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  • 1.
    Abdalla, Maie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Suez Canal University, Egypt.
    Landerholm, Kalle
    Ryhov County Hospital, Sweden.
    Andersson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Andersson, Roland
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov County Hospital, Sweden.
    Myrelid, Pär
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Risk of Rectal Cancer After Colectomy for Patients With Ulcerative Colitis: A National Cohort Study2017In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 15, no 7, 1055-1060 p., e2Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 2.
    Abdelrahman, Islam
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Elmasry, Moustafa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Olofsson, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Division of overall duration of stay into operative stay and postoperative stay improves the overall estimate as a measure of quality of outcome in burn care.2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 3, e0174579Article in journal (Refereed)
    Abstract [en]

    Patients and Methods: Surgically managed burn patients admitted between 2010-14 were included. Operative stay was defined as the time from admission until the last operation, postoperative stay as the time from the last operation until discharge. The difference in variation was analysed with F-test. A retrospective review of medical records was done to explore reasons for extended postoperative stay. Multivariable regression was used to assess factors associated with operative stay and postoperative stay.less thanbr /greater thanResults: Operative stay/TBSA% showed less variation than total duration/TBSA% (F test = 2.38, pless than0.01). The size of the burn, and the number of operations, were the independent factors that influenced operative stay (R2 0.65). Except for the size of the burn other factors were associated with duration of postoperative stay: wound related, psychological and other medical causes, advanced medical support, and accommodation arrangements before discharge, of which the two last were the most important with an increase of (mean) 12 and 17 days (pless than0.001, R2 0.51).less thanbr /greater thanConclusion: Adjusted operative stay showed less variation than total hospital stay and thus can be considered a more accurate outcome measure for surgically managed burns. The size of burn and number of operations are the factors affecting this outcome measure.

  • 3.
    Abdelrahman, Islam
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Elmasry, Moustafa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. a Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Improvement in mortality at a National Burn Centre since 2000: Was it the result of increased resources?2017In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 96, no 25, e6727Article in journal (Refereed)
    Abstract [en]

    Abstract The aim of this study was to find out whether the charging costs (calculated using interventional burn score) increased as mortality decreased. During the last 2 decades, mortality has declined significantly in the Linköping Burn Centre. The burn score that we use has been validated as a measure of workload and is used to calculate the charging costs of each burned patient. We compared the charging costs and mortality in 2 time periods (2000–2007 and 2008–2015). A total of 1363 admissions were included. We investigated the change in the burn score, as a surrogate for total costs per patient. Multivariable regression was used to analyze risk-adjusted mortality and burn score. The median total body surface area % (TBSA%) was 6.5% (10–90 centile 1.0–31.0), age 33 years (1.3–72.2), duration of stay/ TBSA% was 1.4 days (0.3–5.3), and 960 (70%) were males. Crude mortality declined from 7.5% in 2000–2007 to 3.4% in 2008–2015, whereas the cumulative burn score was not increased (P=.08). Regression analysis showed that risk-adjusted mortality decreased (odds ratio 0.42, P=.02), whereas the adjusted burn score did not change (P=.14, model R2 0.86). Mortality decreased but there was no increase in the daily use of resources as measured by the interventional burn score. The data suggest that the improvements in quality obtained have been achieved within present routines for care of patients (multidisciplinary/ orientated to patients’ safety).

    Abbreviation: TBSA% = total body surface area %.

  • 4.
    Abdelrahman, Islam Mohamedy
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Elmasry, Moustafa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Response to comments on: A prospective randomized cost billing comparison of local fasciocutaneous perforator versus free Gracilis flap reconstruction for lower limb in a developing economy2017In: Journal of Plastic, Reconstructive & Aesthetic Surgery, ISSN 1748-6815, E-ISSN 1532-1959, Vol. 70, no 9, 1307-1308 p.Article in journal (Other academic)
  • 5.
    Abrahamsson, Annelie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Capodanno, Alessandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Rzepecka, Anna
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Dabrosin, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Downregulation of tumor suppressive microRNAs in vivo in dense breast tissue of postmenopausal women2017In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 54, 92134-92142 p.Article in journal (Refereed)
    Abstract [en]

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

  • 6.
    Adini, B.
    et al.
    Tel Aviv University, Israel.
    Bodas, M.
    Tel Aviv University, Israel.
    Nilsson, Heléne
    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 Disaster Medicine and Traumatology.
    Peleg, K.
    Tel Aviv University, Israel; Gertner Institute Health Policy and Epidemiol, Israel.
    Policies for managing emergency medical services in mass casualty incidents2017In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 48, no 9, 1878-1883 p.Article in journal (Refereed)
    Abstract [en]

    Introduction: Diverse decision-making is needed in managing mass casualty incidents (MCIs), by emergency medical services (EMS). The aim of the study was to review consensus among international experts concerning policies of EMS management during MCIs. Methods: Applicability of 21 EMS policies was tested through a 2-cycle modified e-Delphi process, in which 38 multi-disciplinary experts from 10 countries participated. Threshold for approving proposed solutions was defined as consensus of amp;gt;80%. Policies that did not achieve the targeted consensus were reviewed to detect variability according to respondents origin country. Results: 16 policies were endorsed in the first cycle including collaboration between ambulance service providers; implementing a unified mode of operation; preparing criteria for ground versus aerial evacuation; and, developing support systems for caregivers exposed to violence. An additional policy which proposed that senior EMS officers should not necessarily act as on-site MCI commanders was endorsed in the second cycle. Demographic breakdown of views concerning non-consensual policies revealed differences according to countries of origin. Assigning ambulances to off-duty team members was highly endorsed by experts from Israel and South Africa and strongly rejected by European respondents. Avoiding entry to risk areas until declared safe was endorsed by European, Asian and Oceanic experts, but rejected by Israeli, South African and North American experts. Conclusions: Despite uniqueness of countries and EMS agencies, solutions to most dilemmas were applicable to all organizations, regardless of location or affiliation. Cultural diversity was found concerning readiness to implement military-civilian collaboration in MCIs and a rigid separation between work-leisure responsibilities. (C) 2017 Elsevier Ltd. All rights reserved.

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

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

  • 8.
    Alim, Abdul
    et al.
    Uppsala University, Sweden; Karolinska Institute, Sweden; Uppsala University, Sweden.
    Ackermann, Paul W.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Eliasson, Pernilla M.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Parmis
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Kristiansson, Per
    Uppsala University, Sweden.
    Pejler, Gunnar
    Uppsala University, Sweden; Swedish University of Agriculture Science, Sweden.
    Peterson, Magnus
    Uppsala University, Sweden.
    Increased mast cell degranulation and co-localization of mast cells with the NMDA receptor-1 during healing after Achilles tendon rupture2017In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 370, no 3, 451-460 p.Article in journal (Refereed)
    Abstract [en]

    The role of inflammation and the mechanism of tendon healing after rupture has historically been a matter of controversy. The purpose of the present study is to investigate the role of mast cells and their relation to the NMDA receptor-1 (a glutamate receptor) during healing after Achilles tendon rupture. Eight female Sprague Dawley rats had their right Achilles tendon transected. Three weeks after rupture, histological quantification of mast cell numbers and their state of degranulation was assessed by histochemistry. Co-localization of mast cell tryptase (a mast cell marker) and NMDA receptor-1 was determined by immunofluorescence. The intact left Achilles tendon was used as control. An increased number of mast cells and a higher proportion of degranulated mast cells were found in the healing Achilles tendon compared to the intact. In addition, increased co-localization of mast cell tryptase and NMDA receptor-1 was seen in the areas of myotendinous junction, mid-tendon proper and bone tendon junction of the healing versus the intact tendon. These findings introduce a possible role for mast cells in the healing phase after Achilles tendon rupture.

  • 9.
    Andersson, Manne
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Cty Council Jonkoping, Dept Surg, Ryhov Cty Hosp, Jonkoping, Sweden.
    Kolodziej, B.
    County Council Jonköping, Sweden.
    Andersson, Roland
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. County Council Jonköping, Sweden.
    Randomized clinical trial of Appendicitis Inflammatory Response score-based management of patients with suspected appendicitis2017In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 104, no 11, 1451-1461 p.Article in journal (Refereed)
    Abstract [en]

    BackgroundThe role of imaging in the diagnosis of appendicitis is controversial. This prospective interventional study and nested randomized trial analysed the impact of implementing a risk stratification algorithm based on the Appendicitis Inflammatory Response (AIR) score, and compared routine imaging with selective imaging after clinical reassessment. MethodPatients presenting with suspicion of appendicitis between September 2009 and January 2012 from age 10years were included at 21 emergency surgical centres and from age 5years at three university paediatric centres. Registration of clinical characteristics, treatments and outcomes started during the baseline period. The AIR score-based algorithm was implemented during the intervention period. Intermediate-risk patients were randomized to routine imaging or selective imaging after clinical reassessment. ResultsThe baseline period included 1152 patients, and the intervention period 2639, of whom 1068 intermediate-risk patients were randomized. In low-risk patients, use of the AIR score-based algorithm resulted in less imaging (192 versus 345 per cent; Pamp;lt;0001), fewer admissions (295 versus 428 per cent; Pamp;lt;0001), and fewer negative explorations (16 versus 32 per cent; P=0030) and operations for non-perforated appendicitis (68 versus 97 per cent; P=0034). Intermediate-risk patients randomized to the imaging and observation groups had the same proportion of negative appendicectomies (64 versus 67 per cent respectively; P=0884), number of admissions, number of perforations and length of hospital stay, but routine imaging was associated with an increased proportion of patients treated for appendicitis (534 versus 463 per cent; P=0020). ConclusionAIR score-based risk classification can safely reduce the use of diagnostic imaging and hospital admissions in patients with suspicion of appendicitis. Registration number: NCT00971438 ( ). Reduces imaging and admissions

  • 10.
    Bausch, Birke
    et al.
    Albert Ludwigs University, Germany.
    Schiavi, Francesca
    Ist Ricovero and Cura Carattere Science, Italy.
    Ni, Ying
    Cleveland Clin, OH 44106 USA.
    Welander, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Patocs, Attila
    Semmelweis University, Hungary; Semmelweis University, Hungary.
    Ngeow, Joanne
    National Cancer Centre Singapore, Singapore; Nanyang Technology University, Singapore.
    Wellner, Ulrich
    University of Lubeck, Germany.
    Malinoc, Angelica
    Albert Ludwigs University, Germany.
    Taschin, Elisa
    Ist Ricovero and Cura Carattere Science, Italy.
    Barbon, Giovanni
    Ist Ricovero and Cura Carattere Science, Italy.
    Lanza, Virginia
    Ist Ricovero and Cura Carattere Science, Italy.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Stenman, Adam
    Karolinska Institute, Sweden.
    Larsson, Catharina
    Karolinska Institute, Sweden.
    Svahn, Fredrika
    Karolinska Institute, Sweden.
    Chen, Jin-Lian
    Cleveland Clin, OH 44106 USA.
    Marquard, Jessica
    Cleveland Clin, OH 44106 USA.
    Fraenkel, Merav
    Hadassah Hebrew University, Israel.
    Walter, Martin A.
    University Hospital, Switzerland.
    Peczkowska, Mariola
    Institute Cardiol, Poland.
    Prejbisz, Aleksander
    Institute Cardiol, Poland.
    Jarzab, Barbara
    Maria Sklodowska Curie Mem Cancer Centre and Institute Oncol, Poland.
    Hasse-Lazar, Kornelia
    Maria Sklodowska Curie Mem Cancer Centre and Institute Oncol, Poland.
    Petersenn, Stephan
    Centre Endocrine Tumors, Germany.
    Moeller, Lars C.
    University of Duisburg Essen, Germany.
    Meyer, Almuth
    HELIOS Klin, Germany.
    Reisch, Nicole
    Ludwigs Maximilians University of Munich, Germany.
    Trupka, Arnold
    City Hospital, Germany.
    Brase, Christoph
    University of Erlangen Nurnberg, Germany.
    Galiano, Matthias
    University Hospital Erlangen, Germany.
    Preuss, Simon F.
    University of Cologne, Germany.
    Kwok, Pingling
    University of Regensburg, Germany.
    Lendvai, Nikoletta
    Semmelweis University, Hungary.
    Berisha, Gani
    Albert Ludwigs University, Germany.
    Makay, Ozer
    Ege University, Turkey.
    Boedeker, Carsten C.
    HELIOS Hanseklinikum Stralsund, Germany.
    Weryha, Georges
    University of Nancy, France.
    Racz, Karoly
    Semmelweis University, Hungary.
    Januszewicz, Andrzej
    Institute Cardiol, Poland.
    Walz, Martin K.
    Kliniken Essen Mitte, Germany; Kliniken Essen Mitte, Germany.
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Opocher, Giuseppe
    Ist Ricovero and Cura Carattere Science, Italy.
    Eng, Charis
    Cleveland Clin, OH 44106 USA; Cleveland Clin, OH 44106 USA.
    Neumann, Hartmut P. H.
    Albert Ludwigs University, Germany.
    Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention2017In: JAMA Oncology, ISSN 2374-2437, E-ISSN 2374-2445, Vol. 3, no 9, 1204-1212 p.Article in journal (Refereed)
    Abstract [en]

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

  • 11.
    Bednarska, Olga
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Casado-Bedmar, Maite
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Salvo-Romero, Eloisa
    University of Autonoma Barcelona, Spain.
    Vicario, Maria
    University of Autonoma Barcelona, Spain.
    Mayer, Emeran A.
    University of Calif Los Angeles, CA 90095 USA.
    Keita, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Vasoactive Intestinal Polypeptide and Mast Cells Regulate Increased Passage of Colonic Bacteria in Patients With Irritable Bowel Syndrome2017In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 153, no 4, 948-+ p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND amp; AIMS: Irritable bowel syndrome (IBS) is associated with intestinal dysbiosis and symptoms of IBS develop following gastroenteritis. We aimed to study the passage of live bacteria through the colonic epithelium, and determine the role of mast cells (MCs) and vasoactive intestinal polypeptide (VIP) in barrier regulation in IBS and healthy individuals. METHODS: Colon biopsies from 32 women with IBS and 15 age-matched healthy women (controls) were mounted in Ussing chambers; we measured numbers of fluorescently labeled Escherichia coli HS and Salmonella typhimurium that passed through from the mucosal side to the serosal side of the tissue. Some biopsies were exposed to agents that block the VIP receptors (VPAC1 and VPAC2) or MCs. Levels of VIP and tryptase were measured in plasma and biopsy lysates. Number of MCs and MCs that express VIP or VIP receptors were quantified by immunofluorescence. Biopsies from an additional 5 patients with IBS and 4 controls were mounted in chambers and Salmonella were added; we studied passage routes through the epithelium by transmission electron microscopy and expression of tight junctions by confocal microscopy. RESULTS: In colon biopsies from patients with IBS, larger numbers of E coli HS and S typhimurium passed through the epithelium than in biopsies from controls (P amp;lt;.0005). In transmission electron microscopy analyses, bacteria were found to cross the epithelium via only the transcellular route. Bacterial passage was reduced in biopsies from patients with IBS and controls after addition of antibodies against VPACs or ketotifen, which inhibits MCs. Plasma samples from patients with IBS had higher levels of VIP than plasma samples from controls. Biopsies from patients with IBS had higher levels of tryptase, larger numbers of MCs, and a higher percentage of MCs that express VPAC1 than biopsies from controls. In biopsies from patients with IBS, addition of Salmonella significantly reduced levels of occludin; subsequent addition of ketotifen significantly reversed this effect. CONCLUSIONS: We found that colonic epithelium tissues from patients with IBS have increased translocation of commensal and pathogenic live bacteria compared with controls. The mechanisms of increased translocation include MCs and VIP.

