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  • 1.
    Abbott, Rebecca
    et al.
    Northwestern Univ, IL 60611 USA.
    Peolsson, Anneli
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    West, Janne
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Elliott, James M.
    Northwestern Univ, IL 60611 USA; Univ Queensland, Australia; Zurich Univ Appl Sci, Switzerland.
    Åslund, Ulrika
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Karlsson, Anette
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    The qualitative grading of muscle fat infiltration in whiplash using fat and water magnetic resonance imaging2018In: The spine journal, ISSN 1529-9430, E-ISSN 1878-1632, Vol. 18, no 5, p. 717-725Article in journal (Refereed)
    Abstract [en]

    BACKGROUND CONTEXT: The development of muscle fat infiltration (MFI) in the neck muscles is associated with poor functional recovery following whiplash injury. Custom software and time-consuming manual segmentation of magnetic resonance imaging (MRI) is required for quantitative analysis and presents as a barrier for clinical translation. PURPOSE: The purpose of this work was to establish a qualitative MRI measure for MFI and evaluate its ability to differentiate between individuals with severe whiplash-associated disorder (WAD), mild or moderate WAD, and healthy controls. STUDY DESIGN/SETTING: This is a cross-sectional study. PATIENT SAMPLE: Thirty-one subjects with WAD and 31 age-and sex-matched controls were recruited from an ongoing randomized controlled trial. OUTCOME MEASURES: The cervical multifidus was visually identified and segmented into eighths in the axial fat/water images (C4-C7). Muscle fat infiltration was assessed on a visual scale: 0 for no or marginal MFI, 1 for light MFI, and 2 for distinct MFI. The participants with WAD were divided in two groups: mild or moderate and severe based on Neck Disability Index % scores. METHODS: The mean regional MFI was compared between the healthy controls and each of the WAD groups using the Mann-Whitney U test. Receiver operator characteristic (ROC) analyses were carried out to evaluate the validity of the qualitative method. RESULTS: Twenty (65%) patients had mild or moderate disability and 11 (35%) were considered severe. Inter- and intra-rater reliability was excellent when grading was averaged by level or when frequency of grade II was considered. Statistically significant differences (pamp;lt;.05) in regional MFI were particularly notable between the severe WAD group and healthy controls. The ROC curve, based on detection of distinct MFI, showed an area-under-the curve of 0.768 (95% confidence interval 0.59-0.94) for discrimination of WAD participants. CONCLUSIONS: These preliminary results suggest a qualitative MRI measure for MFI is reliable and valid, and may prove useful toward the classification of WAD in radiology practice. (C) 2017 Elsevier Inc. All rights reserved.

  • 2.
    Abdalla, Maie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Suez Canal University, Egypt.
    Landerholm, Kalle
    Ryhov County Hospital, Sweden.
    Andersson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Andersson, Roland
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov County Hospital, Sweden.
    Myrelid, Pär
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Risk of Rectal Cancer After Colectomy for Patients With Ulcerative Colitis: A National Cohort Study2017In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 15, no 7, p. 1055-1060, article id e2Article in journal (Refereed)
    Abstract [en]

    BACKGROUND amp; AIMS: Patients with ulcerative colitis (UC) have an increased risk of rectal cancer, therefore reconstruction with an ileal pouch-anal anastomosis (IPAA) generally is preferred to an ileorectal anastomosis (IRA) after subtotal colectomy. Similarly, completion proctectomy is recommended for patients with ileostomy and a diverted rectum, although this approach has been questioned because anti-inflammatory agents might reduce cancer risk. We performed a national cohort study in Sweden to assess the risk of rectal cancer in patients with UC who have an IRA, IPAA, or diverted rectum after subtotal colectomy.

    METHODS: We collected data from the Swedish National Patient Register for a cohort of 5886 patients with UC who underwent subtotal colectomy with an IRA, IPAA, or diverted rectum from 1964 through 2010. Patients who developed rectal cancer were identified from the Swedish National Cancer Register. The risk of rectal cancer was compared between this cohort and the general population by standardized incidence ratio analysis.

    RESULTS: Rectal cancer occurred in 20 of 1112 patients (1.8%) who received IRA, 1 of 1796 patients (0.06%) who received an IPAA, and 25 of 4358 patients (0.6%) with a diverted rectum. Standardized incidence ratios for rectal cancer were 8.7 in patients with an IRA, 0.4 in patients with an IPAA, and 3.8 in patients with a diverted rectum. Risk factors for rectal cancer were primary sclerosing cholangitis in patients with an IRA (hazard ratio, 6.12), and colonic severe dysplasia or cancer before subtotal colectomy in patients with a diverted rectum (hazard ratio, 3.67).

    CONCLUSIONS: In an analysis of the Swedish National Patient Register, we found that the risk for rectal cancer after colectomy in patients with UC is low, in relative and absolute terms, after reconstruction with an IPAA. An IRA and diverted rectum are associated with an increased risk of rectal cancer, compared with the general population, but the absolute risk is low. Patients and their health care providers should consider these findings in making decisions to leave the rectum intact, perform completion proctectomy, or reconstruct the colon with an IRA or IPAA.

  • 3.
    Abrahamsson, Annelie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Capodanno, Alessandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Rzepecka, Anna
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Dabrosin, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Downregulation of tumor suppressive microRNAs in vivo in dense breast tissue of postmenopausal women2017In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 54, p. 92134-92142Article in journal (Refereed)
    Abstract [en]

    Women with dense breast tissue on mammography are at higher risk of developing breast cancer but the underlying mechanisms are not well understood. De-regulation of microRNAs (miRNAs) has been associated with the onset of breast cancer. miRNAs in the extracellular space participate in the regulation of the local tissue microenvironment. Here, we recruited 39 healthy postmenopausal women attending their mammography-screen that were assessed having extreme dense or entirely fatty breasts (nondense). Microdialysis was performed in breast tissue and a reference catheter was inserted in abdominal subcutaneous fat for local sampling of extracellular compounds. Three miRNAs, associated with tumor suppression, miR-193b, miR-365a, and miR-452 were significantly down-regulated in dense breast tissue compared with nondense breast tissue. In addition, miR-452 exhibited significant negative correlations with several pro-inflammatory cytokines in vivo, which was confirmed in vitro by overexpression of miR-452 in breast cancer cells. No differences were found of miR-21, -29a, -30c, 146a, -148a, -203, or -451 in breast tissue and no miRs were different in plasma. Extracellular miRNAs may be among factors that should be included in studies of novel prevention strategies for breast cancer.

  • 4.
    Abrahamsson, Annelie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Dabrosin, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Tissue specific expression of extracellular microRNA in human breast cancers and normal human breast tissue in vivo2015In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 6, no 26, p. 22959-22969Article in journal (Refereed)
    Abstract [en]

    Extracellular circulating microRNAs (miRNAs) have been suggested to be biomarkers for disease monitoring but data are inconsistent, one reason being that blood miRNA is of heterogeneous origin. Here, we sampled extracellular microRNAs locally in situ using microdialysis. Three different cohorts of women were included; postmenopausal women with ongoing breast cancer investigated within the cancer and in normal adjacent breast tissue, postmenopausal women investigated in their normal healthy breast and subcutaneous fat before and after six weeks of tamoxifen therapy, premenopausal women during the menstrual cycle. Samples were initially screened using TaqMan array cards with subsequently absolute quantification. 124 miRNA were expressed in microdialysates. After absolute quantifications extracellular miRNA-21 was found to be significantly increased in breast cancer. In addition, the levels were significantly higher in pre-menopausal breast tissue compared with postmenopausal. In breast tissue of pre-menopausal women miRNA-21 exhibited a cyclic variation during the menstrual cycle and in postmenopausal women six weeks of tamoxifen treatment decreased miRNA-21 suggesting that this miRNA may be important for breast carcinogenesis. None of these changes were found in plasma or microdialysates from subcutaneous fat. Our data revealed tissue specific changes of extracellular circulating miRNAs that would be otherwise unraveled using blood samples.

  • 5.
    Abrahamsson, Annelie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Rzepecka, Anna
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Dabrosin, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Equal Pro-inflammatory Profiles of CCLs, CXCLs, and Matrix Metalloproteinases in the Extracellular Microenvironment In Vivo in Human Dense Breast Tissue and Breast Cancer2018In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 8, article id 1994Article in journal (Refereed)
    Abstract [en]

    The inflammatory microenvironment affects breast cancer progression. Proteins that govern the inflammatory response are secreted into the extracellular space, but this compartment still needs to be characterized in human breast tissues in vivo. Dense breast tissue is a major risk factor for breast cancer by yet unknown mechanisms and no non-toxic prevention for these patients exists. Here, we used the minimal invasive technique of microdialysis for sampling of extracellular proteins in live tissues in situ in breast cancers of women before surgery and in healthy women having dense or non-dense breast tissue on mammography. Proteins were profiled using a proximity extension assay. Out of the 32 proteins assessed, 26 exhibited similar profiles in breast cancers and dense breast tissues; CCL-4, -7, -8, -11, -15, -16, -22, -23, and -25, CXCL-5, -8, -9, -16 as well as sIL-6R, IL-18, vascular endothelial growth factor, TGF-a, fibroblast growth factor 19, matrix metalloproteinase (MMP)-1, -2, -3, and urokinase-type plasminogen activator were all increased, whereas CCL-3, CX3CL1, hepatocyte growth factor, and MMP-9 were unaltered in the two tissues. CCL-19 and -24, CXCL-1 and -10, and IL-6 were increased in dense breast tissue only, whereas IL-18BP was increased in breast cancer only. Our results provide novel insights in the inflammatory microenvironment in human breast cancer in situ and define potential novel therapeutic targets. Additionally, we show previously unrecognized similarities of the pro-inflammatory microenvironment in dense breast tissue and breast cancer in vivo suggesting that anti-inflammatory breast cancer prevention trials for women with dense breast tissue may be feasible.

  • 6.
    Abrahamsson, Annelie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Rzepecka, Anna
    Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Dabrosin, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Increased nutrient availability in dense breast tissue of postmenopausal women in vivo2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 42733Article in journal (Refereed)
    Abstract [en]

    Metabolic reprogramming is a hallmark of cancer. Nutrient availability in the tissue microenvironment determines cellular events and may play a role in breast carcinogenesis. High mammographic density is an independent risk factor for breast cancer. Whether nutrient availability differs in normal breast tissues with various densities is unknown. Therefore we investigated whether breast tissues with various densities exhibited differences in nutrient availability. Healthy postmenopausal women from the regular mammographic screening program who had either predominantly fatty breast tissue (nondense), n = 18, or extremely dense breast tissue (dense), n = 20, were included. Microdialysis was performed for the in vivo sampling of amino acids (AAs), analyzed by ultra-high performance liquid chromatography with tandem mass spectroscopy, glucose, lactate and vascular endothelial growth factor (VEGF) in breast tissues and, as a control, in abdominal subcutaneous (s.c.) fat. We found that dense breast tissue exhibited significantly increased levels of 20 proteinogenic AAs and that 18 of these AAs correlated significantly with VEGF. No differences were found in the s.c. fat, except for one AA, suggesting tissue-specific alterations in the breast. Glucose and lactate were unaltered. Our findings provide novel insights into the biology of dense breast tissue that may be explored for breast cancer prevention strategies.

