapy before cystectomy is recommended. To our knowledge the subset of patients likely to benefit has not been identified. We validate emmprin and survivin as markers of chemotherapy response. Materials and Methods Tumor specimens were obtained before therapy from a total of 250 patients with T1-T4 bladder cancer enrolled in 2 randomized trials comparing neoadjuvant chemotherapy before cystectomy with a surgery only arm. Protein expression was determined by immunohistochemistry. Results Expression was categorized according to predefined cutoffs reported in the literature. Data were analyzed with the Kaplan-Meier method and Cox models. Patients in the chemotherapy cohort with negative emmprin expression had significantly higher down staging overall survival than those with positive expression (71% vs 38%, p <0.001). The values for cancer specific survival were 76% and 56%, respectively (p <0.027). In the cystectomy only cohort emmprin expression was not associated with overall survival (46% vs 35%, p = 0.23) or cancer specific survival (55% vs 51%, p = 0.64). Emmprin negative patients had an absolute risk reduction of 25% in overall survival (95% CI 11-40) and a number needed to treat of 4 (95% CI 2.5-9.3). Survivin expression was not useful as a biomarker in this study. Limitations were the retrospective design and heterogeneity coupled with the time difference between the trials. Conclusions Patients with emmprin negative tumors have a better response to neoadjuvant chemotherapy before cystectomy than those with positive expression. © 2015 American Urological Association Education and Research, Inc.

  • 333.
    Henriksson, Hanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Development of body composition and its relationship with physical activity in healthy Swedish children: A longitudinal study until 4.5 years of age including evaluation of methods to assess physical activity and energy intake2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Childhood obesity according to the World Health Organization is one of the most serious public health challenges of the 21st century. The proportion of childhood obesity is high both globally and in Sweden. This is of great concern since obese children tend to stay obese in adulthood. In order to develop strategies to prevent early childhood obesity more knowledge is needed regarding factors explaining why children become overweight and obese. Preventive strategies require accurate and easy-to-use methods to assess physical activity in response to energy expenditure as well as energy intake in young children, but such methods are largely lacking or have shown limited accuracy. The aims of this thesis were: 1) to describe the longitudinal development of body composition from 1 week to 4.5 years of age; 2) to study relationships between measures of body composition and the physical activity level (PAL) at 1.5 and 3 years of age; 3) to evaluate if heart rate recording and movement registration using Actiheart can capture variations in total energy expenditure (TEE) and activity energy expenditure (AEE) at 1.5 and 3 years; 4) to evaluate the potential of a 7-day activity diary to assess PAL at 1.5 and 3 years of age; 5) to evaluate a new tool (TECH) using mobile phones for assessing energy intake at 3 years of age.

    Healthy children were investigated at 1 and 12 weeks (n=44), at 1.5 (n=44), 3 (n=33) and 4.5 (n=26) years of age. Body composition was measured using air-displacement plethysmography at 1 and 12 weeks and at 4.5 years of age. At 1.5 and 3 years, body composition, TEE, PAL and AEE were assessed using the doubly labelled water method and indirect calorimetry. Heart rate and movements were recorded using Actiheart (four days) and physical activities were registered using the 7-day diary. Energy intake was assessed using TECH during one complete 24-hour period.

    Average percentage of total body fat (TBF) and average fat mass index (FMI) were higher (+3 to +81 %), while fat-free mass index (FFMI) was slightly lower (-2 to -9 %), in children in the study from 12 weeks until 4.5 years of age when compared to corresponding reference values. A relationship between TBF% and PAL was found both at 1.5 and 3 years of age. At 3 years, but not at 1.5 years, this could be explained by a relationship between PAL and FFMI. Actiheart recordings explained a significant but small fraction (8%) of the variation in free-living TEE at 1.5 and 3 years, and in AEE (6 %) at 3 years, above that explained by body composition variables. At 1.5 and 3 years of age, PAL estimated by means of the activity diary using metabolic equivalent (MET) values by Ainsworth et al. was not significantly different from reference PAL, but the accuracy for individuals was low. Average energy intake assessed by TECH was not significantly different from TEE. However, the accuracy for individuals was poor.

    The results of this thesis suggest that 1) The higher body fatness of the children in the study compared to the corresponding reference values may indicate the presence of a secular trend in body composition development characterized by a high body fatness. 2) Body fatness might counteract physical activity at 1.5 years of age when the capacity to perform physical activity is limited, but not at 3 years of age when such a capacity has been developed. 3) Actiheart recordings explained a significant but small fraction of the variation in TEE at 1.5 and 3 years, and in AEE at 3 years of age, above that explained by body composition variables. 4) The activity diary and TECH produced mean values in agreement with reference PAL and TEE, respectively, but the accuracy for individual children was low.

    In conclusion, the results of this thesis suggest the presence of a secular trend in body composition development in healthy Swedish children, from infancy up to 4.5 years of age, which is characterized by a high body fatness. Methods to assess physical activity and energy intake at 1.5 and 3 years of age provided some promising results on a group level, although further research is needed to increase the accuracy of these methods in individual children.