  • 12.
    Behrens, Kira
    et al.
    Leibniz Institute Expt Virol, Germany; Walter and Eliza Hall Institute Medical Research, Australia.
    Maul, Katrin
    Leibniz Institute Expt Virol, Germany.
    Tekin, Nilguen
    Leibniz Institute Expt Virol, Germany; Leibniz Institute Expt Virol, Germany.
    Kriebitzsch, Neele
    Leibniz Institute Expt Virol, Germany.
    Indenbirken, Daniela
    Leibniz Institute Expt Virol, Germany.
    Prassolov, Vladimir
    Engelhardt Institute Molecular Biol, Russia.
    Mueller, Ursula
    Leibniz Institute Expt Virol, Germany.
    Serve, Hubert
    Goethe University of Frankfurt, Germany.
    Cammenga, Jörg
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Stocking, Carol
    Leibniz Institute Expt Virol, Germany.
    RUNX1 cooperates with FLT3-ITD to induce leukemia2017In: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 214, no 3, 737-752 p.Article in journal (Refereed)
    Abstract [en]

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

  • 13.
    Bengtsson, Daniel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Kalmar County Hospital, Sweden.
    Joost, Patrick
    Lund University, Sweden.
    Aravidis, Christos
    Uppsala University, Sweden.
    Stenmark Askmalm, Marie
    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. Off Medical Serv, Sweden; Lund University, Sweden.
    Backman, Ann-Sofie
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Melin, Beatrice
    Umeå University, Sweden.
    von Salome, Jenny
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Zagoras, Theofanis
    Sahlgrens University Hospital, Sweden.
    Gebre-Medhin, Samuel
    Lund University, Sweden; Karolinska University Hospital, Sweden.
    Burman, Pia
    Lund University, Sweden.
    Corticotroph Pituitary Carcinoma in a Patient With Lynch Syndrome (LS) and Pituitary Tumors in a Nationwide LS Cohort2017In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 102, no 11, 3928-3932 p.Article in journal (Refereed)
    Abstract [en]

    Context: Lynch syndrome (LS) is a cancer-predisposing syndrome caused by germline mutations in genes involved in DNA mismatch repair (MMR). Patients are at high risk for several types of cancer, but pituitary tumors have not previously been reported. Case: A 51-year-old man with LS (MSH2 mutation) and a history of colon carcinoma presented with severe Cushing disease and a locally aggressive pituitary tumor. The tumor harbored a mutation consistent with the patients germline mutation and displayed defect MMR function. Sixteen months later, the tumor had developed into a carcinoma with widespread liver metastases. The patient prompted us to perform a nationwide study in LS. Nationwide Study: A diagnosis consistent with a pituitary tumor was sought for in the Swedish National Patient Registry. In 910 patients with LS, representing all known cases in Sweden, another two clinically relevant pituitary tumors were found: an invasive nonsecreting macroadenoma and a microprolactinoma (i.e., in total three tumors vs. one expected). Conclusion: Germline mutations in MMR genes may contribute to the development and/or the clinical course of pituitary tumors. Because tumors with MMR mutations are susceptible to treatment with immune checkpoint inhibitors, we suggest to actively ask for a family history of LS in the workup of patients with aggressive pituitary tumors.

  • 14.
    Bernink, Jochem H.
    et al.
    University of Amsterdam, Netherlands; Royal Netherlands Academic Arts and Science KNAW, Netherlands.
    Mjösberg, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    Spits, Hergen
    University of Amsterdam, Netherlands.
    Letter: Human ILC1: To Be or Not to Be in IMMUNITY, vol 46, issue 5, pp 756-7572017In: Immunity, ISSN 1074-7613, E-ISSN 1097-4180, Vol. 46, no 5, 756-757 p.Article in journal (Other academic)
    Abstract [en]

    n/a

  • 15.
    Björnsson Hallgren, Hanna C
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Adolfsson, Lars E
    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.
    Johansson, Kajsa
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Öberg, Birgitta
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Petersson, Anna
    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.
    Holmgren, Theresa M
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Specific exercises for subacromial pain: Good results maintained for 5 years2017In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 88, no 6, 600-605 p.Article in journal (Refereed)
    Abstract [en]

    Background and purpose — We have previously shown that specific exercises reduced the need for surgery in subacromial painpatients at 1-year follow-up. We have now investigated whetherthis result was maintained after 5 years and compared the outcomesof surgery and non-surgical treatment.Patients and methods — 97 patients were included in the previouslyreported randomized study of patients on a waiting list forsurgery. These patients were randomized to specifi c or unspecifi cexercises. After 3 months of exercises the patients were asked ifthey still wanted surgery and this was also assessed at the present5-year follow-up. The 1-year assessment included Constant–Murley score, DASH, VAS at night, rest and activity, EQ-5D, andEQ-VAS. All these outcome assessments were repeated after 5years in 91 of the patients.Results — At the 5-year follow-up more patients in the specifi cexercise group had declined surgery, 33 of 47 as compared with16 of 44 (p = 0.001) in the unspecifi c exercise group. The meanConstant–Murley score continued to improve between the 1- and5-year follow-ups in both surgically and non-surgically treatedgroups. On a group level there was no clinically relevant changebetween 1 and 5 years in any of the other outcome measuresregardless of treatment.Interpretation — This 5-year follow-up of a previously publishedrandomized controlled trial found that specifi c exercisesreduced the need for surgery in patients with subacromial pain.Patients not responding to specifi c exercises may achieve similargood results with surgery. These fi ndings emphasize that a specifi cexercise program may serve as a selection tool for surgery.

  • 16.
    Blockhuys, Stephanie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Chalmers University of Technology, Sweden.
    Rani Agarwal, Nisha
    Chalmers University of Technology, Sweden; McMaster University, Canada; McMaster University, Canada.
    Hildesjö, Camilla
    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 Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Jarlsfelt, Ingvar
    Ryhov Hospital, Sweden.
    Wittung-Stafshede, Pernilla
    Chalmers University of Technology, Sweden.
    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.
    Second harmonic generation for collagen I characterization in rectal cancer patients with and without preoperative radiotherapy2017In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 22, no 10, 106006Article in journal (Refereed)
    Abstract [en]

    Rectal cancer is treated with preoperative radiotherapy (RT) to downstage the tumor, reduce local recurrence, and improve patient survival. Still, the treatment outcome varies significantly and new biomarkers are desired. Collagen I (Col-I) is a potential biomarker, which can be visualized label-free by second harmonic generation (SHG). Here, we used SHG to identify Col-I changes induced by RT in surgical tissue, with the aim to evaluate the clinical significance of RT-induced Col-I changes. First, we established a procedure for quantitative evaluation of Col-I by SHG in CDX2-stained tissue sections. Next, we evaluated Col-I properties in material from 31 non-RT and 29 RT rectal cancer patients. We discovered that the Col-I intensity and anisotropy were higher in the tumor invasive margin than in the inner tumor and normal mucosa, and RT increased and decreased the intensity in inner tumor and normal mucosa, respectively. Furthermore, higher Col-I intensity in the inner tumor was related to increased distant recurrence in the non-RT group but to longer survival in the RT group. In conclusion, we present a new application of SHG for quantitative analysis of Col-I in surgical material, and the first data suggest Col-I intensity as a putative prognostic biomarker in rectal cancer. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License.

  • 17.
    Blomgran, Parmis
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Inflammation and tendon healing2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Tendons heal through three different overlapping phases; the inflammatory, proliferative and remodeling phase. Many studies have investigated what factors influence healing of tendons. However, little was known about inflammation and the immune cells present during Achilles tendon healing by the time this thesis started. We developed a flow cytometry method for our rat model of tendon healing, which enabled us to study different leukocyte subpopulations during Achilles tendon healing.

    The general aim of this thesis was to understand more about inflammation and the immune cell populations present during tendon healing and how the immune cell composition changes during normal tendon healing. Moreover, we investigated how different factors that are known to influence tendon healing affected the composition of the immune cell population.

    First, we described the immune cells during the time course of tendon healing focusing on different subpopulations of macrophages and T cells. Then, we studied how these cells were influenced by reduced mechanical loading. Mechanical loading prolonged the presence of M1 macrophages and delayed the switch to regulatory T cells and M2 macrophages compared to reduced mechanical loading. Next, the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the leukocyte composition revealed that, even though NSAIDs influence the mechanical properties of healing tendon, this effect was not mediated via changes in the leukocyte sub-populations during early and mid-time tendon healing. Further, the effect of corticosteroids during the inflammatory and remodeling phases of tendon healing was an improved healing of tendons and a reduction of CD8a T cells when corticosteroid was administered after the inflammatory phase. Lastly, we investigated if impairment of tendon healing by NSAIDs was related to mechanotransduction or microdamage during mechanical loading and showed that NSAIDs impair tendon healing by reducing the response to microdamage.

    In conclusion, these studies show that inflammation plays an important role during Achilles tendon healing, and factors that influence healing can also alter the presence or polarization of immune cell populations. 

    List of papers
    1. A possible link between loading, inflammation and healing: Immune cell populations during tendon healing in the rat
    Open this publication in new window or tab >>A possible link between loading, inflammation and healing: Immune cell populations during tendon healing in the rat
    2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 29824Article in journal (Refereed) Published
    Abstract [en]

    Loading influences tendon healing, and so does inflammation. We hypothesized that the two are connected. 48 rats underwent Achilles tendon transection. Half of the rats received Botox injections into calf muscles to reduce mechanical loading. Cells from the regenerating tissue were analyzed by flow cytometry. In the loaded group, the regenerating tissue contained 83% leukocytes (CD45(+)) day 1, and 23% day 10. The M1/M2 macrophage ratio (CCR7/CD206) peaked at day 3, while T helper (CD3(+)CD4(+)) and T-reg cells (CD25(+) Foxp3(+)) increased over time. With Botox, markers associated with down-regulation of inflammation were more common day 5 (CD163, CD206, CD25, Foxp3), and M1 or M2 macrophages and T-reg cells were virtually absent day 10, while still present with full loading. The primary variable, CCR7/CD206 ratio day 5, was higher with full loading (p = 0.001) and the T-reg cell fraction was lower (p amp;lt; 0.001). Free cage activity loading is known to increase size and strength of the tendon in this model compared to Botox. Loading now appeared to delay the switch to an M2 type of inflammation with more T-reg cells. It seems a prolonged M1 phase due to loading might make the tendon regenerate bigger.

    Place, publisher, year, edition, pages
    NATURE PUBLISHING GROUP, 2016
    National Category
    Cell and Molecular Biology
    Identifiers
    urn:nbn:se:liu:diva-130383 (URN)10.1038/srep29824 (DOI)000379584000001 ()27405922 (PubMedID)
    Note

    Funding Agencies|Swedish Research Council [K2013-52X-02031-47-5]; Swedish National Centre for Research in Sports; King Gustaf V and Queen Victoria Free Mason Foundation

    Available from: 2016-08-15 Created: 2016-08-05 Last updated: 2017-11-28
    2. Cox-2 inhibition and the composition of inflammatory cell populations during early and mid-time tendon healing
    Open this publication in new window or tab >>Cox-2 inhibition and the composition of inflammatory cell populations during early and mid-time tendon healing
    2017 (English)In: Muscles, ligaments and Tendons journal, ISSN 2240-4554, Vol. 7, no 2, 223-229 p.Article in journal (Refereed) Published
    Abstract [en]

    Background: During early tendon healing, the cells within the regenerating tissue are, to a large part, inflammatory leukocytes (CD45+). In a rat Achilles tendon healing model, the inflammation resolves between 5 and 10 days. In the same model, Cox inhibitors (NSAIDs) impair healing when given during the first 5 days, but have a positive effect if given later. We tested the hypothesis that a Cox inhibitor would exert these effects by influencing inflammation, and thereby the composition of the inflammatory cell subpopulations.Methods: Achilles tendon transection was performed in 44 animals. Animals were randomized to either parecoxib or saline injections. Healing was evaluated by mechanical testing day 7 after surgery and by flow cytometry day 3 and 10.Results: Cross-sectional area, peak force and stiffness were reduced by parecoxib 31, 33, and 25% respectively (p=0.005, p=0.002, and p=0.005). By flow cytometry, there was a strong effect of time (p<0.001) on virtually all inflammatory cell subpopulations (CD45, CD11b, CD68, CCR7, CD163, CD206, CD3, CD4), but no significant effect of parecoxib at any time point.Conclusion: The results suggest that the negative effects of Cox inhibitors on tendon healing might be exerted mainly via mechanisms not directly related to inflammatory cells.