  • 7.
    Abrahamsson, Annelie
    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 Oncology.
    Rzepecka, Anna
    Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Romu, Thobias
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Borga, Magnus
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Lundberg, Peter
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Kihlberg, Johan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Dabrosin, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Dense breast tissue in postmenopausal women is associated with a pro-inflammatory microenvironment in vivo2016In: Oncoimmunology, ISSN 2162-4011, E-ISSN 2162-402X, Vol. 5, no 10, article id e1229723Article in journal (Refereed)
    Abstract [en]

    Inflammation is one of the hallmarks of carcinogenesis. High mammographic density has been associated with increased risk of breast cancer but the mechanisms behind are poorly understood. We evaluated whether breasts with different mammographic densities exhibited differences in the inflammatory microenvironment.Postmenopausal women attending the mammography-screening program were assessed having extreme dense, n = 20, or entirely fatty breasts (nondense), n = 19, on their regular mammograms. Thereafter, the women were invited for magnetic resonance imaging (MRI), microdialysis for the collection of extracellular molecules in situ and a core tissue biopsy for research purposes. On the MRI, lean tissue fraction (LTF) was calculated for a continuous measurement of breast density. LTF confirmed the selection from the mammograms and gave a continuous measurement of breast density. Microdialysis revealed significantly increased extracellular in vivo levels of IL-6, IL-8, vascular endothelial growth factor, and CCL5 in dense breast tissue as compared with nondense breasts. Moreover, the ratio IL-1Ra/IL-1 was decreased in dense breasts. No differences were found in levels of IL-1, IL-1Ra, CCL2, leptin, adiponectin, or leptin:adiponectin ratio between the two breast tissue types. Significant positive correlations between LTF and the pro-inflammatory cytokines as well as between the cytokines were detected. Stainings of the core biopsies exhibited increased levels of immune cells in dense breast tissue.Our data show that dense breast tissue in postmenopausal women is associated with a pro-inflammatory microenvironment and, if confirmed in a larger cohort, suggests novel targets for prevention therapies for women with dense breast tissue.

  • 8.
    Abtahi, Jahan
    et al.
    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.
    Henefalk, G.
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    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.
    Randomised trial of bisphosphonate-coated dental implants: Radiographic follow-up after five years of loading2016In: International Journal of Oral and Maxillofacial Surgery, ISSN 0901-5027, E-ISSN 1399-0020, Vol. 45, no 12, p. 1564-1569Article in journal (Refereed)
    Abstract [en]

    The results of a randomised trial with bisphosphonate-coated dental implants have been reported previously. Each patient received one coated and one uncoated implant in a double-blind split-mouth design study. After 6 months of osseointegration, resonance frequency analysis indicated better fixation of the coated implants. Reduced marginal bone resorption was also shown. However, it was not known whether the advantage of the bisphosphonate coating would persist over time. The radiographic results at 5 years after implant installation are reported herein. A blinded investigator measured marginal resorption on fresh radiographs obtained for 14 of the 16 patients (two had died) and compared these with the post-implantation images. Non-parametric statistics were used. All implants functioned well. The median marginal bone loss for control implants was found to be 0.70 mm, which is less than usually reported in the literature. The bisphosphonate-coated implants showed even less resorption (median 0.20 mm). The median difference within each pair of implants after 5 years of use was 0.34 mm (95% confidence interval 0.00-0.75 mm; P = 0.04). The present data suggest that bisphosphonate-coated implants enable prolonged preservation of the marginal bone.

  • 9.
    Adolfsson, Lars
    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.
    Editorial Material: Is surgery for the subacromial pain syndrome ever indicated? in ACTA ORTHOPAEDICA, vol 86, issue 6, pp 639-6402015In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 86, no 6, p. 639-640Article in journal (Other academic)
    Abstract [en]

    n/a

  • 10.
    Adolfsson, Lars
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Nestorson, Jens
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Scheer, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Extensive soft tissue lesions in redislocated after simple elbow dislocations2017In: Journal of shoulder and elbow surgery, ISSN 1058-2746, E-ISSN 1532-6500, Vol. 26, no 7, p. 1294-1297Article in journal (Refereed)
    Abstract [en]

    Background: The majority of simple elbow dislocations (no associated fractures) can be treated nonoperatively with a short period of immobilization followed by guided aftercare. This case series describes the soft tissue injuries in a rare subset of patients in whom the elbow redislocated despite adequate immobilization. Methods: During a 6-year period, 8 patients were identified. They were all treated with reduction and casting in 90 degrees of flexion or more. At 1 week of follow-up, redislocation had occurred in all patients and open soft tissue repair was performed. The injuries were documented and the patients were followed up clinically and with radiographs. Results: Extensive soft tissue injuries, including both collateral ligament injuries and muscle origin avulsions from either or both sides, were found in all patients. The functional result at follow-up was satisfactory in all patients. Conclusion: Vast soft tissue injuries including both collateral ligaments and muscle origins should be expected in the event of early severe instability of a dislocated elbow joint. (C) 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. All rights reserved.

  • 11.
    Agebratt, Christian
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Ström, Edvin
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Romu, Thobias
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Borga, Magnus
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Leandersson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Nyström, Fredrik H.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    A Randomized Study of the Effects of Additional Fruit and Nuts Consumption on Hepatic Fat Content, Cardiovascular Risk Factors and Basal Metabolic Rate2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 1, p. e0147149-Article in journal (Refereed)
    Abstract [en]

    Background

    Fruit has since long been advocated as a healthy source of many nutrients, however, the high content of sugars in fruit might be a concern.

    Objectives

    To study effects of an increased fruit intake compared with similar amount of extra calories from nuts in humans.

    Methods

    Thirty healthy non-obese participants were randomized to either supplement the diet with fruits or nuts, each at +7 kcal/kg bodyweight/day for two months. Major endpoints were change of hepatic fat content (HFC, by magnetic resonance imaging, MRI), basal metabolic rate (BMR, with indirect calorimetry) and cardiovascular risk markers.

    Results

    Weight gain was numerically similar in both groups although only statistically significant in the group randomized to nuts (fruit: from 22.15±1.61 kg/m2 to 22.30±1.7 kg/m2, p = 0.24 nuts: from 22.54±2.26 kg/m2 to 22.73±2.28 kg/m2, p = 0.045). On the other hand BMR increased in the nut group only (p = 0.028). Only the nut group reported a net increase of calories (from 2519±721 kcal/day to 2763±595 kcal/day, p = 0.035) according to 3-day food registrations. Despite an almost three-fold reported increased fructose-intake in the fruit group (from 9.1±6.0 gram/day to 25.6±9.6 gram/day, p<0.0001, nuts: from 12.4±5.7 gram/day to 6.5±5.3 gram/day, p = 0.007) there was no change of HFC. The numerical increase in fasting insulin was statistical significant only in the fruit group (from 7.73±3.1 pmol/l to 8.81±2.9 pmol/l, p = 0.018, nuts: from 7.29±2.9 pmol/l to 8.62±3.0 pmol/l, p = 0.14). Levels of vitamin C increased in both groups while α-tocopherol/cholesterol-ratio increased only in the fruit group.

    Conclusions

    Although BMR increased in the nut-group only this was not linked with differences in weight gain between groups which potentially could be explained by the lack of reported net caloric increase in the fruit group. In healthy non-obese individuals an increased fruit intake seems safe from cardiovascular risk perspective, including measurement of HFC by MRI.

  • 12.
    Ahle, Margareta
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Drott, Peder
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Elfvin, Anders
    Department of Pediatrics, Institution of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Andersson, Roland E.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Department of Surgery, Ryhov County Hospital, Jönköping, Sweden .
    Maternal, fetal and perinatal factors associated with necrotizing enterocolitis in Sweden: A national case-control study2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, PLoS ONE, ISSN 1932-6203, Vol. 13, no 3, article id e0194352Article in journal (Refereed)
    Abstract [en]

    Objective

    To analyze associations of maternal, fetal, gestational, and perinatal factors with necrotizing enterocolitis in a matched case-control study based on routinely collected, nationwide register data.

    Study design

    All infants born in 1987 through 2009 with a diagnosis of necrotizing enterocolitis in any of the Swedish national health care registers were identified. For each case up to 6 controls, matched for birth year and gestational age, were selected. The resulting study population consisted of 720 cases and 3,567 controls. Information on socioeconomic data about the mother, maternal morbidity, pregnancy related diagnoses, perinatal diagnoses of the infant, and procedures in the perinatal period, was obtained for all cases and controls and analyzed with univariable and multivariable logistic regressions for the whole study population as well as for subgroups according to gestational age.

    Results

    In the study population as a whole, we found independent positive associations with necrotizing enterocolitis for isoimmunization, fetal distress, cesarean section, neonatal bacterial infection including sepsis, erythrocyte transfusion, persistent ductus arteriosus, cardiac malformation, gastrointestinal malformation, and chromosomal abnormality. Negative associations were found for maternal weight, preeclampsia, maternal urinary infection, premature rupture of the membranes, and birthweight. Different patterns of associations were seen in the subgroups of different gestational age.

    Conclusion

    With some interesting exceptions, especially in negative associations, the results of this large, population based study, are in keeping with earlier studies. Although restrained by the limitations of register data, the findings mirror conceivable pathophysiological processes and underline that NEC is a multifactorial disease.

  • 13.
    Ahnesjö, Anders
    et al.
    Uppsala University, Sweden.
    van Veelen, Bob
    Elekta Brachytherapy, Netherlands.
    Carlsson Tedgren, Åsa
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Karolinska University Hospital, Sweden.
    Collapsed cone dose calculations for heterogeneous tissues in brachytherapy using primary and scatter separation source data2017In: Computer Methods and Programs in Biomedicine, ISSN 0169-2607, E-ISSN 1872-7565, Vol. 139, p. 17-29Article in journal (Refereed)
    Abstract [en]

    Background and Objective: Brachytherapy is a form of radiation therapy using sealed radiation sources inserted within or in the vicinity of the tumor of, e.g., gynecological, prostate or head and neck cancers. Accurate dose calculation is a crucial part of the treatment planning. Several reviews have called for clinical software with model-based algorithms that better take into account the effects of patient individual distribution of tissues, source-channel and shielding attenuation than the commonly employed TG-43 formalism which simply map homogeneous water dose distributions onto the patient. In this paper we give a comprehensive and thorough derivation of such an algorithm based on collapsed cone point-kernel superposition, and describe details of its implementation into a commercial treatment planning system for clinical use. Methods: A brachytherapy version of the collapsed-cone algorithm using analytical raytraces of the primary photon radiation followed by successive scattering dose calculation for once and multiply scattered photons is described in detail, including derivation of the corresponding set of recursive equations for energy transport along cone axes/transport lines and the coupling to clinical source modeling. Specific implementation issues for setting up of the calculation grid, handling of intravoxel gradients and voxels partly containing non patient applicator material are given. Results: Sample runs for two clinical cases are shown, one being a gynecological application with a tungsten-shielded applicator and one a breast implant. These two cases demonstrate the impact of improved dose calculation versus TG-43 formalism. Conclusions: Use of model-based dose calculation algorithms for brachytherapy taking the three-dimensional treatment geometry into account increases the dosimetric accuracy in planning and follow up of treatments. The comprehensive description and derivations provided gives a rigid background for further clinical, educational and research applications. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  • 14.
    Aljabery, Firas
    et al.
    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 Urology in Östergötland.
    Halili, Shefqet
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Hildebrand, Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Vesico-Uterine Fistula after TURB in pregnancy, a rare cause of genitourinary fistula2018In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 52, no 2, p. 162-163Article in journal (Refereed)
    Abstract [en]

    n/a

  • 15.
    Aljabery, Firas
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Lindblom, Gunnar
    Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Skoog, Susann
    Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Shabo, Ivan
    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.
    Olsson, Hans
    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.
    Rosell, Johan
    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.
    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.
    PET/CT versus conventional CT for detection of lymph node metastases in patients with locally advanced bladder cancer.2015In: BMC urology, ISSN 1471-2490, Vol. 15, no 1, p. 87-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We studied patients treated with radical cystectomy for locally advanced bladder cancer to compare the results of both preoperative positron emission tomography/computed tomography (PET/CT) and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes.