  • 334.
    Henriksson, Hanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Bonn, E. Stephanie
    Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden.
    Bergström, Anna
    Karolinska Institutet, Institute of Enviromental Medicine, Stockholm, Sweden.
    Bälter, Katarina
    Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden.
    Bälter, Olle
    Royal Institute of Technology, School of Computer Science and Communication, Stockholm, Sweden.
    Delisle, Christine
    Karolinska Institutet, Department of Biosciences and Nutrition, Huddinge, Sweden.
    Forsum, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Löf, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Karolinska Institutet, Department of Biosciences and Nutrition, Huddinge, Sweden.
    A New Mobile Phone-Based Tool for Assessing Energy and Certain Food Intakes in Young Children: A Validation Study2015In: JMIR mhealth and uhealth, E-ISSN 2291-5222, Vol. 3, no 2, e38Article in journal (Refereed)
    Abstract [en]

    Background: Childhood obesity is an increasing health problem globally. Obesity may be established already at pre-school age. Further research in this area requires accurate and easy-to-use methods for assessing the intake of energy and foods. Traditional methods have limited accuracy, and place large demands on the study participants and researchers. Mobile phones offer possibilities for methodological advancements in this area since they are readily available, enable instant digitalization of collected data, and also contain a camera to photograph pre- and post-meal food items. We have recently developed a new tool for assessing energy and food intake in children using mobile phones called the Tool for Energy Balance in Children (TECH). Objective: The main aims of our study are to (1) compare energy intake by means of TECH with total energy expenditure (TEE) measured using a criterion method, the doubly labeled water (DLW) method, and (2) to compare intakes of fruits and berries, vegetables, juice, and sweetened beverages assessed by means of TECH with intakes obtained using a Web-based food frequency questionnaire (KidMeal-Q) in 3 year olds. Methods: In this study, 30 Swedish 3 year olds were included. Energy intake using TECH was compared to TEE measured using the DLW method. Intakes of vegetables, fruits and berries, juice, as well as sweetened beverages were assessed using TECH and compared to the corresponding intakes assessed using KidMeal-Q. Wilcoxon matched pairs test, Spearman rank order correlations, and the Bland-Altman procedure were applied. Results: The mean energy intake, assessed by TECH, was 5400 kJ/24h (SD 1500). This value was not significantly different (P=.23) from TEE (5070 kJ/24h, SD 600). However, the limits of agreement (2 standard deviations) in the Bland-Altman plot for energy intake estimated using TECH compared to TEE were wide (2990 kJ/24h), and TECH overestimated high and underestimated low energy intakes. The Bland-Altman plots for foods showed similar patterns. The mean intakes of vegetables, fruits and berries, juice, and sweetened beverages estimated using TECH were not significantly different from the corresponding intakes estimated using KidMeal-Q. Moderate but statistically significant correlations (ρ=.42-.46, P=.01-.02) between TECH and KidMeal-Q were observed for intakes of vegetables, fruits and berries, and juice, but not for sweetened beverages. Conclusion: We found that one day of recordings using TECH was not able to accurately estimate intakes of energy or certain foods in 3 year old children.

  • 335.
    Henriksson, Hanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Eriksson, Britt
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Forsum, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Flinke Carlsson, Eva
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Löf, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Development of body composition and its relationship with physical activity: A longitudinal study of Swedish children until 4·5 years of age2015Manuscript (preprint) (Other academic)
    Abstract [en]

    In order to develop strategies to prevent early childhood obesity more knowledge about longitudinal body composition development is needed. Previous studies have shown that there is a negative relationship between the physical activity level (PAL) and total body fat (TBF) in children. The aims of this study were: 1) To describe the longitudinal development of body composition from 1 week to 4·5 years of age. 2) To study the relationships between measures of body composition and PAL at 3 years of age. 3) To compare the relationships between body composition measures and PAL at 3 years of age to the corresponding relationships at 1·5 years of age. Body composition was measured using air-displacement plethysmography at 1 week, 12 weeks and at 4·5 years of age. At 1·5 and 3 years body composition and PAL were assessed using the doubly labelled water method and indirect calorimetry. The results showed that TBF% and fat mass index (FMI) were higher than corresponding reference values, during infancy and childhood. We found a relationship between TBF% and PAL at 3 years of age but this was explained by a relationship between PAL and fat-free mass index (FFMI). The corresponding relationship at 1·5 years of age could not be explained by a relationship between PAL and FFMI. In conclusion, the children in this study had higher body fatness compared to the corresponding reference values. This may indicate an identification of a secular trend in body composition development which is characterized by a high body fatness. Our findings also suggest that body fatness might counteract physical activity at 1·5 years of age when the capacity to perform physical activity is limited, however this result was not observed at 3 years of age when such a capacity has been developed.