    Place, publisher, year, edition, pages
    Rome, Italy: CIC Edizioni Internazionali, 2017
    Keyword
    tendon healing; NSAID; inflammation; rat model; flow cytometry
    National Category
    Pharmacology and Toxicology
    Identifiers
    urn:nbn:se:liu:diva-142352 (URN)
    Available from: 2017-10-27 Created: 2017-10-27 Last updated: 2017-10-30
    3. Systemic corticosteroids improve tendon healing when given after the early inflammatory phase
    Open this publication in new window or tab >>Systemic corticosteroids improve tendon healing when given after the early inflammatory phase
    2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 12468Article in journal (Refereed) Published
    Abstract [en]

    Inflammation initiates tendon healing and then normally resolves more or less completely. Unresolved inflammation might disturb the remodeling process. We hypothesized that suppression of inflammation during the early remodeling phase by systemic dexamethasone treatment can improve healing. 36 rats underwent Achilles tendon transection and were randomized to dexamethasone or saline on days 0-4 after surgery (early inflammatory phase), and euthanasia day 7. Another 54 rats received injections days 5-9 (early remodeling phase) and were euthanized day 12 for mechanical, histological and flow cytometric evaluation. Dexamethasone treatment days 0-4 reduced the cross-sectional area, peak force and stiffness by day 7 to less than half (p amp;lt; 0.001 for all), while material properties (peak stress and elastic modulus) were not significantly affected. In contrast, dexamethasone treatment days 5-9 increased peak force by 39% (p = 0.002) and stiffness by 58% (p amp;lt; 0.001). The cross-sectional area was reduced by 42% (p amp;lt; 0.001). Peak stress and elastic modulus were more than doubled (p amp;lt; 0.001 for both). Semi-quantitative histology at day 12 showed that late dexamethasone treatment improved collagen alignment, and flow cytometry revealed reduced numbers of CD8a(+) cytotoxic T cells in the tendon callus. These results suggest that downregulation of lingering inflammation during the early remodeling phase can improve healing.

    Place, publisher, year, edition, pages
    NATURE PUBLISHING GROUP, 2017
    National Category
    Biomaterials Science
    Identifiers
    urn:nbn:se:liu:diva-142175 (URN)10.1038/s41598-017-12657-0 (DOI)000412032600034 ()28963482 (PubMedID)
    Note

    Funding Agencies|Swedish Research Council [K2013-52X-02031-47-5]; Swedish National Centre for Research in Sports; Ostergotland county (ALF)

    Available from: 2017-10-23 Created: 2017-10-23 Last updated: 2017-11-16
    4. COX-2 inhibition impairs mechanical stimulation of early tendon healing in rats by reducing the response to microdamage
    Open this publication in new window or tab >>COX-2 inhibition impairs mechanical stimulation of early tendon healing in rats by reducing the response to microdamage
    2015 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 119, no 5, 534-540 p.Article in journal (Refereed) Published
    Abstract [en]

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

    Place, publisher, year, edition, pages
    AMER PHYSIOLOGICAL SOC, 2015
    Keyword
    tendon healing; COX-2; NSAIDs; mechanical stimulation; microdamage
    National Category
    Physiology Pharmacology and Toxicology
    Identifiers
    urn:nbn:se:liu:diva-122063 (URN)10.1152/japplphysiol.00239.2015 (DOI)000360694300013 ()26159755 (PubMedID)
    Note

    Funding Agencies|Swedish Research Council [K2013-52X-02031-47-5]; Swedish National Centre for Research in Sports; King Gustaf V and Queen Victoria Free Mason Foundation

    Available from: 2015-12-18 Created: 2015-10-19 Last updated: 2017-12-01
  • 18.
    Blomgran, Parmis
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    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.
    Cox-2 inhibition and the composition of inflammatory cell populations during early and mid-time tendon healing2017In: Muscles, ligaments and Tendons journal, ISSN 2240-4554, Vol. 7, no 2, 223-229 p.Article in journal (Refereed)
    Abstract [en]

    Background: During early tendon healing, the cells within the regenerating tissue are, to a large part, inflammatory leukocytes (CD45+). In a rat Achilles tendon healing model, the inflammation resolves between 5 and 10 days. In the same model, Cox inhibitors (NSAIDs) impair healing when given during the first 5 days, but have a positive effect if given later. We tested the hypothesis that a Cox inhibitor would exert these effects by influencing inflammation, and thereby the composition of the inflammatory cell subpopulations.Methods: Achilles tendon transection was performed in 44 animals. Animals were randomized to either parecoxib or saline injections. Healing was evaluated by mechanical testing day 7 after surgery and by flow cytometry day 3 and 10.Results: Cross-sectional area, peak force and stiffness were reduced by parecoxib 31, 33, and 25% respectively (p=0.005, p=0.002, and p=0.005). By flow cytometry, there was a strong effect of time (p<0.001) on virtually all inflammatory cell subpopulations (CD45, CD11b, CD68, CCR7, CD163, CD206, CD3, CD4), but no significant effect of parecoxib at any time point.Conclusion: The results suggest that the negative effects of Cox inhibitors on tendon healing might be exerted mainly via mechanisms not directly related to inflammatory cells.

  • 19.
    Blomgran, Parmis
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Hammerman, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Systemic corticosteroids improve tendon healing when given after the early inflammatory phase2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 12468Article in journal (Refereed)
    Abstract [en]

    Inflammation initiates tendon healing and then normally resolves more or less completely. Unresolved inflammation might disturb the remodeling process. We hypothesized that suppression of inflammation during the early remodeling phase by systemic dexamethasone treatment can improve healing. 36 rats underwent Achilles tendon transection and were randomized to dexamethasone or saline on days 0-4 after surgery (early inflammatory phase), and euthanasia day 7. Another 54 rats received injections days 5-9 (early remodeling phase) and were euthanized day 12 for mechanical, histological and flow cytometric evaluation. Dexamethasone treatment days 0-4 reduced the cross-sectional area, peak force and stiffness by day 7 to less than half (p amp;lt; 0.001 for all), while material properties (peak stress and elastic modulus) were not significantly affected. In contrast, dexamethasone treatment days 5-9 increased peak force by 39% (p = 0.002) and stiffness by 58% (p amp;lt; 0.001). The cross-sectional area was reduced by 42% (p amp;lt; 0.001). Peak stress and elastic modulus were more than doubled (p amp;lt; 0.001 for both). Semi-quantitative histology at day 12 showed that late dexamethasone treatment improved collagen alignment, and flow cytometry revealed reduced numbers of CD8a(+) cytotoxic T cells in the tendon callus. These results suggest that downregulation of lingering inflammation during the early remodeling phase can improve healing.

  • 20.
    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, 2439-2444 p.Article 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.

  • 21.
    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, 1160-1166 p.Article 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.

  • 22.
    Bäckström, Denise
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping.
    Injury mortality in Sweden; changes over time and the effect of age and injury mechanism2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Injuries are one of the most common causes of death in the world. Varying types of injuries dominate in different parts of the world, which also have separate influences mortality. In Scandinavia blunt injuries dominates and the majority of those who die do so pre hospital. Over time different injury pattern may vary and by analyzing this we can assess when, where and how preventive work can be reinforced. The aim of this thesis was to study injury epidemiology in Sweden and assess the contribution of different injury patters on mortality.

    Method: We used the Swedish cause of death and the national patient registries which have a complete national coverage. ICISS was calculated (based on ICD-10) in the in hospital population. We have chosen to do this investigation with a broad perspective using the term injury, which includes trauma but also other diagnoses like suffocation and drowning.

    Results: During the study period (1999-2012) the number of deaths because of injury was 1213, 25 388, and 18 332 among children, working age and elderly, respectively. Mortality declined in the children and in the working age but inclined in the elderly. Mortality increased with each age group except between the ages of 15–25 and 26–35 years. One thousand two hundred sixty four (97%) of those who died because of penetrating trauma (sharp objects and firearms) were killed by intentional trauma (assault and intentional self-harm). One thousand and seventeen (83%) of the children died prehospital. In the working age 22 211 (80%) of 25 388 died pre hospital. Nine thousand six hundred and eighteen (53%) of 18 332 of the elderly died prehospital. During 2001- 2011 the risk adjusted in hospital mortality decreased in traffic and assault but not in fall related injuries.

    Discussion: Largely, the anticipated injury mortality picture was found, with blunt injuries (traffic accidents) dominating in the working age and falls in elderly. Further a significant portion of the deaths occurred pre hospital. The intentional injuries are dominated by intentional selfharm. The decrease in child injury mortality is notable as Sweden already has one of the lowest incidences in child injury mortality in the world. The decrease in injury mortality in the working age also implies that preventive work has had an effect. The incline in injury mortality in elderly on the other hand needs to be further studied. Areas of particular importance for future preventive work is the incline in injury mortality in elderly and intentional injuries among children. 

    List of papers
    1. Change in child mortality patterns after injuries in Sweden: a nationwide 14-year study.
    Open this publication in new window or tab >>Change in child mortality patterns after injuries in Sweden: a nationwide 14-year study.
    2017 (English)In: European Journal of Trauma and Emergency Surgery, ISSN 1863-9933, E-ISSN 1863-9941, Vol. 43, no 3, 343-349 p.Article in journal (Refereed) Published
    Abstract [en]

    INTRODUCTION: Sweden has one of the world's lowest child injury mortality rates, but injuries are still the leading cause of death among children. Child injury mortality in the country has been declining, but this decline seems to decrease recently. Our objective was therefore to further examine changes in the mortality of children's death from injury over time and to assess the contribution of various effects on mortality. The underlying hypothesis for this investigation is that the incidence of lethal injuries in children, still is decreasing and that this may be sex specific.

    PATIENTS AND METHODS: We studied all deaths from injury in Sweden under-18-year-olds during the 14 years 1999-2012. We identified those aged under 18 whose underlying cause of death was recorded as International Classification of Diseases, 10th Revision (ICD-10) diagnosis from V01 to X39 in the Swedish cause of death, where all dead citizens are registered.

    RESULTS: From the 1 January 1999 to 31 December 2012, 1213 children under the age of 18 died of injuries in Sweden. The incidence declined during this period (r = -0.606, p = 0.02) to 3.3 deaths/100,000 children-years (95 % CI 2.6-4.2). Death from unintentional injury was more common than that after intentional injury (p < 0.0001). There was a reduction in the incidence of unintentional injuries during the study period (r = -0.757, p = 0.03). The most common causes of death were injury to the brain (n = 337, 41 %), followed by drowning (n = 109, 13 %). The number of deaths after intentional injury increased (r = 0.585, p = 0.03) and at the end of the period was 1.5 deaths/100,000 children-years. The most common causes of death after intentional injuries were asphyxia (n = 177, 45 %), followed by injury to the brain (n = 76, 19 %).

    DISCUSSION: Mortality patterns in injured children in Sweden have changed from being dominated by unintentional injuries to a more equal distribution between unintentional and intentional injuries as well as between sexes and the overall rate has declined further. These findings are important as they might contribute to the preventive work that is being done to further reduce mortality in injured children.

    Place, publisher, year, edition, pages
    Springer, 2017
    Keyword
    Children, Injury, Mortality, Scandinavia, Trauma
    National Category
    Other Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-135548 (URN)10.1007/s00068-016-0660-y (DOI)000402789500010 ()27084542 (PubMedID)
    Note

    Funding agencies: Swedish Carnegie Hero Fund

    Available from: 2017-03-16 Created: 2017-03-16 Last updated: 2017-11-02Bibliographically approved
    2. Deaths caused by injury among people of working age (18-64) are decreasing, while those among older people (64+) are increasing.
    Open this publication in new window or tab >>Deaths caused by injury among people of working age (18-64) are decreasing, while those among older people (64+) are increasing.
    Show others...
    2017 (English)In: European Journal of Trauma and Emergency Surgery, ISSN 1863-9933, E-ISSN 1863-9941Article in journal (Refereed) Epub ahead of print
    Abstract [en]

    BACKGROUND: Injury is an important cause of death in all age groups worldwide, and contributes to many losses of human and economic resources. Currently, we know a few data about mortality from injury, particularly among the working population. The aim of the present study was to examine death from injury over a period of 14 years (1999-2012) using the Swedish Cause of Death Registry (CDR) and the National Patient Registry, which have complete national coverage.

    METHOD: CDR was used to identify injury-related deaths among adults (18 years or over) during the years 1999-2012. ICD-10 diagnoses from V01 to X39 were included. The significance of changes over time was analyzed by linear regression.

    RESULTS: The incidence of prehospital death decreased significantly (coefficient -0.22, r (2) = 0.30; p = 0.041) during the study period, while that of deaths in hospital increased significantly (coefficient 0.20, r (2) = 0.75; p < 0.001). Mortality/100,000 person-years in the working age group (18-64 years) decreased significantly (coefficient -0.40, r (2) = 0.37; p = 0.020), mainly as a result of decrease in traffic-related deaths (coefficient -0.34, r (2) = 0.85; p < 0.001). The incidence of deaths from injury among elderly (65 years and older) patients increased because of the increase in falls (coefficient 1.71, r (2) = 0.84; p < 0.001) and poisoning (coefficient 0.13, r (2) = 0.69; p < 0.001).

    CONCLUSION: The epidemiology of injury in Sweden has changed during recent years in that mortality from injury has declined in the working age group and increased among those people 64 years old and over.

    Place, publisher, year, edition, pages
    Springer, 2017
    Keyword
    Elderly, Injury, Mortality, Prehospital, Trauma, Working age
    National Category
    Public Health, Global Health, Social Medicine and Epidemiology
    Identifiers
    urn:nbn:se:liu:diva-142763 (URN)10.1007/s00068-017-0827-1 (DOI)28825159 (PubMedID)
    Available from: 2017-11-02 Created: 2017-11-02 Last updated: 2017-12-04Bibliographically approved
  • 23.
    Bäckström, Denise
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping.
    Larsen, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Steinvall, Ingrid
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Gedeborg, Rolf
    Department of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden..
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Deaths caused by injury among people of working age (18-64) are decreasing, while those among older people (64+) are increasing.2017In: European Journal of Trauma and Emergency Surgery, ISSN 1863-9933, E-ISSN 1863-9941Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Injury is an important cause of death in all age groups worldwide, and contributes to many losses of human and economic resources. Currently, we know a few data about mortality from injury, particularly among the working population. The aim of the present study was to examine death from injury over a period of 14 years (1999-2012) using the Swedish Cause of Death Registry (CDR) and the National Patient Registry, which have complete national coverage.

    METHOD: CDR was used to identify injury-related deaths among adults (18 years or over) during the years 1999-2012. ICD-10 diagnoses from V01 to X39 were included. The significance of changes over time was analyzed by linear regression.

    RESULTS: The incidence of prehospital death decreased significantly (coefficient -0.22, r (2) = 0.30; p = 0.041) during the study period, while that of deaths in hospital increased significantly (coefficient 0.20, r (2) = 0.75; p < 0.001). Mortality/100,000 person-years in the working age group (18-64 years) decreased significantly (coefficient -0.40, r (2) = 0.37; p = 0.020), mainly as a result of decrease in traffic-related deaths (coefficient -0.34, r (2) = 0.85; p < 0.001). The incidence of deaths from injury among elderly (65 years and older) patients increased because of the increase in falls (coefficient 1.71, r (2) = 0.84; p < 0.001) and poisoning (coefficient 0.13, r (2) = 0.69; p < 0.001).