    METHODS: Patients who had bladder cancer and were candidates for cystectomy underwent preoperative PET/CT using 18-fluorodeoxyglucose (FDG) and conventional CT. The results regarding lymph node involvement were independently evaluated by two experienced radiologists and were subsequently compared with histopathology results, the latter of which were reassessed by an experienced uropathologist (HO).

    RESULTS: There were 54 evaluable patients (mean age 68 years, 47 [85 %] males and 7 [15 %] females) with pT and pN status as follows: < pT2-14 (26 %), pT2-10 (18 %), and > pT2-30 (56 %); pN0 37 (69 %) and pN+ 17 (31 %). PET/CT showed positive lymph nodes in 12 patients (22 %), and 7 of those cases were confirmed by histopathology; the corresponding results for conventional CT were 11 (20 %) and 7 patients (13 %), respectively. PET/CT had 41 % sensitivity, 86 % specificity, 58 % PPV, and 76 % NPV, whereas the corresponding figures for conventional CT were 41 %, 89 %, 64 %, and 77 %. Additional analyses of the right and left side of the body or in specified anatomical regions gave similar results.

    CONCLUSIONS: In this study, PET/CT and conventional CT had similar low sensitivity in detecting and localizing regional lymph node metastasis in bladder cancer.

  • 16.
    Aljabery, Firas
    et al.
    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 Urology in Östergötland.
    Olsson, Hans
    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, Clinical pathology.
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Shabo, Ivan
    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. Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    M2-macrophage infiltration and macrophage traits of tumor cells in urinary bladder cancer2018In: Urologic Oncology, ISSN 1078-1439, E-ISSN 1873-2496, Vol. 36, no 4, article id 159.e19Article in journal (Refereed)
    Abstract [en]

    Background

    Tumor-associated macrophages (TAMs) constitute a subset of nonneoplastic cells in tumor stroma and influence cancer progression in solid tumors. The clinical significance of TAMs in urinary bladder cancer(UBC) is controversial.

    Methods

    We prospectively studied 103 patients with stage pT1–T4 UBC treated with cystectomy and pelvic lymph node dissection. Tumor sections were immunostained with M2-specific macrophage marker CD163 and proliferation marker Ki-67. The expression of these markers in cancer cells as well as macrophage infiltration (MI) in tumor stroma was analyzed in relation to clinical data and outcome.

    Results

    The mean rate of CD163 and Ki-67 expressed by cancer cells were 35% and 78%, respectively. With borderline significance, MI was associated with lower rate of lymph node metastasis (P = 0.06). CD163 expression in cancer cells was proportional to MI (P<0.014). Patients with CD163-positive tumors and strong MI had significantly longer cancer-specific survival (CSS) (76 months), compared to patient with CD163-positive tumors and weak MI (28 months) (P = 0.02).

    Conclusions

    M2-specific MI tends to be inversely correlated with LN metastasis and improved CSS in UBC. MI might have protective impact in CD163-positive tumors. Expression of CD163 in cancer cells is significantly correlated with MI and might have a tumor promoting impact.

  • 17.
    Aljabery, Firas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Shabo, Ivan
    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. Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Department of Breast and Endocrine Surgery, Karolinska University Hospital, Solna Stockholm, Sweden .
    Olsson, Hans
    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, Clinical pathology.
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Jahnson, Staffan
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology.
    Radio-guided sentinel lymph node detection and lymph node mapping in invasive urinary bladder cancer: a prospective clinical study.2017In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 120, no 3, p. 329-336Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To investigate the possibility of detecting sentinel lymph nodes (SNs) in patients with urinary bladder cancer (BCa) intra-operatively and whether the histopathological status of the identified SNs reflected that of the lymphatic field.

    PATIENTS AND METHODS: We studied 103 patients with BCa pathological stage T1-T4 who were treated with cystectomy and pelvic lymph node (LN) dissection during 2005-2011 at the Department of Urology, Linköping University Hospital. Radioactive tracer Nanocoll 70 MBq and blue dye were injected into the bladder wall around the primary tumour before surgery. SNs were detected ex vivo during the operation with a handheld Geiger probe (Gamma Detection System; Neoprobe Corp., Dublin, OH, USA). All LNs were formalin-fixed, sectioned three times, mounted on slides and stained with haematoxylin and eosin. An experienced uropathologist evaluated the slides.

    RESULTS: The mean age of the patients was 69 years, and 80 (77%) were male. Pathological staging was T1-12 (12%), T2-20 (19%), T3-48 (47%) and T4-23 (22%). A mean (range) number of 31 (7-68) nodes per patient were examined, totalling 3 253 nodes. LN metastases were found in 41 patients (40%). SNs were detected in 83 of the 103 patients (80%). Sensitivity and specificity for detecting metastatic disease by SN biopsy (SNB) varied between LN stations, with average values of 67% and 90%, respectively. LN metastatic density (LNMD) had a significant prognostic impact; a value of ≥8% was significantly related to shorter survival. Lymphovascular invasion (LVI) occurred in 65% of patients (n = 67) and was significantly associated with shorter cancer-specific survival (P < 0.001).

    CONCLUSION: We conclude that SNB is not a reliable technique for peri-operative localization of LN metastases during cystectomy for BCa; however, LNMD has a significant prognostic value in BCa and may be useful in the clinical context and in BCa oncological and surgical research. LVI was also found to be a prognostic factor.

  • 18.
    Amirhosseini, Mehdi
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Andersson, Göran
    Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Fahlgren, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Mechanical instability and titanium particles induce similar transcriptomic changes in a rat model for periprosthetic osteolysis and aseptic loosening2017In: Bone Reports, ISSN 2352-1872, Vol. 7, p. 17-25Article in journal (Refereed)
    Abstract [en]

    Wear debris particles released from prosthetic bearing surfaces and mechanical instability of implants are two main causes of periprosthetic osteolysis. While particle-induced loosening has been studied extensively, mechanisms through which mechanical factors lead to implant loosening have been less investigated. This study compares the transcriptional profiles associated with osteolysis in a rat model for aseptic loosening, induced by either mechanical instability or titanium particles. Rats were exposed to mechanical instability or titanium particles. After 15 min, 3, 48 or 120 h from start of the stimulation, gene expression changes in periprosthetic bone tissue was determined by microarray analysis. Microarray data were analyzed by PANTHER Gene List Analysis tool and Ingenuity Pathway Analysis (IPA). Both types of osteolytic stimulation led to gene regulation in comparison to unstimulated controls after 3, 48 or 120 h. However, when mechanical instability was compared to titanium particles, no gene showed a statistically significant difference (fold change = ± 1.5 and adjusted p-value = 0.05) at any time point. There was a remarkable similarity in numbers and functional classification of regulated genes. Pathway analysis showed several inflammatory pathways activated by both stimuli, including Acute Phase Response signaling, IL-6 signaling and Oncostatin M signaling. Quantitative PCR confirmed the changes in expression of key genes involved in osteolysis observed by global transcriptomics. Inflammatory mediators including interleukin (IL)-6, IL-1ß, chemokine (C-C motif) ligand (CCL)2, prostaglandin-endoperoxide synthase (Ptgs)2 and leukemia inhibitory factor (LIF) showed strong upregulation, as assessed by both microarray and qPCR. By investigating genome-wide expression changes we show that, despite the different nature of mechanical implant instability and titanium particles, osteolysis seems to be induced through similar biological and signaling pathways in this rat model for aseptic loosening. Pathways associated to the innate inflammatory response appear to be a major driver for osteolysis. Our findings implicate early restriction of inflammation to be critical to prevent or mitigate osteolysis and aseptic loosening of orthopedic implants.

  • 19.
    Andersson, Ellen
    et al.
    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 Norrköping.
    Albertsson, Maria
    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.
    Holmqvist, Annica
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    GRACE: Geriatric patients tReated with Avastin in CRC multiple linEs2017In: Clinical Practice, ISSN 2044-9038, E-ISSN 2044-9046, Vol. 14, no 3, p. 175-182Article in journal (Refereed)
    Abstract [en]

    Continuous treatment with bevacizumab in elderly patients with mCRC: A phase IV prospective, open-label, single-arm trial to evaluate outcomes and safety with continuous bevacizumab treatment in combination with chemotherapy over disease progression.

  • 20.
    Andersson, Peter
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Muhrbeck, Måns
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Veen, Harald
    Int Comm Red Cross, Switzerland.
    Osman, Zaher
    Int Comm Red Cross, Switzerland.
    von Schreeb, Johan
    Karolinska Institute, Sweden.
    Hospital Workload for Weapon-Wounded Females Treated by the International Committee of the Red Cross: More Work Needed than for Males2018In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 42, no 1, p. 93-98Article in journal (Refereed)
    Abstract [en]

    Civilians constitute 33-51% of victims in armed conflicts. Several reports on civilian injuries exist, but few have focused on injuries afflicting females. We analyzed routinely collected data on weapon-related injuries from the International Committee of the Red Cross (ICRC) hospital in northwestern Pakistan in order to define injury patterns and types of surgical treatment for females. A total of 3028 patient files (376 females) from consecutively admitted patients to the ICRC-hospital in Peshawar from February 2009 to May 2012 were included. Information regarding injury-mechanism, time since injury, vital parameters at admission, type of injury, treatment and basic outcome was extracted from the files and analyzed. Comparisons between gender and age-groups were done by cross-table analyses or nonparametric tests. Females were younger than males (20 vs. 25 years), arrived sooner after injury (24 vs. 48 h) (p amp;lt; 0.001 for both) and were victims of bombs and missiles more frequently (64.4 vs. 54.6%) (p amp;lt; 0.001). Vital parameters such as systolic blood pressure (110 vs. 113 mmHg) and pulse rate (100 vs. 86) were more affected at admission (p amp;lt; 0.001 for both). Females were subjected to surgery (83.0 vs. 77.4%) (p amp;lt; 0.05) and were given blood transfusions more often (18.8 vs. 13.6%) (p amp;lt; 0.01). No differences in amputations or in-hospital mortality were found. Females treated at the ICRC-hospital in northwestern Pakistan are markedly affected by indiscriminate weapons such as bombs and missiles. Their average consumption of surgery is greater than for males, and this might be relevant in planning for staffing and facility needs in similar contexts.

  • 21.
    Andersson, Thord
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV). Dept. of C4ISR, Swedish Defence Research Agency, Linköping, Sweden, .
    Borga, Magnus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Geodesic registration for interactive atlas-based segmentation using learned multi-scale anatomical manifolds2018In: Pattern Recognition Letters, ISSN 0167-8655, E-ISSN 1872-7344, Vol. 112, p. 340-345Article in journal (Refereed)
    Abstract [en]

    Atlas-based segmentation is often used to segment medical image regions. For intensity-normalized data, the quality of these segmentations is highly dependent on the similarity between the atlas and the target under the used registration method. We propose a geodesic registration method for interactive atlas-based segmentation using empirical multi-scale anatomical manifolds. The method utilizes unlabeled images together with the labeled atlases to learn empirical anatomical manifolds. These manifolds are defined on distinct scales and regions and are used to propagate the labeling information from the atlases to the target along anatomical geodesics. The resulting competing segmentations from the different manifolds are then ranked according to an image-based similarity measure. We used image volumes acquired using magnetic resonance imaging from 36 subjects. The performance of the method was evaluated using a liver segmentation task. The result was then compared to the corresponding performance of direct segmentation using Dice Index statistics. The method shows a significant improvement in liver segmentation performance between the proposed method and direct segmentation. Furthermore, the standard deviation in performance decreased significantly. Using competing complementary manifolds defined over a hierarchy of region of interests gives an additional improvement in segmentation performance compared to the single manifold segmentation.