  • 336.
    Henriksson, Hanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Karolinska Institute, Sweden .
    Forsum, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Löf, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Evaluation of Actiheart and a 7d activity diary for estimating free-living total and activity energy expenditure using criterion methods in 1 center dot 5- and 3-year-old children2014In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 111, no 10, 1830-1840 p.Article in journal (Refereed)
    Abstract [en]

    Accurate and easy-to-use methods to assess free-living energy expenditure in response to physical activity in young children are scarce. In the present study, we evaluated the capacity of (1) 4d recordings obtained using the Actiheart (mean heart rate (mHR) and mean activity counts (mAC)) to provide assessments of total energy expenditure (TEE) and activity energy expenditure (AEE) and (2) a 7d activity diary to provide assessments of physical activity levels (PAL) using three sets of metabolic equivalent (MET) values (PAL(Torun), PAL(Adolph) and PAL(Ainsworth)) in forty-four and thirty-one healthy Swedish children aged 1 center dot 5 and 3 years, respectively. Reference TEE, PAL(ref) and AEE were measured using criterion methods, i.e. the doubly labelled water method and indirect calorimetry. At 1 center dot 5 years of age, mHR explained 8% (P=0 center dot 006) of the variation in TEE above that explained by fat mass and fat-free mass. At 3 years of age, mHR and mAC explained 8 (P=0 center dot 004) and 6 (P=0 center dot 03)% of the variation in TEE and AEE, respectively, above that explained by fat mass and fat-free mass. At 1 center dot 5 and 3 years of age, average PAL(Ainsworth) values were 1 center dot 44 and 1 center dot 59, respectively, and not significantly different from PAL(ref) values (1 center dot 39 and 1 center dot 61, respectively). By contrast, average PAL(Torun) (1 center dot 5 and 3 years) and PAL(Adolph) (3 years) values were lower (Pless than0 center dot 05) than the corresponding PAL(ref) values. In conclusion, at both ages, Actiheart recordings explained a small but significant fraction of free-living energy expenditure above that explained by body composition variables, and our activity diary produced mean PAL values in agreement with reference values when using MET values published by Ainsworth.

  • 337.
    Henriksson, Pontus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Body composition of parents and their infants: methodological, anthropometric, metabolic and genetic studies2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Body composition in infancy may be of importance for later health. In particular, infant body composition may be relevant regarding obesity risk in childhood. Recent advances in body composition methodology using air displacement plethysmography (ADP) have provided possibilities to accurately measure body composition of infants in a quick and non-invasive manner. The aims of this thesis were to study associations of parental body composition using ADP, glucose homeostasis during pregnancy and infant genetics with infant body composition also using ADP. When using ADP in adults, a correction for the thoracic gas volume (TGV) is needed and TGV can be predicted using equations developed in nonpregnant adults. Thus another aim was to study the validity of using such equations during pregnancy.

    Parent couples were invited to this study at a routine visit to a maternity clinic in Linköping between September 2008 and October 2010. When the mother was in gestational week 32, parental body composition using ADP and maternal glucose homeostasis variables were assessed. Size and body composition of healthy, singleton and full term (≥ 37 gestational weeks) infants were measured at 1 and 12 weeks of age and a total of 211 infants  were included in the studies. Weight and length at 1 year of age were reported by parents. Saliva samples were collected from the infants to obtain DNA for genotyping of the fat mass and obesity associated (FTO) gene.

    Body composition results calculated using measured and predicted TGV were compared in 27 women. Results showed that predicted TGV yields a very marginal overestimation (0.5 %) of fat mass (FM). Further, each kg increase in maternal and paternal fat-free mass (FFM) was associated with 15.6 g (P=0.001) and 9.1 g (P=0.007), respectively, more FFM in their 1-week old infants. FM of fathers was not related to infant FM. However, maternal FM was positively associated with FM of daughters (5.8 g/kg, P=0.007), but not of sons (P=0.79) at 1 week of age. Similarly, each standard deviation increase in maternal HOMA-IR (homeostatic model assessment-insulin resistance) was related to 52.7 more g of FM (P<0.001) in 1-weekold daughters, but no such relationship was found for sons (P=0.79). The number of risk alleles at the FTO locus rs9939609 was not associated with infant body mass index (BMI) or infant FM at 1 or 12 weeks of age. However, the number of risk alleles was positively associated (P≤0.033) with infant length at 1 and 12 weeks of age, and the results suggested that this association was stronger in boys than in girls.

    The results presented in this thesis show that: i) The use of predicted TGV when applying ADP in gestational week 32 overestimated % FM only slightly. ii) Associations between parental and infant body composition are present early in life. Thus, parental FFM was positively related to FFM in 1-week-old infants. Furthermore, maternal FM and insulin resistance (HOMA-IR) were positively related to FM of 1-week-old daughters, but no such relationships were observed for sons. iii) The FTO genotype is not associated with infant body fatness at 1 or 12 weeks of age. However, the results suggested that the number of FTO risk alleles is positively associated with infant length, especially in boys.

    In conclusion, parental and genetic factors were associated with infant size and body composition and these relationships may be of importance for future body composition and health.