    CONCLUSION: The epidemiology of injury in Sweden has changed during recent years in that mortality from injury has declined in the working age group and increased among those people 64 years old and over.

  • 24.
    Bäckström, Denise
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Change in child mortality patterns after injuries in Sweden: a nationwide 14-year study.2017In: European Journal of Trauma and Emergency Surgery, ISSN 1863-9933, E-ISSN 1863-9941, Vol. 43, no 3, 343-349 p.Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Sweden has one of the world's lowest child injury mortality rates, but injuries are still the leading cause of death among children. Child injury mortality in the country has been declining, but this decline seems to decrease recently. Our objective was therefore to further examine changes in the mortality of children's death from injury over time and to assess the contribution of various effects on mortality. The underlying hypothesis for this investigation is that the incidence of lethal injuries in children, still is decreasing and that this may be sex specific.

    PATIENTS AND METHODS: We studied all deaths from injury in Sweden under-18-year-olds during the 14 years 1999-2012. We identified those aged under 18 whose underlying cause of death was recorded as International Classification of Diseases, 10th Revision (ICD-10) diagnosis from V01 to X39 in the Swedish cause of death, where all dead citizens are registered.

    RESULTS: From the 1 January 1999 to 31 December 2012, 1213 children under the age of 18 died of injuries in Sweden. The incidence declined during this period (r = -0.606, p = 0.02) to 3.3 deaths/100,000 children-years (95 % CI 2.6-4.2). Death from unintentional injury was more common than that after intentional injury (p < 0.0001). There was a reduction in the incidence of unintentional injuries during the study period (r = -0.757, p = 0.03). The most common causes of death were injury to the brain (n = 337, 41 %), followed by drowning (n = 109, 13 %). The number of deaths after intentional injury increased (r = 0.585, p = 0.03) and at the end of the period was 1.5 deaths/100,000 children-years. The most common causes of death after intentional injuries were asphyxia (n = 177, 45 %), followed by injury to the brain (n = 76, 19 %).

    DISCUSSION: Mortality patterns in injured children in Sweden have changed from being dominated by unintentional injuries to a more equal distribution between unintentional and intentional injuries as well as between sexes and the overall rate has declined further. These findings are important as they might contribute to the preventive work that is being done to further reduce mortality in injured children.

  • 25.
    Chisalita, Simona I.
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Chong, Lee Ti
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Wajda, Maciej
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Adolfsson, Lars
    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.
    Woisetschläger, Mischa
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Spångeus, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Association of Insulin-like Growth Factor-1, Bone Mass and Inflammation to Low-energy Distal Radius Fractures and Fracture Healing in Elderly Women Attending Emergency Care2017In: ORTHOPAEDIC SURGERY, ISSN 1757-7853, Vol. 9, no 4, 380-385 p.Article in journal (Refereed)
    Abstract [en]

    ObjectiveElderly patients suffer fractures through low-energy mechanisms. The distal radius is the most frequent fracture localization. Insulin-like growth factor-1 (IGF1) plays an important role in the maintenance of bone mass and its levels decline with advancing age and in states of malnutrition. Our aim was to investigate the association of IGF1 levels, bone mass, nutritional status, and inflammation to low-energy distal radius fractures and also study if fracture healing is influenced by IGF1, nutritional status, and inflammation. MethodsPostmenopausal women, 55 years or older, with low-energy distal radius fractures occurring due to falling on slippery ground, indoors or outdoors, were recruited in the emergency department (ED) and followed 1 and 5 weeks after the initial trauma with biomarkers for nutritional status and inflammation. Fractures were diagnosed according to standard procedure by physical examination and X-ray. All patients were conservatively treated with plaster casts in the ED. Patients who needed interventions were excluded from our study. Fracture healing was evaluated from radiographs. Fracture healing assessment was made with a five-point scale where the radiological assessment included callus formation, fracture line, and stage of union. Blood samples were taken within 24 h after fracture and analyzed in the routine laboratory. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA). ResultsThirty-eight Caucasian women, aged 70.5 8.9 years (mean +/- SD) old, were recruited. Nutritional status, as evaluated by albumin (40.3 +/- 3.1 g/L), IGF1 (125.3 +/- 39.9 g/L), body mass index (26.9 +/- 3.6 kg/m(2)), arm diameter (28.9 +/- 8.9 cm), and arm skinfold (2.5 +/- 0.7 cm), was normal. A positive correlation was found between IGF1 at visit 1 and the lowest BMD for hip, spine, or radius (r = 0.39, P = 0.04). High sensitive C-reactive protein (hsCRP) and leukocytes were higher at the fracture event compared to 5 weeks later (P = 0.07 and P amp;lt; 0.001, respectively). Fracture healing parameters (i.e. callus formation, fracture line, and stage of union) were positively correlated with the initial leukocyte count and to difference in thrombocyte count between visit 1 and 3. ConclusionsIn elderly women with low-energy distal radius fractures, an association between IGF1 and lowest measures of BMD was found, indicating that low IGF1 could be an indirect risk factor for fractures. Fracture healing was associated with initial leukocytosis and a lower thrombocyte count, suggesting that inflammation and thrombocytes are important components in fracture healing.

  • 26.
    Cossarizza, Andrea
    et al.
    University of Modena, Italy; Reggio Emilia School Med, Italy.
    Chang, Hyun-Dong
    Institute Leibniz Assoc, Germany.
    Radbruch, Andreas
    Institute Leibniz Assoc, Germany.
    Andrae, Immanuel
    Technical University of Munich, Germany.
    Annunziato, Francesco
    University of Florence, Italy.
    Bacher, Petra
    Charite University of Medical Berlin, Germany.
    Barnaba, Vincenzo
    Sapienza University of Roma, Italy; Fdn Cenci Bolognetti, Italy.
    Battistini, Luca
    Santa Lucia Fdn, Italy.
    Bauer, Wolfgang M.
    Medical University of Vienna, Austria.
    Baumgart, Sabine
    Institute Leibniz Assoc, Germany.
    Becher, Burkhard
    University of Zurich, Switzerland.
    Beisker, Wolfgang
    German Research Centre Environm Heatlh, Germany.
    Berek, Claudia
    Institute Leibniz Assoc, Germany.
    Blanco, Alfonso
    University of Coll Dublin, Ireland.
    Borsellino, Giovanna
    Santa Lucia Fdn, Italy.
    Boulais, Philip E.
    Albert Einstein Coll Med, NY 10467 USA; Ruth L and David S Gottesman Institute Stem Cell and Regen, NY USA.
    Brinkman, Ryan R.
    BC Cancer Agency, Canada; University of British Columbia, Canada.
    Buescher, Martin
    Miltenyi Biotec GmbH, Germany.
    Busch, Dirk H.
    Technical University of Munich, Germany; National Centre Infect Research, Germany; Technical University of Munich, Germany.
    Bushnell, Timothy P.
    University of Rochester, NY 14642 USA; University of Rochester, NY 14642 USA.
    Cao, Xuetao
    Zhejiang University, Peoples R China; Second Mil Medical University, Peoples R China; Second Mil Medical University, Peoples R China; Chinese Academic Medical Science, Peoples R China; Chinese Academic Medical Science, Peoples R China.
    Cavani, Andrea
    NIHMP, Italy.
    Chattopadhyay, Pratip K.
    Vaccine Research Centre, MD USA.
    Cheng, Qingyu
    Charite University of Medical Berlin, Germany.
    Chow, Sue
    Princess Margaret Hospital, Canada.
    Clerici, Mario
    University of Milan, Italy; Fdn Don C Gnocchi, Italy.
    Cooke, Anne
    University of Cambridge, England.
    Cosma, Antonio
    University of Paris Sud, France.
    Cosmi, Lorenzo
    University of Firenze, Italy.
    Cumano, Ana
    Pasteur Institute, France.
    Duc Dang, Van
    Institute Leibniz Assoc, Germany.
    Davies, Derek
    Francis Crick Institute, England.
    De Biasi, Sara
    University of Modena and Reggio Emilia, Italy.
    Del Zotto, Genny
    Ist Giannina Gaslini, Italy.
    Della Bella, Silvia
    University of Milan, Italy; Lab Clin and Expt Immunol, Italy.
    Dellabona, Paolo
    Ist Science San Raffaele, Italy.
    Deniz, Gunnur
    Istanbul University, Turkey.
    Dessing, Mark
    Sony Europe Ltd, England.
    Diefenbach, Andreas
    Charite University of Medical Berlin, Germany.
    Di Santo, James
    Institute Pasteur, France.
    Dieli, Francesco
    University of Palermo, Italy.
    Dolf, Andreas
    University of Bonn, Germany.
    Donnenberg, Vera S.
    University of Pittsburgh, PA USA.
    Doerner, Thomas
    Charite University of Medical Berlin, Germany.
    Ehrhardt, Gotz R. A.
    University of Toronto, Canada.
    Endl, Elmar
    University of Bonn, Germany.
    Engel, Pablo
    University of Barcelona, Spain.
    Engelhardt, Britta
    University of Bern, Switzerland.
    Esser, Charlotte
    Leibniz Research Institute Environm Med, Germany.
    Everts, Bart
    Leiden University, Netherlands.
    Falk, Christine S.
    MHH Hannover Medical Sch, Germany; TTU IICH, Germany.
    Fehniger, Todd A.
    Washington University, MO USA.
    Filby, Andrew
    Newcastle University, England.
    Fillatreau, Simon
    INSERM, France; University of Paris 05, France; Hop Necker Enfants Malad, France.
    Follo, Marie
    University of Freiburg, Germany.
    Foerster, Irmgard
    University of Bonn, Germany.
    Foster, John
    Owl Biomed Inc, CA USA.
    Foulds, Gemma A.
    Nottingham Trent University, England.
    Frenette, Paul S.
    Albert Einstein Coll Med, NY 10467 USA.
    Galbraith, David
    University of Arizona, AZ USA.
    Garbi, Natalio
    University of Bonn, Germany; Arizona Cancer Centre, AZ USA; Institute Expt Immunol, Germany.
    Dolores Garcia-Godoy, Maria
    Josep Carreras Leukemia Research Institute, Spain.
    Geginat, Jens
    Ist Nazl Genet Molecolare Romeo Enrica Invernizzi, Italy.
    Ghoreschi, Kamran
    Eberhard Karls University of Tubingen, Germany.
    Gibellini, Lara
    University of Modena and Reggio Emilia, Italy.
    Goettlinger, Christoph
    University of Cologne, Germany.
    Goodyear, Carl S.
    University of Glasgow, Scotland.
    Gori, Andrea
    University of Milano Bicocca, Italy.
    Grogan, Jane
    Genentech Inc, CA USA.
    Gross, Mor
    Weizmann Institute Science, Israel.
    Gruetzkau, Andreas
    Institute Leibniz Assoc, Germany.
    Grummitt, Daryl
    Owl Biomed Inc, CA USA.
    Hahn, Jonas
    University of Klinikum Erlangen, Germany.
    Hammer, Quirin
    Institute Leibniz Assoc, Germany.
    Hauser, Anja E.
    Institute Leibniz Assoc, Germany; Charite University of Medical Berlin, Germany.
    Haviland, David L.
    Houston Methodist Hospital, TX USA.
    Hedley, David
    Princess Margaret Hospital, Canada.
    Herrera, Guadalupe
    University of Valencia, Spain; University of Valencia, Spain.
    Herrmann, Martin
    University of Klinikum Erlangen, Germany.
    Hiepe, Falk
    Charite University of Medical Berlin, Germany.
    Holland, Tristan
    Arizona Cancer Centre, AZ USA; Institute Expt Immunol, Germany.
    Hombrink, Pleun
    Sanquin Research and Landsteiner Lab, Netherlands.
    Houston, Jessica P.
    New Mexico State University, NM 88003 USA.
    Hoyer, Bimba F.
    Charite University of Medical Berlin, Germany.
    Huang, Bo
    Huazhong University of Science and Technology, Peoples R China; Chinese Academic Medical Science, Peoples R China; Chinese Academic Medical Science, Peoples R China; Peking Union Medical Coll, Peoples R China; Chinese Academic Medical Science, Peoples R China.
    Hunter, Christopher A.
    University of Penn, PA 19104 USA.
    Iannone, Anna
    University of Modena and Reggio Emilia, Italy.
    Jaeck, Hans-Martin
    University Hospital Erlangen, Germany.
    Javega, Beatriz
    University of Valencia, Spain.
    Jonjic, Stipan
    University of Rijeka, Croatia; University of Rijeka, Croatia.
    Juelke, Kerstin
    Institute Leibniz Assoc, Germany.
    Jung, Steffen
    Weizmann Institute Science, Israel.
    Kaiser, Toralf
    Institute Leibniz Assoc, Germany.
    Kalina, Tomas
    Charles University of Prague, Czech Republic; University Hospital Motol, Czech Republic.
    Keller, Baerbel
    University of Freiburg, Germany.
    Khan, Srijit
    University of Toronto, Canada.
    Kienhoefer, Deborah
    University of Klinikum Erlangen, Germany.
    Kroneis, Thomas
    Medical University of Graz, Austria.
    Kunkel, Desiree
    Charite University of Medical Berlin, Germany.
    Kurts, Christian
    University of Bonn, Germany.
    Kvistborg, Pia
    Netherlands Cancer Institute, Netherlands.
    Lannigan, Joanne
    University of Virginia, VA 22908 USA.
    Lantz, Olivier
    Institute Curie, France; Institute Curie, France; Institute Curie, France.
    Larbi, Anis
    Biol Aging Program, Singapore; ASTAR, Singapore; University of Sherbrooke, Canada; ElManar University, Tunisia.
    LeibundGut-Landmann, Salome
    University of Zurich, Switzerland.
    Leipold, Michael D.
    Stanford University, CA USA.
    Levings, Megan K.
    University of British Columbia, Canada; British Columbia Childrens Hospital, Canada.
    Litwin, Virginia
    Covance, IN USA.
    Liu, Yanling
    University of Toronto, Canada.
    Lohoff, Michael
    University of Marburg, Germany; University of Marburg, Germany.
    Lombardi, Giovanna
    Guys Hospital, England.
    Lopez, Lilly
    Beckman Coulter Inc, FL USA.
    Lovett-Racke, Amy
    Ohio State University, OH 43210 USA.
    Lubberts, Erik
    University of Medical Centre, Netherlands.
    Ludewig, Burkhard
    Kantonsspital St Gallen, Switzerland.
    Lugli, Enrico
    Humanitas Clin and Research Centre, Italy; Humanitas Clin and Research Centre, Italy.
    Maecker, Holden T.
    Stanford University, CA USA.
    Martrus, Gloria
    Leibniz Institute Expt Virol, Germany.
    Matarese, Giuseppe
    University of Napoli Federico II, Italy; IEOS, Italy.
    Maueroeder, Christian
    University of Klinikum Erlangen, Germany.
    McGrath, Mairi
    Institute Leibniz Assoc, Germany.
    McInnes, Iain
    University of Glasgow, Scotland.
    Mei, Henrik E.
    Institute Leibniz Assoc, Germany.
    Melchers, Fritz
    Max Planck Institute Infect Biol, Germany.
    Melzer, Susanne
    University of Leipzig, Germany.
    Mielenz, Dirk
    University of Erlangen Nurnberg, Germany.
    Mills, Kingston
    University of Dublin, Ireland.
    Mjösberg, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute Stockholm, Sweden.
    Moore, Jonni
    University of Penn, PA USA.
    Moran, Barry
    University of Dublin, Ireland.
    Moretta, Alessandro
    University of Genoa, Italy; Centre Eccellenza Ric Biomed CEBR, Italy.
    Moretta, Lorenzo
    Bambino Gesu Pediat Hospital, Italy.
    Mosmann, Tim R.
    University of Rochester, NY 14642 USA.
    Mueller, Susann
    UFZ Helmholtz Centre Environm Research, Germany.
    Muller, Werner
    University of Manchester, England.
    Munz, Christian
    University of Zurich, Switzerland.
    Multhoff, Gabriele
    Technical University of Munchen TUM, Germany; Helmholtz Zentrum Munchen, Germany.
    Enrique Munoz, Luis
    University of Klinikum Erlangen, Germany.
    Murphy, Kenneth M.
    Washington University of St Louis, MO USA; Washington University of St Louis, MO USA.
    Nakayama, Toshinori
    Chiba University, Japan.
    Nasi, Milena
    University of Modena and Reggio Emilia, Italy.
    Neudoerfl, Christine
    MHH Hannover Medical Sch, Germany.
    Nolan, John
    Scintillon Institute, CA USA.
    Nourshargh, Sussan
    William Harvey Research Institute, England; Queen Mary University of London, England.
    OConnor, Jose-Enrique
    University of Valencia, Spain.
    Ouyang, Wenjun
    Amgen Inc, CA USA.
    Oxenius, Annette
    Swiss Federal Institute Technology, Switzerland.
    Palankar, Raghav
    University of Medical Greifswald, Germany.
    Panse, Isabel
    University of Oxford, England.
    Peterson, Part
    University of Tartu, Estonia.
    Peth, Christian
    Miltenyi Biotec GmbH, Germany.
    Petriz, Jordi
    Josep Carreras Leukemia Research Institute, Spain.
    Philips, Daisy
    Netherlands Cancer Institute, Netherlands.
    Pickl, Winfried
    Medical University of Vienna, Austria.
    Piconese, Silvia
    Sapienza University of Roma, Italy; Fdn Cenci Bolognetti, Italy.
    Pinti, Marcello
    University of Modena and Reggio Emilia, Italy.
    Graham Pockley, A.
    Nottingham Trent University, England; Chromocyte Ltd, England.
    Justyna Podolska, Malgorzata
    University of Klinikum Erlangen, Germany.
    Pucillo, Carlo
    University of Udine, Italy.
    Quataert, Sally A.
    University of Rochester, NY 14642 USA.
    Radstake, Timothy R. D. J.
    University of Medical Centre Utrecht, Netherlands; University of Medical Centre Utrecht, Netherlands.
    Rajwa, Bartek
    Purdue University, IN 47907 USA.
    Rebhahn, Jonathan A.
    University of Rochester, NY 14642 USA.
    Recktenwald, Diether
    Desatoya LLC, NV USA.
    Remmerswaal, Ester B. M.
    Academic Medical Centre, Netherlands; Academic Medical Centre, Netherlands.
    Rezvani, Katy
    University of Texas MD Anderson Cancer Centre, TX 77030 USA.
    Rico, Laura G.
    Josep Carreras Leukemia Research Institute, Spain.
    Paul Robinson, J.
    Purdue University, IN 47907 USA.
    Romagnani, Chiara
    Institute Leibniz Assoc, Germany.
    Rubartelli, Anna
    IRCCS, Italy.
    Ruland, Juergen
    Technical University of Munich, Germany; German Cancer Research Centre, Germany.
    Sakaguchi, Shimon
    Osaka University, Japan; Kyoto University, Japan.
    Sala-de-Oyanguren, Francisco
    University of Valencia, Spain.
    Samstag, Yvonne
    Ruprecht Karls University of Heidelberg, Germany.
    Sanderson, Sharon
    University of Oxford, England.
    Sawitzki, Birgit
    Free University of Berlin, Germany; Institute Medical Immunol, Germany.
    Scheffold, Alexander
    Institute Leibniz Assoc, Germany; Charite University of Medical Berlin, Germany.
    Schiemann, Matthias
    Technical University of Munich, Germany.
    Schildberg, Frank
    Harvard Medical Sch, MA USA.
    Schimisky, Esther
    Miltenyi Biotec GmbH, Germany.
    Schmid, Stephan A.
    University of Klinikum Regensburg, Germany.
    Schmitt, Steffen
    German Cancer Research Centre, Germany.
    Schober, Kilian
    Technical University of Munich, Germany.
    Schueler, Thomas
    Otto Von Guericke University, Germany.
    Ronald Schulz, Axel
    Institute Leibniz Assoc, Germany.
    Schumacher, Ton
    Netherlands Cancer Institute, Netherlands.
    Scotta, Cristiano
    Guys Hospital, England.
    Vincent Shankey, T.
    AsedaSciences, IN USA.
    Shemer, Anat
    Weizmann Institute Science, Israel.
    Simon, Anna-Katharina
    University of Oxford, England.
    Spidlen, Josef
    BC Cancer Agency, Canada.
    Stall, Alan M.
    BD Life Science, CA USA.
    Stark, Regina
    Sanquin Research and Landsteiner Lab, Netherlands.
    Stehle, Christina
    Institute Leibniz Assoc, Germany.
    Stein, Merle
    University of Erlangen Nurnberg, Germany.
    Steinmetz, Tobit
    University of Erlangen Nurnberg, Germany.
    Stockinger, Hannes
    Medical University of Vienna, Austria.
    Takahama, Yousuke
    University of Tokushima, Japan.
    Tarnok, Attila
    Fraunhofer Institute Cell Therapy and Immunol IZI, Germany; IMISE, Germany.
    Tian, ZhiGang
    University of Science and Technology China, Peoples R China; University of Science and Technology China, Peoples R China; Zhejiang University, Peoples R China.
    Tornack, Julia
    Max Planck Institute Infect Biol, Germany.
    Traggiai, Elisabetta
    NIBR, Switzerland.
    Trotter, Joe
    BD Life Science, CA USA.
    Ulrich, Henning
    University of Sao Paulo, Brazil.
    van der Braber, Marlous
    Netherlands Cancer Institute, Netherlands.
    van Lier, Rene A. W.
    Sanquin Research and Landsteiner Lab, Netherlands.
    Veldhoen, Marc
    Institute Molecular Med, Portugal.
    Vento-Asturias, Salvador
    Arizona Cancer Centre, AZ USA.
    Vieira, Paulo
    Institute Pasteur, France.
    Voehringer, David
    University Hospital Erlangen, Germany.
    Volk, Hans-Dieter
    Labor Berlin, Germany.
    von Volkmann, Konrad
    APE Appl Phys and Elect, Germany.
    Waisman, Ari
    Johannes Gutenberg University of Mainz, Germany.
    Walker, Rachael
    Babraham Institute, England.
    Ward, Michael D.
    Thermo Fisher Science, OR USA.
    Warnatz, Klaus
    University of Freiburg, Germany.
    Warth, Sarah
    Charite University of Medical Berlin, Germany.
    Watson, James V.
    Medinfomat Ltd, England.
    Watzl, Carsten
    TU Dortmund, Germany.
    Wegener, Leonie
    Miltenyi Biotec GmbH, Germany.
    Wiedemann, Annika
    Charite University of Medical Berlin, Germany.
    Wienands, Juergen
    University of Medical Gottingen, Germany.
    Wing, James
    Osaka University, Japan; Kyoto University, Japan.
    Wurst, Peter
    University of Bonn, Germany.
    Yu, Liping
    BD Bioscience, CA USA.
    Yue, Alice
    Simon Fraser University, Canada.
    Zhang, Qianjun
    Emerald Biotech Co Ltd, Peoples R China.
    Zhao, Yi
    Sichuan University, Peoples R China.
    Ziegler, Susanne
    Leibniz Institute Expt Virol, Germany.
    Zimmermann, Jakob
    University of Bern, Switzerland.
    Guidelines for the use of flow cytometry and cell sorting in immunological studies2017In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 47, no 10, 1584-1797 p.Article in journal (Refereed)
    Abstract [en]