  • 22.
    Andersson, Thord
    et al.
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Romu, Thobias
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Karlsson, Anette
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Norén, Bengt
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Forsgren, Mikael
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Smedby, Örjan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Borga, Magnus
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Consistent intensity inhomogeneity correction in water–fat MRI2015In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 42, no 2, p. 468-476Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    To quantitatively and qualitatively evaluate the water-signal performance of the consistent intensity inhomogeneity correction (CIIC) method to correct for intensity inhomogeneities METHODS: Water-fat volumes were acquired using 1.5 Tesla (T) and 3.0T symmetrically sampled 2-point Dixon three-dimensional MRI. Two datasets: (i) 10 muscle tissue regions of interest (ROIs) from 10 subjects acquired with both 1.5T and 3.0T whole-body MRI. (ii) Seven liver tissue ROIs from 36 patients imaged using 1.5T MRI at six time points after Gd-EOB-DTPA injection. The performance of CIIC was evaluated quantitatively by analyzing its impact on the dispersion and bias of the water image ROI intensities, and qualitatively using side-by-side image comparisons.

    RESULTS:

    CIIC significantly ( P1.5T≤2.3×10-4,P3.0T≤1.0×10-6) decreased the nonphysiological intensity variance while preserving the average intensity levels. The side-by-side comparisons showed improved intensity consistency ( Pint⁡≤10-6) while not introducing artifacts ( Part=0.024) nor changed appearances ( Papp≤10-6).

    CONCLUSION:

    CIIC improves the spatiotemporal intensity consistency in regions of a homogenous tissue type. J. Magn. Reson. Imaging 2014.

  • 23.
    Apellániz-Ruiz, Maria
    et al.
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain.
    Tejero, Héctor
    Translational Bioinformatics Unit, Spanish National Cancer Research Centre, Madrid, Spain.
    Inglada-Pérez, Lucía
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain. ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain.
    Sánchez-Barroso, Lara
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain.
    Gutiérrez-Gutiérrez, Gerardo
    Neurology Section, Hospital Universitario Infanta Sofía, Madrid, Spain.
    Calvo, Isabel
    Medical Oncology Department, Hospital Montepríncipe, Madrid, Spain. Medical Oncology Department, Centro Integral Oncológico Clara Campal, Madrid, Spain.
    Castelo, Beatriz
    Medical Oncology Department, Hospital Universitario La Paz, Madrid, Spain.
    Redondo, Andrés
    Medical Oncology Department, Hospital Universitario La Paz, Madrid, Spain.
    García-Donás, Jesus
    Gynecological and Genitourinary Tumors Programme, Centro Integral Oncológico Clara Campal, Madrid, Spain.
    Romero-Laorden, Nuria
    Gynecological and Genitourinary Tumors Programme, Centro Integral Oncológico Clara Campal, Madrid, Spain.
    Sereno, Maria
    Medical Oncology Department, Hospital Universitario Infanta Sofía, Madrid, Spain.
    Merino, María
    Medical Oncology Department, Hospital Universitario Infanta Sofía, Madrid, Spain.
    Currás-Freixes, Maria
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain.
    Montero-Conde, Cristina
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain.
    Mancikova, Veronika
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Al-Shahrour, Fatima
    Translational Bioinformatics Unit, Spanish National Cancer Research Centre, Madrid, Spain.
    Cascon, Alberto
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain. ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain.
    Robledo, Mercedes
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain.ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain .
    Rodriguez-Antona, Cristina
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain.ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain .
    Targeted sequencing reveals low-frequency variants in EPHA genes as markers of paclitaxel-induced peripheral neuropathy.2017In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 23, no 5, p. 1227-1235Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Neuropathy is the dose limiting toxicity of paclitaxel and a major cause for decreased quality of life. Genetic factors have been shown to contribute to paclitaxel neuropathy susceptibility; however, the major causes for inter-individual differences remain unexplained. In this study we identified genetic markers associated with paclitaxel-induced neuropathy through massive sequencing of candidate genes.

    EXPERIMENTAL DESIGN: We sequenced the coding region of 4 EPHA genes, 5 genes involved in paclitaxel pharmacokinetics and 30 Charcot-Marie-Tooth genes, in 228 cancer patients with no/low neuropathy or high grade neuropathy during paclitaxel treatment. An independent validation series included 202 paclitaxel-treated patients. Variation-/ gene-based analyses were used to compare variant frequencies among neuropathy groups and Cox regression models were used to analyze neuropathy evolution along treatment.

    RESULTS: Gene-based analysis identified EPHA6 as the gene most significantly associated with paclitaxel-induced neuropathy. Low frequency non-synonymous variants in EPHA6 were present exclusively in patients with high neuropathy and all affected the ligand binding domain. Accumulated dose analysis in the discovery series showed a significantly higher neuropathy risk for EPHA5/6/8 low-frequency non-synonymous variant carriers (HR=14.60, 95%CI=2.33-91.62, P=0.0042) and an independent cohort confirmed an increased neuropathy risk (HR=2.07, 95%CI=1.14-3.77, P=0.017). Combining the series gave an estimated 2.50-fold higher risk of neuropathy (95%CI=1.46-4.31; P=9.1x10(-4)).

    CONCLUSION: This first study sequencing EPHA genes revealed that low frequency variants in EPHA6, EPHA5 and EPHA8 contribute to the susceptibility to paclitaxel-induced neuropathy. Furthermore, EPHAs neuronal injury repair function suggests that these genes might constitute important neuropathy markers for many neurotoxic drugs.

  • 24.
    Ardenfors, Oscar
    et al.
    Stockholm University, Sweden.
    Gudowska, Irena
    Stockholm University, Sweden.
    Flejmer, Anna M.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Dasu, Alexandru
    The Skandion Clinic, Sweden.
    Impact of irradiation setup in proton spot scanning brain therapy on organ doses from secondary radiation2018In: Radiation Protection Dosimetry, ISSN 0144-8420, E-ISSN 1742-3406, Vol. 180, no 1-4, p. 261-266Article in journal (Refereed)
    Abstract [en]

    A Monte Carlo model of a proton spot scanning pencil beam was used to simulate organ doses from secondary radiation produced from brain tumour treatments delivered with either a lateral field or a vertex field to one adult and one paediatric patient. Absorbed doses from secondary neutrons, photons and protons and neutron equivalent doses were higher for the vertex field in both patients, but the differences were low in absolute terms. Absorbed doses ranged between 0.1 and 43 μGy.Gy−1 in both patients with the paediatric patient receiving higher doses. The neutron equivalent doses to the organs ranged between 0.5 and 141 μSv.Gy−1 for the paediatric patient and between 0.2 and 134 μSv.Gy−1 for the adult. The highest neutron equivalent dose from the entire treatment was 7 mSv regardless of field setup and patient size. The results indicate that different field setups do not introduce large absolute variations in out-of-field doses produced in patients undergoing proton pencil beam scanning of centrally located brain tumours.

  • 25.
    Ardern, Clare
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. School of Allied Health, La Trobe University, Melbourne, Australia.
    Österberg, Annika
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Tagesson, Sofi
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Gauffin, Håkan
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Webster, Kate E.
    La Trobe University, Australia.
    Kvist, Joanna
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Satisfaction With Knee Function After Primary Anterior Cruciate Ligament Reconstruction Is Associated With Self-Efficacy, Quality of Life, and Returning to the Preinjury Physical Activity2016In: Arthroscopy: The Journal of Arthroscopy And Related, ISSN 0749-8063, E-ISSN 1526-3231, Vol. 32, no 8, p. 1631-1638Article in journal (Refereed)
    Abstract [en]

    Purpose: To assess whether patient-reported outcomes (psychological factors, appraisals of knee function, and physical activity participation) were associated with satisfaction with knee function after anterior cruciate ligament (ACL) reconstruction. Methods: Participants who were aged 18 to 45 years and a minimum 12 months post primary ACL reconstruction completed a questionnaire battery evaluating knee self-efficacy, knee-related quality of life, self-reported function, and physical activity participation. Participants responses to the question "If you were to spend the rest of your life with your knee just the way it has been in the last week, would you feel.... (7-point ordinal scale; 1 = happy, 7 = unhappy)" were categorized as satisfied, mostly satisfied, or dissatisfied and used as the primary outcome. Ordinal regression was used to examine associations between independent variables and the primary outcome. Results: A total of 177 participants were included at an average of 3 years after primary ACL reconstruction. At follow-up, 44% reported they would be satisfied, 28% mostly satisfied, and 28% dissatisfied with the outcome of ACL reconstruction. There were significant differences in psychological responses and appraisal of knee function between the 3 groups (P = .001), and significantly more people in the satisfied group had returned to their preinjury activity (58%) than in the mostly satisfied (28%) and dissatisfied (26%) groups (P = .001). Multivariable analysis demonstrated that the odds of being satisfied increased by a factor of 3 with higher self-efficacy, greater knee-related quality of life, and returning to the preinjury activity. Conclusions: People who had returned to their preinjury physical activity and who reported higher knee-related self-efficacy and quality of life were more likely to be satisfied with the outcome of ACL reconstruction.

  • 26.
    Aronsson, Mattias
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Carlsson, Per
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Hager, Jakob
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hultcrantz, R.
    Karolinska Institute, Sweden.
    Cost-effectiveness of high-sensitivity faecal immunochemical test and colonoscopy screening for colorectal cancer2017In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 104, no 8, p. 1078-1086Article in journal (Refereed)
    Abstract [en]

    Background: Colorectal cancer screening can decrease morbidity and mortality. However, there are widespread differences in the implementation of programmes and choice of strategy. The primary objective of this study was to estimate lifelong costs and health outcomes of two of the currently most preferred methods of screening for colorectal cancer: colonoscopy and sensitive faecal immunochemical test (FIT). Methods: A cost-effectiveness analysis of colorectal cancer screening in a Swedish population was performed using a decision analysis model, based on the design of the Screening of Swedish Colons (SCREESCO) study, and data from the published literature and registries. Lifelong cost and effects of colonoscopy once, colonoscopy every 10 years, FIT twice, FIT biennially and no screening were estimated using simulations. Results: For 1000 individuals invited to screening, it was estimated that screening once with colonoscopy yielded 49 more quality-adjusted life-years (QALYs) and a cost saving of (sic)64 800 compared with no screening. Similarly, screening twice with FIT gave 26 more QALYs and a cost saving of (sic)17 600. When the colonoscopic screening was repeated every tenth year, 7 additional QALYs were gained at a cost of (sic)189 400 compared with a single colonoscopy. The additional gain with biennial FIT screening was 25 QALYs at a cost of (sic)154 300 compared with two FITs. Conclusion: All screening strategies were cost-effective compared with no screening. Repeated and single screening strategies with colonoscopy were more cost-effective than FIT when lifelong effects and costs were considered. However, other factors such as patient acceptability of the test and availability of human resources also have to be taken into account.

  • 27.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Apropå! En arrogant organisation2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114Article in journal (Other academic)
    Abstract [en]

    n/a

  • 28.
    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.
    Atypical fractures, a biased perspective2016In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 47, no 1, p. S28-S30Article in journal (Refereed)
    Abstract [en]

    When stress fractures started to show up in the femurs of elderly ladies, it was soon evident that bisphosphonate use lay behind, and the absolute risk increase due to bisphosphonate use was reasonably well estimated already in 2008. Thereafter followed a period of confusion: the term atypical fracture was introduced, with a definition so vague that the true stress fractures tended to disappear in a cloud of ambiguity. This cast doubt on the association with bisphosphonates. The association was then re-established by large epidemiological studies based on radiographic adjudication. Atypical fractures are largely caused by bisphosphonates. With a correct indication, bisphosphonates prevent many more fractures than they cause, at least during the first years of use. With an incorrect indication they are likely to cause more harm than good. (C) 2016 Elsevier Ltd. All rights reserved.

  • 29.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Beslut att operera kopplat till ortopeders attityder till kirurgi2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, no 41Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 30.
    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.
    Editorial Material: ACADEMIC AUTHORSHIP How I was nearly duped into "authoring" a fake paper in BMJ-BRITISH MEDICAL JOURNAL, vol 351, issue h6605, pp2015In: BMJ-BRITISH MEDICAL JOURNAL, ISSN 1756-1833, Vol. 351, no h6605Article in journal (Other academic)
    Abstract [en]

    n/a

  • 31.
    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.
    Editorial Material: Why do we operate proximal humeral fractures?2015In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 86, no 3, p. 279-279Article in journal (Other academic)
  • 32.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Placeboeffekten är övervärderad: »Återgång till medelvärdet« kan förklara förbättring efter skenbehandling – men misstolkas ofta2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114Article in journal (Refereed)
  • 33.
    Aspenberg, Per
    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 Orthopaedics in Linköping.
    Malouf, Jorge
    Hospital San Pablo, Spain.
    Tarantino, Umberto
    University of Roma Tor Vergata, Italy.
    Garcia-Hernandez, Pedro A.
    University Hospital, Mexico.
    Corradini, Costantino
    University of Milan, Italy.
    Overgaard, Soren
    Odense University Hospital, Denmark; University of Southern Denmark, Denmark.
    Stepan, Jan J.
    Charles University of Prague, Czech Republic; Charles University of Prague, Czech Republic.
    Borris, Lars
    University Hospital, Denmark.
    Lespessailles, Eric
    CHR Orleans, France; University of Orleans, France.
    Frihagen, Frede
    Oslo University Hospital, Norway.
    Papavasiliou, Kyriakos
    Aristotle University of Thessaloniki, Greece.
    Petto, Helmut
    Eli Lilly, Austria.
    Ramon Caeiro, Jose
    University of Santiago de Compostela, Spain.
    Marin, Fernando
    Eli Lilly Research Centre, England.
    Effects of Teriparatide Compared with Risedronate on Recovery After Pertrochanteric Hip Fracture Results of a Randomized, Active-Controlled, Double-Blind Clinical Trial at 26 Weeks2016In: Journal of Bone and Joint Surgery. American volume, ISSN 0021-9355, E-ISSN 1535-1386, Vol. 98, no 22Article in journal (Refereed)
    Abstract [en]

    Background: Osteoporosis drugs might affect fracture-healing. We therefore studied the effects of teriparatide in comparison with risedronate on recovery after pertrochanteric hip fractures. Methods: The study was a randomized, multicenter, active-controlled, 78-week trial comparing teriparatide (20 mg/day) with risedronate (35 mg/week) initiated within 2 weeks after fixation of a low-trauma pertrochanteric hip fracture (AO/OTA 31-A1 or 31-A2). The main inclusion criteria were a bone mineral density T-score of amp;lt;=-22.0 and 25-OH-vitamin D of amp;gt;= 9.2 ng/mL. During the first 26 weeks, patients received study medication with oral or injectable placebo plus calcium and vitamin D in a double-blinded fashion. Secondary (Timed Up-and-Go [TUG] test, hip pain, Short Form [SF]-36 health status, and safety) and exploratory (radiographic outcomes and ability to walk) 26-week end points are reported. Results: Of the 224 patients who were randomized, 171 (86 teriparatide, 85 risedronate) were included in the analysis. The mean age was 77 +/- 8 years, 77% were female, and 26% had a prior history of low-trauma fracture. The teriparatide group completed the TUG test in a shorter time at 6, 12, 18, and 26 weeks (differences of 25.7, -4.4, -3.1, and -3.1 seconds, respectively; p = 0.021 for the overall difference). They also reported less pain on a visual analog scale immediately after the TUG test at 12 and 18 weeks (adjusted absolute differences of 10.6 and 11.9 mm, respectively; p amp;lt; 0.05). There were no significant between-group differences in the SF-36 score, Charnley hip pain score, ability to walk, or use of walking aids during follow-up. Radiographic healing at 6, 12, and 26 weeks, mechanical failure of the implant (teriparatide, 7; risedronate, 8), loss of reduction (teriparatide, 2; risedronate, 4), and nonunion (0 cases) were not significantly different. Mild hypercalcemia and hyperuricemia were more frequent with teriparatide. Conclusions: Teriparatide was associated with less pain and a shorter time to complete the TUG test between 6 and 26 weeks compared with risedronate. Other fracture-recovery outcomes were similar. The results should be interpreted with caution as these were secondary end points.

  • 34.
    Aspenberg, Per
    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 Orthopaedics in Linköping.
    Schepull, Torsten
    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.
    Substantial creep in healing human Achilles tendons: A pilot study2015In: MLTJ Muscles, Ligaments and Tendons Journal, ISSN 2240-4554, Vol. 5, no 3, p. 151-155Article in journal (Other academic)
    Abstract [en]

    Background: healing after rupture of the Achilles tendon can be described in terms of mechanical properties of the new-formed tissue, constituting the tendon callus. In previous human studies, the elastic modulus and the density remained almost constant during 3 months after mobilization started, and then improved up to one year. So far, time-dependent deformation of the healing human tendon has not been reported.

    Methods: in a series of 16 patients, operated with Achilles tendon suture, we implanted tantalum beads into the tendon and measured the distance between them repeatedly during 3 min of constant loading, using an ordinary image intensifier. The patients unloaded their leg for 30 min before the test. To avoid bias, all images were investigated in a randomized and blinded order.

    Results: total strain during 3 min of constant loading at 7 weeks post injury amounted to 5%, and at 19 weeks to 3%. About half of the strain, after the loading was applied, occurred during the second and third min. Considerable strain also occurred just before loading, when the patient was told that a load would be applied, but before this was actually done.

    Conclusion: the measurements were crude, and this study should be seen as a pilot. Still, viscoelastic properties seem to dominate the mechanical behavior the healing Achilles tendon from start of mobilization to 19 weeks, at least when tested after 30 min rest. This deserves further studies with more precise methods.

  • 35.
    Ballester, Facundo
    et al.
    University of Valencia, Spain.
    Carlsson Tedgren, Åsa
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Karolinska University Hospital, Sweden.
    Granero, Domingo
    Hospital Gen University, Spain.
    Haworth, Annette
    Peter MacCallum Cancer Centre, Australia; RMIT University, Australia.
    Mourtada, Firas
    Helen F Graham Cancer Centre, DE 19713 USA.
    Paiva Fonseca, Gabriel
    CNEN SP, Brazil; Maastricht University, Netherlands.
    Zourari, Kyveli
    University of Athens, Greece.
    Papagiannis, Panagiotis
    University of Athens, Greece.
    Rivard, Mark J.
    Tufts University, MA 02111 USA.
    Siebert, Frank-Andre
    University Hospital Schleswig Holstein, Germany.
    Sloboda, Ron S.
    Cross Cancer Institute, Canada; University of Alberta, Canada.
    Smith, Ryan L.
    Alfred Hospital, Australia.
    Thomson, Rowan M.
    Carleton University, Canada.
    Verhaegen, Frank
    Maastricht University, Netherlands; McGill University, Canada.
    Vijande, Javier
    University of Valencia, Spain; IFIC CSIC UV, Spain.
    Ma, Yunzhi
    CHU Quebec, Canada; University of Laval, Canada; University of Laval, Canada.
    Beaulieu, Luc
    CHU Quebec, Canada; University of Laval, Canada; University of Laval, Canada.
    A generic high-dose rate Ir-192 brachytherapy source for evaluation of model-based dose calculations beyond the TG-43 formalism2015In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 42, no 6, p. 3048-3062Article in journal (Refereed)
    Abstract [en]

    Purpose: In order to facilitate a smooth transition for brachytherapy dose calculations from the American Association of Physicists in Medicine (AAPM) Task Group No. 43 (TG-43) formalism to model-based dose calculation algorithms (MBDCAs), treatment planning systems (TPSs) using a MBDCA require a set of well-defined test case plans characterized by Monte Carlo (MC) methods. This also permits direct dose comparison to TG-43 reference data. Such test case plans should be made available for use in the software commissioning process performed by clinical end users. To this end, a hypothetical, generic high-dose rate (HDR) Ir-192 source and a virtual water phantom were designed, which can be imported into a TPS. Methods: A hypothetical, generic HDR Ir-192 source was designed based on commercially available sources as well as a virtual, cubic water phantom that can be imported into any TPS in DICOM format. The dose distribution of the generic Ir-192 source when placed at the center of the cubic phantom, and away from the center under altered scatter conditions, was evaluated using two commercial MBDCAs [Oncentra (R) Brachy with advanced collapsed-cone engine (ACE) and BrachyVision AcuRos (TM)]. Dose comparisons were performed using state-of-the-art MC codes for radiation transport, including ALGEBRA, BrachyDose, GEANT4, MCNP5, MCNP6, and pENELopE2008. The methodologies adhered to recommendations in the AAPM TG-229 report on high-energy brachytherapy source dosimetry. TG-43 dosimetry parameters, an along-away dose-rate table, and primary and scatter separated (PSS) data were obtained. The virtual water phantom of (201)(3) voxels (1 mm sides) was used to evaluate the calculated dose distributions. Two test case plans involving a single position of the generic HDR Ir-192 source in this phantom were prepared: (i) source centered in the phantom and (ii) source displaced 7 cm laterally from the center. Datasets were independently produced by different investigators. MC results were then compared against dose calculated using TG-43 and MBDCA methods. Results: TG-43 and PSS datasets were generated for the generic source, the PSS data for use with the ACE algorithm. The dose-rate constant values obtained from seven MC simulations, performed independently using different codes, were in excellent agreement, yielding an average of 1.1109 +/- 0.0004 cGy/(h U) (k = 1, Type A uncertainty). MC calculated dose-rate distributions for the two plans were also found to be in excellent agreement, with differences within type A uncertainties. Differences between commercial MBDCA and MC results were test, position, and calculation parameter dependent. On average, however, these differences were within 1% for ACUROS and 2% for ACE at clinically relevant distances. Conclusions: A hypothetical, generic HDR Ir-192 source was designed and implemented in two commercially available TPSs employing different MBDCAs. Reference dose distributions for this source were benchmarked and used for the evaluation of MBDCA calculations employing a virtual, cubic water phantom in the form of a CT DICOM image series. The implementation of a generic source of identical design in all TPSs using MBDCAs is an important step toward supporting univocal commissioning procedures and direct comparisons between TPSs. (C) 2015 American Association of Physicists in Medicine.

  • 36.
    Bar-Sever, Zvi
    et al.
    Tel Aviv Univ, Israel.
    Biassoni, Lorenzo
    Great Ormond St Hosp Children NHS Fdn Trust, England.
    Shulkin, Barry
    St Jude Childrens Res Hosp, TN 38105 USA.
    Kong, Grace
    Peter MacCallum Canc Ctr, Australia.
    Hofman, Michael S.
    Peter MacCallum Canc Ctr, Australia.
    Lopci, Egesta
    Humanitas Clin and Res Hosp, Italy.
    Manea, Irina
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Koziorowski, Jacek
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Faculty of Medicine and Health Sciences.
    Castellani, Rita
    Ist Nazl Tumori, Italy.
    Boubaker, Ariane
    Clin Source, Switzerland.
    Lambert, Bieke
    Univ Ghent, Belgium.
    Pfluger, Thomas
    Ludwig Maximilian Univ Hosp, Germany.
    Nadel, Helen
    British Columbia Childrens Hosp, Canada.
    Sharp, Susan
    Cincinnati Childrens Hosp Med Ctr, OH 45229 USA.
    Giammarile, Francesco
    IAEA, Austria.
    Guidelines on nuclear medicine imaging in neuroblastoma2018In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, no 11, p. 2009-2024Article in journal (Refereed)
    Abstract [en]

    Nuclear medicine has a central role in the diagnosis, staging, response assessment and long-term follow-up of neuroblastoma, the most common solid extracranial tumour in children. These EANM guidelines include updated information on I-123-mIBG, the most common study in nuclear medicine for the evaluation of neuroblastoma, and on PET/CT imaging with F-18-FDG, F-18-DOPA and Ga-68-DOTA peptides. These PET/CT studies are increasingly employed in clinical practice. Indications, advantages and limitations are presented along with recommendations on study protocols, interpretation of findings and reporting results.

  • 37.
    Bausch, Birke
    et al.
    Albert Ludwigs University, Germany.
    Schiavi, Francesca
    Ist Ricovero and Cura Carattere Science, Italy.
    Ni, Ying
    Cleveland Clin, OH 44106 USA.
    Welander, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Patocs, Attila
    Semmelweis University, Hungary; Semmelweis University, Hungary.
    Ngeow, Joanne
    National Cancer Centre Singapore, Singapore; Nanyang Technology University, Singapore.
    Wellner, Ulrich
    University of Lubeck, Germany.
    Malinoc, Angelica
    Albert Ludwigs University, Germany.
    Taschin, Elisa
    Ist Ricovero and Cura Carattere Science, Italy.
    Barbon, Giovanni
    Ist Ricovero and Cura Carattere Science, Italy.
    Lanza, Virginia
    Ist Ricovero and Cura Carattere Science, Italy.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Stenman, Adam
    Karolinska Institute, Sweden.
    Larsson, Catharina
    Karolinska Institute, Sweden.
    Svahn, Fredrika
    Karolinska Institute, Sweden.
    Chen, Jin-Lian
    Cleveland Clin, OH 44106 USA.
    Marquard, Jessica
    Cleveland Clin, OH 44106 USA.
    Fraenkel, Merav
    Hadassah Hebrew University, Israel.
    Walter, Martin A.
    University Hospital, Switzerland.
    Peczkowska, Mariola
    Institute Cardiol, Poland.
    Prejbisz, Aleksander
    Institute Cardiol, Poland.
    Jarzab, Barbara
    Maria Sklodowska Curie Mem Cancer Centre and Institute Oncol, Poland.
    Hasse-Lazar, Kornelia
    Maria Sklodowska Curie Mem Cancer Centre and Institute Oncol, Poland.
    Petersenn, Stephan
    Centre Endocrine Tumors, Germany.
    Moeller, Lars C.
    University of Duisburg Essen, Germany.
    Meyer, Almuth
    HELIOS Klin, Germany.
    Reisch, Nicole
    Ludwigs Maximilians University of Munich, Germany.
    Trupka, Arnold
    City Hospital, Germany.
    Brase, Christoph
    University of Erlangen Nurnberg, Germany.
    Galiano, Matthias
    University Hospital Erlangen, Germany.
    Preuss, Simon F.
    University of Cologne, Germany.
    Kwok, Pingling
    University of Regensburg, Germany.
    Lendvai, Nikoletta
    Semmelweis University, Hungary.
    Berisha, Gani
    Albert Ludwigs University, Germany.
    Makay, Ozer
    Ege University, Turkey.
    Boedeker, Carsten C.
    HELIOS Hanseklinikum Stralsund, Germany.
    Weryha, Georges
    University of Nancy, France.
    Racz, Karoly
    Semmelweis University, Hungary.
    Januszewicz, Andrzej
    Institute Cardiol, Poland.
    Walz, Martin K.
    Kliniken Essen Mitte, Germany; Kliniken Essen Mitte, Germany.
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Opocher, Giuseppe
    Ist Ricovero and Cura Carattere Science, Italy.
    Eng, Charis
    Cleveland Clin, OH 44106 USA; Cleveland Clin, OH 44106 USA.
    Neumann, Hartmut P. H.
    Albert Ludwigs University, Germany.
    Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention2017In: JAMA Oncology, ISSN 2374-2437, E-ISSN 2374-2445, Vol. 3, no 9, p. 1204-1212Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE Effective cancer prevention is based on accurate molecular diagnosis and results of genetic family screening, genotype-informed risk assessment, and tailored strategies for early diagnosis. The expanding etiology for hereditary pheochromocytomas and paragangliomas has recently included SDHA, TMEM127, MAX, and SDHAF2 as susceptibility genes. Clinical management guidelines for patients with germline mutations in these 4 newly included genes are lacking. OBJECTIVE To study the clinical spectra and age-related penetrance of individuals with mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes. DESIGN, SETTING, AND PATIENTS This study analyzed the prospective, longitudinally followed up European-American-Asian Pheochromocytoma-Paraganglioma Registry for prevalence of SDHA, TMEM127, MAX, and SDHAF2 germline mutation carriers from 1993 to 2016. Genetic predictive testing and clinical investigation by imaging from neck to pelvis was offered to mutation-positive registrants and their relatives to clinically characterize the pheochromocytoma/paraganglioma diseases associated with mutations of the 4 new genes. MAIN OUTCOMES AND MEASURES Prevalence and spectra of germline mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes were assessed. The clinical features of SDHA, TMEM127, MAX, and SDHAF2 disease were characterized. RESULTS Of 972 unrelated registrants without mutations in the classic pheochromocytoma- and paraganglioma-associated genes (632 female [65.0%] and 340 male [35.0%]; age range, 8-80; mean [SD] age, 41.0 [13.3] years), 58 (6.0%) carried germline mutations of interest, including 29 SDHA, 20 TMEM127, 8 MAX, and 1 SDHAF2. Fifty-three of 58 patients (91%) had familial, multiple, extra-adrenal, and/or malignant tumors and/or were younger than 40 years. Newly uncovered are 7 of 63 (11%) malignant pheochromocytomas and paragangliomas in SDHA and TMEM127 disease. SDHA disease occurred as early as 8 years of age. Extra-adrenal tumors occurred in 28 mutation carriers (48%) and in 23 of 29 SDHA mutation carriers (79%), particularly with head and neck paraganglioma. MAX disease occurred almost exclusively in the adrenal glands with frequently bilateral tumors. Penetrance in the largest subset, SDHA carriers, was 39% at 40 years of age and is statistically different in index patients (45%) vs mutation-carrying relatives (13%; P amp;lt; .001). CONCLUSIONS AND RELEVANCE The SDHA, TMEM127, MAX, and SDHAF2 genes may contribute to hereditary pheochromocytoma and paraganglioma. Genetic testing is recommended in patients at clinically high risk if the classic genes are mutation negative. Gene-specific prevention and/or early detection requires regular, systematic whole-body investigation.

  • 38.
    Behrens, Kira
    et al.
    Leibniz Institute Expt Virol, Germany; Walter and Eliza Hall Institute Medical Research, Australia.
    Maul, Katrin
    Leibniz Institute Expt Virol, Germany.
    Tekin, Nilguen
    Leibniz Institute Expt Virol, Germany; Leibniz Institute Expt Virol, Germany.
    Kriebitzsch, Neele
    Leibniz Institute Expt Virol, Germany.
    Indenbirken, Daniela
    Leibniz Institute Expt Virol, Germany.
    Prassolov, Vladimir
    Engelhardt Institute Molecular Biol, Russia.
    Mueller, Ursula
    Leibniz Institute Expt Virol, Germany.
    Serve, Hubert
    Goethe University of Frankfurt, Germany.
    Cammenga, Jörg
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Stocking, Carol
    Leibniz Institute Expt Virol, Germany.
    RUNX1 cooperates with FLT3-ITD to induce leukemia2017In: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 214, no 3, p. 737-752Article in journal (Refereed)
    Abstract [en]

    Acute myeloid leukemia (AML) is induced by the cooperative action of deregulated genes that perturb self-renewal, proliferation, and differentiation. Internal tandem duplications (ITDs) in the FLT3 receptor tyrosine kinase are common mutations in AML, confer poor prognosis, and stimulate myeloproliferation. AML patient samples with FLT3-ITD express high levels of RUNX1, a transcription factor with known tumor-suppressor function. In this study, to understand this paradox, we investigated the impact of RUNX1 and FLT3-ITD coexpression. FLT3-ITD directly impacts on RUNX1 activity, whereby up-regulated and phosphorylated RUNX1 cooperates with FLT3-ITD to induce AML. Inactivating RUNX1 in tumors releases the differentiation block and down-regulates genes controlling ribosome biogenesis. We identified Hhex as a direct target of RUNX1 and FLT3-ITD stimulation and confirmed high HHEX expression in FLT3-ITD AMLs. HHEX could replace RUNX1 in cooperating with FLT3-ITD to induce AML. These results establish and elucidate the unanticipated oncogenic function of RUNX1 in AML. We predict that blocking RUNX1 activity will greatly enhance current therapeutic approaches using FLT3 inhibitors.

  • 39.
    Bergfelt, Emma
    et al.
    Uppsala University, Sweden.
    Kozlowski, Piotr
    University of Örebro, Sweden.
    Ahlberg, Lucia
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences.
    Hulegardh, Erik
    Sahlgrens University Hospital, Sweden.
    Hagglund, Hans
    Karolinska Institute, Sweden.
    Karlsson, Karin
    Skåne University Hospital, Sweden.
    Markuszewska-Kuczymska, Alicja
    University of Umeå Hospital, Sweden.
    Tomaszewska-Toporska, Beata
    Skåne University Hospital, Sweden.
    Smedmyr, Bengt
    Uppsala University, Sweden.
    Astrom, Maria
    University of Örebro, Sweden.
    Amini, Rose-Marie
    Uppsala University, Sweden.
    Hallbook, Helene
    Uppsala University, Sweden.
    Satisfactory outcome after intensive chemotherapy with pragmatic use of minimal residual disease (MRD) monitoring in older patients with Philadelphia-negative B cell precursor acute lymphoblastic leukaemia: a Swedish registry-based study2015In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 32, no 4, p. 135-Article in journal (Refereed)
    Abstract [en]

    The introduction of minimal residual disease (MRD) monitoring, in the Swedish national guidelines for acute lymphoblastic leukaemia, was evaluated in 35 patients aged 46-79 years (median 61), who were diagnosed from 2007 to 2011 and treated with high-intensity, block-based chemotherapy (ABCDV/VABA induction). Both a high complete remission rate (91 %) and acceptable overall survival (OS) rate (47 %) at 5 years were achieved. MRD by flow cytometry was measured in 73 % of the patients reaching complete remission after the first course, but was omitted by the clinicians for eight patients who were either over 70 years of age or already met conventional high-risk criteria. Factors negatively influencing OS were age over 65 years and WHO status greater than= 2. MRD less than 0.1 % after induction had positive impact on continuous complete remission but not on OS. Only five patients were allocated to allogeneic haematopoietic stem cell transplantation in first remission, mainly due to conventional high risk factors. Thus, use of intensive remission induction therapy is effective in a selection of older patients. In a population for whom the possibilities of treatment escalation are limited, the optimal role of MRD monitoring remains to be determined.

  • 40.
    Berggren, Daniel Moreno
    et al.
    Uppsala Univ, Sweden.
    Folkvaljon, Yasin
    Uppsala Univ Hosp, Sweden.
    Engvall, Marie
    Uppsala Univ, Sweden.
    Sundberg, Johan
    Uppsala Univ, Sweden.
    Lambe, Mats
    Uppsala Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Antunovic, Petar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Garelius, Hege
    Sahlgrens Univ Hosp, Sweden.
    Lorenz, Fryderyk
    Umea Univ, Sweden.
    Nilsson, Lars
    Skane Univ Hosp, Sweden.
    Rasmussen, Bengt
    Orebro Univ Hosp, Sweden.
    Lehmann, Soren
    Uppsala Univ, Sweden.
    Hellstrom-Lindberg, Eva
    Karolinska Inst, Sweden.
    Jadersten, Martin
    Karolinska Inst, Sweden.
    Ejerblad, Elisabeth
    Uppsala Univ, Sweden.
    Prognostic scoring systems for myelodysplastic syndromes (MDS) in a population-based setting: a report from the Swedish MDS register2018In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 181, no 5, p. 614-627Article in journal (Refereed)
    Abstract [en]

    The myelodysplastic syndromes (MDS) have highly variable outcomes and prognostic scoring systems are important tools for risk assessment and to guide therapeutic decisions. However, few population-based studies have compared the value of the different scoring systems. With data from the nationwide Swedish population-based MDS register we validated the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R) and the World Health Organization (WHO) Classification-based Prognostic Scoring System (WPSS). We also present population-based data on incidence, clinical characteristics including detailed cytogenetics and outcome from the register. The study encompassed 1329 patients reported to the register between 2009 and 2013, 14% of these had therapy-related MDS (t-MDS). Based on the MDS register, the yearly crude incidence of MDS in Sweden was 2amp;lt;boldamp;gt;amp;lt;/boldamp;gt;9 per 100000 inhabitants. IPSS-R had a significantly better prognostic power than IPSS (Pamp;lt;0amp;lt;boldamp;gt;amp;lt;/boldamp;gt;001). There was a trend for better prognostic power of IPSS-R compared to WPSS (P=0amp;lt;boldamp;gt;amp;lt;/boldamp;gt;05) and for WPSS compared to IPSS (P=0amp;lt;boldamp;gt;amp;lt;/boldamp;gt;07). IPSS-R was superior to both IPSS and WPSS for patients aged 70years. Patients with t-MDS had a worse outcome compared to de novo MDS (d-MDS), however, the validity of the prognostic scoring systems was comparable for d-MDS and t-MDS. In conclusion, population-based studies are important to validate prognostic scores in a real-world setting. In our nationwide cohort, the IPSS-R showed the best predictive power.

  • 41.
    Bergkvist, Max
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Iredahl, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Tesselaar, Erik
    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 Radiation Physics.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Assessment of microcirculation of the skin using Tissue Viability Imaging: A promising technique for detecting venous stasis in the skin2015In: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, Vol. 101, p. 20-25Article in journal (Refereed)
    Abstract [en]

    Background: : Venous occlusion in the skin is difficult to detect by existing measurement techniques. Our aim was to find out whether Tissue Viability Imaging (TiVi) was better at detecting venous occlusion by comparing it with results of laser Doppler flowmetry (LDF) during graded arterial and venous stasis in human forearm skin. Methods: : Arterial and venous occlusions were simulated in 10 healthy volunteers by inflating a blood pressure cuff around the upper right arm. Changes in the concentration of red blood cells (RBC) were measured using TiVi, while skin perfusion and concentration of moving red blood cells (CMBC) were measured using static indices of LDF during exsanguination and subsequent arterial occlusion, postocclusive reactive hyperaemia, and graded increasing and decreasing venous stasis. Results: : During arterial occlusion there was a significant reduction in the mean concentration of RBC from baseline, as well as in perfusion and CMBC (p less than 0.008). Venous occlusion resulted in a significant 28% increase in the concentration of RBC (p = 0.002), but no significant change in perfusion (mean change -14%) while CMBC decreased significantly by 24% (p = 0.02). With stepwise increasing occlusion pressures there was a significant rise in the TiVi index and reduction in perfusion (p = 0.008), while the reverse was seen when venous flow was gradually restored. Conclusion: : The concentration of RBC measured with TiVi changes rapidly and consistently during both total and partial arterial and venous occlusions, while the changes in perfusion, measured by LDF, were less consistent This suggests that TiVi could be a more useful, non-invasive clinical monitoring tool for detecting venous stasis in the skin than LDF.

  • 42.
    Bergkvist, Max
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Zötterman, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Henricson, Joakim
    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, Department of Dermatology and Venerology.
    Iredahl, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Vascular Occlusion in a Porcine Flap Model: Effects on Blood Cell Concentration and Oxygenation.2017In: Plastic and reconstructive surgery. Global open, ISSN 2169-7574, Vol. 5, no 11, article id e1531Article in journal (Refereed)
    Abstract [en]

    Background: Venous congestion in skin flaps is difficult to detect. This study evaluated the ability of tissue viability imaging (TiVi) to measure changes in the concentration of red blood cells (CRBC), oxygenation, and heterogeneity during vascular provocations in a porcine fasciocutaneous flap model.

    Methods: In 5 pigs, cranial gluteal artery perforator flaps were raised (8 flaps in 5 pigs). The arterial and venous blood flow was monitored with ultrasonic flow probes. CRBC, tissue oxygenation, and heterogeneity in the skin were monitored with TiVi during baseline, 50% and 100% venous occlusion, recovery, 100% arterial occlusion and final recovery, thereby simulating venous and arterial occlusion of a free fasciocutaneous flap. A laser Doppler probe was used as a reference for microvascular perfusion in the flap.

    Results: During partial and complete venous occlusion, increases in CRBC were seen in different regions of the flap. They were more pronounced in the distal part. During complete arterial occlusion, CRBC decreased in all but the most distal parts of the flap. There were also increases in tissue oxygenation and heterogeneity during venous occlusion.

    Conclusions: TiVi measures regional changes in CRBC in the skin of the flap during arterial and venous occlusion, as well as an increase in oxygenated hemoglobin during venous occlusion that may be the result of reduced metabolism and impaired delivery of oxygen to the tissue. TiVi may provide a promising method for measuring flap viability because it is hand-held, easy to-use, and provides spatial information on venous congestion.

  • 43.
    Bergman, Emma Ahlen
    et al.
    Karolinska Univ Hosp, Sweden.
    Hartana, Ciputra Adijaya
    Karolinska Univ Hosp, Sweden.
    Johansson, Markus
    Sundsvall Hosp, Sweden; Umea Univ, Sweden.
    Linton, Ludvig B.
    Karolinska Univ Hosp, Sweden.
    Berglund, Sofia
    Karolinska Univ Hosp, Sweden.
    Hyllienmark, Martin
    TLA Targeted Immunotherapies AB, Sweden.
    Lundgren, Christian
    Karolinska Univ Hosp, Sweden.
    Holmstrom, Benny
    Akad Univ Hosp, Sweden.
    Palmqvist, Karin
    Umea Univ, Sweden; Ostersund Cty Hosp, Sweden.
    Hansson, Johan
    Uppsala Univ, Sweden.
    Alamdari, Farhood
    Vastmanland Hosp, Sweden.
    Huge, Ylva
    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 Urology in Östergötland.
    Aljabery, Firas
    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 Urology in Östergötland.
    Riklund, Katrine
    Umea Univ, Sweden.
    Winerdal, Malin E.
    Karolinska Univ Hosp, Sweden.
    Krantz, David
    Karolinska Univ Hosp, Sweden.
    Zirakzadeh, A. Ali
    Karolinska Univ Hosp, Sweden; Umea Univ, Sweden.
    Marits, Per
    Karolinska Univ Hosp, Sweden.
    Sjoholm, Louise K.
    Karolinska Inst, Sweden.
    Sherif, Amir
    Umea Univ, Sweden; Umea Univ, Sweden.
    Winqvist, Ola
    Karolinska Univ Hosp, Sweden.
    Increased CD4(+) T cell lineage commitment determined by CpG methylation correlates with better prognosis in urinary bladder cancer patients2018In: Clinical Epigenetics, E-ISSN 1868-7083, Vol. 10, article id 102Article in journal (Refereed)
    Abstract [en]

    Background: Urinary bladder cancer is a common malignancy worldwide. Environmental factors and chronic inflammation are correlated with the disease risk. Diagnosis is performed by transurethral resection of the bladder, and patients with muscle invasive disease preferably proceed to radical cystectomy, with or without neoadjuvant chemotherapy. The anti-tumour immune responses, known to be initiated in the tumour and draining lymph nodes, may play a major role in future treatment strategies. Thus, increasing the knowledge of tumour-associated immunological processes is important. Activated CD4(+) T cells differentiate into four main separate lineages: Th1, Th2, Th17 and Treg, and they are recognized by their effector molecules IFN-gamma, IL-13, IL-17A, and the transcription factor Foxp3, respectively. We have previously demonstrated signature CpG sites predictive for lineage commitment of these four major CD4(+ )T cell lineages. Here, we investigate the lineage commitment specifically in tumour, lymph nodes and blood and relate them to the disease stage and response to neoadjuvant chemotherapy. Results: Blood, tumour and regional lymph nodes were obtained from patients at time of transurethral resection of the bladder and at radical cystectomy. Tumour-infiltrating CD4(+ )lymphocytes were significantly hypomethylated in all four investigated lineage loci compared to CD4(+) lymphocytes in lymph nodes and blood (lymph nodes vs rumour-infiltrating lymphocytes: IFNG -4229 bp p amp;lt; 0.0001, IL13 -11 bp p amp;lt; 0.05, IL17A -122 bp p amp;lt; 0.01 and FOXP3 -77 bp pamp;gt; 0.05). Examination of individual lymph nodes displayed different methylation signatures, suggesting possible correlation with future survival. More advanced post-cystectomy tumour stages correlated significantly with increased methylation at the IFNG -4229 bp locus. Patients with complete response to neoadjuvant chemotherapy displayed significant hypomethylation in CD4(+ )T cells for all four investigated loci, most prominently in IFNG p amp;lt; 0.0001. Neoadjuvant chemotherapy seemed to result in a relocation of Th1-committed CD4(+) T cells from blood, presumably to the tumour, indicated by shifts in the methylation patterns, whereas no such shifts were seen for lineages corresponding to IL13, IL17A and FOXP3. Conclusion: Increased lineage commitment in CD4(+) T cells, as determined by demethylation in predictive CpG sites, is associated with lower post-cystectomy tumour stage, complete response to neoadjuvant chemotherapy and overall better outcome, suggesting epigenetic profiling of CD4(+) T cell lineages as a useful readout for clinical staging.

  • 44.
    Bernhardsson, Magnus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Osteoblast precursors and inflammatory cells arrive simultaneously to sites of a trabecular-bone injury2018In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 89, no 4, p. 457-461Article in journal (Refereed)
    Abstract [en]

    Background and purpose - Fracture healing in the shaft is usually described as a sequence of events, starting with inflammation, which triggers mesenchymal tissue formation in successive steps. Most clinical fractures engage cancellous bone. We here describe fracture healing in cancellous bone, focusing on the timing of inflammatory and mesenchymal cell type appearance at the site of injury. Material and methods - Rats received a proximal tibial drill hole, A subgroup received clodronate-containing liposomes before or after surgery. The tibiae were analyzed with micro-CT and immunohistochemistry 1 to 7 days after injury. Results - Granulocytes (myeloperoxidase) appeared in moderate numbers within the hole at day 1 and then gradually disappeared. Macrophage expression (CD68) was seen on day 1, increased until day 3, and then decreased. Mesenchymal cells (vimentin) had already accumulated in the periphery of the hole on day 1. Mesenchymal cells dominated in the entire lesion on day 3, now producing extracellular matrix. A modest number of preosteoblasts (RUNX2) were seen on day 1 and peaked on day 4. Osteoid was seen on day 4 in the traumatized region, with a distinct border to the uninjured surrounding marrow. Clodronate liposomes given before the injury reduced the volume of bone formation at day 7, but no reduction in macrophage numbers could be detected. Interpretation - The typical sequence of events in shaft fractures was not seen. Mesenchymal cells appeared simultaneously with granulocyte and macrophage arrival. Clodronate liposomes, known to reduce macrophage numbers, seemed to be associated with the delineation of the volume of tissue to be replaced by bone.

  • 45.
    Bernhardsson, Magnus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Sandberg, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    Anti-RANKL treatment improves screw fixation in cancellous bone in rats2015In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 46, no 6, p. 990-995Article in journal (Refereed)
    Abstract [en]

    Bisphosphonates improve implant fixation in randomised clinical trials of knee prostheses, hip prostheses and dental implants. However, a limited amount of bone resorption is required for bisphosphonates to exert an effect. Anti-RANKL treatment does not have this limitation, and we therefore tested whether if they might be more effective for improvement of implant fixation. This is of interest, as anti-RANKL treatment with denosumab is now in common clinical use. Male SD rats received a stain-less steel screw in the right proximal tibia and a drill hole in the left (n = 42). They were randomised to subcutaneous injections of either alendronate (20 mu g/kg/day), alendronate (200 mu g/kg/day), osteoprotegerin with an Fc tag (OPG-Fc; 8 mg/kg, twice weekly), or saline control. After 4 weeks, the fixation of the steel screw was measured by pull-out test. The tibia with the drill hole was evaluated with mu CT. OPG-Fc increased the pull-out force compared to saline controls by 153% (p less than 0.001). There was no significant difference between OPG-Fc and the alendronate groups. OPG-Fc increased the bone density (BV/TV) in the previous drill hole compared to controls 7-fold (p less than 0.001). This increase was higher than with any alendronate dose (p less than 0.001). OPG-Fc increased the bone density of the L5 vertebral body, but there was no significant difference between OPG-Fc and alendronate. Our results suggest that screw fixation in cancellous bone can be dramatically improved by an antiRANKL agent. The effect was comparable to very high bisphosphonate doses. Screw insertion in cancellous bone elicits a metaphyseal fracture healing response, and our findings might be relevant not only for implant fixation, but also for fracture healing in cancellous bone.

  • 46.
    Bernhardsson, Magnus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Sandberg, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    Experimental models for cancellous bone healing in the rat Comparison of drill holes and implanted screws2015In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 86, no 6, p. 745-750Article in journal (Refereed)
    Abstract [en]

    Background and purpose - Cancellous bone appears to heal by mechanisms different from shaft fracture healing. There is a paucity of animal models for fractures in cancellous bone, especially with mechanical evaluation. One proposed model consists of a screw in the proximal tibia of rodents, evaluated by pull-out testing. We evaluated this model in rats by comparing it to the healing of empty drill holes, in order to explain its relevance for fracture healing in cancellous bone. To determine the sensitivity to external influences, we also compared the response to drugs that influence bone healing. Methods - Mechanical fixation of the screws was measured by pull-out test and related to the density of the new bone formed around similar, but radiolucent, PMMA screws. The pull-out force was also related to the bone density in drill holes at various time points, as measured by microCT. Results - The initial bone formation was similar in drill holes and around the screw, and appeared to be reflected by the pull-out force. Both models responded similarly to alendronate or teriparatide (PTH). Later, the models became different as the bone that initially filled the drill hole was resorbed to restore the bone marrow cavity, whereas on the implant surface a thin layer of bone remained, making it change gradually from a trauma-related model to an implant fixation model. Interpretation - The similar initial bone formation in the different models suggests that pull-out testing in the screw model is relevant for assessment of metaphyseal bone healing. The subsequent remodeling would not be of clinical relevance in either model.

  • 47.
    Bernhardsson, Magnus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Sandberg, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Ressner, Marcus
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Koziorowski, Jacek
    Linköping University, Department of Medical and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Faculty of Medicine and Health Sciences.
    Malmqvist, Jonas
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Shining dead bone-cause for cautious interpretation of [F-18]NaF PET scans2018In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 89, no 1, p. 124-127Article in journal (Refereed)
    Abstract [en]

    Background and purpose — [18F]Fluoride ([18F]NaF) PET scan is frequently used for estimation of bone healing rate and extent in cases of bone allografting and fracture healing. Some authors claim that [18F]NaF uptake is a measure of osteoblastic activity, calcium metabolism, or bone turnover. Based on the known affinity of fluoride to hydroxyapatite, we challenged this view.

    Methods — 10 male rats received crushed, frozen allogeneic cortical bone fragments in a pouch in the abdominal wall on the right side, and hydroxyapatite granules on left side. [18F]NaF was injected intravenously after 7 days. 60 minutes later, the rats were killed and [18F]NaF uptake was visualized in a PET/CT scanner. Specimens were retrieved for micro CT and histology.

    Results — MicroCT and histology showed no signs of new bone at the implant sites. Still, the implants showed a very high [18F]NaF uptake, on a par with the most actively growing and remodeling sites around the knee joint.

    Interpretation — [18F]NaF binds with high affinity to dead bone and calcium phosphate materials. Hence, an [18F]NaF PET/CT scan does not allow for sound conclusions about new bone ingrowth into bone allograft, healing activity in long bone shaft fractures with necrotic fragments, or remodeling around calcium phosphate coated prostheses

  • 48.
    Bernhardsson, Magnus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Tätting, Love
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Sandberg, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Schilcher, Jörg
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Marrow compartment contribution to cortical defect healing2018In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 89, no 1, p. 119-123Article in journal (Refereed)
    Abstract [en]

    Background and purpose - Healing of shaft fractures is commonly described as regards external callus. We wanted to clarify the role of the bone marrow compartment in the healing of stable shaft fractures. Patients and methods - A longitudinal furrow was milled along the longitudinal axis of the femoral shaft in mice. The exposed bone marrow under the furrow was scooped out. The mice were then randomized to no further treatment, or to receiving 2 silicone plugs in the medullary canal distal and proximal to the defect. The plugs isolated the remaining marrow from contact with the defect. Results were studied with histology and flow cytometry. Results - Without silicone plugs, the marrow defect was filled with new bone marrow-like tissue by day 5, and new bone was seen already on day 10. The new bone was seen only at the level of the cortical injury, where it seemed to form simultaneously in the entire region of the removed cortex. The new bone seemed not to invade the marrow compartment, and there was a sharp edge between new bone and marrow. The regenerated marrow was similar to uninjured marrow, but contained considerably more cells. In the specimens with plugs, the marrow compartment was either filled with loose scar tissue, or empty, and there was only minimal bone formation, mainly located around the edges of the cortical injury. Interpretation - Marrow regeneration in the defect seemed to be a prerequisite for normal cortical healing. Shaft fracture treatment should perhaps pay more attention to the local bone marrow.

  • 49.
    Berntsen, Sveinung
    et al.
    Uppsala University, Sweden; University of Agder, Norway.
    Aaronson, Neil K.
    Netherlands Cancer Institute, Netherlands.
    Buffart, Laurien
    Vrije University of Amsterdam Medical Centre, Netherlands; Vrije University of Amsterdam Medical Centre, Netherlands.
    Börjeson, Sussanne
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Demmelmaier, Ingrid
    Uppsala University, Sweden.
    Hellbom, Maria
    Lund University, Sweden.
    Hojman, Pernille
    Copenhagen University Hospital, Denmark.
    Igelstrom, Helena
    Uppsala University, Sweden.
    Johansson, Birgitta
    Uppsala University, Sweden.
    Pingel, Ronnie
    Uppsala University, Sweden.
    Raastad, Truls
    Norwegian School Sport Science, Norway.
    Velikova, Galina
    University of Leeds, England.
    Asenlof, Pernilla
    Uppsala University, Sweden.
    Nordin, Karin
    Uppsala University, Sweden; University of Agder, Norway.
    Design of a randomized controlled trial of physical training and cancer ( Phys-Can) the impact of exercise intensity on cancer related fatigue, quality of life and disease outcome2017In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 17, article id 218Article in journal (Refereed)
    Abstract [en]

    Background: Cancer-related fatigue is a common problem in persons with cancer, influencing health-related quality of life and causing a considerable challenge to society. Current evidence supports the beneficial effects of physical exercise in reducing fatigue, but the results across studies are not consistent, especially in terms of exercise intensity. It is also unclear whether use of behaviour change techniques can further increase exercise adherence and maintain physical activity behaviour. This study will investigate whether exercise intensity affects fatigue and health related quality of life in persons undergoing adjuvant cancer treatment. In addition, to examine effects of exercise intensity on mood disturbance, adherence to oncological treatment, adverse effects from treatment, activities of daily living after treatment completion and return to work, and behaviour change techniques effect on exercise adherence. We will also investigate whether exercise intensity influences inflammatory markers and cytokines, and whether gene expressions following training serve as mediators for the effects of exercise on fatigue and health related quality of life. Methods/design: Six hundred newly diagnosed persons with breast, colorectal or prostate cancer undergoing adjuvant therapy will be randomized in a 2 x 2 factorial design to following conditions; A) individually tailored low-to-moderate intensity exercise with or without behaviour change techniques or B) individually tailored high intensity exercise with or without behaviour change techniques. The training consists of both resistance and endurance exercise sessions under the guidance of trained coaches. The primary outcomes, fatigue and health related quality of life, are measured by self-reports. Secondary outcomes include fitness, mood disturbance, adherence to the cancer treatment, adverse effects, return to activities of daily living after completed treatment, return to work as well as inflammatory markers, cytokines and gene expression. Discussion: The study will contribute to our understanding of the value of exercise and exercise intensity in reducing fatigue and improving health related quality of life and, potentially, clinical outcomes. The value of behaviour change techniques in terms of adherence to and maintenance of physical exercise behaviour in persons with cancer will be evaluated.

  • 50.
    Bjerrum, Ole Weis
    et al.
    Rigshosp, Denmark.
    Samuelsson, Jan
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Ghanima, Waleed
    Univ Oslo, Norway; Univ Oslo, Norway.
    Kauppila, Marjut
    Turku Univ Hosp, Finland.
    Andersen, Christen Lykkegaard
    Rigshosp, Denmark; Roskilde Hosp, Denmark.
    Thromboembolism prophylaxis in patients with Philadelphia-negative myeloproliferative neoplasms-Clinical practice among Nordic specialists2018In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 100, no 5, p. 475-478Article in journal (Refereed)
    Abstract [en]

    Background: Patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) have higher risks of developing thromboembolisms compared to the general population. International guidelines on the management of MPNs therefore include recommendations concerning thromboembolism prophylaxis. In clinical practice, strict adherence to guidelines may be challenging and dependent on factors such as physician experience, outpatient clinic setting, and access to therapy; however, no data exist on physician adherence or patient compliance to thromboembolism prophylaxis in MPNs. Objectives: The Nordic Myeloproliferative Neoplasm Study Group (NMPN) performed a survey among Nordic hematology specialists with the aim of documenting the implementation of international recommendations in a region of Northern Europe with similar healthcare systems. Results: The study showed that Nordic specialists managed their patients in accordance with international guidelines concerning medical intervention, but to a lesser degree regarding the management of additional cardiovascular risk factors. The survey also drew attention to the common clinical dilemma of combining antiaggregatory agents with vitamin K antagonists (VKA), or novel oral anticoagulants (NOAC), as well as phlebotomy limits in female polycythemia vera patients. Conclusions: The results of this study highlight the importance of considering all risk factors for thrombosis and an optimal collaboration with the primary healthcare sector.

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