  • 338.
    Henriksson, Pontus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. University of Granada, Spain.
    Cadenas-Sanchez, Cristina
    University of Granada, Spain.
    Leppanen, Marja H.
    University of Jyvaskyla, Finland.
    Delisle Nystrom, Christine
    Karolinska Institute, Sweden.
    Ortega, Francisco B.
    University of Granada, Spain; Karolinska Institute, Sweden.
    Pomeroy, Jeremy
    Marshfield Clin Research Fdn, WI 54449 USA.
    Ruiz, Jonatan R.
    University of Granada, Spain; Karolinska Institute, Sweden.
    Löf, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    Associations of Fat Mass and Fat-Free Mass with Physical Fitness in 4-Year-Old Children: Results from the MINISTOP Trial2016In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 8, no 8, 473- p.Article in journal (Refereed)
    Abstract [en]

    Physical fitness is a powerful marker of health in youth. Studies in adolescents and adults suggest that higher fat mass is related to worse physical fitness. However, there is limited knowledge whether fat mass and fat-free mass are associated with physical fitness already in preschoolers. Baseline data from the MINISTOP (Mobile-based INtervention Intended to STop Obesity in Preschoolers) trial was utilized for this cross-sectional analysis. Body composition was assessed using air-displacement plethysmography. Fat mass index [fat mass (kg)/height(2) (m)] and fat-free mass index [fat-free mass (kg)/height(2) (m)] were used to provide height-adjusted measures of body composition. Physical fitness was measured using the PREFIT (FITness testing in PREschool children) battery, which assesses cardiorespiratory fitness, upper-body and lower-body muscular strength as well as motor fitness. In total, this study included 303 children (168 boys and 135 girls), who were on average 4.48 +/- 0.15 years old. Higher fat mass index was associated with worse cardiorespiratory fitness (standardized beta = -0.17, p = 0.002), lower-body muscular strength (beta = -0.17, p = 0.003) and motor fitness (beta = -0.21, p amp;lt; 0.001) in regression analyses adjusted for age, sex and mutually adjusted for fat-mass index and fat-free mass index. Conversely, higher fat-free mass index was associated with better cardiorespiratory fitness (beta = 0.18, p = 0.002), upper-body muscular strength (beta = 0.39, p amp;lt; 0.001), lower-body muscular strength (beta = 0.22, p amp;lt; 0.001) and motor fitness (beta = 0.17, p = 0.004). Thus, fat mass and fat-free mass in preschoolers appear to have joint but opposite associations with physical fitness, an important marker for current and future health.

  • 339.
    Henriksson, Pontus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Eriksson, B
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Forsum, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Löf, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Gestational weight gain according to Institute of Medicine recommendations in relation to infant size and body composition.2015In: Pediatric Obesity, ISSN 2047-6302, E-ISSN 2047-6310, Vol. 10, no 5, 388-394 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Intrauterine life may be a critical period for programming childhood obesity; however, there is insufficient knowledge concerning how gestational weight gain (GWG) affects infant fat mass (FM) and fat-free mass (FFM).

    OBJECTIVES: The aim of this study was to investigate relationships between GWG according to Institute of Medicine (IOM) recommendations and infant size, FM and FFM. We also investigated if the associations were different for normal-weight and overweight/obese women.

    METHODS: This study included 312 healthy Swedish mother-infant pairs. Infant body composition at 1 week of age was assessed using air-displacement plethysmography. Maternal GWG was defined as below, within or above the 2009 IOM recommendations. Multiple regression analyses were used.

    RESULTS: Compared with women whose weight gain was within IOM recommendations, women with weight gain below the recommendations had infants that were shorter (-0.7 cm, P = 0.008) when adjusting for confounders. Normal-weight women exceeding IOM recommendations had infants with higher FM (+58 g, P = 0.008) compared with normal-weight women who gained within the recommendations. No corresponding association was observed for overweight/obese women.

    CONCLUSIONS: Inadequate GWG was associated with shorter infants, while excessive GWG was associated with greater infant FM for women who were of normal weight before pregnancy.

  • 340.
    Henriksson, Pontus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Lof, M.
    Karolinska Institute, Sweden.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Forsum, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Variation in the fat mass and obesity-related (FTO) genotype is not associated with body fatness in infants, but possibly with their length2014In: Pediatric Obesity, ISSN 2047-6302, E-ISSN 2047-6310, Vol. 9, no 5, E112-E115 p.Article in journal (Refereed)
    Abstract [en]

    BackgroundData relating variation at the fat mass and obesity-related (FTO) locus (rs9939609) to fat mass in infancy are inconclusive. ObjectiveTo study relationships between FTO genotype and infant size (at 1 and 12 weeks and at 1 year of age) and body composition (at 1 and 12 weeks). MethodsBody composition was assessed using air displacement plethysmography in 207 infants. FTO was genotyped using the TaqMan assay. ResultsThe number of risk alleles was related to length at 1 and 12 weeks (P=0.007-0.033) but not to fat mass. The relationship to length was stronger in boys than in girls. ConclusionsOur results suggest that the FTO genotype is not related during infancy to fat mass but is related to length in boys but not in girls.

  • 341.
    Henriksson, Pontus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Lof, Marie
    Karolinska Institute, Sweden.
    Forsum, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Glucose Homeostasis Variables in Pregnancy versus Maternal and Infant Body Composition2015In: Nutrients, ISSN 2072-6643, Vol. 7, no 7, 5615-5627 p.Article in journal (Refereed)
    Abstract [en]

    Intrauterine factors influence infant size and body composition but the mechanisms involved are to a large extent unknown. We studied relationships between the body composition of pregnant women and variables related to their glucose homeostasis, i.e., glucose, HOMA-IR (homeostasis model assessment-insulin resistance), hemoglobin A(1c) and IGFBP-1 (insulin-like growth factor binding protein-1), and related these variables to the body composition of their infants. Body composition of 209 women in gestational week 32 and of their healthy, singleton and full-term one-week-old infants was measured using air displacement plethysmography. Glucose homeostasis variables were assessed in gestational week 32. HOMA-IR was positively related to fat mass index and fat mass (r(2) = 0.32, p less than 0.001) of the women. Maternal glucose and HOMA-IR values were positively (p 0.006) associated, while IGFBP-1was negatively (p = 0.001) associated, with infant fat mass. HOMA-IR was positively associated with fat mass of daughters (p less than 0.001), but not of sons (p = 0.65) (Sex-interaction: p = 0.042). In conclusion, glucose homeostasis variables of pregnant women are related to their own body composition and to that of their infants. The results suggest that a previously identified relationship between fat mass of mothers and daughters is mediated by maternal insulin resistance.

