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  • 101.
    Blomstrand, Hakon
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.
    Scheibling, Ursula
    Ryhov Cty Hosp, Sweden.
    Bratthall, Charlotte
    Kalmar Cty Hosp, Sweden.
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, S-58758 Linkoping, Sweden.
    Elander, Nils
    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.
    Real world evidence on gemcitabine and nab-paclitaxel combination chemotherapy in advanced pancreatic cancer2019In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 19, article id 40Article in journal (Refereed)
    Abstract [en]

    BackgroundIn the recent phase III trial MPACT the combination of gemcitabine and nab-paclitaxel (Gem/NabP) showed increased overall survival compared to gemcitabine alone in the treatment of advanced pancreatic ductal adenocarcinoma (aPDA). Until now there has been limited information on the clinical benefit and toxicity of the combination regimen in a real world setting. In addition the value for patients with locally advanced rather than metastatic aPDA has been unclear, since the former category of patients was not included in the MPACT trial.MethodsA multicentre retrospective observational study in the South Eastern Region of Sweden was performed, with the first 75 consecutive patients diagnosed with aPDA (both locally advanced and metastatic disease) who received first-line treatment with Gem/NabP.ResultsIn the overall population median progression free survival (PFS) and overall survival (OS) were 5.2 (3.4-7.0 95% CI) and 10.9 (7.8-14.0 95% CI) months, respectively. Patients with metastatic disease displayed a median OS of 9.4 (4.9-13.9) and a median PFS of 4.5 (3.3-5.7) months whereas the same parameters in the locally advanced subgroup were 17.1 (7.6-26.6) and 6.8 (5.2-8.4) months, respectively. Grade 3-4 hematologic toxicity was recorded: Neutropenia, leukopenia, thrombocytopenia, and anaemia were observed in 23, 20, 5, and 4% of patients, respectively. Dose reductions were performed in 80% of the patients.ConclusionThis study confirms the effectiveness and safety of first-line Gem/NabP in both locally advanced and metastatic PDA in a real world setting.

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  • 102.
    Blystad, Ida
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences.
    Håkansson, Irene
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Tisell, Anders
    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, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Smedby, Örjan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Larsson, Elna-Marie
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Uppsala University, Sweden.
    Quantitative MRI for Analysis of Active Multiple Sclerosis Lesions without Gadolinium-Based Contrast Agent2016In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 37, no 1, p. 94-100Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Contrast-enhancing MS lesions are important markers of active inflammation in the diagnostic work-up of MS and in disease monitoring with MR imaging. Because intravenous contrast agents involve an expense and a potential risk of adverse events, it would be desirable to identify active lesions without using a contrast agent. The purpose of this study was to evaluate whether pre-contrast injection tissue-relaxation rates and proton density of MS lesions, by using a new quantitative MR imaging sequence, can identify active lesions. MATERIALS AND METHODS: Forty-four patients with a clinical suspicion of MS were studied. MR imaging with a standard clinical MS protocol and a quantitative MR imaging sequence was performed at inclusion (baseline) and after 1 year. ROIs were placed in MS lesions, classified as nonenhancing or enhancing. Longitudinal and transverse relaxation rates, as well as proton density were obtained from the quantitative MR imaging sequence. Statistical analyses of ROI values were performed by using a mixed linear model, logistic regression, and receiver operating characteristic analysis. RESULTS: Enhancing lesions had a significantly (P < .001) higher mean longitudinal relaxation rate (1.22 0.36 versus 0.89 +/- 0.24), a higher mean transverse relaxation rate (9.8 +/- 2.6 versus 7.4 +/- 1.9), and a lower mean proton density (77 +/- 11.2 versus 90 +/- 8.4) than nonenhancing lesions. An area under the receiver operating characteristic curve value of 0.832 was obtained. CONCLUSIONS: Contrast-enhancing MS lesions often have proton density and relaxation times that differ from those in nonenhancing lesions, with lower proton density and shorter relaxation times in enhancing lesions compared with nonenhancing lesions.

  • 103.
    Blystad, Ida
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Warntjes, Marcel Jan Bertus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Smedby, Örjan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). KTH Royal Institute Technology, Sweden.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Larsson, Elna-Marie
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Uppsala University, Sweden.
    Tisell, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Quantitative MRI for analysis of peritumoral edema in malignant gliomas2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 5, article id e0177135Article in journal (Refereed)
    Abstract [en]

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

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  • 104.
    Bogl, H. P.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. 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.
    Schilcher, J.
    Gavle Central Hospital, Sweden.
    Undisturbed local bone formation capacity in patients with atypical femoral fractures: a case series2017In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 28, no 8, p. 2439-2444Article in journal (Refereed)
    Abstract [en]

    We excised the fracture site in 8 patients with incomplete atypical femoral fractures by drilling an 11-mmdiameter hole. New bone formation could be seen in the hole within a normal time frame. Delayed healing of these fractures might be unrelated to an impaired capacity to form bone. Introduction Incomplete atypical femoral fractures (undisplaced cracks) heal slowly or not at all, and often progress to a complete fracture with minimal trauma. The impaired healing has been attributed to an impaired biologic healing capacity related to bisphosphonate use, or, alternatively, to the mechanical environment within the fracture crack. This study aimed to investigate the capacity for bone formation after resection of the fracture site. Methods Between 2008 and 2014, we recruited eight patients with incomplete atypical femoral fractures. All used oral bisphosphonates before the fracture for on average 8 years (range 4 to 15) and complained of thigh pain. The fractures were stabilized with reamed cephalomedullary nails. During surgery, the fracture site in the lateral cortex was resected with a cylindrical drill (diameter 11.5 mm). The cylindrical cortical defect allowed radiographic evaluation of new bone formation, and the patients were followed clinically and radiologically for 24 months (range 15 to 92). Results After 3 months, newly formed bone could be seen in the cortical defects in all patients. After 13-26 months, the previous defects showed continuous cortical bone. At final follow-up, all patients reported full recovery of pre-surgical complaints. No complications occurred and no reoperations were performed. Conclusions New bone formation occurred within a time frame that appears normal for healing of cortical bone defects. This suggests that the capacity to form new bone is intact.

  • 105.
    Boije, Karin
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Drocic, Amra
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Engstrom, My
    Univ Gothenburg, Sweden.
    Bjerså, Kristofer
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Univ Gothenburg, Sweden.
    Patients Perceptions of Experiences of Recovering From Acute Pancreatitis An Interview Study2019In: Gastroenterology Nursing, ISSN 1042-895X, E-ISSN 1538-9766, Vol. 42, no 3, p. 233-241Article in journal (Refereed)
    Abstract [en]

    The incidence of registered admissions in inpatient care with a diagnosis of acute pancreatitis was 58 per 100,000 capita in Sweden during the year 2013. Although acute pancreatitis is a well-explored area, there is a demand for research from the patients perceptions. The aim of this study was to describe patients perceptions of recovering from acute pancreatitis. Data collection for this phenomenographical study included 16 individual semistructured interviews. Analysis was done according to the 7 steps suggested by Sjostrom and Dahlgren (2002). Recovery after acute pancreatitis was perceived within 5 categories; a time of physical suffering, an emotional journey, challenges to the usual life and its good qualities, barriers and need for social support, and healthcare as an important factor. Physical and emotional symptoms influence recovery after acute pancreatitis by challenging the good things and things that are taken for granted in everyday life. Promoting factors toward good recovery was a proper support from the social network as well as healthcare providers.

  • 106.
    Bojmar, Linda
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Zhang, Haiying
    Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medical College, New York, USA.
    Costa da Silva, Bruno
    Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medical College, New York, USA.
    Karlsson, Elin
    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.
    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.
    Vincent, Theresa
    Departments of Physiology and Biophysics and Cell and Developmental Biology, Weill Cornell Medical College, New York, USA / Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Stål, Olle
    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.
    Lyden, David
    Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medical College, New York, USA.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    miR-18a is regulated between progressive compartments of cancers, and incorporated in exosomes with the potential of creating premetastatic niches and predict cancer outcome2015Manuscript (preprint) (Other academic)
    Abstract [en]

    The ultimate cause of death for many cancer patients is the spread of the cancer via metastasis. Even so, there are still a lack of knowledge regarding the metastasis process. This study was performed to investigate the role of metastamirs in exosomes and their metastatic patterns. We used the well-established isogeneic murine cancer model of low metastatic 67NR cells, mimicking luminal/basal breast tumors, and highly metastatic 4T1 cells with characteristics of basal breast  tumors. We studied the exosomal properties and pre-metastatic effects in this metastasis model and compared human materials and exosomes of several other tumor types. Our data clearly demonstrated that exosomes from the highly metastatic cells home to the metastatic organs of their parental cells whereas exosomes from cells with low metastatic potential mostly located to lymph nodes. The exosome protein cargos also resembled their parental cells and potentially affects their target organs, and cells, differently. Furthermore, the exosomes from the highly metastatic cells had a more pronounced effect on tumor growth and pre-metastatic changes than the low metastatic exosomes. The microRNA-18a, a predictor of metastasis, was present to a higher extent in metastatic exosomes as compared to low metastatic exosomes, and altered the tumor progressive properties. Our findings support the role of exomirs as important players in the metastatic process, the value as biomarkers and potential therapeutic targets.

  • 107.
    Boknäs, Niklas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology. Australian Centre for Blood Diseases, Monash University, Melbourne, Australia.
    Macwan, Ankit
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences.
    Södergren, Anna L.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ramström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Örebro University, School of Medical Sciences, Örebro, Sweden.
    Platelet function testing at low platelet counts: When can you trust your analysis?2019In: RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS, ISSN 2475-0379, Vol. 3, no 2, p. 285-290Article in journal (Refereed)
    Abstract [en]

    Background: Although flow cytometry is often brought forward as a preferable method in the setting of thrombocytopenia, the relative effects of low sample counts on results from flow cytometry-based platelet function testing (FC-PFT) in comparison with light transmission aggregometry (LTA) and multiple electrode aggregometry (MEA) has not been reported. Objectives: To compare the effects of different sample platelet counts (10, 50, 100, and 200x10(9)L(-1)) on platelet activation measured with FC-PFT, LTA, and MEA using the same anticoagulant and agonist concentrations as for the commercial MEA test. Methods: Platelets were stimulated with two commonly used platelet agonists (ADP [6.5 mu molL(-1)] and PAR1-AP [TRAP, 32 mu molL(-1)]). The specified sample platelet counts were obtained by combining platelet-rich and platelet poor hirudinized plasma in different proportions with or without red blood cells. Results: For FC, P-selectin exposure and PAC-1 binding was reduced at 10x10(9)L(-1) after stimulation with PAR1-AP (by approximately 20% and 50%, respectively), but remained relatively unchanged when ADP was used as agonist (n=9). The platelet count-dependent effects observed with PAR1-AP were eliminated when samples were pre-incubated with apyrase, implying that reduced purinergic signaling was the main underlying factor (n=5). Both aggregometry-based PFTs showed a 50% reduction at 50x10(9)L(-1) and more than 80% reduction at 10x10(9)L(-1), irrespective of agonist used (n=7). Conclusions: Although FC-PFT is generally preferable to aggregometry-based PFTs in situations with low sample platelet counts, a careful optimization of experimental parameters is still required in order to eliminate platelet count-related effects.

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  • 108.
    Boknäs, Niklas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Ramström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Orebro Univ, Sweden.
    Faxälv, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Flow cytometry-based platelet function testing is predictive of symptom burden in a cohort of bleeders2018In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 29, no 5, p. 512-519Article in journal (Refereed)
    Abstract [en]

    Platelet function disorders (PFDs) are common in patients with mild bleeding disorders (MBDs), yet the significance of laboratory findings suggestive of a PFD remain unclear due to the lack of evidence for a clinical correlation between the test results and the patient phenotype. Herein, we present the results from a study evaluating the potential utility of platelet function testing using whole-blood flow cytometry in a cohort of 105 patients undergoing investigation for MBD. Subjects were evaluated with a test panel comprising two different activation markers (fibrinogen binding and P-selectin exposure) and four physiologically relevant platelet agonists (ADP, PAR1-AP, PAR4-AP, and CRP-XL). Abnormal test results were identified by comparison with reference ranges constructed from 24 healthy controls or with the fifth percentile of the entire patient cohort. We found that the abnormal test results are predictive of bleeding symptom severity, and that the greatest predictive strength was achieved using a subset of the panel, comparing measurements of fibrinogen binding after activation with all four agonists with the fifth percentile of the patient cohort (p=0.00008, hazard ratio 8.7; 95% CI 2.5-40). Our results suggest that whole-blood flow cytometry-based platelet function testing could become a feasible alternative for the investigation of MBDs. We also show that platelet function testing using whole-blood flow cytometry could provide a clinically relevant quantitative assessment of platelet-related hemostasis.