    n/a

  • 27.
    De Kleuver, Marinus
    et al.
    Radboud University of Nijmegen, Netherlands.
    Faraj, Sayf S. A.
    Vrije University of Amsterdam, Netherlands.
    Holewijn, Roderick M.
    Vrije University of Amsterdam, Netherlands.
    Germscheid, Niccole M.
    AOSpine Int, Switzerland.
    Adobor, Raphael D.
    Oslo University Hospital, Norway.
    Andersen, Mikkel
    Middelfart Hospital, Denmark.
    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.
    Dahl, Benny
    University of Copenhagen, Denmark; Texas Childrens Hospital, TX 77030 USA; Baylor Coll Med, TX 77030 USA.
    Keskinen, Heli
    University of Turku, Finland; Turku University Hospital, Finland.
    Olai, Anders
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Spinal Surgery.
    Polly, David W.
    University of Minnesota, MN 55455 USA.
    Van Hooff, Miranda L.
    Radboud University of Nijmegen, Netherlands; Sint Maartensklin, Netherlands.
    Haanstra, Tsjitske M.
    Radboud University of Nijmegen, Netherlands; Vrije University of Amsterdam, Netherlands.
    Defining a core outcome set for adolescent and young adult patients with a spinal deformity A collaborative effort for the Nordic Spine Surgery Registries2017In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 88, no 6, 612-618 p.Article in journal (Refereed)
    Abstract [en]

    Background and purpose - Routine outcome measurement has been shown to improve performance in several fields of healthcare. National spine surgery registries have been initiated in 5 Nordic countries. However, there is no agreement on which outcomes are essential to measure for adolescent and young adult patients with a spinal deformity. The aim of this study was to develop a core outcome set (COS) that will facilitate benchmarking within and between the 5 countries of the Nordic Spinal Deformity Society (NSDS) and other registries worldwide. Material and methods - From August 2015 to September 2016, 7 representatives (panelists) of the national spinal surgery registries from each of the NSDS countries participated in a modified Delphi study. With a systematic literature review as a basis and the International Classification of Functioning, Disability and Health framework as guidance, 4 consensus rounds were held. Consensus was defined as agreement between at least 5 of the 7 representatives. Data were analyzed qualitatively and quantitatively. Results - Consensus was reached on the inclusion of 13 core outcome domains: "satisfaction with overall outcome of surgery", "satisfaction with cosmetic result of surgery", "pain interference", physical functioning", "health-related quality of life", "recreation and leisure", "pulmonary fatigue", "change in deformity", "selfimage", "pain intensity", "physical function", "complications", and "re-operation". Panelists agreed that the SRS-22r, EQ-5D, and a pulmonary fatigue questionnaire (yet to be developed) are the most appropriate set of patient-reported measurement instruments that cover these outcome domains. Interpretation - We have identified a COS for a large subgroup of spinal deformity patients for implementation and validation in the NSDS countries. This is the first study to further develop a COS in a global perspective.

  • 28.
    Delisle Nyström, C.
    et al.
    Karolinska Institute, Sweden.
    Pomeroy, J.
    Marshfield Clin Research Institute, WI USA.
    Henriksson, P.
    Karolinska Institute, Sweden; University of Granada, Spain.
    Forsum, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Ortega, F. B.
    Karolinska Institute, Sweden; University of Granada, Spain.
    Maddison, R.
    Deakin University, Australia.
    Migueles, J. H.
    University of Granada, Spain.
    Löf, M.
    Karolinska Institute, Sweden.
    Evaluation of the wrist-worn ActiGraph wGT3x-BT for estimating activity energy expenditure in preschool children2017In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 71, no 10, 1212-1217 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/OBJECTIVES: Easy-to-use and accurate methods to assess free-living activity energy expenditure (AEE) in preschool children are required. The aims of this study in healthy preschool children were to (a) evaluate the ability of the wrist-worn ActiGraph wGT3x-BT to predict free-living AEE and (b) assess wear compliance using a 7-day, 24-h protocol. SUBJECTS/METHODS: Participants were 40 Swedish children (5.5 +/- 0.2 years) in the Mobile-based intervention intended to stop obesity in preschoolers (MINISTOP) obesity prevention trial. Total energy expenditure (TEE) was assessed using the doubly labeled water method during 14 days. AEE was calculated as (TEEx0.9) minus predicted basal metabolic rate. The ActiGraph accelerometer was worn on the wrist for 7 days and outputs used were mean of the daily and awake filtered vector magnitude (mean VM total and mean VM waking). RESULTS: The ActiGraph was worn for 7 (n = 34, 85%), 6 (n = 4, 10%), 5 (n = 1, 2.5%) and 4 (n = 1, 2.5%) days (a valid day was. 600 awake minutes). Alone, mean VM total and mean VM waking were able to explain 14% (P = 0.009) and 24% (P = 0.001) of the variation in AEE, respectively. By incorporating fat and fat-free mass in the models 58% (mean VM total) and 62% (mean VM waking) in the variation of AEE was explained (P amp;lt; 0.001). CONCLUSIONS: The wrist-worn ActiGraph wGT3x-BT in combination with body composition variables explained up to the 62% of the variation in AEE. Given the high wear compliance, the wrist-worn ActiGraph has the potential to provide useful information in studies where physical activity in preschool children is measured.

  • 29.
    Dietrich, Franciele
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Minist Educ Brazil, Brazil; Pontificia University of Catolica Rio Grande Sul PUCRS, Brazil.
    Hammerman, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Parmis
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Tätting, Love
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Faccin Bampi, Vinicius
    Pontificia University of Catolica Rio Grande Sul PUCRS, Brazil.
    Braga Silva, Jefferson
    Pontificia University of Catolica Rio Grande Sul PUCRS, Brazil.
    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.
    Correction: Effect of platelet-rich plasma on rat Achilles tendon healing is related to microbiota (vol 15, pg 1, 2017)2017In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 88, no 4, 463-463 p.Article in journal (Refereed)
    Abstract [en]

    n/a

  • 30.
    Dietrich, Franciele
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. CAPES Fdn, Brazil; Pontificia University of Catolica Rio Grande do Sul PUCRS, Brazil.
    Hammerman, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Parmis
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Tätting, Love
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Faccin Bampi, Vinicius
    Pontificia University of Catolica Rio Grande do Sul PUCRS, Brazil.
    Braga Silva, Jefferson
    Pontificia University of Catolica Rio Grande do Sul PUCRS, Brazil.
    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.
    Effect of platelet-rich plasma on rat Achilles tendon healing is related to microbiota2017In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 88, no 4, 416-421 p.Article in journal (Refereed)
    Abstract [en]

    Background and purpose - In 3 papers in Acta Orthopaedica 10 years ago, we described that platelet-rich plasma (PRP) improves tendon healing in a rat Achilles transection model. Later, we found that microtrauma has similar effects, probably acting via inflammation. This raised the suspicion that the effect ascribed to growth factors within PRP could instead be due to unspecific influences on inflammation. While testing this hypothesis, we noted that the effect seemed to be related to the microbiota. Material and methods - We tried to reproduce our old findings with local injection of PRP 6h after tendon transection, followed by mechanical testing after 11 days. This failed. After fruitless variations in PRP production protocols, leukocyte concentration, and physical activity, we finally tried rats carrying potentially pathogenic bacteria. In all, 242 rats were used. Results - In 4 consecutive experiments on pathogen-free rats, no effect of PRP on healing was found. In contrast, apparently healthy rats carrying Staphylococcus aureus showed increased strength of the healing tendon after PRP treatment. These rats had higher levels of cytotoxic T-cells in their spleens. Interpretation - The failure to reproduce older experiments in clean rats was striking, and the difference in response between these and Staphylococcus-carrying rats suggests that the PRP effect is dependent on the immune status. PRP functions may be more complex than just the release of growth factors. Extrapolation from our previous findings with PRP to the situation in humans therefore becomes even more uncertain.1

  • 31.
    Eberhardson, M.
    et al.
    Danderyd Hospital, Sweden; Karolinska Institute, Sweden.
    Soderling, J. K.
    Karolinska Institute, Sweden.
    Neovius, M.
    Karolinska Institute, Sweden.
    Cars, T.
    Public Healthcare Serv, Sweden; Uppsala University, 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.
    Ludvigsson, J. F.
    Karolinska Institute, Sweden; Örebro University Hospital, Sweden.
    Askling, J.
    Karolinska Institute, Sweden.
    Ekbom, A.
    Karolinska Institute, Sweden.
    Olen, O.
    Karolinska Institute, Sweden; Sachs Childrens Hospital, Sweden.
    Anti-TNF treatment in Crohns disease and risk of bowel resection-a population based cohort study2017In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 46, no 6, 589-598 p.Article in journal (Refereed)
    Abstract [en]

    Background: TNF inhibitors (TNFi) have been shown to reduce the need for surgery in Crohns disease, but few studies have examined their effect beyond the first year of treatment. Aim: To conduct a register-based observational cohort study in Sweden 2006-2014 to investigate the risk of bowel resection in bowel surgery naive TNFi-treated Crohns disease patients and whether patients on TNFi amp;gt;= 12 months are less likely to undergo bowel resection than patients discontinuing treatment before 12 months. Methods: We identified all individuals in Sweden with Crohns disease through the Swedish National Patient Register 1987-2014 and evaluated the incidence of bowel resection after first ever dispensation of adalimumab or infliximab from 2006 and up to 7 years follow-up. Results: We identified 1856 Crohns disease patients who had received TNFi. Among these patients, 90% treatment retention was observed at 6 months after start of TNFi and 65% remained on the drug after 12 months. The cumulative rates of surgery in Crohns disease patients exposed to TNFi years 1-7 were 7%, 13%, 17%, 20%, 23%, 25% and 28%. Rates of bowel resection were similar between patients with TNFi survival amp;lt; 12 months and amp;gt;= 12 months respectively (P=.27). No predictors (eg, sex, age, extension or duration of disease) for bowel resection were identified. Conclusions: The risk of bowel resection after start of anti-TNF treatment is higher in regular health care than in published RCTs. Patients on sustained TNFi treatment beyond 12 months have bowel resection rates similar to those who discontinue TNFi treatment earlier.

  • 32.
    Elmasry, Moustafa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Suez Canal University, Egypt.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Abdelrahman, Islam Mohamedy
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Suez Canal University, Egypt.
    Olofsson, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Changes in patterns of treatment of burned children at the Linkoping Burn Centre, Sweden, 2009-20142017In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 43, no 5, 1111-1119 p.Article in journal (Refereed)
    Abstract [en]

    Introduction: Children are a relatively large group among patients with burns in Sweden. We changed the management of childrens burns to a flexible, outpatient-based plan. The aim was to follow up the outpatient management for childrens burns during the period 20092014, and track it, to find out to what extent the patients had been treated flexibly as outpatients, and to clarify the reasons behind those who did not fit in the plan. Methods: Descriptive retrospective analysis dividing the patients into three groups: inpatients only, flexible management, and outpatients. Other variables recorded included: age, sex, percentage total body surface area burned (TBSA%), percentage full thickness burn (FTB%), cause of burn, county of residence, operations required, number of visits to the outpatient department, costs, and duration of overnight stay in the hospital. Results: The study group included 620 children: nine were managed strictly as inpatients, 204 as flexible outpatients, and 407 strictly as outpatients. Among the total there were 269 children who came from remote areas (43%), and of these 260 were treated as outpatients and flexible outpatients. Median TBSA% in the whole group was 1 (10th-90th centile 0-9) with the biggest median TBSA% 12 (5-38) in the inpatient group. The most common cause of injury was scalds (332/620,-54%). Costs/patient (US$) was lower in the flexible outpatient group than in the inpatient group (median 10 557 (3213-35802) and 35343 (7344-66554), respectively). Conclusion: Based on the results, we expect that the flexible outpatient treatment plan for children with minor to moderate burns can be expanded in the future. The results encourage us to continue the service and to further reduce duration of stay in hospital below the level already achieved (25% of the whole period of care). (C) 2017 Elsevier Ltd and ISBI. All rights reserved.

  • 33.
    Elmasry, Moustafa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Plastic Surgery Unit, Department of Surgery, Suez Canal University, Egypt.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Thorfinn, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Abbas, A.H.
    Plastic Surgery Unit, Department of Surgery, Suez Canal University, Egypt.
    Adly, O.A.
    Plastic Surgery Unit, Department of Surgery, Suez Canal University, Egypt.
    Abdelrahman, Islam
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Nagi, M.A.
    Plastic Surgery Unit, Department of Surgery, Suez Canal University, Egypt.
    Sjöberg, Folke
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology.
    Scald management protocols - outcome differences in two different time periods using different treatment strategies.2016In: Annals of burns and fire disasters, ISSN 1592-9558, Vol. 29, no 2, 139-143 p.Article in journal (Refereed)
    Abstract [en]

    Over the years the treatment of scalds in our centre has changed, moving more towards the use of biological dressings (xenografts). Management of scalds with mid dermal or deep dermal injuries differs among centers using different types of dressings, and recently biological membrane dressings were recommended for this type of injury. Here we describe differences in treatment outcome in different periods of time. All patients with scalds who presented to the Linkoping Burn Centre during two periods, early (1997-98) and later (2010-12) were included. Data were collected in the unit database and analyzed retrospectively. A lower proportion of autograft operations was found in the later period, falling from 32% to 19%. Hospital stay was shorter in the later period (3.5 days shorter, p=0.01) and adjusted duration of hospital stay/TBSA% was shorter (1.2 to 0.7, p=0.07). The two study groups were similar in most of the studied variables: we could not report any significant differences regarding outcome except for unadjusted duration of hospital stay. Further studies are required to investigate functional and aesthetic outcome differences between the treatment modalities.

  • 34.
    Elmasry, Moustafa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Thorfinn, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Abdelrahman, Islam
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Plastic Surgery Unit, Department of Surgery, Suez Canal University, Ismailia, Egypt.
    Olofsson, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Staged excisions of moderate-sized burns compared with total excision with immediate autograft: an evaluation of two strategies.2017In: International journal of burns and trauma, ISSN 2160-2026, Vol. 7, no 1, 6-11 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Different surgical techniques have evolved since excision and autografting became the treatment of choice for deep burns in the 1970s. The treatment plan at the Burn Center, Linköping University Hospital, Sweden, has shifted from single-stage excision and immediate autografting to staged excisions and temporary cover with xenografts before autografting. The aim of this study was to find out if the change in policy resulted in extended duration of hospital stay/total body surface area burned (LOS/TBSA%).

    METHODS: Retrospective clinical cohort including surgically-managed patients with burns of 15%-60% TBSA% within each treatment group. The first had early full excisions of deep dermal and full thickness burns and immediate autografts (1997-98), excision and immediate autograft group) and the second had staged excisions before final autografts using xenografts for temporary cover (2010-11, staged excision group).

    RESULTS: The study included 57 patients with deep dermal and full-thickness burns, 28 of whom had excision and immediate autografting, and 29 of whom had staged excisions with xenografting before final autografting. Adjusted (LOS/TBSA%) was close to 1, and did not differ between groups. Mean operating time for the staged excision group was shorter and the excised area/operation was smaller. The total operating time/TBSA% did not differ between groups.

    CONCLUSION: Staged excisions with temporary cover did not affect adjusted LOS/TBSA% or total operating time. Staged excisions may be thought to be more expensive because of the cost of covering the wound between stages, but this needs to be further investigated as do the factors that predict long term outcome.

  • 35.
    El-Serafi, Ahmed T.
    et al.
    Sharjah Institute for Medical Research and College of Medicine, University of Sharjah, Sharjah, UAE(a); Faculty of Medicine, Suez Canal University, Egypt.
    El-Serafi, Ibrahim T.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Division of Experimental Cancer Medicine, Faculty of MDepartment of Laboratory Medicine, Karolinska Institutet, Sweden .
    Elmasry, Moustafa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Plastic Surgery Unit, Surgery Department, Suez Canal University, Egypt.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Skin regeneration in three dimensions, current status, challenges and opportunities2017In: Differentiation, ISSN 0301-4681, E-ISSN 1432-0436, Vol. 96, 4 p.26-29 p.Article, review/survey (Refereed)
    Abstract [en]

    Skin regeneration is a life-saving need for many patients, whom list is stretched from burn victims to motor-car accidents. Spraying cells, either keratinocytes or stem cells, were associated with variable results and, in many cases, unfavorable outcomes. As the spatial configuration of the skin is distinctive, many trials investigated the bio-printing or the construction of three dimensional skin models where different layers of the skin were preserved. Although some of these models showed the histological configuration of the skin, their acceptance by the wound was questionable as a consequence of delayed vascularization. In this mini-review, different models for three dimensional regeneration of the skin will be discussed with their main points of strength and challenges as well as their possible opportunities.

  • 36.
    Engerström, Lars
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Nolin, Thomas
    Central Hospital Kristianstad, Sweden.
    Mårdh, Caroline
    Landstinget Värmland, Sweden.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Karlström, Göran
    Landstinget Varmland, Sweden.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Walther, Sten
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Impact of Missing Physiologic Data on Performance of the Simplified Acute Physiology Score 3 Risk-Prediction Model*2017In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 45, no 12, 2006-2013 p.Article in journal (Refereed)
    Abstract [en]

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

  • 37.
    Enne, Marcelo
    et al.
    Ipanema Federal Hospital, Brazil.
    Schadde, Erik
    Cantonal Hospital Winterthur, Switzerland; Rush University, IL 60612 USA.
    Björnsson, Bergthor
    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.
    Hernandez Alejandro, Roberto
    University of Rochester, NY USA.
    Steinbruck, Klaus
    Bonsucesso Federal Hospital, Brazil.
    Viana, Eduardo
    Ipanema Federal Hospital, Brazil.
    Robles Campos, Ricardo
    Virgen Arrixaca University Hospital, Spain.
    Malago, Massimo
    Royal Free Hospital, England.
    Clavien, Pierre-Alain
    University of Zurich Hospital, Switzerland.
    De Santibanes, Eduardo
    Hospital Italiano Buenos Aires, Argentina.
    Gayet, Brice
    Institute Mutualiste Montsouris, France.
    ALPPS as a salvage procedure after insufficient future liver remnant hypertrophy following portal vein occlusion2017In: HPB, ISSN 1365-182X, E-ISSN 1477-2574, Vol. 19, no 12, 1126-1129 p.Article in journal (Refereed)
    Abstract [en]

    Background: A minimum future liver remnant (FLR) of 30% is required to avoid post hepatectomy liver failure (PHLF). Portal vein occlusion (PVO) is the main strategy to induce hypertrophy of the FLR, but some patients will not reach sufficient FLR hypertrophy to enable resection. Recently ALPPS has emerged as a "Salvage Procedure" for PVO failure. The aim of this study was to report the short term outcomes of ALPPS following PVO failure. Methods: A retrospective analysis of patients enrolled within the international ALPPS Registry between October 2012 and November 2015 (NCT01924741) was performed. Patients with documented PVO failure were included. The outcomes reported included feasibility, FLR growth rate and safety of ALPPS. Complications were recorded as per Clavien-Dindo classification. Results: From 510 patients enrolled in the Registry there were 22 patients with previous PVO failure. Two patients were excluded due to missing data and twenty patients were analysed. All of them completed the proposed ALPPS with a medium FLR increase of 88% (23-115%) between two stages and no 90-day mortality. Conclusion: In experienced centers, ALPPS following PVO failure is feasible and safe. The FLR hypertrophy was similar to other ALPPS series. ALPPS is a potential rescue strategy after PVO failure.

  • 38.
    Eriksson, Carl
    et al.
    Örebro University, Sweden.
    Marsal, Jan
    Lund University, Sweden; Skåne University Hospital, Sweden.
    Bergemalm, Daniel
    Örebro University, Sweden.
    Vigren, Lina
    Ystad Hospital, Sweden.
    Bjork, Jan
    Karolinska Institute, Sweden.
    Eberhardson, Michael
    Karolinska Institute, Sweden.
    Karling, Pontus
    Umeå University, Sweden.
    Soderman, Charlotte
    St Goran Hospital, Sweden.
    Myrelid, Pär
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Cao, Yang
    Örebro University, Sweden; Karolinska Institute, Sweden.
    Sjöberg, Daniel
    Uppsala University, Sweden.
    Thorn, Mari
    Uppsala University, Sweden.
    Karlen, Per
    Danderyd Hospital, Sweden.
    Hertervig, Erik
    Skåne University Hospital, Sweden.
    Strid, Hans
    Södra Älvsborgs Sjukhus, Sweden.
    Ludvigsson, Jonas F.
    Karolinska Institute, Sweden; Örebro University Hospital, Sweden.
    Almer, Sven
    Karolinska Institute, Sweden.
    Halfvarson, Jonas
    Örebro University, Sweden.
    Long-term effectiveness of vedolizumab in inflammatory bowel disease: a national study based on the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG)2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 6-7, 722-729 p.Article in journal (Refereed)
    Abstract [en]

    Objectives: Clinical trials have demonstrated the efficacy of vedolizumab in inflammatory bowel disease (IBD). However, these findings may not reflect the clinical practice. Therefore, we aimed to describe a vedolizumab-treated patient population and assess long-term effectiveness.Materials and methods: Patients initiating vedolizumab between 1 June 2014 and 30 May 2015 were identified through the Swedish National Quality Registry for IBD. Prospectively collected data on treatment and disease activity were extracted. Clinical remission was defined as Patient Harvey Bradshaw indexamp;lt;5 in Crohns disease (CD) and Patient Simple Clinical Colitis Activity indexamp;lt;3 in ulcerative colitis (UC).Results: Two-hundred forty-six patients (147CD, 92 UC and 7 IBD-Unclassified) were included. On study entry, 86% had failed TNF-antagonist and 48% of the CD patients had undergone1 surgical resection. After a median follow-up of 17 (IQR: 14-20) months, 142 (58%) patients remained on vedolizumab. In total, 54% of the CD- and 64% of the UC patients were in clinical remission at the end of follow-up, with the clinical activity decreasing (pamp;lt;.0001 in both groups). Faecal-calprotectin decreased in CD (pamp;lt;.0001) and in UC (p=.001), whereas CRP decreased in CD (p=.002) but not in UC (p=.11). Previous anti-TNF exposure (adjusted HR: 4.03; 95% CI: 0.96-16.75) and elevated CRP at baseline (adjusted HR: 2.22; 95% CI: 1.10-4.35) seemed to be associated with discontinuation because of lack of response. Female sex was associated with termination because of intolerance (adjusted HR: 2.75; 95% CI: 1.16-6.48).Conclusion: Vedolizumab-treated patients represent a treatment-refractory group. A long-term effect can be achieved, even beyond 1 year of treatment.

  • 39.
    Esserman, Laura J.
    et al.
    University of Calif San Francisco, CA 94115 USA.
    Yau, Christina
    University of Calif San Francisco, CA 94115 USA; Buck Institute Research Aging, CA USA.
    Thompson, Carlie K.
    University of Calif San Francisco, CA 94115 USA.
    vant Veer, Laura J.
    University of Calif San Francisco, CA 94115 USA.
    Borowsky, Alexander D.
    University of Calif Davis, CA 95616 USA.
    Hoadley, Katherine A.
    University of N Carolina, NC USA.
    Tobin, Nicholas P.
    Karolinska Institute, Sweden; University Hospital, 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.
    Fornander, Tommy
    Karolinska Institute, Sweden; University Hospital, Sweden.
    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.
    Benz, Christopher C.
    University of Calif San Francisco, CA 94115 USA; Buck Institute Research Aging, CA USA.
    Lindstrom, Linda S.
    University Hospital, Sweden; Karolinska Institute, Sweden.
    Use of Molecular Tools to Identify Patients With Indolent Breast Cancers With Ultralow Risk Over 2 Decades2017In: JAMA Oncology, ISSN 2374-2437, E-ISSN 2374-2445, Vol. 3, no 11, 1503-1510 p.Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE The frequency of cancers with indolent behavior has increased with screening. Better tools to identify indolent tumors are needed to avoid overtreatment. OBJECTIVE To determine if a multigene classifier is associated with indolent behavior of invasive breast cancers in women followed for 2 decades. DESIGN, SETTING, AND PARTICIPANTS This is a secondary analysis of a randomized clinical trial of tamoxifen vs no systemic therapy, with more than 20-year follow-up. An indolent threshold (ultralow risk) of the US Food and Drug Administration-cleared MammaPrint 70-gene expression score was established above which no breast cancer deaths occurred after 15 years in the absence of systemic therapy. Immunohistochemical markers (n = 727 women) and Agilent microarrays, for MammaPrint risk scoring (n = 652 women), were performed from formalin-fixed paraffin-embedded primary tumor blocks. Participants were postmenopausal women with clinically detected node-negative breast cancers treated with mastectomy or lumpectomy and radiation enrolled in the Stockholm tamoxifen (STO-3) trial, 1976 to 1990. EXPOSURES After 2 years of tamoxifen vs no systemic therapy, regardless of hormone receptor status, patients without relapse who reconsented were further randomized to 3 additional years or none. MAIN OUTCOMES AND MEASURES Breast cancer-specific survival assessed by Kaplan-Meier analyses and multivariate Cox proportional hazard modeling, adjusted for treatment, patient age, year of diagnosis, tumor size, grade, hormone receptors, and ERBB2/HER2 and Ki67 status. RESULTS In this secondary analysis of node-negative postmenopausal women, conducted in the era before mammography screening, among the 652 women with MammaPrint scoring available (median age, 62.8 years of age), 377 (58%) and 275 (42%) were MammaPrint low and high risk, respectively, while 98 (15%) were ultralow risk. At 20 years, women with 70-gene high and low tumors but not ultralow tumors had a significantly higher risk of disease-specific death compared with ultralow-risk patients by Cox analysis (hazard ratios, 4.73 [95% CI, 1.38-16.22] and 4.54 [95% CI, 1.40-14.80], respectively). There were no deaths in the ultralow-risk tamoxifen-treated arm at 15 years, and these patients had a 20-year disease-specific survival rate of 97%, whereas for untreated patients the survival rate was 94%. Recursive partitioning identified ultralow risk as the most significant predictor of good outcome. In tumors "not ultralow risk," tumor size greater than 2 cm was the most predictive of outcome. CONCLUSIONS AND RELEVANCE The ultralow-risk threshold of the 70-gene MammaPrint assay can identify patients whose long-term systemic risk of death from breast cancer after surgery alone is exceedingly low.

  • 40.
    Floodeen, H.
    et al.
    Örebro University Hospital, Sweden; University of Örebro, 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.
    Hagberg, L. A.
    Örebro County Council, Sweden.
    Matthiessen, P.
    Örebro University Hospital, Sweden; University of Örebro, Sweden.
    Costs and resource use following defunctioning stoma in low anterior resection for cancer - A long-term analysis of a randomized multicenter trial2017In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 43, no 2, 330-336 p.Article in journal (Refereed)
    Abstract [en]

    Background: Defunctioning stoma in low anterior resection (LAR) for rectal cancer can prevent major complications, but overall cost-effectiveness for the healthcare provider is unknown. This study compared inpatient healthcare resources and costs within 5 years of LAR between two randomized groups of patients undergoing LAR with and without defunctioning stoma. Method: Five-year follow-up of a randomized, multicenter trial on LAR (NCT 00636948) with (stoma; n = 116) or without (no stoma; n = 118) defunctioning stoma comparing inpatient healthcare resources and costs. Unplanned stoma formation, days with stoma, length of hospital stay, reoperations, and total associated inpatient costs were analyzed. Results: Average costs were (sic) 21.663 per patient with defunctioning stoma and (sic) 15.922 per patient without defunctioning stoma within 5 years of LAR, resulting in an average cost-saving of (sic) 5.741. There was no difference between groups regarding the total number of days with any stoma (stoma = 33 398 vs. no stoma = 34 068). The total number of unplanned reoperations were 70 (no stoma) and 32 (stoma); p amp;lt; 0.001. In the group randomized to no stoma at LAR, 30.5% (36/118) required an unplanned stoma later. Conclusion: Randomization to defunctioning stoma in LAR was more expensive than no stoma, despite the cost-savings associated with a reduced frequency of anastomotic leakage. Both groups required the same total number of days with a stoma within five years of LAR. (C) 2016 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  • 41.
    Forkel, Marianne
    et al.
    Karolinska Institute, Sweden.
    Berglin, Lena
    Karolinska Institute, Sweden.
    Kekalainen, Eliisa
    Karolinska Institute, Sweden.
    Carlsson, Adrian
    Karolinska Institute, Sweden.
    Svedin, Emma
    Karolinska Institute, Sweden.
    Michaelsson, Jakob
    Karolinska Institute, Sweden.
    Nagasawa, Maho
    University of Amsterdam, Netherlands.
    Erjefalt, Jonas S.
    Lund University, Sweden.
    Mori, Michiko
    Lund University, Sweden.
    Flodstrom-Tullberg, Malin
    Karolinska Institute, Sweden.
    Bergquist, Annika
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Ljunggren, Hans-Gustaf
    Karolinska Institute, Sweden.
    Westgren, Magnus
    Karolinska Institute, Sweden.
    Lindforss, Ulrik
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Friberg, Danielle
    KI, Sweden.
    Jorns, Carl
    Karolinska Institute, Sweden.
    Ellis, Ewa
    Karolinska Institute, Sweden.
    Bjorkstrom, Niklas K.
    Karolinska Institute, Sweden.
    Mjösberg, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    Composition and functionality of the intrahepatic innate lymphoid cell-compartment in human nonfibrotic and fibrotic livers2017In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 47, no 8, 1280-1294 p.Article in journal (Refereed)
    Abstract [en]

    Human innate lymphoid cells have been described to exist in different organs, with functional deregulation of these cells contributing to several disease states. Here, we performed the first detailed characterization of the phenotype, tissue-residency properties, and functionality of ILC1s, ILC2s, and ILC3s in the human adult and fetal liver. In addition, we investigated changes in the ILC compartment in liver fibrosis. A unique composition of tissue-resident ILCs was observed in nonfibrotic livers as compared with that in mucosal tissues, with NKp44(-) ILC3s accounting for the majority of total intrahepatic ILCs. The frequency of ILC2s, representing a small fraction of ILCs in nonfibrotic livers, increased in liver fibrosis and correlated directly with the severity of the disease. Notably, intrahepatic ILC2s secreted the profibrotic cytokine IL-13 when exposed to IL-33 and thymic stromal lymphopoetin (TSLP); these cytokines were produced by hepatocytes, hepatic stellate cells (HSCs), and Kupffer cells in response to TLR-3 stimulation. In summary, the present results provide the first detailed characterization of intrahepatic ILCs in human adult and fetal liver. The results indicate a role for ILC2s in human liver fibrosis, implying that targeting ILC2s might be a novel therapeutic strategy for its treatment.

  • 42.
    Gauffin, Håkan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Sonesson, Sofi
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Meunier, Andreas
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Magnusson, Henrik
    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.
    Kvist, Joanna
    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.
    Knee Arthroscopic Surgery in Middle-Aged Patients With Meniscal Symptoms A 3-Year Follow-up of a Prospective, Randomized Study2017In: American Journal of Sports Medicine, ISSN 0363-5465, E-ISSN 1552-3365, Vol. 45, no 9, 2077-2084 p.Article in journal (Refereed)
    Abstract [en]

    Background: The optimal treatment for middle-aged patients with knee pain and meniscal lesions has been extensively debated. Most previous studies have revealed only short-term beneficial results of knee arthroscopic surgery. The authors have previously shown a positive benefit of knee arthroscopic surgery and an exercise program after 1 year when compared with an exercise program alone. Purpose: To evaluate if knee arthroscopic surgery combined with an exercise program provided an additional long-term benefit after 3 years compared with an exercise program alone in middle-aged patients with meniscal symptoms. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Of 179 eligible patients, aged 45 to 64 years, 150 were randomized to (1) a 3-month exercise program (nonsurgery group) or (2) the same as group 1 plus knee arthroscopic surgery within 4 weeks (surgery group). The primary outcome was the change in the Knee Injury and Osteoarthritis Outcome Score (KOOS) subscore of pain between baseline and the 3-year follow-up. Results from the 1-year follow-up have been published previously. Results: Both treatment groups improved significantly in the KOOS pain subscore at 3 years follow-up in the intention-to-treat and as-treated analyses (P amp;lt; .001). The between-group difference for the change in the KOOS pain subscore between baseline and the 3-year follow-up was no longer statistically significant, neither in the intention-to-treat analysis (7.6 points; 95% CI, -0.6 to 15.9; P = .068) nor in the as-treated analysis (5.3 points; 95% CI, -3.1 to 13.8; P = .216). The factorial analysis of the effect of the intervention and age, onset of pain, and mechanical symptoms indicated that older patients improved more, regardless of treatment, and surgery may be more beneficial for patients without mechanical symptoms (as-treated analysis). The effect of the predictive factors on the KOOS pain subscore was uncertain because of the small sample size in the subgroup analyses. Conclusion: The benefit of knee arthroscopic surgery, seen at 1 year in middle-aged patients with meniscal symptoms, was diminished at 3 years and was no longer statistically significant.

  • 43.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Höög, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Johansson, Kenth
    Landstinget i Kalmar län och Sahlgrenska universitetssjukhus, Västra Götalandsregion.
    Optiska metoder för identifiering av bisköldkörtel och sköldkörtel2017Conference paper (Refereed)
    Abstract [sv]

    Identifiering av bisköldkörtlar är viktigt vid sköldkörtel- och bisköldkörtelkirurgi och kan vara svårt då de liknar omgivande vävnad såsom fett och lymfkörtlar. Peroperativ detektering av dessa vävnader kan förbättra möjligheten att bota patienter med hyperparathyroidism och minska risken för bisköldkörtelskador vid thyroideakirurgi. Optiska metoder är potentiella tekniker för att möjliggöra detta. Optiska tekniker utvärderades på vävnadsprover från patienter vid bisköldkörtel- och sköldkörteloperation. Teknikerna bestod av nära infraröd fluorescens (NIR) spektroskopi och optisk koherenstomografi (OCT) som ger en bild av vävnadens mikrostruktur liknande till ultraljud med högre upplösning (10 μm).

  • 44.
    Hammerman, Malin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Parmis
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Dansac, Arie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Eliasson, Pernilla T.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Different gene response to mechanical loading during early and late phases of rat Achilles tendon healing2017In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 123, no 4, 800-815 p.Article in journal (Refereed)
    Abstract [en]

    Mechanical loading stimulates tendon healing both when applied in the inflammatory phase and in the early remodeling phase of the process, although not necessarily via the same mechanisms. We investigated the gene response to mechanical loading in these two phases of tendon healing. The right Achilles tendon in rats was transected, and the hindlimbs were unloaded by tail suspension. The rats were exposed to 5 min of treadmill running 3 or 14 days after tendon transection. Thereafter, they were resuspended for 15 min or 3 h until euthanasia. The controls were suspended continuously. Gene analysis was first performed by microarray analysis followed by quantitative RTPCR on selected genes, focusing on inflammation. Fifteen minutes after loading, the most important genes seemed to be the transcription factors EGR1 and C-FOS, regardless of healing phase. These transcription factors might promote tendon cell proliferation and differentiation, stimulate collagen production, and regulate inflammation. Three hours after loading on day 3, inflammation was strongly affected. Seven inflammation-related genes were upregulated according to PCR: CCL20, CCL7, IL-6, NFIL3, PTX3, SOCS1, and TLR2. These genes can be connected to macrophages, T cells, and recruitment of leukocytes. According to Ingenuity Pathway Analysis, the recruitment of leukocytes was increased by loading on day 3, which also was confirmed by histology. This inflammation-related gene response was not seen on day 14. Our results suggest that the immediate gene response after mechanical loading is similar in the early and late phases of healing but the late gene response is different. NEW amp; NOTEWORTHY This study investigates the direct effect of mechanical loading on gene expression during different healing phases in tendon healing. One isolated episode of mechanical loading was studied in otherwise unloaded healing tendons. This enabled us to study a time sequence, i.e., which genes were the first ones to be regulated after the loading episode.

    The full text will be freely available from 2018-07-13 10:34
  • 45.
    Hasselgren, Kristina
    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.
    Malago, Massimo
    UCL, England.
    Vyas, Soumil
    UCL, England.
    Robles Campos, Ricardo
    Vizgen De La Arrixaca University Hospital, Spain.
    Brusadin, Roberto
    Vizgen De La Arrixaca University Hospital, Spain.
    Linecker, Michael
    University of Zurich Hospital, Switzerland.
    Petrowsky, Henrik
    University of Zurich Hospital, Switzerland.
    Clavien, Pierre Alain
    University of Zurich Hospital, Switzerland.
    Machado, Marcel Autran
    University of Sao Paulo, Brazil.
    Hernandez-Alejandro, Roberto
    University of Rochester, NY USA.
    Wanis, Kerollos
    Western University, Canada.
    Walter, Lars
    Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Sandström, 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 Surgery in Linköping.
    Björnsson, Bergthor
    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.
    Neoadjuvant chemotherapy does not affect future liver remnant growth and outcomes of associating liver partition and portal vein ligation for staged hepatectomy2017In: Surgery, ISSN 0039-6060, E-ISSN 1532-7361, Vol. 161, no 5, 1255-1265 p.Article in journal (Refereed)
    Abstract [en]

    Background. The only potentially curative treatment for patients with colorectal liver metastases is hepatectomy. Associating liver partition and portal vein ligation for staged hepatectomy has emerged as a method of treatment for patients with inadequate future liver remnant. One concern about associating liver partition and portal vein ligation for staged hepatectomy is that preoperative chemotherapy may negatively affect the volume increase of the future liver remnant and outcomes. Methods. This study from the International Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy Registry (NCT01924741) includes 442 patients with colorectal liver metastases registered from 2012-2016. Future liver remnant hypertrophy (absolute increase, percent increase, and kinetic growth rate) and clinical outcome were analyzed retrospectively in relation to type and amount of chemotherapy. The analyzed groups included patients with no chemotherapy, 1 regimen of chemotherapy, amp;gt; 1 regimen, and a group that received monoclonal antibodies in addition to chemotherapy. Results. Ninety percent of the patients received neoadjuvant oncologic therapy including 42% with 1 regimen of chemotherapy, 44% with monoclonal antibodies, and 4% with amp;gt; 1 regimen. Future liver remnant increased between 74-92% with the largest increase in the group with 1 regimen of chemotherapy. The increase in milliliters was between 241 mL (amp;gt; 1 regimen) and 306 mL (1 regimen). Kinetic growth rate was between 14-18% per week and was greatest for the group with 1 regimen of chemotherapy. No statistical significance was found between the groups with any of the measurements of future liver remnant hypertrophy. Conclusion. Neoadjuvant chemotherapy, including monoclonal antibodies, does not negatively affect future liver remnant growth. Patients with colorectal liver metastases who might be potential candidates for associating liver partition and portal vein ligation for staged hepatectomy should be considered for neoadjuvant chemotherapy. (Surgery 2017;161:1255-65.)

  • 46.
    Henriksson, Hanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden; University of Granada, Spain.
    Eriksson, Britt
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Forsum, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Flinke Carlsson, Eva
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Henriksson, Pontus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. University of Granada, Spain.
    Löf, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    Longitudinal assessment of body composition in healthy Swedish children from 1 week until 4 years of age2017In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 71, no 11, 1345-1352 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/OBJECTIVES: Knowledge of longitudinal body composition development is required to identify the mechanisms behind childhood overweight and obesity and to prevent these conditions. However, accurate data on this development in early childhood are lacking. Our aim was to describe the longitudinal body composition development in healthy young Swedish children. SUBJECTS/METHODS: Body size and composition were assessed in 26 children using air-displacement plethysmography (1 and 12 weeks and 4.4 years of age) and isotope dilution (1.5 and 3 years of age) and compared with available reference data. RESULTS: Body fat (%) for boys (n = 16) was 12.8 +/- 3.9 (1 week), 25.6 +/- 4.8 (12 weeks), 28.2 +/- 3.8 (1.5 years), 27.3 +/- 5.1 (3 years) and 26.1 +/- 3.5 (4.4 years). For girls (n = 10) these values were 15.3 +/- 2.9, 25.7 +/- 3.9, 27.9 +/- 3.3, 26.3 +/- 7.2 and 26.0 +/- 5.3, respectively. These values were above the Fomon reference values at 1.5 years of age and later and higher than the Butte reference (Po0.05) for boys at 1.5 years of age. At all ages the coefficients of variation were higher for body fat (%) (12-30%) than for BMI (4-11%). CONCLUSIONS: At 4 years of age our children had more body fat than indicated by reference data. This high level may have already been established at 1.5 years of age but our small sample and the lack of appropriate reference data limit the possibility of drawing firm conclusions. Our results demonstrate the limitations of BMI when investigating overweight and obesity in early life and highlight the need for appropriate reference body composition data in infants and young children.

  • 47.
    Herrera, I.
    et al.
    SINTEF, Norway.
    Grotan, T. O.
    SINTEF, Norway.
    Woltjer, R.
    Swedish Def Research Agency FOI, Sweden.
    Nevhage, B.
    Swedish Def Research Agency FOI, Linkoping, Sweden.
    Nilsson, S.
    Swedish Def Research Agency FOI, Linkoping, Sweden.
    Trnka, J.
    Swedish Def Research Agency FOI, Linkoping, Sweden.
    Adini, B.
    Ben Gurion University of Negev, Israel.
    Cohen, O.
    Ben Gurion University of Negev, Israel.
    Forsberg, Rebecca
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Disaster Medicine and Traumatology.
    Jonson, Carl-Oscar
    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 Disaster Medicine and Traumatology.
    Applying resilience concepts in crisis management and critical infrastructures-the DARWIN project2017In: RISK, RELIABILITY AND SAFETY: INNOVATING THEORY AND PRACTICE, CRC PRESS-TAYLOR & FRANCIS GROUP , 2017, 2137-2144 p.Conference paper (Refereed)
    Abstract [en]

    Recent crises and disasters, both natural and man-made have led to the conclusion that there is a need for a resilient approach to preparing for and dealing with such events is needed. In this context, the DARWIN project aims to improve response to expected and unexpected crises affecting critical infrastructures and social structures by developing management guidelines on resilience concepts and innovative training modules for crisis management. The guidelines will cover essential resilience abilities of stakeholders to anticipate, monitor, respond, adapt, learn and evolve, to ensure efficient operation in face of crises. This paper uses a selection of resilience concepts to illustrate how resilience management guidelines can be used to understand and improve crises management. The application of the concepts to this specific case is an experiment to guide further work. This experiment shows that resilience guidelines should enable discovery on how multiple actors operate in a flexible manner and adapt in rapidly changing environment. Further work, needs to specify a set of guidelines co-developed and tested with end-users.

  • 48.
    Hilborn, Erik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    Alexeyenko, Andrey
    Karolinska Institute, Sweden; National Bioinformat Infrastruct Sweden, Sweden.
    Jansson, Agneta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    The regulation of hydroxysteroid 17 beta-dehydrogenase type 1 and 2 gene expression in breast cancer cell lines by estradiol, dihydrotestosterone, microRNAs, and genes related to breast cancer2017In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 37, 62183-62194 p.Article in journal (Refereed)
    Abstract [en]

    Aim. To investigate the influence of estrogen, androgen, microRNAs, and genes implicated in breast cancer on the expression of HSD17B1 and HSD17B2. Materials. Breast cancer cell lines ZR-75-1, MCF7, T47D, SK-BR-3, and the immortalized epithelial cell line MCF10A were used. Cells were treated either with estradiol or dihydrotestosterone for 6, 24, 48 hours, or 7 days or treated with miRNAs or siRNAs predicted to influence HSD17B expression Results and discussion. Estradiol treatment decreased HSD17B1 expression and had a time-dependent effect on HSD17B2 expression. This effect was lost in estrogen receptor-alpha down-regulated or negative cell lines. Dihydrotestosterone treatment increased HSD17B2 expression, with limited effect on HSD17B1 expression. No effect was seen in cells without AR or in combination with the AR inhibitor hydroxyflutamide. The miRNA-17 up-regulated HSD17B1, while miRNA-210 and miRNA-7-5p had up- and down-regulatory effect and miRNA-1304-3p reduced HSD17B1 expression. The miRNA-204-5p, 498, 205-3p and 579-3p reduced HSD17B2 expression. Downregulation of CX3CL1, EPHB6, and TP63 increased HSD17B1 and HSD17B2 expression, while GREB1 downregulation suppressed HSD17B1 and promoted HSD17B2 expression. Conclusion. We show that HSD17B1 and HSD17B2 are controlled by estradiol, dihydrotestosterone, and miRNAs, as well as modulated by several breast cancer-related genes, which could have future clinical applications.

  • 49.
    Hilborn, Erik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    Jansson, Agneta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Estrogen and androgen-converting enzymes 17 beta-hydroxysteroid dehydrogenase and their involvement in cancer: with a special focus on 17 beta-hydroxysteroid dehydrogenase type 1, 2, and breast cancer2017In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 18, 30552-30562 p.Article, review/survey (Refereed)
    Abstract [en]

    Sex steroid hormones such as estrogens and androgens are involved in the development and differentiation of the breast tissue. The activity and concentration of sex steroids is determined by the availability from the circulation, and on local conversion. This conversion is primarily mediated by aromatase, steroid sulfatase, and 17 beta-hydroxysteroid dehydrogenases. In postmenopausal women, this is the primary source of estrogens in the breast. Up to 70-80% of all breast cancers express the estrogen receptor-a, responsible for promoting the growth of the tissue. Further, 60-80% express the androgen receptor, which has been shown to have tissue protective effects in estrogen receptor positive breast cancer, and a more ambiguous response in estrogen receptor negative breast cancers. In this review, we summarize the function and clinical relevance in cancer for 17 beta-hydroxysteroid dehydrogenases 1, which facilitates the reduction of estrone to estradiol, dehydroepiandrosterone to androstendiol and dihydrotestosterone to 3 alpha- and 3 beta-diol as well as 17 beta-hydroxysteroid dehydrogenases 2 which mediates the oxidation of estradiol to estrone, testosterone to androstenedione and androstendiol to dehydroepiandrosterone. The expression of 17 beta-hydroxysteroid dehydrogenases 1 and 2 alone and in combination has been shown to predict patient outcome, and inhibition of 17 beta-hydroxysteroid dehydrogenases 1 has been proposed to be a prime candidate for inhibition in patients who develop aromatase inhibitor resistance or in combination with aromatase inhibitors as a first line treatment. Here we review the status of inhibitors against 17 beta-hydroxysteroid dehydrogenases 1. In addition, we review the involvement of 17 beta-hydroxysteroid dehydrogenases 4, 5, 7, and 14 in breast cancer.

  • 50.
    Hollman Frisman, Gunilla
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Wåhlin, Ingrid
    Intensive Care Department, Kalmar Hospital, Linnaeus University, Kalmar.
    Orwelius, Lotti
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Ågren, Susanna
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Health-promoting conversations: A novel approach to families experiencing critical illness in the ICU environment.2017In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702Article in journal (Refereed)
    Abstract [en]

    AIMS AND OBJECTIVES: The aim of this study was to identify and describe the outcomes of a nurse-led intervention, "Health-promoting conversations with families," regarding family functioning and well-being in families with a member who was critically ill.

    BACKGROUND: Families who have a critically ill family member in an intensive care unit face a demanding situation, threatening the normal functioning of the family. Yet, there is a knowledge gap regarding family members' well-being during and after critical illness.

    DESIGN: The study utilized a qualitative inductive-descriptive design.

    METHODS: Eight families participated in health-promoting conversations aimed to create a context for change related to the families' identified problems and resources. Fifteen qualitative interviews were conducted with 18 adults who participated in health-promoting conversations about a critical illness in the family. Eight participants were patients (6 men, 2 women) and 10 were family members (2 male partners, 5 female partners, 1 mother, 1 daughter, 1 female grandchild). The interviews were analyzed by conventional content analysis.

    RESULTS: Family members experienced strengthened togetherness, a caring attitude, and confirmation through health-promoting conversations. The caring and calming conversations were appreciated despite the reappearance of exhausting feelings. Working through the experience and being confirmed promoted family well-being.

    CONCLUSION: Health-promoting conversations were considered to be healing, as the family members take part in sharing each other's feelings, thoughts, and experiences with the critical illness.

    RELEVANCE TO CLINICAL PRACTICE: Health-promoting conversations could be a simple and effective nursing intervention for former intensive care patients and their families in any cultural context. This article is protected by copyright. All rights reserved.

    The full text will be freely available from 2018-07-19 15:55
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