  • 342.
    Henriksson, Pontus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Löf, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Nutrition. Linköping University, Faculty of Health Sciences.
    Forsum, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Nutrition. Linköping University, Faculty of Health Sciences.
    Assessment and prediction of thoracic gas volume in pregnant women: an evaluation in relation to body composition assessment using air displacement plethysmography2013In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 109, no 1, 111-117 p.Article in journal (Refereed)
    Abstract [en]

    Assessment of body fat (BF) in pregnant women is important when investigating the relationship between maternal nutrition and offspring health. Convenient and accurate body composition methods applicable during pregnancy are therefore needed. Air displacement plethysmography, as applied in Bod Pod, represents such a method since it can assess body volume (BV) which, in combination with body weight, can be used to calculate body density and body composition. However, BV must be corrected for the thoracic gas volume (TGV) of the subject. In non-pregnant women, TGV may be predicted using equations, based on height and age. It is unknown, however, whether these equations are valid during pregnancy. Thus, we measured the TGV of women in gestational week 32 (n 27) by means of plethysmography and predicted their TGV using equations established for non-pregnant women. Body weight and BV of the women was measured using Bod Pod. Predicted TGV was significantly (P = 0.033) higher than measured TGV by 6% on average. Calculations in hypothetical women showed that this overestimation tended to be more pronounced in women with small TGV than in women with large TGV. The overestimation of TGV resulted in a small but significant (P = 0.043) overestimation of BF, equivalent to only 0.5% BF, on average. A Bland-Altman analysis showed that the limits of agreement were narrow (from -1.9 to 2.9% BF). Thus, although predicted TGV was biased and too high, the effect on BF was marginal and probably unimportant in many situations.

  • 343.
    Henriksson, Pontus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Löf, Marie
    Department of Biosciences and Nutrition, Karolinska Institute, NOVUM, Huddinge, Sweden.
    Forsum, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Glucose, insulin, and the insulin-like growth factor binding protein 1 in the circulation of pregnant women in relation to their own body composition and to that of their infants2015Manuscript (preprint) (Other academic)
    Abstract [en]

    Aim: Intrauterine factors influence infant size and body composition but the mechanisms involved are incompletely known. We studied relationships between the body composition of pregnant women and variables related to their glucose homeostasis, i.e. glucose, insulin, HOMA-IR (homeostasis model assessment-insulin resistance), haemoglobin A1c and IGFBP-1 (insulin-like growth factor binding protein 1), in their circulation and related these variables to the body composition of their infants.

    Methods: Body composition of 209 women in gestational week 32 and of their healthy, singleton and full-term one-week-old infants was measured using air displacement plethysmography. Glucose homeostasis variables were assessed in gestational week 32.

    Results: Insulin/HOMA-IR were positively related to body mass index, fat mass index and fat mass (r2=0.32-0.36, P<0.001) of the women. Their glucose, insulin and HOMA-IR values were positively (P≤0.009) associated, while IGFBP-1was negatively (P=0.001) associated, with infant fat mass. Insulin and HOMA-IR were positively associated with fat mass of daughters (P<0.001), but not of sons (P≥0.65) (Sex-interaction: P≤ 0.042).

    Conclusion: Glucose homeostasis variables of pregnant women are related to their own body composition and to that of their infants. The results suggested that a previously identified relationship between fat mass of mothers and daughters is mediated by insulin resistance.

  • 344.
    Henriksson, Pontus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Löf, Marie
    Department of Biosciences and Nutrition, Karolinska Institute, NOVUM, Huddinge, Sweden.
    Forsum, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Parental fat-free mass is related to the fat-free mass of infants and maternal fat mass is related to the fat mass of infant girls2015In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 104, no 5, 491-497 p.Article in journal (Refereed)
    Abstract [en]

    Aim: Existing studies suggest that weight and body composition of parents influence the size and body composition of their offspring, but are often inconclusive and conducted by means of inappropriate body composition methodology. Our aim was to study infant size and body composition variables in relation to body composition variables of their mothers and fathers in a well-nourished population using an accurate methodology.

    Methods: Between 2008 and 2011, we used air displacement plethysmography to measure the body composition of 209 parent–infant units. Parents were measured when women were in gestational week 32. Their healthy, singleton, full-term infants were measured at 1 week.

    Results: Infant fat-free mass in grams was positively related (p ≤ 0.007) to the fat-free mass in kilograms of the mothers (15.6 g/kg) and the fathers (9.1 g/kg). Furthermore, the fat mass of the daughters, but not of the sons, was positively related to the fat mass of the mothers (5.8 g/kg, p = 0.007).