  • 109.
    Bolckmans, R.
    et al.
    Oxford Univ Hosp NHS Fdn Trust, England.
    Singh, S.
    Oxford Univ Hosp NHS Fdn Trust, England.
    Ratnatunga, K.
    Oxford Univ Hosp NHS Fdn Trust, England.
    Wickramasinghe, D.
    St Marks Hosp, England.
    Sahnan, K.
    St Marks Hosp, England.
    Adegbola, S.
    St Marks Hosp, England.
    Kalman, Thordis Disa
    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.
    Jones, H.
    Oxford Univ Hosp NHS Fdn Trust, England.
    Travis, S.
    Oxford Univ Hosp NHS Fdn Trust, England.
    Warusavitarne, J.
    St Marks Hosp, England.
    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.
    George, B.
    Oxford Univ Hosp NHS Fdn Trust, England.
    Temporary faecal diversion in ileocolic resection for Crohns disease: is there an impact on long-term surgical recurrence?2020In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 22, no 4, p. 430-438Article in journal (Refereed)
    Abstract [en]

    Aim Temporary faecal diversion after ileocolic resection (ICR) for Crohns disease reduces postoperative anastomotic complications in high-risk patients. The aim of this study was to assess if this approach also reduces long-term surgical recurrence. Method This was a multicentre retrospective review of prospectively maintained databases. Patient demographics, medical and surgical details were collected by three specialist centres. All patients had undergone an ICR between 2000 and 2012. The primary end-point was surgical recurrence. Results Three hundred and twelve patients (80%) underwent an ICR without covering ileostomy (one stage). Seventy-seven (20%) had undergone an ICR with end ileostomy/double-barrel ileostomy/enterocolostomy followed by closure (two stage). The median follow-up was 105 months [interquartile range (IQR) 76-136 months]. The median time to ileostomy closure was 9 months (IQR 5-12 months). There was no significant difference in surgical recurrence between the one- and two-stage groups (18% vs 16%, P = 0.94). We noted that smokers (20% vs 34%, P = 0.01) and patients with penetrating disease (28% vs 52%, P amp;lt; 0.01) were more likely to be defunctioned. A reduced recurrence rate was observed in the small high-risk group of patients who were smokers with penetrating disease behaviour treated with a two-stage strategy (0/10 vs 4/7, P = 0.12). Conclusion Despite having higher baseline risk factors, the results in terms of rate of surgical recurrence over 9 years are similar for patients having a two-stage compared with a one-stage procedure.

  • 110.
    Bolckmans, Roel
    et al.
    Oxford Univ Hosp Natl Hlth Serv Fdn Trust, England.
    Kalman, Thordis Disa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Singh, Sandeep
    Oxford Univ Hosp Natl Hlth Serv Fdn Trust, England.
    Ratnatunga, Keshara C.
    Oxford Univ Hosp Natl Hlth Serv Fdn Trust, England.
    Myrelid, Pär
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Travis, Simon
    Oxford Univ Hosp Natl Hlth Serv Fdn Trust, England.
    George, Bruce D.
    Oxford Univ Hosp Natl Hlth Serv Fdn Trust, England.
    Does Smoking Cessation Reduce Surgical Recurrence After Primary Ileocolic Resection for Crohns Disease?2020In: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 63, no 2, p. 200-206Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Tobacco smoking is a known risk factor for recurrence of Crohns disease after surgical resection. OBJECTIVE: This study assessed the effect of smoking cessation on long-term surgical recurrence after primary ileocolic resection for Crohns disease. DESIGN: A retrospective review of a prospectively maintained database was conducted. SETTINGS: Patient demographic data and medical and surgical details were combined from 2 specialist centers. After ethical approval, patients were contacted in case of missing data regarding smoking habit. PATIENTS: All patients undergoing ileocolic resection between 2000 and 2012 for histologically confirmed Crohns disease were included. Those with previous intestinal resection, strictureplasty for Crohns disease, leak after ileocolic resection, or who were never reversed were excluded. MAIN OUTCOME MEASURES: The primary end point was surgical recurrence measured by Kaplan-Meier survival analysis and secondary medical therapy at time of follow-up. RESULTS: Over a 12-year period, 290 patients underwent ileocolic resection. Full smoking data were available for 242 (83%) of 290 patients. There were 169 nonsmokers (70%; group 1), 42 active smokers at the time of ileocolic resection who continued smoking up to last follow-up (17%; group 2), and 31 (13%) who quit smoking after ileocolic resection (group 3). The median time of smoking exposure after ileocolic resection for group 3 was 3 years (interquartile range, 0-6 y), and median follow-up time for the whole group was 112 months (9 mo; interquartile range, 84-148 mo). Kaplan-Meier survival analysis showed a significantly higher surgical recurrence rate for group 2 compared with group 3 (16/42 (38%) vs 3/31 (10%); p = 0.02; risk ratio = 3.9 (95% CI, 1-12)). In addition, significantly more patients in group 2 without surgical recurrence received immunomodulatory maintenance therapy compared with group 3 (12/26 (46%) vs 4/28 (14%); p = 0.01; risk ratio = 3.2 (95% CI, 1-9)). LIMITATIONS: The study was limited by its retrospective design and small number of patients. CONCLUSIONS: Smoking cessation after primary ileocolic resection for Crohns disease may significantly reduce long-term risk of surgical recurrence and is associated with less use of maintenance therapy. See Video Abstract at http://links.lww.com/DCR/B86.

  • 111.
    Bondi, J.
    et al.
    Akershus University Hospital, Norway; Drammen Hospital, Norway.
    Avdagic, J.
    Akershus University Hospital, Norway; Innlandet Hospital, Norway.
    Karlbom, U.
    Uppsala University Hospital, Sweden.
    Hallböök, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Kalman, Thordis Disa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Saltyte Benth, J.
    Akershus University Hospital, Norway; University of Oslo, Norway.
    Naimy, N.
    Akershus University Hospital, Norway.
    Oresland, T.
    Akershus University Hospital, Norway; University of Oslo, Norway.
    Randomized clinical trial comparing collagen plug and advancement flap for trans-sphincteric anal fistula2017In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 104, no 9, p. 1160-1166Article in journal (Refereed)
    Abstract [en]

    Background: The role of a collagen plug for treating anal fistula is not well established. A randomized prospective multicentre non-inferiority study of surgical treatment of trans-sphincteric cryptogenic fistulas was undertaken, comparing the anal fistula plug with the mucosal advancement flap with regard to fistula recurrence rate and functional outcome. Methods: Patients with an anal fistula were evaluated for eligibility in three centres, and randomized to either mucosal advancement flap surgery or collagen plug, with clinical follow-up at 3 and 12 months. The primary outcome was the fistula recurrence rate. Anal pain (visual analogue scale), anal incontinence (St Marks score) and quality of life (Short Form 36 questionnaire) were also reported. Results: Ninety-four patients were included; 48 were allocated to the plug procedure and 46 to advancement flap surgery. The median follow-up was 12 (range 9-24) months. The recurrence rate at 12 months was 66 per cent (27 of 41 patients) in the plug group and 38 per cent (15 of 40) in the flap group (P = 0.006). Anal pain was reduced after operation in both groups. Anal incontinence did not change in the follow-up period. Patients reported an increased quality of life after 3 months. There were no differences between the groups with regard to pain, incontinence or quality of life. Conclusion: There was a considerably higher recurrence rate after the anal fistula plug procedure than following advancement flap repair.

  • 112.
    Borga, Magnus
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Andersson, Thord
    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.
    Semi-Supervised Learning of Anatomical Manifolds for Atlas-Based Segmentation of Medical Images2016In: Proceedings of the 23rd International Conference on Pattern Recognition (ICPR), IEEE Computer Society, 2016, p. 3146-3149Conference paper (Refereed)
    Abstract [en]

    This paper presents a novel method for atlas-based segmentation of medical images. The method uses semi- supervised learning of a graph describing a manifold of anatom- ical variations of whole-body images, where unlabelled data are used to find a path with small deformations from the labelled atlas to the target image. The method is evaluated on 36 whole-body magnetic resonance images with manually segmented livers as ground truth. Significant improvement (p < 0.001) was obtained compared to direct atlas-based registration. 

  • 113.
    Borga, Magnus
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Thomas, E. Louise
    Department of Life Sciences Faculty of Science and Technology University of Westminster, London, United Kingdom.
    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).
    Rosander, Johannes
    Advanced MR Analytics AB, Linköping, Sweden.
    Fitzpatrick, Julie
    Department of Life Sciences Faculty of Science and Technology University of Westminster, London, United Kingdom.
    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.
    Bell, Jimmy D
    Department of Life Sciences Faculty of Science and Technology University of Westminster, London, United Kingdom.
    Validation of a Fast Method for Quantification of Intra-abdominal and Subcutaneous Adipose Tissue for Large Scale Human Studies2015In: NMR in Biomedicine, ISSN 1099-1492, Vol. 28, no 12, p. 1747-1753Article in journal (Refereed)
    Abstract [en]

    Central obesity is the hallmark of a number of non-inheritable disorders. The advent of imaging techniques such as magnetic resonance imaging (MRI) has allowed for a fast and accurate assessment of body fat content and distribution. However, image analysis continues to be one of the major obstacles for the use of MRI in large scale studies. In this study we assess the validity of the recently proposed fat-muscle-quantitation-system (AMRATM Profiler) for the quantification of intra-abdominal adipose tissue (IAAT) and abdominal subcutaneous adipose tissue (ASAT) from abdominal MR images.  Abdominal MR images were acquired from 23 volunteers with a broad range of BMIs and analysed using SliceOmatic, the current gold-standard, and the AMRATM Profiler based on a non-rigid image registration of a library of segmented atlases. The results show that there was a highly significant correlation between the fat volumes generated by both analysis methods, (Pearson correlation r = 0.97 p<0.001), with the AMRATM Profiler analysis being significantly faster (~3 mins) than the conventional SliceOmatic approach (~40 mins). There was also excellent agreement between the methods for the quantification of IAAT (AMRA 4.73 ± 1.99 vs SliceOmatic 4.73 ± 1.75 litres, p=0.97). For the AMRATM Profiler analysis, the intra-observer coefficient of variation was 1.6 % for IAAT and 1.1 % for ASAT, the inter-observer coefficient of variation was 1.4 % for IAAT and 1.2 % for ASAT, the intra-observer correlation was 0.998 for IAAT and 0.999 for ASAT, and the inter-observer correlation was 0.999 for both IAAT and ASAT. These results indicate that precise and accurate measures of body fat content and distribution can be obtained in a fast and reliable form by the AMRATM Profiler, opening up the possibility of large-scale human phenotypic studies.

  • 114.
    Borga, Magnus
    et al.
    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).
    West, Janne
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Bell, Jimmy
    Westminster University, London, UK.
    Harvey, Nicholas
    University of Southampton, IK.
    Romu, Thobias
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Heymsfield, Steven
    Pennington Biomedical Research Center, Baton Rouge, LA, US.
    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. Advanced MR Analytics AB, Linköping, Sweden.
    Advanced body composition assessment: From body mass index to body composition profiling2018In: Journal of Investigative Medicine, ISSN 1081-5589, E-ISSN 1708-8267, Vol. 66, p. 887-895Article, review/survey (Refereed)
    Abstract [en]

    This paper gives a brief overview of common non-invasive techniques for body composition analysis and a more in-depth review of a body composition assessment method based on fat-referenced quantitative magnetic resonance imaging (MRI). Earlier published studies of this method are summarized, and a previously un-published validation study, based on 4.753 subjects from the UK Biobank imaging cohort, comparing the quantitative MRI method with dual-energy x-ray absorptiometry (DXA) is presented. For whole-body measurements of adipose tissue (AT) or fat and lean tissue (LT), DXA and quantitative MRI show excellent agreement with linear correlation of 0.99 and 0.97, and coefficient of variation (CV) of 4.5 % and 4.6 % for fat (computed from AT) and lean tissue respectively, but the agreement was found significantly lower for visceral adipose tissue, with a CV of more than 20 %. The additional ability of MRI to also measure muscle volumes, muscle AT infiltration and ectopic fat in combination with rapid scanning protocols and efficient image analysis tools make quantitative MRI a powerful tool for advanced body composition assessment. 

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    Advanced body composition assessment: From body mass index to body composition profiling
  • 115.
    Bostner, Josefine
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Alayev, Anya
    Yeshiva Univ, NY 10033 USA.
    Berman, Adi Y.
    Yeshiva Univ, NY 10033 USA.
    Fornander, Tommy
    Karolinska Inst, Sweden.
    Nordenskjöld, Bo
    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.
    Holz, Marina K.
    Yeshiva Univ, NY 10033 USA; Albert Einstein Coll Med, NY 10467 USA; Albert Einstein Coll Med, NY 10467 USA.
    Stål, Olle
    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.
    Raptor localization predicts prognosis and tamoxifen response in estrogen receptor-positive breast cancer2018In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 168, no 1, p. 17-27Article in journal (Refereed)
    Abstract [en]

    Deregulated PI3K/mTOR signals can promote the growth of breast cancer and contribute to endocrine treatment resistance. This report aims to investigate raptor and its intracellular localization to further understand its role in ER-positive breast cancer. Raptor protein expression was evaluated by immunohistochemistry in 756 primary breast tumors from postmenopausal patients randomized to tamoxifen or no tamoxifen. In vitro, the MCF7 breast cancer cell line and tamoxifen-resistant MCF7 cells were studied to track the raptor signaling changes upon resistance, and raptor localization in ER alpha-positive cell lines was compared with that in ER alpha-negative cell lines. Raptor protein expression in the nucleus was high in ER/PgR-positive and HER2-negative tumors with low grade, features associated with the luminal A subtype. Presence of raptor in the nucleus was connected with ER alpha signaling, here shown by a coupled increase of ER alpha phosphorylation at S167 and S305 with accumulation of nuclear raptor. In addition, the expression of ER alpha-activated gene products correlated with nuclear raptor. Similarly, in vitro we observed raptor in the nucleus of ER alpha-positive, but not of ER-negative cells. Interestingly, raptor localized to the nucleus could still be seen in tamoxifen-resistant MCF7 cells. The clinical benefit from tamoxifen was inversely associated with an increase of nuclear raptor. High cytoplasmic raptor expression indicated worse prognosis on long-term follow-up. We present a connection between raptor localization to the nucleus and ER alpha-positive breast cancer, suggesting raptor as a player in stimulating the growth of the luminal A subtype and a possible target along with endocrine treatment.

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  • 116.
    Bostner, Josefine
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Karlsson, Elin
    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.
    Bivik Eding, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Perez-Tenorio, Gizeh
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Franzén, Hanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Konstantinell, Aelita
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Fornander, Tommy
    Karolinska University Hospital, Sweden.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    S6 kinase signaling: tamoxifen response and prognostic indication in two breast cancer cohorts2015In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 22, no 3, p. 331-343Article in journal (Refereed)
    Abstract [en]

    Detection of signals in the mammalian target of rapamycin (mTOR) and the estrogen receptor (ER) pathways may be a future clinical tool for the prediction of adjuvant treatment response in primary breast cancer. Using immunohistological staining, we investigated the value of the mTOR targets p70-S6 kinase (S6K) 1 and 2 as biomarkers for tamoxifen benefit in two independent clinical trials comparing adjuvant tamoxifen with no tamoxifen or 5 years versus 2 years of tamoxifen treatment. In addition, the prognostic value of the S6Ks was evaluated. We found that S6K1 correlated with proliferation, HER2 status, and cytoplasmic AKT activity, whereas high protein expression levels of S6K2 and phosphorylated (p) S6K were more common in ER-positive, and low-proliferative tumors with pAKT-s473 localized to the nucelus. Nuclear accumulation of S6K1 was indicative of a reduced tamoxifen effect (hazard ratio (HR): 1.07, 95% CI: 0.53-2.81, P=0.84), compared with a significant benefit from tamoxifen treatment in patients without tumor S6K1 nuclear accumulation (HR: 0.42, 95% CI: 0.29-0.62, Pless than0.00001). Also S6K1 and S6K2 activation, indicated by pS6K-t389 expression, was associated with low benefit from tamoxifen (HR: 0.97, 95% CI: 0.50-1.87, P=0.92). In addition, high protein expression of S6K1, independent of localization, predicted worse prognosis in a multivariate analysis, P=0.00041 (cytoplasm), P=0.016 (nucleus). In conclusion, the mTOR-activated kinases S6K1 and S6K2 interfere with proliferation and response to tamoxifen. Monitoring their activity and intracellular localization may provide biomarkers for breast cancer treatment, allowing the identification of a group of patients less likely to benefit from tamoxifen and thus in need of an alternative or additional targeted treatment.

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  • 117.
    Boström, A.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Thulin, K.
    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 Orthopaedics in Norrköping.
    Fredriksson, Mats
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science.
    Reese, D.
    IFK Norrköping, Norrköping, Sweden.
    Rockborn, Peter
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Norrköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences.
    Hammar, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Risk factors for acute and overuse sport injuries in Swedish children 11 to 15 years old: What about resistance training with weights?2016In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 26, no 3, p. 317-323Article in journal (Refereed)
    Abstract [en]

    To determine the 1-year self-reported incidence of overuse and traumatic sport injuries and risk factors for injuries in children participating in a summer sports camp representing seven different sports. 4363 children, 11 to 15 years old participating in a summer camp in seven different sports answered a questionnaire. Injury in this cross-sectional study was defined as a sport-related trauma or overload leading to pain and dysfunction preventing the person from participation in training or competition for at least 1 week. A number of risk factors for injury were investigated such as sex, age, number of hours spent on training in general, and on resistance training with weights. Nearly half [49%, 95% confidence interval (CI) 48–51%] of the participants had been injured as a result of participation in a sport during the preceding year, significantly more boys than girls (53%, 95% CI 50–55% vs 46%, 95% CI 43–48%; P < 0.001). Three factors contributed to increased incidence of sport injuries: age, sex, and resistance training with weights. Time spent on resistance training with weights was significantly associated with sport injuries in a logistic regression analysis. In children age 11 to 15 years, the risk of having a sport-related injury increased with age and occurred more often in boys than in girls. Weight training was the only modifiable risk factor that contributed to a significant increase in the incidence of sport injuries.

  • 118.
    Brannstrom, Fredrik
    et al.
    Umeå University, Sweden.
    Bjerregaard, Jon K.
    Odense University Hospital, Denmark.
    Winbladh, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment.
    Nilbert, Mef
    Lund University, Sweden; University of Copenhagen, Denmark.
    Revhaug, Arthur
    University of Tromsoe, Norway.
    Wagenius, Gunnar
    Karolinska Institute, Sweden.
    Morner, Malin
    Karolinska Institute, Sweden.
    Multidisciplinary team conferences promote treatment according to guidelines in rectal cancer2015In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 54, no 4, p. 447-453Article in journal (Refereed)
    Abstract [en]

    Background. Multidisciplinary team (MDT) conferences have been introduced into standard cancer care, though evidence that it benefits the patient is weak. We used the national Swedish Rectal Cancer Register to evaluate predictors for case discussion at a MDT conference and its impact on treatment. Material and methods. Of the 6760 patients diagnosed with rectal cancer in Sweden between 2007 and 2010, 78% were evaluated at a MDT. Factors that influenced whether a patient was discussed at a preoperative MDT conference were evaluated in 4883 patients, and the impact of MDT evaluation on the implementation of preoperative radiotherapy was evaluated in 1043 patients with pT3c-pT4 M0 tumours, and in 1991 patients with pN + M0 tumours. Results. Hospital volume, i.e. the number of rectal cancer surgical procedures performed per year, was the major predictor for MDT evaluation. Patients treated at hospitals with less than 29 procedures per year had an odds ratio (OR) for MDT evaluation of 0.15. Age and tumour stage also influenced the chance of MDT evaluation. MDT evaluation significantly predicted the likelihood of being treated with preoperative radiotherapy in patients with pT3c-pT4 M0 tumours (OR 5.06, 95% CI 3.08 - 8.34), and pN + M0 (OR 3.55, 95% CI 2.60 -4.85), even when corrected for co-morbidity and age. Conclusion. Patients with rectal cancer treated at high-volume hospitals are more likely to be discussed at a MDT conference, and that is an independent predictor of the use of adjuvant radiotherapy. These results indirectly support the introduction into clinical practice of discussing all rectal cancer patients at MDT conferences, not least those being treated at low-volume hospitals.

  • 119.
    Brink, Rob C.
    et al.
    University of Medical Centre Utrecht, Netherlands.
    Schlosser, Tom P. C.
    University of Medical Centre Utrecht, Netherlands.
    Colo, Dino
    University of Medical Centre Utrecht, Netherlands.
    Vavruch, Ludvig
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    van Stralen, Marijn
    University of Medical Centre Utrecht, Netherlands.
    Vincken, Koen L.
    University of Medical Centre Utrecht, Netherlands.
    Malmqvist, Marcus
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Kruyt, Moyo C.
    University of Medical Centre Utrecht, Netherlands.
    Tropp, Hans
    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 Spinal Surgery.
    Castelein, Rene M.
    University of Medical Centre Utrecht, Netherlands.
    Anterior Spinal Overgrowth Is the Result of the Scoliotic Mechanism and Is Located in the Disc2017In: Spine, ISSN 0362-2436, E-ISSN 1528-1159, Vol. 42, no 11, p. 818-822Article in journal (Refereed)
    Abstract [en]

    Study Design. Cross-sectional study. Objective. To investigate the presence and magnitude of anterior spinal overgrowth in neuromuscular scoliosis and compare this with the same measurements in idiopathic scoliosis and healthy spines. Summary of Background Data. Anterior spinal overgrowth has been described as a potential driver for the onset and progression of adolescent idiopathic scoliosis (AIS). Whether this anterior overgrowth is specific for AIS or also present in nonidiopathic scoliosis has not been reported. Methods. Supine computed tomography (CT) scans of thirty AIS patients (thoracic Cobb 21-81 degrees), thirty neuromuscular (NM) scoliotic patients (thoracic Cobb 19-101 degrees) and 30 nonscoliotic controls were used. The difference in length in per cents between the anterior and posterior side {[(Delta A-P)/P] * 100%, abbreviated to A-P%} of each vertebral body and intervertebral disc, and between the anterior side of the spine and the spinal canal (A-C%) were determined. Results. The A-P% of the thoracic curves did not differ between the AIS (+1.2 perpendicular to 2.2%) and NM patients (+0.9 +/- 4.1%, P = 0.663), both did differ, however, from the same measurements in controls (-3.0 +/- 1.6%; Pamp;lt; 0.001) and correlated linearly with the Cobb angle (AIS r = 0.678, NM r = 0.687). Additional anterior length was caused by anterior elongation of the discs (AIS: A-P% disc +17.5 +/- 12.7% vs. A-P% body - 2.5 +/- 2.6%; Pamp;lt; 0.001, NM: A-P% disc + 19.1 +/- 18.0% vs. A-P% body -3.5 +/- 5.1%; Pamp;lt; 0.001). The A-C% T1-S1 in AIS and NM patients were similar (+ 7.9 +/- 1.8% and + 8.7 +/- 4.0%, P = 0.273), but differed from the controls (+4.2 +/- 3.3%; Pamp;lt; 0.001). Conclusion. So called anterior overgrowth has been postulated as a possible cause for idiopathic scoliosis, but apparently it occurs in scoliosis with a known origin as well. This suggests that it is part of a more generalized scoliotic mechanism, rather than its cause. The fact that the intervertebral discs contribute more to this increased anterior length than the vertebral bodies suggests an adaptation to altered loading, rather than a primary growth disturbance.

  • 120.
    Brink, Rob C.
    et al.
    Department of Orthopaedic Surgery, G05.228, University Medical Center Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands..
    Vavruch, Ludvig
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Schlösser, Tom P. C.
    Department of Orthopaedic Surgery, G05.228, University Medical Center Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands..
    Abul-Kasim, Kasim
    Division of Neuroradiology, Diagnostic Centre for Imaging and Functional Medicine, Faculty of Medicine, Lund University, Skåne University Hospital, Malmö, Sweden..
    Ohlin, Acke
    Department of Orthopaedic Surgery, Faculty of Medicine, Lund University, Skåne University Hospital, Malmö, Sweden..
    Tropp, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. 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 Orthopaedics in Linköping.
    Castelein, René M.
    Department of Orthopaedic Surgery, G05.228, University Medical Center Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands. r.m.castelein@umcutrecht.nl..
    Vrtovec, Tomaž
    Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia..
    Three-dimensional pelvic incidence is much higher in (thoraco)lumbar scoliosis than in controls2019In: European spine journal, ISSN 0940-6719, E-ISSN 1432-0932, Vol. 28, no 3, p. 544-550Article in journal (Refereed)
    Abstract [en]

    Purpose

    The pelvic incidence (PI) is used to describe the sagittal spino-pelvic alignment. In previous studies, radiographs were used, leading to less accuracy in establishing the three-dimensional (3D) spino-pelvic parameters. The purpose of this study is to analyze the differences in the 3D sagittal spino-pelvic alignment in adolescent idiopathic scoliosis (AIS) subjects and non-scoliotic controls.

    Methods

    Thirty-seven female AIS patients that underwent preoperative supine low-dose computed tomography imaging of the spine, hips and pelvis as part of their general workup were included and compared to 44 non-scoliotic age-matched female controls. A previously validated computerized method was used to measure the PI in 3D, as the angle between the line orthogonal to the inclination of the sacral endplate and the line connecting the center of the sacral endplate with the hip axis.

    Results

    The PI was on average 46.8° ± 12.4° in AIS patients and 41.3° ± 11.4° in controls (p = 0.025), with a higher PI in Lenke type 5 curves (50.6° ± 16.2°) as compared to controls (p = 0.042), whereas the Lenke type 1 curves (45.9° ± 12.2°) did not differ from controls (p = 0.141).

    Conclusion

    Lenke type 5 curves show a significantly higher PI than controls, whereas the Lenke type 1 curves did not differ from controls. This suggests a role of pelvic morphology and spino-pelvic alignment in the pathogenesis of idiopathic scoliosis. Further longitudinal studies should explore the exact role of the PI in the initiation and progression of different AIS types.

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  • 121.
    Bruun, Jarle
    et al.
    Oslo University Hospital, Norway; Oslo University Hospital, Norway; University of Oslo, Norway.
    Kolberg, Matthias
    Oslo University Hospital, Norway; Oslo University Hospital, Norway; University of Oslo, Norway.
    Ahlquist, Terje C.
    Oslo University Hospital, Norway; Oslo University Hospital, Norway.
    Royrvik, Ellen C.
    Oslo University Hospital, Norway; University of Oslo, Norway; University of Oxford, England.
    Nome, Torfinn
    Oslo University Hospital, Norway; University of Oslo, Norway.
    Leithe, Edward
    Oslo University Hospital, Norway; Oslo University Hospital, Norway; University of Oslo, Norway.
    Lind, Guro E.
    Oslo University Hospital, Norway; Oslo University Hospital, Norway; University of Oslo, Norway.
    Merok, Marianne A.
    Oslo University Hospital, Norway; University of Oslo, Norway; Oslo University Hospital, Norway.
    Rognum, Torleiv O.
    University of Oslo, Norway; Norwegian Institute Public Heatlh, Norway.
    Bjorkoy, Geir
    University of Coll Sor Trondelag, Norway.
    Johansen, Terje
    University of Tromso, Norway.
    Lindblom, Annika
    Karolinska Institute, Sweden.
    Sun, Xiao-Feng
    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.
    Svindland, Aud
    University of Oslo, Norway; Oslo University Hospital, Norway.
    Liestol, Knut
    University of Oslo, Norway; Fac Math and Nat Science, Norway.
    Nesbakken, Arild
    Oslo University Hospital, Norway; University of Oslo, Norway; Oslo University Hospital, Norway; University of Oslo, Norway.
    Skotheim, Rolf I.
    Oslo University Hospital, Norway; Oslo University Hospital, Norway; University of Oslo, Norway; Fac Math and Nat Science, Norway.
    Lothe, Ragnhild A.
    Oslo University Hospital, Norway; Oslo University Hospital, Norway; University of Oslo, Norway; University of Oslo, Norway.
    Regulator of Chromosome Condensation 2 Identifies High-Risk Patients within Both Major Phenotypes of Colorectal Cancer2015In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 21, no 16, p. 3759-3770Article in journal (Refereed)
    Abstract [en]

    Purpose: Colorectal cancer has high incidence and mortality worldwide. Patients with microsatellite instable (MSI) tumors have significantly better prognosis than patients with microsatellite stable (MSS) tumors. Considerable variation in disease outcome remains a challenge within each subgroup, and our purpose was to identify biomarkers that improve prediction of colorectal cancer prognosis. Experimental Design: Mutation analyses of 42 MSI target genes were performed in two independent MSI tumor series (n = 209). Markers that were significantly associated with prognosis in the test series were assessed in the validation series, followed by functional and genetic explorations. The clinical potential was further investigated by immunohistochemistry in a population-based colorectal cancer series (n = 903). Results: We identified the cell-cycle gene regulator of chromosome condensation 2 (RCC2) as a cancer biomarker. We found a mutation in the 50 UTR region of RCC2 that in univariate and multivariate analyses was significantly associated with improved outcome in the MSI group. This mutation caused reduction of protein expression in dual luciferase gene reporter assays. siRNA knockdown in MSI colon cancer cells (HCT15) caused reduced cell proliferation, cell-cycle arrest, and increased apoptosis. Massive parallel sequencing revealed few RCC2 mutations in MSS tumors. However, weak RCC2 protein expression was significantly associated with poor prognosis, independent of clinical highrisk parameters, and stratifies clinically important patient subgroups with MSS tumors, including elderly patients (greater than 75 years), stage II patients, and those with rectal cancer. Conclusions: Impaired RCC2 affects functional and clinical endpoints of colorectal cancer. High-risk patients with either MSI or MSS tumors can be identified with cost-effective routine RCC2 assays. (C) 2015 AACR.

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  • 122.
    Burocziova, Monika
    et al.
    Czech Acad Sci, Czech Republic.
    Burdova, Kamila
    Czech Acad Sci, Czech Republic.
    Martinikova, Andra S.
    Czech Acad Sci, Czech Republic.
    Kasparek, Petr
    Czech Acad Sci, Czech Republic.
    Kleiblova, Petra
    Charles Univ Prague, Czech Republic.
    Danielsen, Stine A.
    Oslo Univ Hosp, Norway; Oslo Univ Hosp, Norway.
    Borecka, Marianna
    Charles Univ Prague, Czech Republic.
    Jenikova, Gabriela
    Czech Acad Sci, Czech Republic.
    Janeckova, Lucie
    Czech Acad Sci, Czech Republic.
    Pavel, Jozef
    Czech Acad Sci, Czech Republic.
    Zemankova, Petra
    Charles Univ Prague, Czech Republic.
    Schneiderova, Michaela
    Charles Univ Prague, Czech Republic; Gen Fac Hosp Prague, Czech Republic.
    Schwarzova, Lucie
    Gen Fac Hosp Prague, Czech Republic; Charles Univ Prague, Czech Republic.
    Ticha, Ivana
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology. Gen Fac Hosp Prague, Czech Republic; Charles Univ Prague, Czech Republic.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Jiraskova, Katerina
    ASCR, Czech Republic.
    Liska, Vaclav
    Charles Univ Prague, Czech Republic.
    Vodickova, Ludmila
    ASCR, Czech Republic; Charles Univ Prague, Czech Republic; Charles Univ Prague, Czech Republic.
    Vodicka, Pavel
    ASCR, Czech Republic; Charles Univ Prague, Czech Republic; Charles Univ Prague, Czech Republic.
    Sedlacek, Radislav
    Czech Acad Sci, Czech Republic.
    Kleibl, Zdenek
    Charles Univ Prague, Czech Republic.
    Lothe, Ragnhild A.
    Oslo Univ Hosp, Norway; Oslo Univ Hosp, Norway.
    Korinek, Vladimir
    Czech Acad Sci, Czech Republic.
    Macurek, Libor
    Czech Acad Sci, Czech Republic.
    Truncated PPM1D impairs stem cell response to genotoxic stress and promotes growth of APC-deficient tumors in the mouse colon2019In: Cell Death and Disease, ISSN 2041-4889, E-ISSN 2041-4889, Vol. 10, article id 818Article in journal (Refereed)
    Abstract [en]

    Protein phosphatase magnesium-dependent 1 delta (PPM1D) terminates cell response to genotoxic stress by negatively regulating the tumor suppressor p53 and other targets at chromatin. Mutations in the exon 6 of the PPM1D result in production of a highly stable, C-terminally truncated PPM1D. These gain-of-function PPM1D mutations are present in various human cancers but their role in tumorigenesis remains unresolved. Here we show that truncated PPM1D impairs activation of the cell cycle checkpoints in human non-transformed RPE cells and allows proliferation in the presence of DNA damage. Next, we developed a mouse model by introducing a truncating mutation in the PPM1D locus and tested contribution of the oncogenic PPM1D(T) allele to colon tumorigenesis. We found that p53 pathway was suppressed in colon stem cells harboring PPM1D(T) resulting in proliferation advantage under genotoxic stress condition. In addition, truncated PPM1D promoted tumor growth in the colon in Apc(min) mice and diminished survival. Moreover, tumor organoids derived from colon of the Apc(min)Ppm1d(T/+) mice were less sensitive to 5-fluorouracil when compared to Apc(min)Ppm1d(+/+)and the sensitivity to 5-fluorouracil was restored by inhibition of PPM1D. Finally, we screened colorectal cancer patients and identified recurrent somatic PPM1D mutations in a fraction of colon adenocarcinomas that are p53 proficient and show defects in mismatch DNA repair. In summary, we provide the first in vivo evidence that truncated PPM1D can promote tumor growth and modulate sensitivity to chemotherapy.

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  • 123.
    Busch, Susann
    et al.
    Gothenburg University, Sweden.
    Sims, Andrew H.
    University of Edinburgh, Scotland.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Ferno, Marten
    Lund University, Sweden.
    Landberg, Goran
    Gothenburg University, Sweden; University of Manchester, England.
    Loss of TGF beta Receptor Type 2 Expression Impairs Estrogen Response and Confers Tamoxifen Resistance2015In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 75, no 7, p. 1457-1469Article in journal (Refereed)
    Abstract [en]

    One third of the patients with estrogen receptor alpha (ER alpha)-positive breast cancer who are treated with the antiestrogen tamoxifen will either not respond to initial therapy or will develop drug resistance. Endocrine response involves crosstalk between ER alpha and TGF beta signaling, such that tamoxifen non-responsiveness or resistance in breast cancer might involve aberrant TGF beta signaling. In this study, we analyzed TGF beta receptor type 2 (TGFBR2) expression and correlated it with ER alpha status and phosphorylation in a cohort of 564 patients who had been randomized to tamoxifen or no-adjuvant treatment for invasive breast carcinoma. We also evaluated an additional four independent genetic datasets in invasive breast cancer. In all the cohorts we analyzed, we documented an association of low TGFBR2 protein and mRNA expression with tamoxifen resistance. Functional investigations confirmed that cell cycle or apoptosis responses to estrogen or tamoxifen in ER alpha-positive breast cancer cells were impaired by TGFBR2 silencing, as was ER alpha phosphorylation, tamoxifen-induced transcriptional activation of TGF beta, and upregulation of the multidrug resistance protein ABCG2. Acquisition of low TGFBR2 expression as a contributing factor to endocrine resistance was validated prospectively in a tamoxifen-resistant cell line generated by long-term drug treatment. Collectively, our results established a central contribution of TGF beta signaling in endocrine resistance in breast cancer and offered evidence that TGFBR2 can serve as an independent biomarker to predict treatment outcomes in ER alpha-positive forms of this disease.

  • 124.
    Butwicka, Agnieszka
    et al.
    Karolinska Inst, Sweden; Med Univ Warsaw, Poland.
    Sariaslan, Amir
    Karolinska Inst, Sweden.
    Larsson, Henrik
    Karolinska Inst, Sweden.
    Halfvarson, Jonas
    Orebro Univ, 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.
    Olen, Ola
    Stockholm South Gen Hosp, Sweden; Karolinska Inst, Sweden.
    Frisen, Louise
    Child and Adolescent Psychiat Res Ctr, Sweden; Karolinska Inst, Sweden.
    Lichtenstein, Paul
    Karolinska Inst, Sweden.
    Ludvigsson, Jonas F.
    Karolinska Inst, Sweden; Orebro Univ, Sweden.
    No association between urbanisation, neighbourhood deprivation and IBD: a population-based study of 4 million individuals2019In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 68, no 5, p. 947-948Article in journal (Other academic)
    Abstract [en]

    n/a

  • 125.
    Bögl, Hans Peter
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Gavle Cent Hosp, Sweden.
    Michaelsson, K.
    Uppsala Univ, Sweden.
    Zdolsek, G.
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Hoijer, J.
    Uppsala Univ, Sweden.
    Schilcher, Jörg
    Linköping University, Department of Biomedical and Clinical Sciences, 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.
    Increased rate of reoperation in atypical femoral fractures is related to patient characteristics and not fracture type. A nationwide cohort study2020In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 31, no 5, p. 951-959Article in journal (Refereed)
    Abstract [en]

    Atypical femoral fractures are burdened with a high rate of reoperation. In our nationwide analysis, the increased rate of reoperation was related to patient background characteristics, such as age and health status, rather than fracture type. Introduction Patients with atypical fractures are complex to treat and burdened with a high risk of reoperation. We hypothesized that patients with surgically treated, complete atypical fractures have a higher risk of any reoperation and reoperation related to healing complications than patients with common femoral shaft fractures but that this increase would become insignificant when adjusted for predefined characteristics. Methods A cohort of 163 patients with atypical fractures and 862 patients with common femoral shaft or subtrochanteric fractures treated from 2008 to 2010 and who had follow-up radiographs and register data available until 31 December 2014 was included. Reoperations were identified by a complementary review of radiographs and register data and were used to calculate risks for any reoperation and reoperations related to healing complications. Results Patients with atypical fractures were more likely to be reoperated for any reason, age-adjusted OR 1.76 (95% CI, 1.08 to 2.86). However, patients with common fractures had a shorter follow-up due to a threefold higher death rate. Accordingly, in a multivariable-adjusted time-to-event model, the increased risk lost statistical significance for any reoperations, cause-specific HR 1.34 (95% CI, 0.85 to 2.13), and for reoperations related to healing complications, HR 1.32 (95% CI, 0.58 to 3.0). Continued use of bisphosphonate in the first year after the fracture did not affect the reoperation rate. Conclusions Our findings suggest that the increased risk of reoperation after an atypical femur fracture is largely explained by patient characteristics and not fracture type.

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  • 126.
    Candela-Juan, C.
    et al.
    La Fe University of and Polytech Hospital, Spain; University of Valencia, Spain.
    Karlsson, Mattias
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Lundell, M.
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Ballester, F.
    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. Swedish Radiat Safety Author, Sweden.
    Dosimetric characterization of two radium sources for retrospective dosimetry studies2015In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 42, no 5, p. 2132-2142Article in journal (Refereed)
    Abstract [en]

    Purpose: During the first part of the 20th century, Ra-226 was the most used radionuclide for brachytherapy. Retrospective accurate dosimetry, coupled with patient follow up, is important for advancing knowledge on long-term radiation effects. The purpose of this work was to dosimetrically characterize two Ra-226 sources, commonly used in Sweden during the first half of the 20th century, for retrospective dose-effect studies. Methods: An 8 mg Ra-226 tube and a 10 mg Ra-226 needle, used at Radiumhemmet (Karolinska University Hospital, Stockholm, Sweden), from 1925 to the 1960s, were modeled in two independent Monte Carlo (MC) radiation transport codes: GEANT4 and MCNP5. Absorbed dose and collision kerma around the two sources were obtained, from which the TG-43 parameters were derived for the secular equilibrium state. Furthermore, results from this dosimetric formalism were compared with results from a MC simulation with a superficial mould constituted by five needles inside a glass casing, placed over a water phantom, trying to mimic a typical clinical setup. Calculated absorbed doses using the TG-43 formalism were also compared with previously reported measurements and calculations based on the Sievert integral. Finally, the dose rate at large distances from a Ra-226 point-like-source placed in the center of 1 m radius water sphere was calculated with GEANT4. Results: TG-43 parameters [including gL(r), F(r,theta), Lambda, and s(K)] have been uploaded in spreadsheets as additional material, and the fitting parameters of a mathematical curve that provides the dose rate between 10 and 60 cm from the source have been provided. Results from TG-43 formalism are consistent within the treatment volume with those of a MC simulation of a typical clinical scenario. Comparisons with reported measurements made with thermoluminescent dosimeters show differences up to 13% along the transverse axis of the radium needle. It has been estimated that the uncertainty associated to the absorbed dose within the treatment volume is 10%-15%, whereas uncertainty of absorbed dose to distant organs is roughly 20%-25%. Conclusions: The results provided here facilitate retrospective dosimetry studies of Ra-226 using modern treatment planning systems, which may be used to improve knowledge on long term radiation effects. It is surely important for the epidemiologic studies to be aware of the estimated uncertainty provided here before extracting their conclusions.

  • 127.
    Carlander, Johan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Department of Surgery and Center for Clinical Research Uppsala University.
    Wagner, Philippe
    Department of Surgery and Center for Clinical Research Uppsala University, Västmanland County Hospital, Västerås, Sweden.
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Nordenström, Erik
    Department of Surgery, Lund University Hospital, Malmö, Sweden.
    Jansson, Svante
    Department of Surgery, Sahlgrenska University Hospital Gothenburg, Göteborg, Sweden.
    Bergkvist, Leif
    Department of Surgery and Center for Clinical Research Uppsala University, Västmanland County Hospital, Västerås, Sweden.
    Johansson, Kenth
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Department Surgery, Västervik Hospital, Västervik,Gothenburg, Göteborg, Sweden .
    Risk of Complications with Energy-Based Surgical Devices in Thyroid Surgery: A National Multicenter Register Study2016In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 40, no 1, p. 117-123Article in journal (Refereed)
    Abstract [en]

    Background

    Energy-based surgical devices (EBD) combining cutting and coagulation are increasingly used in thyroid surgery. However, there is a lack of information about potential benefits and risk of complications outside controlled trials. The aims of this national multicenter register study were to describe the use of EDB, their potential effect on complication rates, and on operation time.

    Materials and methods

    The Scandinavian Quality Register for Thyroid and Parathyroid surgery includes 35 surgical units in Sweden and covered 88 % of the thyroid procedures performed during 2008–2009. The use of the EBD was specifically registered for 12 months, and 1297 patients were included. Surgically related complications and operation time were evaluated. The clamp-and-tie group (C-A-T) constituted the control group for comparison with procedures where EBD was used.

    Results

    The thyroid procedures performed included C-A-T (16.6 %), bipolar electrosurgery (ES: 56.5 %), electronic vessel sealing (EVS: 12.2 %), and ultrasonic dissection (UD: 14.5 %). Mean operative time was longer with EVS (p < 0.001) and shorter with UD (p < 0.05) than in the other groups. The bipolar ES group and the EVS group had higher incidence of calcium treatment at discharge and after 6 weeks than the UD group. No significant difference in nerve injury was found between the groups. There was a significant more frequent use of topical hemostatic agents in the EBD group compared to C-A-T.

    Conclusion

    In this national multicenter study, the use of UD shortened and EVS increased operating time. There was a higher risk of calcium treatment at discharge and after 6 weeks after use of EVS and bipolar ES than after UD use. There was a significant more frequent use of topical hemostatic agents in the EBD groups compared to C-A-T.

  • 128.
    Carlfjord, Siw
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsing-Strid, Emma
    University Health Care Research Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Johansson, Kajsa
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Holmgren, Theresa
    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 Orthopaedics in Linköping.
    Öberg, Birgitta
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Practitioner experiences from the structured implementation of evidence-based practice in primary care physiotherapy: A qualitative study2019In: Journal of Evaluation In Clinical Practice, ISSN 1356-1294, E-ISSN 1365-2753, Vol. 25, no 4, p. 622-629Article in journal (Refereed)
    Abstract [en]

    Rationale, Aims, and Objectives

    To provide best available care, the practitioners in primary health care (PHC) must have adequate knowledge about effective interventions. The implementation of such interventions is challenging. A structured implementation strategy developed by researchers at Linköping University, Sweden, was used for the implementation of an evidence‐based assessment and treatment programme for patients with subacromial pain among physiotherapists in PHC. To further develop strategies for implementation of evidence‐based practices, it was deemed important to study the implementation from the practitioners' perspective. The aim of this study was to explore the practitioners' experiences from the implementation.

    Methods

    A qualitative design with focus group discussions was applied. The implementation in terms of perceptions of process and outcome was evaluated by focus group discussions with, in total, 16 physiotherapists in the target group. Data were analysed using the method qualitative content analysis.

    Results

    The components of the strategy were viewed positively, and the applicability and evidence base behind the programme were appreciated. The programme was perceived to be adopted, and the practitioners described a changed behaviour and increased confidence in handling patients with subacromial pain. Both patient‐ and provider‐related challenges to the implementation were mentioned.

    Conclusions

    The practitioners' experiences from the implementation were mainly positive. A strategy with collaboration between academy and practice, and with education and implementation teams as facilitators, resulted in changes in practice. Critical voices concerned interprofessional collaboration and that the programme was focused explicitly on the shoulder, not including other components of physical function.

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  • 129.
    Carlsson, Per
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Sjödahl, Rune
    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.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Robotassisterad kirurgi ökar – trots osäker kostnadseffektivitet2016In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 113, no 48, p. 1-5Article, review/survey (Refereed)
  • 130.
    Carlsson Tedgren, Åsa
    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 Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Karolinska University Hospital, Sweden.
    Plamondon, Mathieu
    CHU Quebec, Canada; CHU Quebec, Canada; University of Laval, Canada; University of Laval, Canada.
    Beaulieu, Luc
    CHU Quebec, Canada; CHU Quebec, Canada; University of Laval, Canada; University of Laval, Canada.
    The collapsed cone algorithm for Ir-192 dosimetry using phantom-size adaptive multiple-scatter point kernels2015In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 60, no 13, p. 5313-5323Article in journal (Refereed)
    Abstract [en]

    The aim of this work was to investigate how dose distributions calculated with the collapsed cone (CC) algorithm depend on the size of the water phantom used in deriving the point kernel for multiple scatter. A research version of the CC algorithm equipped with a set of selectable point kernels for multiple-scatter dose that had initially been derived in water phantoms of various dimensions was used. The new point kernels were generated using EGSnrc in spherical water phantoms of radii 5 cm, 7.5 cm, 10 cm, 15 cm, 20 cm, 30 cm and 50 cm. Dose distributions derived with CC in water phantoms of different dimensions and in a CT-based clinical breast geometry were compared to Monte Carlo (MC) simulations using the Geant4-based brachytherapy specific MC code Algebra. Agreement with MC within 1% was obtained when the dimensions of the phantom used to derive the multiple-scatter kernel were similar to those of the calculation phantom. Doses are overestimated at phantom edges when kernels are derived in larger phantoms and underestimated when derived in smaller phantoms (by around 2% to 7% depending on distance from source and phantom dimensions). CC agrees well with MC in the high dose region of a breast implant and is superior to TG43 in determining skin doses for all multiple-scatter point kernel sizes. Increased agreement between CC and MC is achieved when the point kernel is comparable to breast dimensions. The investigated approximation in multiple scatter dose depends on the choice of point kernel in relation to phantom size and yields a significant fraction of the total dose only at distances of several centimeters from a source/implant which correspond to volumes of low doses. The current implementation of the CC algorithm utilizes a point kernel derived in a comparatively large (radius 20 cm) water phantom. A fixed point kernel leads to predictable behaviour of the algorithm with the worst case being a source/implant located well within a patient/phantom for which low doses at phantom edges can be overestimated by 2-5 %. It would be possible to improve the situation by using a point kernel for multiple-scatter dose adapted to the patient/phantom dimensions at hand.

  • 131.
    Casado Bedmar, Maria Teresa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Heil, Stéphanie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    Söderholm, Johan D
    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.
    Keita, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Upregulation of intestinal mucosal mast cells expressing VPAC1 in close proximity to vasoactive intestinal polypeptide in inflammatory bowel disease and murine colitis2019In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 31, no 3, article id e13503Article in journal (Refereed)
    Abstract [en]

    Background

    Mast cells (MCs) and vasoactive intestinal polypeptide (VIP) have been proposed as regulators of the intestinal barrier and inflammation. Our aim was to map the distribution in inflammatory bowel disease (IBD) and murine colitis.

    Methods

    MCs, VIP, and VIP‐receptors (VPACs) were quantified by immunofluorescence and enzyme‐immunoassay (EIA) in ileal tissues (villus epithelium (VE) and adjacent VE, ie, VE next to the follicle‐associated epithelium, (FAE)) from Crohn's disease (CD; n = 16) and non‐IBD patients, and in colonic specimens of ulcerative colitis (UC; n = 12) and healthy controls (HCs). In addition, VIP levels were measured in plasma from HCs, non‐IBD, and IBD in remission (CD n = 30; UC n = 30). Colon, ileum, and plasma from mice with dextran sulfate sodium (DSS)‐induced colitis and control mice were analyzed likewise.

    Key Results

    FAE‐adjacent VE in ileum of CD possessed more MCs (P < 0.05) and MCs expressing VPAC1 (P < 0.05), but not VPAC2, compared to controls. Both adjacent and regular VE of CD had more MCs co‐localizing/in close proximity to VIP (P < 0.05). In UC colon, more MCs (P < 0.0005), MCs close to VIP (P < 0.0005), and MCs expressing VPAC1 (P < 0.05) were found compared to controls. VIP levels were elevated in plasma from CD and UC compared to controls (P < 0.0005). Colon of DSS mice showed more MCs and MCs close to VIP (P < 0.05) compared to control mice. In vitro experiments revealed MCs expressing VPACs and internalized VIP after 120 minutes of VIP‐stimulation.

    Conclusions and Inferences

    Communication between MCs and VIP is upregulated during IBD and mice colitis. In CD patients, the epithelium next to FAE seems to be more involved than the surrounding VE, suggesting increased MC‐VIP‐interactions in this intestinal region.

  • 132.
    Chen, Ke-Ling
    et al.
    Sichuan University, Peoples R China.
    Lv, Zhao-Ying
    Sichuan University, Peoples R China.
    Yang, Hong-Wei
    Sichuan University, Peoples R China.
    Liu, Yong
    Sichuan University, Peoples R China.
    Long, Fei-Wu
    Sichuan University, Peoples R China.
    Zhou, Bin
    Sichuan University, Peoples R China.
    Sun, Xiao-Feng
    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. Sichuan University, Peoples R China.
    Peng, Zhi-Hai
    Shanghai Jiao Tong University, Peoples R China.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China.
    Li, Yuan
    Sichuan University, Peoples R China.
    Effects of Tocilizumab on Experimental Severe Acute Pancreatitis and Associated Acute Lung Injury2016In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 44, no 8, p. E664-E677Article in journal (Refereed)
    Abstract [en]

    Objective: To examine the therapeutic effects of tocilizumab, an antibody against interleukin-6 receptor, on experimental severe acute pancreatitis and associated acute lung injury. The optimal dose of tocilizumab and the activation of interleukin-6 inflammatory signaling were also investigated. Design: Randomized experiment. Setting: Research laboratory at a university hospital. Subject: Experimental severe acute pancreatitis in rats. Interventions: Severe acute pancreatitis was induced by retrograde injection of sodium taurocholate (50 mg/kg) into the biliopancreatic duct. In dose-study, rats were administered with different doses of tocilizumab (1, 2, 4, 8, and 16 mg/kg) through the tail vein after severe acute pancreatitis induction. In safety-study, rats without severe acute pancreatitis induction were treated with high doses of tocilizumab (8, 16, 32, and 64 mg/kg). Serum and tissue samples of rats in time-study were collected for biomolecular and histologic evaluations at different time points (2, 6, 12, 18, and 24 hr). Measurements and Main Results: 1) Under the administration of tocilizumab, histopathological scores of pancreas and lung were decreased, and severity parameters related to severe acute pancreatitis and associated lung injury, including serum amylase, C-reactive protein, lung surfactant protein level, and myeloperoxidase activity, were all significant alleviated in rat models. 2) Dose-study demonstrated that 2 mg/kg tocilizumab was the optimal treatment dose. 3) Basing on multi-organ pathologic evaluation, physiological and biochemical data, no adverse effect and toxicity of tocilizumab were observed in safety-study. 4) Pancreatic nuclear factor-kappa B and signal transducer and activator of transcription 3 were deactivated, and the serum chemokine (C-X-C motif) ligand 1 was down-regulated after tocilizumab administration. Conclusions: Our study demonstrated tocilizumab, as a marketed drug commonly used for immune-mediated diseases, was safe and effective for the treatment of experimental severe acute pancreatitis and associated acute lung injury. Our findings provide experimental evidences for potential clinical application of tocilizumab in severe acute pancreatitis and associated complications.

  • 133.
    Cheng, Dantong
    et al.
    Shanghai Jiao Tong University, Peoples R China.
    Zhao, Senlin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Shanghai Jiao Tong University, Peoples R China.
    Tang, Huamei
    Shanghai Jiao Tong University, Peoples R China.
    Zhang, Dongyuan
    Shanghai Jiao Tong University, Peoples R China.
    Sun, Hongcheng
    Shanghai Jiao Tong University, Peoples R China.
    Yu, Fudong
    Shanghai Jiao Tong University, Peoples R China.
    Jiang, Weiliang
    Shanghai Jiao Tong University, Peoples R China.
    Yue, Ben
    Shanghai Jiao Tong University, Peoples R China.
    Wang, Jingtao
    Shanghai Jiao Tong University, Peoples R China.
    Zhang, Meng
    Fudan University, Peoples R China.
    Yu, Yang
    Shanghai Jiao Tong University, Peoples R China.
    Liu, Xisheng
    Shanghai Jiao Tong University, Peoples R China.
    Sun, Xiao-Feng
    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.
    Zhou, Zongguang
    Sichuan University, Peoples R China.
    Qin, Xuebin
    Temple University, PA 19122 USA.
    Zhang, Xin
    Zhejiang Prov Peoples Hospital, Peoples R China.
    Yan, Dongwang
    Shanghai Jiao Tong University, Peoples R China.
    Wen, Yugang
    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. Shanghai Jiao Tong University, Peoples R China.
    Peng, Zhihai
    Shanghai Jiao Tong University, Peoples R China.
    MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad42016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 29, p. 45199-45213Article in journal (Refereed)
    Abstract [en]

    Background: Tumor metastasis is one of the leading causes of poor prognosis for colorectal cancer (CRC) patients. Loss of Smad4 contributes to aggression process in many human cancers. However, the underlying precise mechanism of aberrant Smad4 expression in CRC development is still little known. Results: miR-20a-5p negatively regulated Smad4 by directly targeting its 3UTR in human colorectal cancer cells. miR-20a-5p not only promoted CRC cells aggression capacity in vitro and liver metastasis in vivo, but also promoted the epithelial-to-mesenchymal transition process by downregulating Smad4 expression. In addition, tissue microarray analysis obtained from 544 CRC patients clinical characters showed that miR-20a-5p was upregulated in human CRC tissues, especially in the tissues with metastasis. High level of miR-20a-5p predicted poor prognosis in CRC patients. Methods: Five miRNA target prediction programs were applied to identify potential miRNA(s) that target(s) Smad4 in CRC. Luciferase reporter assay and transfection technique were used to validate the correlation between miR-20a-5p and Smad4 in CRC. Wound healing, transwell and tumorigenesis assays were used to explore the function of miR-20a-5p and Smad4 in CRC progression in vitro and in vivo. The association between miR-20a-5p expression and the prognosis of CRC patients was evaluated by Kaplan-Meier analysis and multivariate cox proportional hazard analyses based on tissue microarray data. Conclusions: miR-20a-5p, as an onco-miRNA, promoted the invasion and metastasis ability by suppressing Smad4 expression in CRC cells, and high miR-20a-5p predicted poor prognosis for CRC patients, providing a novel and promising therapeutic target in human colorectal cancer.

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  • 134.
    Christerson, Ulrika
    et al.
    Linnaeus Univ, Sweden.
    Keita, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Tinnerfelt Winberg, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Söderholm, Johan D
    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.
    Gustafson-Svard, Christina
    Linnaeus Univ, Sweden.
    Possible Involvement of Intracellular Calcium-Independent Phospholipase A2 in the Release of Secretory Phospholipases from Mast Cells: Increased Expression in Ileal Mast Cells of Crohns Disease2019In: CELLS, ISSN 2073-4409, Vol. 8, no 7, article id 672Article in journal (Refereed)
    Abstract [en]

    Increased activity of secretory phospholipases A(2) (sPLA(2)) type-II was previously observed in ileum of Crohns disease (CD). Our aims were to explore the involvement of calcium-independent (i)PLA(2 beta) in the release of sPLA(2)s from the human mast cell (MC) line (HMC-1) and investigate expressions of cytosolic (c)PLA(2) alpha, iPLA(2)beta, sPLA(2)-IIA and sPLA(2)-V in MCs of CD ileum. The release of sPLA(2) was investigated in HMC-1 by immunocytochemistry and ELISA. The expression intensities of PLA(2)s in mucosal MCs, and the proportion of PLA(2)-positive MCs, were investigated in normal ileum and in ileum from patients with CD by immunohistochemistry. The calcium ionophore-stimulated release of sPLA(2)-IIA and sPLA(2)-V from HMC-1 was reduced by the iPLA(2)-inhibitor bromoenol lactone. All four PLA(2)s were detectable in mucosal MCs, both in normal ileum and in CD, but the proportion of iPLA(2)beta-containing mucosal MCs and the expression intensity of sPLA(2)-IIA was increased in CD. Results indicate that iPLA(2)beta is involved in the secretion of sPLA(2)s from HMC-1, and suggest that iPLA(2)beta-mediated release of sPLA(2) from intestinal MCs may contribute to CD pathophysiology. Ex vivo studies on isolated mucosal mast cells are however needed to clarify the precise role of MC PLA(2)s in the inflammatory processes of CD.

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  • 135.
    Christofer Juhlin, C.
    et al.
    Yale University, CT 06520 USA; Yale University, CT 06520 USA; Karolinska Institute, Sweden.
    Stenman, Adam
    Karolinska Institute, Sweden.
    Haglund, Felix
    Karolinska Institute, Sweden.
    Clark, Victoria E.
    Yale University, CT 06520 USA.
    Brown, Taylor C.
    Yale University, CT 06520 USA; Yale University, CT 06520 USA.
    Baranoski, Jacob
    Yale University, CT 06520 USA.
    Bilguvar, Kaya
    Yale University, CT 06520 USA; Yale University, CT 06520 USA.
    Goh, Gerald
    Yale University, CT 06520 USA; Yale University, CT 06520 USA.
    Welander, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Svahn, Fredrika
    Karolinska Institute, Sweden.
    Rubinstein, Jill C.
    Yale University, CT 06520 USA; Yale University, CT 06520 USA.
    Caramuta, Stefano
    Karolinska Institute, Sweden.
    Yasuno, Katsuhito
    Yale University, CT 06520 USA.
    Guenel, Murat
    Yale University, CT 06520 USA.
    Backdahl, Martin
    Karolinska Institute, Sweden.
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    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.
    Prasad, Manju L.
    Yale University, CT 06520 USA.
    Korah, Reju
    Yale University, CT 06520 USA; Yale University, CT 06520 USA.
    Lifton, Richard P.
    Yale University, CT 06520 USA; Yale University, CT 06520 USA; Yale Centre Mendelian Genom, CT USA.
    Carling, Tobias
    Yale University, CT 06520 USA; Yale University, CT 06520 USA.
    Whole-exome sequencing defines the mutational landscape of pheochromocytoma and identifies KMT2D as a recurrently mutated gene2015In: Genes, Chromosomes and Cancer, ISSN 1045-2257, E-ISSN 1098-2264, Vol. 54, no 9, p. 542-554Article in journal (Refereed)
    Abstract [en]

    As subsets of pheochromocytomas (PCCs) lack a defined molecular etiology, we sought to characterize the mutational landscape of PCCs to identify novel gene candidates involved in disease development. A discovery cohort of 15 PCCs wild type for mutations in PCC susceptibility genes underwent whole-exome sequencing, and an additional 83 PCCs served as a verification cohort for targeted sequencing of candidate mutations. A low rate of nonsilent single nucleotide variants (SNVs) was detected (6.1/sample). Somatic HRAS and EPAS1 mutations were observed in one case each, whereas the remaining 13 cases did not exhibit variants in established PCC genes. SNVs aggregated in apoptosis-related pathways, and mutations in COSMIC genes not previously reported in PCCs included ZAN, MITF, WDTC1, and CAMTA1. Two somatic mutations and one constitutional variant in the well-established cancer gene lysine (K)-specific methyltransferase 2D (KMT2D, MLL2) were discovered in one sample each, prompting KMT2D screening using focused exome-sequencing in the verification cohort. An additional 11 PCCs displayed KMT2D variants, of which two were recurrent. In total, missense KMT2D variants were found in 14 (11 somatic, two constitutional, one undetermined) of 99 PCCs (14%). Five cases displayed somatic mutations in the functional FYR/SET domains of KMT2D, constituting 36% of all KMT2D-mutated PCCs. KMT2D expression was upregulated in PCCs compared to normal adrenals, and KMT2D overexpression positively affected cell migration in a PCC cell line. We conclude that KMT2D represents a recurrently mutated gene with potential implication for PCC development. (c) 2015 The Authors. Genes, Chromosomes and Cancer Published by Wiley Periodicals, Inc.

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  • 136.
    Cibula, David
    et al.
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    Poetter, Richard
    Med Univ Vienna, Austria.
    Planchamp, Francois
    Inst Bergoni, France.
    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.
    Fischerova, Daniela
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    Haie-Meder, Christine
    Inst Gustave Roussy, France.
    Koehler, Christhardt
    Asklepios Hambourg Altona and Univ Cologne, Germany.
    Landoni, Fabio
    Univ Milano Bicocca, Italy.
    Lax, Sigurd
    Gen Hosp Graz Sued West, Austria.
    Lindegaard, Jacob Christian
    Aarhus Univ, Denmark.
    Mahantshetty, Umesh
    Tata Mem Hosp, India.
    Mathevet, Patrice
    Lausanne Univ, Switzerland.
    McCluggage, W. Glenn
    Belfast Hlth and Social Care Trust, North Ireland.
    McCormack, Mary
    Univ Coll London Hosp, England.
    Naik, Raj
    Queen Elizabeth Hosp, England.
    Nout, Remi
    Leiden Univ, Netherlands.
    Pignata, Sandro
    IRCCS, Italy.
    Ponce, Jordi
    Univ Hosp Bellvitge IDIBELL, Spain.
    Querleu, Denis
    Inst Bergoni, France.
    Raspagliesi, Francesco
    Fdn IRCCS Ist Nazl Tumori, Italy.
    Rodolakis, Alexandros
    Univ Athens, Greece.
    Tamussino, Karl
    Med Univ Graz, Austria.
    Wimberger, Pauline
    Dresden Univ, Germany.
    Raspollini, Maria Rosaria
    Univ Hosp, Italy.
    Correction: The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology Guidelines for the Management of Patients with Cervical Cancer (vol 472, pg 919, 2018)2018In: Virchows Archiv, ISSN 0945-6317, E-ISSN 1432-2307, Vol. 472, no 6, p. 937-938Article in journal (Other academic)
    Abstract [en]

    n/a

  • 137.
    Cibula, David
    et al.
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    Poetter, Richard
    Med Univ Vienna, Austria.
    Planchamp, Francois
    Inst Bergonie, France.
    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.
    Fischerova, Daniela
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    Haie-Meder, Christine
    Inst Gustave Roussy, France.
    Koehler, Christhardt
    Asklepios Hambourg Altona, Germany; Univ Cologne, Germany.
    Landoni, Fabio
    Univ Milano Bicocca, Italy.
    Lax, Sigurd
    Gen Hosp Graz Sued West, Austria.
    Lindegaard, Jacob Christian
    Aarhus Univ, Denmark.
    Mahantshetty, Umesh
    Tata Mem Hosp, India.
    Mathevet, Patrice
    Lausanne Univ, Switzerland.
    McCluggage, W. Glenn
    Belfast Hlth and Social Care Trust, North Ireland.
    McCormack, Mary
    Univ Coll London Hosp, England.
    Naik, Raj
    Queen Elizabeth Hosp, England.
    Nout, Remi
    Leiden Univ, Netherlands.
    Pignata, Sandro
    IRCCS, Italy.
    Ponce, Jordi
    Univ Hosp Bellvitge IDIBELL, Spain.
    Querleu, Denis
    Inst Bergonie, France.
    Raspagliesi, Francesco
    Fdn IRCCS Ist Nazl Tumori, Italy.
    Rodolakis, Alexandros
    Univ Athens, Greece.
    Tamussino, Karl
    Med Univ Graz, Austria.
    Wimberger, Pauline
    Dresden Univ, Germany.
    Raspollini, Maria Rosaria
    Univ Hosp, Italy.
    Correction to: Correction: The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology Guidelines for the Management of Patients with Cervical Cancer (vol 472, pg 919, 2018)2018In: Virchows Archiv, ISSN 0945-6317, E-ISSN 1432-2307, Vol. 473, no 3, p. 391-391Article in journal (Other academic)
    Abstract [en]

    n/a

  • 138.
    Cibula, David
    et al.
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    Poetter, Richard
    Med Univ Vienna, Austria.
    Planchamp, Francois
    Inst Bergoni, France.
    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.
    Fischerova, Daniela
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    Haie-Meder, Christine
    Inst Gustave Roussy, France.
    Koehler, Christhardt
    Asklepios Hambourg Altona and Univ Cologne, Germany.
    Landoni, Fabio
    Univ Milano Bicocca, Italy.
    Lax, Sigurd
    Gen Hosp Graz Sued West, Austria.
    Lindegaard, Jacob Christian
    Aarhus Univ, Denmark.
    Mahantshetty, Umesh
    Tata Mem Hosp, India.
    Mathevet, Patrice
    Lausanne Univ, Switzerland.
    McCluggage, W. Glenn
    Belfast Hlth and Social Care Tmst, North Ireland.
    McCormack, Mary
    Univ Coll London Hosp, England.
    Naik, Raj
    Queen Elizabeth Hosp, England.
    Nout, Remi
    Leiden Univ, Netherlands.
    Pignata, Sandro
    IRCCS, Italy.
    Ponce, Jordi
    Univ Hosp Bellvitge IDIBELL, Spain.
    Querleu, Denis
    Inst Bergoni, France.
    Raspagliesi, Francesco
    Fdn IRCCS Ist Nazl Tumori, Italy.
    Rodolakis, Alexandros
    Univ Athens, Greece.
    Tamussino, Karl
    Med Univ Graz, Austria.
    Wimberger, Pauline
    Dresden Univ, Germany.
    Raspollini, Maria Rosaria
    Univ Hosp, Italy.
    The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology Guidelines for the Management of Patients with Cervical Cancer2018In: Virchows Archiv, ISSN 0945-6317, E-ISSN 1432-2307, Vol. 472, no 6, p. 919-936Article in journal (Refereed)
    Abstract [en]

    The European Society of Gynecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) jointly develop clinically relevant and evidence-based guidelines in order to improve the quality of care for women with cervical cancer across Europe and worldwide. The ESGO/ESTRO/ESP nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of cervical cancer (23 experts across Europe). To ensure that the guidelines are evidence based, the current literature identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 159 international reviewers, selected through ESGO/ESTRO/ESP and including patient representatives. The guidelines cover comprehensively staging, management, and follow-up for patients with cervical cancer. Management includes fertility sparing treatment; stage T1a, T1b1/T2a1, clinically occult cervical cancer diagnosed after simple hysterectomy; early and locally advanced cervical cancer; primary distant metastatic disease; cervical cancer in pregnancy; and recurrent disease. Principles of radiotherapy and pathological evaluation are defined.

  • 139.
    Cibula, David
    et al.
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    Poetter, Richard
    Med Univ Vienna, Austria.
    Planchamp, Francois
    Inst Bergonie, France.
    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.
    Fischerova, Daniela
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    Meder, Christine Haie
    Inst Gustave Roussy, France.
    Koehler, Christhardt
    Asklepios Hambourg Altona, Germany; Univ Cologne, Germany.
    Landoni, Fabio
    Univ Milano Bicocca, Italy.
    Lax, Sigurd
    Gen Hosp Graz Sued West, Austria.
    Lindegaard, Jacob Christian
    Aarhus Univ, Denmark.
    Mahantshetty, Umesh
    Tata Mem Hosp, India.
    Mathevet, Patrice
    Lausanne Univ, Switzerland.
    McCluggage, W. Glenn
    Belfast Hlth and Social Care Trust, North Ireland.
    McCormack, Mary
    Univ Coll London Hosp, England.
    Naik, Raj
    Queen Elizabeth Hosp, England.
    Nout, Remi
    Leiden Univ, Netherlands.
    Pignata, Sandro
    Ist Nazl Studio and Cura Tumori, Italy.
    Ponce, Jordi
    Univ Hosp Bellvitge IDIBELL, Spain.
    Querleu, Denis
    Inst Bergonie, France.
    Raspagliesi, Francesco
    Not Found:[Cibula, David; Fischerova, Daniela] Charles Univ Prague, Fac Med 1, Gynecol Oncol Ctr, Dept Obstet and Gynecol, Prague, Czech Republic; [Cibula, David; Fischerova, Daniela] Gen Univ Hosp, Prague, Czech Republic; [Poetter, Richard] Med Univ Vienna, Dept Radiotherapy, Vienna, Austria; [Planchamp, Francois; Querleu, Denis] Inst Bergonie, Bordeaux, France; [Avall-Lundqvist, Elisabeth] Linkoping Univ, Linkoping, Sweden; [Meder, Christine Haie] Inst Gustave Roussy, Dept Radiotherapy, Villejuif, France; [Koehler, Christhardt] Asklepios Hambourg Altona, Hamburg, Germany; [Koehler, Christhardt] Univ Cologne, Med Fac, Dept Gynecol, Cologne, Germany; [Landoni, Fabio] Univ Milano Bicocca, Monza, Italy; [Lax, Sigurd] Gen Hosp Graz Sued West, Graz, Austria; [Lindegaard, Jacob Christian] Aarhus Univ, Dept Oncol, Aarhus, Denmark; [Mahantshetty, Umesh] Tata Mem Hosp, Dept Radiat Oncol, Mumbai, Maharashtra, India; [Mathevet, Patrice] Lausanne Univ, Lausanne, Switzerland; [McCluggage, W. Glenn] Belfast Hlth and Social Care Trust, Dept Pathol, Belfast, Antrim, North Ireland; [McCormack, Mary] Univ Coll London Hosp, London, England; [Naik, Raj] Queen Elizabeth Hosp, Gateshead, England; [Nout, Remi] Leiden Univ, Dept Radiat Oncol, Leiden, Netherlands; [Pignata, Sandro] Ist Nazl Studio and Cura Tumori, IRCCS, Fdn G Pascale, Naples, Italy; [Ponce, Jordi] Univ Hosp Bellvitge IDIBELL, Barcelona, Spain; [Rodolakis, Alexandros] Ist Nazl Tumori, Fdn IRCCS, Milan, Italy; [Tamussino, Karl] Univ Athens, Athens, Greece; [Wimberger, Pauline] Med Univ Graz, Graz, Austria; [Wimberger, Pauline] Dresden Univ, TU Dresden, Dresden, Germany; [Raspollini, Maria Rosaria] Univ Hosp, Florence, Italy;.
    Rodolakis, Alexandros
    Ist Nazl Tumori, Italy.
    Tamussino, Karl
    Univ Athens, Greece.
    Wimberger, Pauline
    Med Univ Graz, Austria; Dresden Univ, Germany.
    Raspollini, Maria Rosaria
    Univ Hosp, Italy.
    The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology Guidelines for the Management of Patients With Cervical Cancer2018In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 28, no 4, p. 641-655Article in journal (Refereed)
    Abstract [en]

    Background Despite significant advances in the screening, detection, and treatment of preinvasive cervical lesions, invasive cervical cancer is the fifth most common cancer in European women. There are large disparities in Europe and worldwide in the incidence, management, and mortality of cervical cancer. Objective The European Society of Gynaecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) jointly develop clinically relevant and evidence-based guidelines in order to improve the quality of care for women with cervical cancer across Europe and worldwide. Methods The ESGO/ESTRO/ESP nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of cervical cancer (23 experts across Europe). To ensure that the guidelines are evidence based, the current literature identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 159 international reviewers, selected through ESGO/ESTRO/ESP and including patient representatives. Results The guidelines cover comprehensively staging, management, and follow-up for patients with cervical cancer. Management includes fertility sparing treatment; stage T1a, T1b1/T2a1, clinically occult cervical cancer diagnosed after simple hysterectomy; early and locally advanced cervical cancer; primary distant metastatic disease; cervical cancer in pregnancy; and recurrent disease. Principles of radiotherapy and pathological evaluation are defined.

  • 140.
    Cibula, David
    et al.
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    Poetter, Richard
    Med Univ Vienna, Austria.
    Planchamp, Francois
    Inst Bergonie, France.
    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.
    Fischerova, Daniela
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    Meder, Christine Haie
    Inst Gustave Roussy, France.
    Koehler, Christhardt
    Asklepios Hambourg Altona, Germany; Univ Cologne, Germany.
    Landoni, Fabio
    Univ Milano Bicocca, Italy.
    Lax, Sigurd
    Gen Hosp Graz Sued West, Austria.
    Lindegaard, Jacob Christian
    Aarhus Univ, Denmark.
    Mahantshetty, Umesh
    Tata Mem Hosp, India.
    Mathevet, Patrice
    Lausanne Univ, Switzerland.
    McCluggage, W. Glenn
    Belfast Hlth and Social Care Trust, North Ireland.
    McCormack, Mary
    Univ Coll Hosp London, England.
    Naik, Raj
    Queen Elizabeth Hosp, England.
    Nout, Remi
    Leiden Univ, Netherlands.
    Pignata, Sandro
    IRCCS, Italy.
    Ponce, Jordi
    Univ Hosp Bellvitge IDIBELL, Spain.
    Querleu, Denis
    Inst Bergonie, France.
    Raspagliesi, Francesco
    Fdn IRCCS Ist Nazl Tumori, Italy.
    Rodolakis, Alexandros
    Univ Athens, Greece.
    Tamussino, Karl
    Med Univ Graz, Austria.
    Wimberger, Pauline
    Tech Univ Dresden, Germany.
    Raspollini, Maria Rosaria
    Univ Hosp, Italy.
    The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology guidelines for the management of patients with cervical cancer2018In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 127, no 3, p. 404-416Article in journal (Refereed)
    Abstract [en]

    Background: Despite significant advances in the screening, detection, and treatment of preinvasive cervical lesions, invasive cervical cancer is the fifth most common cancer in European women. There are large disparities in Europe and worldwide in the incidence, management, and mortality of cervical cancer. Objective: The European Society of Gynaecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) jointly develop clinically relevant and evidence-based guidelines in order to improve the quality of care for women with cervical cancer across Europe and worldwide. Methods: The ESGO/ESTRO/ESP nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of cervical cancer (23 experts across Europe). To ensure that the guidelines are evidence based, the current literature identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 159 international reviewers, selected through ESGO/ESTRO/ESP and including patient representatives. Results: The guidelines cover comprehensively staging, management, and follow-up for patients with cervical cancer. Management includes fertility sparing treatment; stage T1a, T1b1/T2a1, clinically occult cervical cancer diagnosed after simple hysterectomy; early and locally advanced cervical cancer; primary distant metastatic disease; cervical cancer in pregnancy; and recurrent disease. Principles of radiotherapy and pathological evaluation are defined. (C) 2018 European Society for Gynaecological Oncology, European Society for Radiotherapy and Oncology, and the European Society of Pathology. Published by Elsevier B.V. All rights reserved.

  • 141.
    Clark-Snow, Rebecca A.
    et al.
    Univ Kansas, KS 66205 USA.
    Vidall, Cheryl
    Alcura UK Ltd, England.
    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.
    Jahn, Patrick
    Univ Hosp Halle, Germany.
    Fixed Combination Antiemetic A literature review on prevention of chemotherapy-induced nausea and vomiting using netupitant/palonosetron2018In: Clinical Journal of Oncology Nursing, ISSN 1092-1095, E-ISSN 1538-067X, Vol. 22, no 2, p. E52-E63Article, review/survey (Refereed)
    Abstract [en]

    BACKGROUND: Prevention of chemotherapy-induced nausea and vomiting (CINV) can be improved with guideline-consistent use of antiemetics. However, adherence to antiemetic guidelines remains often insufficient. Therefore, new strategies that improve adherence are needed. OBJECTIVES: To review the latest antiemetic guideline recommendations and provide an update on the use of NEPA, a fixed combination antiemetic composed of the neurokinin-1 receptor antagonist (RA) netupitant and the 5-hydroxytryptamine-3 RA palonosetron (Akynzeo (R)). METHODS: Analysis of the literature was performed, including guidelines, published literature, congress data on NEPA, and relevant articles on CINV. FINDINGS: Nurses are in a unique position to promote guideline-consistent antiemetic prophylaxis and are central in the education of patients and caregivers. Thus, nurses continuous education on antiemetic treatments is key for the prevention and management of CINV. NEPA offers a simplified antiemetic therapy with the potential to increase guideline adherence.

  • 142.
    Covarrubias, Yesenia
    et al.
    Univ Calif San Diego, CA 92093 USA.
    Fowler, Kathryn J.
    Univ Calif San Diego, CA 92093 USA.
    Mamidipalli, Adrija
    Univ Calif San Diego, CA 92093 USA.
    Hamilton, Gavin
    Univ Calif San Diego, CA 92093 USA.
    Wolfson, Tanya
    Univ Calif San Diego, CA 92093 USA.
    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). AMRA Med AB, Linkoping, Sweden.
    Jacobsen, Garth
    Univ Calif San Diego, CA 92093 USA.
    Horgan, Santiago
    Univ Calif San Diego, CA 92093 USA.
    Schwimmer, Jeffrey B.
    Univ Calif San Diego, CA 92093 USA; Rady Childrens Hosp San Diego, CA USA.
    Reeder, Scott B.
    Univ Wisconsin, WI 53706 USA; Univ Wisconsin, WI 53706 USA; Univ Wisconsin, WI USA; Univ Wisconsin, WI USA.
    Sirlin, Claude B.
    Univ Calif San Diego, CA 92093 USA.
    Pilot study on longitudinal change in pancreatic proton density fat fraction during a weight-loss surgery program in adults with obesity2019In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 50, no 4, p. 1092-1102Article in journal (Refereed)
    Abstract [en]

    Background Quantitative-chemical-shift-encoded (CSE)-MRI methods have been applied to the liver. The feasibility and potential utility CSE-MRI in monitoring changes in pancreatic proton density fat fraction (PDFF) have not yet been demonstrated. Purpose To use quantitative CSE-MRI to estimate pancreatic fat changes during a weight-loss program in adults with severe obesity and nonalcoholic fatty liver disease (NAFLD). To explore the relationship of reduction in pancreatic PDFF with reductions in anthropometric indices. Study Type Prospective/longitudinal. Population Nine adults with severe obesity and NAFLD enrolled in a weight-loss program. Field Strength/Sequence CSE-MRI fat quantification techniques and multistation-volumetric fat/water separation techniques were performed at 3 T. Assessment PDFF values were recorded from parametric maps colocalized across timepoints. Statistical Tests Rates of change of log-transformed variables across time were determined (linear-regression), and their significance assessed compared with no change (Wilcoxon test). Rates of change were correlated pairwise (Spearmans correlation). Results Mean pancreatic PDFF decreased by 5.7% (range 0.7-17.7%) from 14.3 to 8.6%, hepatic PDFF by 11.4% (2.6-22.0%) from 14.8 to 3.4%, weight by 30.9 kg (17.3-64.2 kg) from 119.0 to 88.1 kg, body mass index by 11.0 kg/m(2) (6.3-19.1 kg/m(2)) from 44.1 to 32.9 kg/m(2), waist circumference (WC) by 25.2 cm (4.0-41.0 cm) from 133.1 to 107.9 cm, HC by 23.5 cm (4.5-47.0 cm) from 135.8 to 112.3 cm, visceral adipose tissue (VAT) by 2.9 L (1.7-5.7 L) from 7.1 to 4.2 L, subcutaneous adipose tissue (SCAT) by 4.0 L (2.9-7.4 L) from 15.0 to 11.0 L. Log-transformed rate of change for pancreatic PDFF was moderately correlated with log-transformed rates for hepatic PDFF, VAT, SCAT, and WC (rho = 0.5, 0.47, 0.45, and 0.48, respectively), although not statistically significant. Data Conclusion Changes in pancreatic PDFF can be estimated by quantitative CSE-MRI in adults undergoing a weight-loss surgery program. Pancreatic and hepatic PDFF and anthropometric indices decreased significantly. Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019;50:1092-1102.

  • 143.
    Czerw, Tomasz
    et al.
    Maria Sklodowska Curie Mem Cancer Centre, Poland; Institute Oncol, Poland.
    Labopin, Myriam
    Hop St Antoine, France; INSERM, France; University of Paris 06, France.
    Schmid, Christoph
    University of Munich, Germany.
    Cornelissen, Jan J.
    Erasmus University, Netherlands.
    Chevallier, Patrice
    CHU Nantes, France.
    Blaise, Didier
    Institute J Paoli I Calmettes, France.
    Kuball, Juergen
    University of Medical Centre, Netherlands.
    Vigouroux, Stephane
    Hop Haut Leveque, France.
    Garban, Frederic
    Hop A Michallon, France.
    Lioure, Bruno
    Nouvel Hop Civil, France.
    Fegueux, Nathalie
    CHU Lapeyronie, France.
    Clement, Laurence
    Centre Hospital University of CHU Nancy, France.
    Sandstedt, Anna
    Linköping University, Department of Social and Welfare Studies. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Maertens, Johan
    University Hospital Gasthuisberg, Belgium.
    Guillerm, Gaelle
    CHU Morvan, France.
    Bordessoule, Dominique
    CHRU Limoges, France.
    Mohty, Mohamad
    Hop St Antoine, France; INSERM, France; University of Paris 06, France.
    Nagler, Arnon
    Hop St Antoine, France; Chaim Sheba Medical Centre, Israel.
    High CD3+and CD34+peripheral blood stem cell grafts content is associated with increased risk of graft-versus-host disease without beneficial effect on disease control after reduced-intensity conditioning allogeneic transplantation from matched unrelated donors for acute myeloid leukemia - an analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation2016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 19, p. 27255-27266Article in journal (Refereed)
    Abstract [en]

    Inconsistent results have been reported regarding the influence of graft composition on the incidence of graft versus host disease (GVHD), disease control and survival after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplantation (allo-PBSCT). These discrepancies may be at least in part explained by the differences in disease categories, disease status at transplant, donor type and conditioning. The current retrospective EBMT registry study aimed to analyze the impact of CD3+ and CD34+ cells dose on the outcome of RIC allo-PBSCT in patients with acute myelogenous leukemia (AML) in first complete remission, allografted from HLA-matched unrelated donors (10 of 10 match). We included 203 adults. In univariate analysis, patients transplanted with the highest CD3+ and CD34+ doses (above the third quartile cut-off point values, amp;gt;347 x 10amp;lt;^amp;gt;6/kg and amp;gt;8.25 x 10amp;lt;^amp;gt;6/kg, respectively) had an increased incidence of grade III-IV acute (a) GVHD (20% vs. 6%, P = .003 and 18% vs. 7%, P = .02, respectively). There was no association between cellular composition of grafts and transplant-related mortality, AML relapse, incidence of chronic GVHD and survival. Neither engraftment itself nor the kinetics of engraftment were affected by the cell dose. In multivariate analysis, CD3+ and CD34+ doses were the only adverse predicting factors for grade III-IV aGVHD (HR = 3.6; 95% CI: 1.45-9.96, P = .006 and 2.65 (1.07-6.57), P = .04, respectively). These results suggest that careful assessing the CD3+ and CD34+ graft content and tailoring the cell dose infused may help in reducing severe acute GVHD risk without negative impact on the other transplantation outcomes.

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  • 144.
    Da Silva, Stéphanie
    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.
    Keita, Åsa V.
    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.
    Mohlin, Sofie
    Translational Cancer Research, Cancer Center at Medicon Village, Lund University, Lund, Sweden.
    Påhlman, Sven
    Translational Cancer Research, Cancer Center at Medicon Village, Lund University, Lund, Sweden.
    Théodorou, Vassilia
    Toxalim UMR 1331 INRA/INP/UPS Neuro-Gastroenterology and Nutrition Unit, Toulouse, France.
    Påhlman, Ingrid
    Albireo AB, Arvid Wallgrens Backe, Gothenburg, Sweden.
    Mattson, Jan P.
    Albireo AB, Arvid Wallgrens Backe, Gothenburg, Sweden.
    Söderholm, Johan D.
    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.
    A novel topical PPARγ agonist induces PPARγ-activity in ulcerative colitis mucosa and prevents and reverses inflammation in induced-colitis models2018In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 24, no 4, p. 792-805Article in journal (Refereed)
    Abstract [en]

    Background: Peroxisome proliferator-activated receptor-gamma (PPARγ) exerts anti-inflammatory effects and is therefore a potential target in ulcerative colitis (UC). A novel PPARγ agonist (AS002) developed for local action was evaluated ex vivo in biopsies from UC patients and in vivo in mice with low-grade dextran sodium sulfate (DSS)- and trinitrobenzene sulfonic acid (TNBS)-induced colitis.Methods: Colonic biopsies from UC patients (n = 18) and healthy controls (n = 6) were incubated with AS002 or rosiglitazone (positive control) to measure mRNA expression of the PPARγ-responsive gene ADIPOPHILIN and protein levels of UC-related cytokines (enzyme-linked immunosorbent assay). AS002 absorption was determined in the colonic mucosa of UC patients. DSS-colitis mice received PPARγ agonists or vehicle daily by intrarectal administration starting 2 days before induction of colitis (preventive) or from days 3 to 8 (curative). Myeloperoxidase (MPO) and cytokine levels in colonic mucosa were determined. In addition, AS002 effects were studied in TNBS colitis.Results: AS002 displayed an absorption pattern of a lipophilic drug totally metabolized in the mucosa. AS002 and rosiglitazone increased ADIPOPHILIN mRNA expression (3-fold) and decreased TNF-α, IL-1β, and IL-13 levels in human UC biopsies. In DSS, in both preventive and curative treatment and in TNBS colitis, AS002 protected against macroscopic and histological damage and lowered MPO and TNF-α, IL-1β, and IL-13 levels.Conclusions: AS002 triggers anti-inflammatory PPARγ activity in the human colonic mucosa of UC patients and prevents and reverses colitis in mice. Our data suggest that AS002 has potential for topical maintenance treatment of UC, which warrants further studies in vivo in patients.

  • 145.
    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.
    An overview of pregnancy and fertility issues in breast cancer patients2015In: Annals of Medicine, ISSN 0785-3890, E-ISSN 1365-2060, Vol. 47, no 8, p. 673-678Article, review/survey (Refereed)
    Abstract [en]

    Breast cancer is one of the most common malignancies of women in the reproductive years. In the Western world there is a trend towards delaying pregnancy to later in life, and in combination with an increased incidence of breast cancer an increased number of women are diagnosed with breast cancer before they have completed their reproductive plans. In addition, breast cancer during pregnancy may affect an increased number of women as the childbearing years are delayed. The survival rate after breast cancer has improved during the last decades, and many young breast cancer survivors will consider a pregnancy subsequent to the completion of adjuvant breast cancer therapy. Traditionally, many women are advised against a pregnancy due to a fear of increased risk of recurrence, especially women with estrogen receptor-positive breast cancer. Due to feasibility issues, evidence from large prospective randomized trials is missing regarding the safety of pregnancy after breast cancer. Today guidelines are based on cohort studies and population-based registry evidence with its limitations. Overall, data suggest that pregnancy after breast cancer therapy is safe, and the current evidence is summarized in this overview.

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  • 146.
    Dabrosin, Nina
    et al.
    Aarhus Univ Hosp, Denmark.
    Dabrosin, Charlotta
    Linköping University, Department of Biomedical and Clinical Sciences, 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.
    Postmenopausal Dense Breasts Maintain Premenopausal Levels of GH and Insulin-like Growth Factor Binding Proteins in Vivo2020In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 105, no 5, article id UNSP dgz323Article in journal (Refereed)
    Abstract [en]

    Context: Dense breast tissue is associated with 4 to 6 times higher risk of breast cancer by poorly understood mechanisms. No preventive therapy for this high-risk group is available. After menopause, breast density decreases due to involution of the mammary gland. In dense breast tissue, this process is haltered by undetermined biological actions. Growth hormone (GH) and insulin-like binding proteins (IGFBPs) play major roles in normal mammary gland development, but their roles in maintaining breast density are unknown. Objective: To reveal in vivo levels of GH, IGFBPs, and other pro-tumorigenic proteins in the extracellular microenvironment in breast cancer, in normal breast tissue with various breast density in postmenopausal women, and premenopausal breasts. We also sought to determine possible correlations between these determinants. Setting and Design: Microdialysis was used to collect extracellular in vivo proteins intratumorally from breast cancers before surgery and from normal human breast tissue from premenopausal women and postmenopausal women with mammographic dense or nondense breasts. Results: Estrogen receptor positive breast cancers exhibited increased extracellular GH (P &lt;.01). Dense breasts of postmenopausal women exhibited similar levels of GH as premenopausal breasts and significantly higher levels than in nondense breasts (P &lt;.001). Similar results were found for IGFBP-1, -2, -3, and -7 (P &lt;.01) and for IGFBP-6 (P &lt;.05). Strong positive correlations were revealed between GH and IGFBPs and pro-tumorigenic matrix metalloproteinases, urokinase-type plasminogen activator, Interleukin 6, Interleukin 8, and vascular endothelial growth factor in normal breast tissue. Conclusions: GH pathways may be targetable for cancer prevention therapeutics in postmenopausal women with dense breast tissue.

  • 147.
    Daghighi, Abtin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Tropp, Hans
    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.
    Computed tomography lung volume estimation and its relation to lung capacities and spine deformation2019In: Journal of spine surgery (Hong Kong), ISSN 2414-4630, Vol. 5, no 1, p. 132-141Article in journal (Refereed)
    Abstract [en]

    Scoliosis is a three-dimensional deformity which is believed to impact lung function, mechanics of respiratory muscles, lung compliance, etc. It is thus of interest to investigated the relationship between degree of scoliosis in terms of apex rotation or Cobb angle respectively and normalized vital capacity (VC). Furthermore it is interesting to study the possibility of estimating lung volumes (and indirectly lung function) using CT volumetric reconstruction.

  • 148.
    Daghighi, Abtin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Tropp, Hans
    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 Spinal Surgery.
    Dahlström, Nils
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Klarbring, Anders
    Linköping University, Department of Management and Engineering, Solid Mechanics. Linköping University, Faculty of Science & Engineering.
    F.E.M. Stress-Investigation of Scolios Apex2018In: Open Biomedical Engineering Journal, ISSN 1874-1207, E-ISSN 1874-1207, Vol. 12, p. 51-71Article in journal (Refereed)
    Abstract [en]

    In scoliosis, kypholordos and wedge properties of the vertebrae should be involved in determining how stress is distributed in the vertebral column. The impact is logically expected to be maximal at the apex.

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  • 149.
    Dahlqvist Leinhard, Olof
    et al.
    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.
    Linge, Jennifer
    Advanced MR Analytics AB, Linköping, Sweden.
    West, Janne
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Bell, Jimmy
    Westminster University, London, UK.
    Borga, Magnus
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering.
    Body Composition Profiling using MRI - Normative Data for Subjects with Cardiovascular Disease Extracted from the UK Biobank Imaging Cohort2016Conference paper (Other academic)
    Abstract [en]

    PURPOSE

    To describe the distribution of MRI-derived body composition measurements in subjects with cardiovascular disease (CVD) compared to subjects without any history of CVD.

    METHOD AND MATERIALS

    1864 males and 2036 females with an age range from 45 to 78 years from the UK Biobank imaging study were included in the study. Visceral adipose tissue volume normalized with height2 (VATi), total abdominal adipose tissue volume normalized with height2 (ATATi), total lean thigh muscle volume normalized with body weight (muscle ratio) and liver proton density fat fraction (PDFF) were measured with a 2-point Dixon imaging protocol covering neck to knee and a 10-point Dixon single slice protocol positioned within the liver using a 1.5T MR-scanner (Siemens, Germany). The MR-images were analyzed using AMRA® Profiler research (AMRA, Sweden). 213 subjects with history of cardiovascular events (angina, heart attack, or stroke) (event group) were age and gender matched to subjects with high blood pressure (HBP group), and subjects without CVD (controls).Kruskal-Wallis and Mann-Whitney U tests were used to test the observed differences for each measurement and group without correction for multiple comparisons.

    RESULTS

    VATi in the event group was 1.73 (1.13 - 2.32) l/m2 (median, 25%-75% percentile) compared to 1.68 (1.19 - 2.23) in the HBP group, and 1.30 (0.82-1.87) in the controls. ATATi in the event group was 4.31 (2.90-5.39) l/m2 compared to 4.05 (3.07-5.12) in the HBP group, and 3.48 (2.48-4.61) in the controls. Muscle ratio in the event group was 0.13 (0.12 - 0.15) l/kg as well as in the HBP group, compared to 0.14 (0.12 - 0.15) in the controls. Liver PDFF in the event group was 2.88 (1.77 - 7.72) % compared to 3.44 (2.04-6.18) in the HBP group, and 2.50 (1.58 - 5.15) in the controls. Kruskal-Wallis test showed significant differences for all variables and group comparisons (p<0.007). The post hoc test showed significant differences comparing the controls to both the event group and the HBP group. These were more significant for VATi and ATATi (p<10-4) than for muscle ratio and PDFF (p<0.03). No significant differences were detected between the event group and the HBP group.

    CONCLUSION

    Cardiovascular disease is strongly associated with high VATi, liver fat, and ATATi, and with low muscle ratio.

    CLINICAL RELEVANCE/APPLICATION

    The metabolic syndrome component in CVD can be effectively described using MRI-based body composition profiling.

  • 150.
    Dahlqvist Leinhard, Olof
    et al.
    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.
    Linge, Jennifer
    Advanced MR Analytics AB, Linköping, Sweden.
    West, Janne
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Bell, Jimmy
    Westminster University, London, UK.
    Borga, Magnus
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Body Composition Profiling using MRI - Normative Data for Subjects with Diabetes Extracted from the UK Biobank Imaging Cohort2016Conference paper (Other academic)
    Abstract [en]

    PURPOSE

    To describe the distribution of MRI derived body composition measurements in subjects with diabetes mellitus (DM) compared to subjects without diabetes.

    METHOD AND MATERIALS

    3900 subjects (1864 males and 2036 females) from the UK Biobank imaging study were included in the study. The age range was 45 to 78 years. Visceral adipose tissue volume normalized with height2 (VATi), total abdominal adipose tissue volume normalized with height2 (ATATi), total lean thigh muscle volume normalized with body weight (muscle ratio) and liver proton density fat fraction (PDFF) were measured with a 6 minutes 2-point Dixon imaging protocol covering neck to knee and a 10-point Dixon single axial slice protocol positioned within the liver using a 1.5T MR-scanner (Siemens, Germany). The MR-images were analyzed using AMRA® Profiler research (AMRA, Sweden). 194 subjects with clinically diagnosed DM (DM group) were age and gender matched to subjects without DM (control group). For each variable and group, the median, 25%-percentile and 75%-percentile was calculated. Mann-Whitney U test was used to test the observed differences.

    RESULTS

    VATi in the DM group was 2.13 (1.43-2.62) l/m2 (median, 25% - 75% percentile) compared to 1.32 (0.86 - 1.79) l/m2 in the control group. ATATi in the DM group was 4.94 (3.86-6.19) l/m2 compared to 3.40 (2.56 - 4.70) l/m2 in the control group. Muscle ratio in the DM group was 0.13 (0.11 - 0.14) l/kg compared to 0.14 (0.12 - 0.15) l/kg in the control group. Liver PDFF in the DM group was 7.23 (2.68 - 13.26) % compared to 2.49 (1.53 - 4.73) % in the control group. Mann-Whitney U test detected significant differences between the DM group and the control group for all variables (p<10-5).

    CONCLUSION

    DM is strongly associated with high visceral fat, liver fat, and total abdominal fat, and low muscle ratio.

    CLINICAL RELEVANCE/APPLICATION

    Body composition profiling shows high potential to provide direct biomarkers to improve characterization and early diagnosis of DM.

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