    Conclusion: This study found associations between the fat-free mass of parents and infants and an association between the fat mass of mothers and their infant girls. These findings may help to understand early life factors behind overweight and obesity.

  • 345.
    Herlofson, B.B.
    et al.
    Department of Oral Surgery and Oral Medicine, Faculty of Dentistry- University of Oslo, Oslo, Norway.
    Wexell, C.L.
    Department of Oral and Maxillofacial Surgery, Southern Alvsborg Hospital, Borås; Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden .
    Nørholt, S.E.
    Aarhus University, Department of Oral and Maxillofacial Surgery, Aarhus University Hospital, Aarhus, Denmark.
    Igland, E.
    Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, University of Oslo, Oslo, Norway.
    Cardemil, Carina
    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, Maxillofacial Unit. Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Ehrenstein, V.
    Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
    Schiødt, V.
    Department of Oral and Maxillofacial Surgery, Rigshospitalet, Copenhagen, Denmark.
    THE SCANDINAVIAN OSTEONECROSIS COHORT STUDY - REPORT ON THE FIRST 4 YEARS OF RESEARCH COLLABORATION2016Conference paper (Other academic)
  • 346.
    Hilborn, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    The role of the androgen receptor and hydroxysteroid 17β dehydrogenase in breast cancer: Impact on tamoxifen treatment2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The healthy breast is a tissue composed of centrally located milk producing glands connected to the nipple by ducts, surrounded by fat tissue and connective tissue. The growth of the breast is primarily mediated by the estrogens, while the androgens mediate tissue homeostasis and protect against growth signals. In breast cancer, the cells of the glands or ducts undergo malignant transformation, and start proliferating in an uncontrollable fashion. Breast cancer is the most common malignancy in women, and it is estimated that 10% of all women will be diagnosed with breast cancer during their life-time. The primary classification of breast cancer is based mainly on the expression of the estrogen receptor, and 70-80% of breast cancers are estrogen receptor positive, and are classified as luminal. The remaining breast cancers are classified into HER2 positive or triple negative breast cancer. Out of all breast cancers, ~80% are androgen receptor positive. This varies in different subtypes, however, with the highest expression in luminal and lowest expression in triple negative breast cancers. The role of androgen receptor varies depending on subtype. It is considered tissue-protective in luminal breast cancer, while it’s role in HER2 positive and triple negative breast cancers is less defined, but is generally considered to be associated with worse outcome. The primary treatment for breast cancer is surgery, followed by chemotherapy and/or radiotherapy to reduce the risk of recurrence. Treatment is also subtype specific, and luminal breast cancers in premenopausalwomen are treated using the estrogen receptor blocker (antagonist) tamoxifen, which blocks estrogen signaling. In postmenopausal women, luminal breast  cancers are treated using tamoxifen or aromatase inhibitors, which prevent the formation of estrogen. The knowledge of which patient will respond and who will develop treatment resistance is of great importance, and the development of markers which can be analyzed prior to treatment in order to reduce the risk of unwanted side effects or complications is the focus of a large body of research. One of the primary goals of this thesis was to establish biomarkers for prognosis and tamoxifen treatment in breast cancer, and paper I, paper II and paper III address this aim.

    Steroid hormones, including estrogens and androgens, are normally synthesized from cholesterol in the adrenal gland, as well as in gender specific tissues such as ovaries in women or the testis or prostate in men. This synthesis takes place as a number of enzymatic conversions, mediated by several different enzymes, and the expression of these enzymes determines the final product of this conversion. In the adrenal gland, testis and prostate, androgens are the end-product, while the ovaries synthesize estrogens. These hormones are transported through the circulation, and upon reaching their target tissues, they mediate their effect. The impact of the steroids on their destination tissue is dependent on their relative concentration and exposure time, which in turn is dependent on the amount in the circulation, but also on the presence of local steroid converting enzymes, which are present in most tissues. The enzymes of the hydroxysteroid 17β dehydrogenase family are present in most tissues, primarily the oxidative member hydroxysteroid 17β dehydrogenase type 2, which facilitate the conversion of estrogens and androgens to the less active forms, thus protecting the tissues from their effect. In breast cancer, the reductive form, hydroxysteroid 17β dehydrogenase type 1 is often up-regulated, and mediates increased activation of estrogens, resulting in increased estrogen signaling, which results in increased proliferation and growth. The second goal of this thesis was to further study the role of hydroxysteroid 17β dehydrogenase enzymes in breast cancer, and paper I and paper IV address different  aspects of their role in breast cancer.

    Following reduction of the expression of hydroxysteroid 17β dehydrogenase type 14, an oxidative member of the family, in breast cancer, the expression of C-X-C ligand 10 was found to be altered. In paper I, in order to determine the role of C-X-C ligand 10 and C-X-C receptor 3 in breast cancer, their expression was quantified using immunohistochemistry in breast cancer patients randomized to tamoxifen or no endocrine treatment irrespectively of estrogen receptor status. The expression of C-XC ligand 10 and C-X-C receptor 3 was found to be associated with increased tamoxifen treatment benefit in the estrogen receptor positive group of patients, indicating that they could be useful markers for determining which patient would respond well to this treatment. Further, C-X-C receptor 3 expression was associated with worse outcome in patients who did not receive tamoxifen, and could be a potential target for inhibitors in order to improve patient outcome. The role of the androgen receptor in breast cancer was evaluated. In paper II the expression was quantified using immunohistochemistry in the same cohort as in paper I. We show that in patients with estrogen receptor negative tumors, the androgen receptor is associated with worse outcome. In patients with high tumoral androgen receptor expression, tamoxifen signaling results in significant improvement in outcome, despite lack of the estrogen receptor. The opposite was observed in patients without tumoral androgen receptor expression, and tamoxifen treatment was associated with adverse outcome. Similar findings were made in the triple negative cases. In the luminal cases, the androgen receptor does not provide further information pertaining to outcome. In paper III we evaluated the role of mutations in the androgen receptor in the cohort of estrogen receptor-negative and androgen receptorpositive cases from paper II. The role of mutations in the androgen receptor appear to have a modest role in regard to patient outcome, but rs17302090 appear associated with tamoxifen treatment benefit. The modulation of the members of the hydroxysteroid 17β dehydrogenase in breast cancer is associated with changes in the local steroid balance, and has been associated with worse outcome and changes in the response to tamoxifen. Further, the inhibition of hydroxysteroid 17β dehydrogenase type 1 has been proposed as an alternate treatment for breast cancer, but no inhibitors are currently used in the clinic. In paper IV, we evaluated several different mechanisms by which the expression of hydroxysteroid 17β dehydrogenase type 1 and type 2 are modulated in breast cancer. We show that the most potent estrogen estradiol, in an estrogen receptor dependent fashion, can result in decreased hydroxysteroid 17β dehydrogenase type 1 expression, and a short term reduction in type 2 expression or long term increased type 2 expression. We also show that the most potent androgen, dihydrotestosterone, can increase hydroxysteroid 17β dehydrogenase type 2 expression, but has limited impact on hydroxysteroid 17β dehydrogenase type 1. Further, we show that a number of genes involved in breast cancer, and microRNA are involved in modulating the expression of the hydroxysteroid 17β dehydrogenase type 1 and type 2 in breast cancer. These findings could potentially be used as an alternative to inhibitors, and help modulate the steroidal balance in target tissue.

  • 347.
    Hilborn, Erik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Gacic, Jelena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Fornander, Tommy
    Karolinska Institute, Sweden.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Jansson, Agneta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Androgen receptor expression predicts beneficial tamoxifen response in oestrogen receptor-alpha-negative breast cancer2016In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 114, no 3, 248-255 p.Article in journal (Refereed)
    Abstract [en]

    Background: Although the androgen receptor (AR) is frequently expressed in breast cancer, its relevance in the disease is not fully understood. In addition, the relevance of AR in determining tamoxifen treatment efficiency requires evaluation. Purpose: To investigate the tamoxifen predictive relevance of the AR protein expression in breast cancer. Methods Patients were randomised to tamoxifen 40 mg daily for 2 or 5 years or to no endocrine treatment. Mean follow-up was 15 years. Hazard ratios were calculated with recurrence-free survival as end point. Results: In patients with oestrogen receptor (ER)-negative tumours, expression of AR predicted decreased recurrence rate with tamoxifen (hazard ratio (HR) = 0.34; 95% confidence interval (CI) = 0.14-0.81; P = 0.015), whereas the opposite was seen in the AR- group (HR = 2.92; 95% CI = 1.16-7.31; P = 0.022). Interaction test was significant P &lt; 0.001. Patients with triple-negative and AR+ tumours benefitted from tamoxifen treatment (HR = 0.12; 95% CI = 0.014-0.95 P = 0.044), whereas patients with AR- tumours had worse outcome when treated with tamoxifen (HR = 3.98; 95% CI = 1.32-12.03; P = 0.014). Interaction test was significant P = 0.003. Patients with ER+ tumours showed benefit from tamoxifen treatment regardless of AR expression. Conclusions: AR can predict tamoxifen treatment benefit in patients with ER- tumours and triple-negative breast cancer.

  • 348.
    Hilborn, Erik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Sivik, Tove
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Fornander, Tommy
    Karolinska University Hospital, Sweden .
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Jansson, Agneta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    C-X-C ligand 10 and C-X-C receptor 3 status can predict tamoxifen treatment response in breast cancer patients2014In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 145, no 1, 73-82 p.Article in journal (Refereed)
    Abstract [en]

    To investigate the expression levels of CXCL10 and CXCR3 in tumors from breast cancer patients randomized to adjuvant tamoxifen treatment or no endocrine treatment, in order to further study the connection to prognosis and prediction of tamoxifen treatment outcome. Immunohistochemistry on tissue microarrays from 912 breast cancer patients randomized to tamoxifen or no endocrine treatment. CXCR3 status was found to be a prognostic tool in predicting distant recurrence, as well as reduced breast cancer-specific survival. In patients with estrogen receptor (ER)-positive tumors, tumors with strong CXCL10 levels had improved effect of tamoxifen treatment in terms of local recurrence-free survival [risk ratio (RR) 0.46 (95 % CI 0.25-0.85, P = 0.01)] compared with patients with tumors expressing weak CXCL10 expression. Further, patients with ER-positive tumors with strong CXCR3 expression had an improved effect of tamoxifen in terms of breast cancer-specific survival [RR 0.34 (95 % CI 0.19-0.62, P less than 0.001)] compared with the group with weak CXCR3 levels [RR 1.33 (95 % CI 0.38-4.79, P = 0.65)]. We show here for the first time that CXCL10 and CXCR3 expression are both predictors of favorable outcome in patients treated with tamoxifen.

  • 349.
    Hildebrand, Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Prenatal diagnosis of structural malformations and chromosome anomalies: Detection, influence of Body Mass Index and ways to improve screening2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Introduction: Prenatal diagnosis of structural malformations and chromosome anomalies is possible in the presence of an effective screening with ultrasound during pregnancy. The continuous evolution of the ultrasound equipment facilitates the examination. However there are challenges in terms of the increasing prevalence of obesity among the pregnant women and the need of training of the personnel performing the scans. In the Southeast region of Sweden all pregnant women are offered screening with ultrasound during pregnancy. From 2009 almost all women in the region are offered two examinations, one in week 11-14 assessment of gestational age and combined screening for aneuploidy. Congenital heart disease (CHD) is the most common congenital defect. About one third of the CHD cases will have a duct-dependent anomaly that is potentially life-threatening if not detected before birth.

    Aims: To assess the sensitivity for detecting structural malformations and chromosome anomalies by a routine ultrasound either in gestational week 11-14 or 18-20. To estimate the influence of a high Body Mass Index (BMI) in detecting fetal structural anomalies by ultrasound. To evaluate the possibility for introducing a more accurate fetal cardiac ultrasound screening based on five different transverse views and color Doppler. To determine if the risk-estimate for trisomy 21 from the screening procedure varies over BMI strata and if obesity is associated with an increased risk of Down syndrome in the offspring.

    Material and methods: Outcome measures from 21189 consecutive ultrasound examinations in the first and second trimester were analyzed and compared. The fetal anomaly diagnoses were also grouped in four BMI-groups. Then, a two-day course in examining of the fetal heart was given, analyzed and followed up. To evaluate the effect of BMI on the combined screening, 10224 patients were divided in six BMI categories. Outcomes were evaluated over BMI strata. The possibility of an association between maternal obesity and Down syndrome was analyzed in a nationwide cohort of 1568604 women giving birth in Sweden.

    Results: At the first trimester scan 13% of all anomalies were detected vs 29% in the second trimester. For aneuploidy the corresponding results were 71% vs 42%, and for lethal anomalies 88% vs 92%. If divided into BMI-groups 26% of the malformations were detected in the group of normal weight women compared to 19% among the obese. For malformations with long-term handicap the corresponding figures were 46% vs 27%. After the course in examination of the fetal heart uncertainty was lower and the familiarity with the new technique was enhanced. The ability to perform the new method remained at follow up. In the combined screening, the observed and expected number with a risk of Downs syndrome >1/300 were similar in each BMI-group. Obese women had an increased risk of giving birth to an infant with Downs syndrome compared with normal weight women.

    Conclusions: There was an advantage to the scan in the second trimester discovering malformations overall and an advantage to the early scan concerning aneuploidy. Lethal malformations were detected at a high level in both groups. The detection rate seemed lower for the obese women. In the screening for Down syndrome, the risk-estimate is unaffected by BMI. Detection of heart malformations needs improvement. By implementing new image modalities and providing hands-on training uncertainty in examining the fetal heart can be reduced.

  • 350.
    Hildebrand, Eric
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Abrandt Dahlgren, Madeleine
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Sved, Catarina
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Gottvall, Tomas
    Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Blomberg, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Janerot Sjöberg, Birgitta
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Impact of a standardized training program on midwive’s ability to assess fetal heart anatomy by ultrasound2014In: BMC Medical Imaging, ISSN 1471-2342, Vol. 14, no 20Article in journal (Refereed)
    Abstract [en]

    Background: Studies of prenatal detection of congenital heart disease (CDH) in the UK, Italy, and Norway indicate that it should be possible to improve the prenatal detection rate of CDH in Sweden. These studies have shown that training programs, visualization of the outflow tracts and color-Doppler all can help to speed up and improve the detection rate and accuracy. We aimed to introduce a more accurate standardized fetal cardiac ultrasound screening protocol in Sweden.

    Methods: A novel pedagogical model for training midwives in standardized cardiac imaging was developed, a model using a think-aloud analysis during a pre- and post-course test and a subsequent group reflection. The self-estimated difficulties and knowledge gaps of four midwives were identified. A two-day course with mixed lectures, demonstrations and handson sessions was followed by a feedback session one month later consisting of an interview and check-up. The long-term effects were tested two years later.

    Results: At the post-course test the self-assessed uncertainty was lower than at the pre-course test. The qualitative evaluation showed that the color Doppler images were difficult to interpret, but the training seems to have enhanced the familiarity with the new technique. The ability to perform the method remained at the new level at follow-up both three months and two years later.

    Conclusions: Our results indicate that by implementing new imaging modalities and providing hands-on training, uncertainty can be reduced and time decreased, but they also show that continuous on-site training with clinical and technical back-up is important.

45678910 301 - 350 of 1006
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf