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  • 1.
    Albinsson-Stenholm, Erina
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Bergsen, Johannes
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Ingues, Simon
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Vilhelmsson, Nathalie
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Guldbrand, Hans
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Region Östergötland, Local Health Care Services in West Östergötland, "Primary Health Care in Motala". Linköping University, Faculty of Medicine and Health Sciences.
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Cityhälsan Centrum, Norrköping.
    Subjects with high fasting insulin also have higher postprandial GLP-1 and glucagon levels than controls with lower insulin2019In: Nutrition Research, ISSN 0271-5317, E-ISSN 1879-0739, Vol. 72, p. 111-120Article in journal (Refereed)
    Abstract [en]

    Little is known about postprandial release of serum ghrelin, glucagon, and glucagon-like peptide-1 (GLP-1) in relation with differing fasting insulin levels. We hypothesized that these hormones are affected by insulin resistance, and hence, we compared different postprandial responses of GLP-1, glucagon, and ghrelin in subjects with relatively high (RHI) or relatively low (RLI) fasting insulin levels. The trial was a randomized crossover study with 4 different meal conditions. Fourteen nonobese or obese, healthy, men and 14 women were randomly assigned to the order of supervised intake of a 750 kcal drink with the same protein contents but with 20 energy-percent (E%) or 55 E% from carbohydrates, and the remaining energy from fat. Participants were also randomized to consume the drinks as 1 large beverage or as five 150-kcal portions every 30 minutes. The 28 subjects were divided into 2 equally sized groups based on fasting insulin levels. Statistics were done with general linear mixed model. Fasting insulin levels were 3-fold higher in the group with RHI compared with the RLI group (RHI: 1004 +/- 510 pg/mL, RLI: 324 +/- 123 pg/mL, P amp;lt; .0005). Serum GLP-1 was highest in the RHI group after both single meals and after 5 drinks and following high- and low-carbohydrate meals (both P amp;lt;= .002), and this was the case also for glucagon levels (both P amp;lt;= .018), whereas ghrelin levels did not differ between groups. Thus, subjects with RHI displayed both higher postprandial serum GLP-1 and glucagon than the participants with RLI, suggesting that glucagon could play a role in the advent of dysglycemia by insulin resistance. (C) 2019 Elsevier Inc. All rights reserved.

  • 2.
    Appelgren, Daniel
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Enocsson, Helena
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Skogman, Barbro H
    Center for Clinical Research Dalarna-Uppsala University, Region Dalarna and Faculty of Medicine and Health Sciences, Örebro University.
    Nordberg, Marika
    Åland Central Hospital, Department of Infectious Diseases, AX-22 100 Mariehamn, Åland, Finland.
    Perander, Linda
    Åland Central Hospital, Department of Infectious Diseases, AX-22 100 Mariehamn, Åland, Finland.
    Nyman, Dag
    Bimelix AB, AX-22 100 Mariehamn, Åland, Finland.
    Nyberg, Clara
    Åland Central Hospital, Department of Infectious Diseases, AX-22 100 Mariehamn, Åland, Finland.
    Knopf, Jasmin
    Department of Internal Medicine 3-Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), DE-91 054 Erlangen, Germany.
    Muñoz, Luis E
    Department of Internal Medicine 3-Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), DE-91 054 Erlangen, Germany.
    Sjöwall, Christopher
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöwall, Johanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Neutrophil Extracellular Traps (NETs) in the Cerebrospinal Fluid Samples from Children and Adults with Central Nervous System Infections.2019In: Cells, ISSN 2073-4409, Vol. 9, no 1, article id E43Article in journal (Refereed)
    Abstract [en]

    Neutrophils operate as part of the innate defence in the skin and may eliminate the Borrelia spirochaete via phagocytosis, oxidative bursts, and hydrolytic enzymes. However, their importance in Lyme neuroborreliosis (LNB) is unclear. Neutrophil extracellular trap (NET) formation, which is associated with the production of reactive oxygen species, involves the extrusion of the neutrophil DNA to form traps that incapacitate bacteria and immobilise viruses. Meanwhile, NET formation has recently been studied in pneumococcal meningitis, the role of NETs in other central nervous system (CNS) infections has previously not been studied. Here, cerebrospinal fluid (CSF) samples from clinically well-characterised children (N = 111) and adults (N = 64) with LNB and other CNS infections were analysed for NETs (DNA/myeloperoxidase complexes) and elastase activity. NETs were detected more frequently in the children than the adults (p = 0.01). NET presence was associated with higher CSF levels of CXCL1 (p < 0.001), CXCL6 (p = 0.007), CXCL8 (p = 0.003), CXCL10 (p < 0.001), MMP-9 (p = 0.002), TNF (p = 0.02), IL-6 (p < 0.001), and IL-17A (p = 0.03). NETs were associated with fever (p = 0.002) and correlated with polynuclear pleocytosis (rs = 0.53, p < 0.0001). We show that neutrophil activation and active NET formation occur in the CSF samples of children and adults with CNS infections, mainly caused by Borrelia and neurotropic viruses. The role of NETs in the early phase of viral/bacterial CNS infections warrants further investigation.

  • 3.
    Engström, Karolina
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Vanky, Farkas
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Rehnberg, Malin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Trinks, Cecilia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Jonasson, Jon
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Green, Anna
    Orebro Univ, Sweden.
    Gunnarsson, Cecilia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Novel SMAD3 p.Arg386Thr genetic variant co-segregating with thoracic aortic aneurysm and dissection2020In: Molecular Genetics & Genomic Medicine, ISSN 2324-9269, article id e1089Article in journal (Refereed)
    Abstract [en]

    Background Pathogenic variants in the SMAD3 gene affecting the TGF-beta/SMAD3 signaling pathway with aortic vessel involvement cause Loeys-Dietz syndrome 3, also known as aneurysms-osteoarthritis syndrome. Methods Description of clinical history of a family in Sweden using clinical data, DNA sequencing, bioinformatics, and pedigree analysis. Results We report a novel SMAD3 variant, initially classified as a genetic variant of uncertain clinical significance (VUS), and later found to be co-segregating with aortic dissection in the family. The index patient presented with a dissecting aneurysm of the aorta including the ascending, descending, and abdominal parts. Genotype analysis revealed a heterozygous missense SMAD3 variant: NM_005902.3(SMAD3): c.11576G amp;gt; C (p.Arg386Thr). The same variant was also identified in a 30 years old formalin-fixed paraffin-embedded block of tissue from a second cousin, who died at 26 years of age from a dissecting aneurysm of the aorta. Conclusion A "variant of uncertain significance" according to the ACMG guidelines has always a scope for reappraisal. Genetic counselling to relatives, and the offering of surveillance service is important to families with aortic aneurysm disease. The report also highlight the potential use of FFPE analysis from deceased relatives to help in the interpretation of variants.

  • 4.
    Gutefeldt, Kerstin
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Hedman, Christina
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Thyberg, Ingrid
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Bachrack Lindström, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Arnqvist, Hans
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    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.
    Low health-related quality of life is strongly linked to upper extremity impairments in type 1 diabetes with a long duration2020In: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165Article in journal (Refereed)
    Abstract [en]

    Purpose: To compare health-related quality of life (HRQOL) in type 1 diabetes and non-diabetic controls and possible links to upper extremity impairments (UEIs). Prevalence of sick-leave and causes were investigated.

    Materials and methods: This Swedish population-based case-control study included type 1 diabetes patients <67 years old and with a diabetes duration ≥20 years. Participants completed a postal questionnaire including Short Form 36, and questions regarding UEIs, and sick-leave.

    Results: In total, 773 patients, aged 50 ± 10 years (diabetes duration 35 ± 10 years), and 708 non-diabetic controls, aged 54 ± 9 years, completed the study. Patients reported significantly lower HRQOL compared with controls. The difference was greatest for general health, vitality, and bodily pain. Patients with shoulder or hand but not finger impairments scored significantly lower than asymptomatic patients. The prevalence of sick leave was higher in patients vs. controls (23% vs. 9%, p < 0.001), and nearly half cited impairments from back, muscles, or joints as the main reason.

    Conclusions: Health-related quality of life is lower in type 1 diabetes than controls and in patients with shoulder and hand impairments than in asymptomatic. Musculoskeletal impairments (back/muscle/joints) have impact on work ability. Identification of UEIs is important for initiating preventative-, therapeutic-, and rehabilitative interventions.

    • Implications for rehabilitation
    • Upper extremity impairments (UEIs) that are common in type 1 diabetes, and associated with reduced health-related quality of life, should preferably be screened for on a regular basis along with other known diabetes complications.

    • Early identification of UEIs is important to improve health by initiating preventive as well as therapeutic multi-professional rehabilitative interventions.

    • Sick leave is higher in type 1 diabetes than in controls. Musculoskeletal impairments, including the back, muscles, and joints, are a common cause for sick leave warranting further studies.

  • 5.
    Hedman, Kristofer
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Stanford University, Stanford, USA.
    Moneghetti, Kegan J.
    Stanford University, Stanford, USA.
    Hsu, David
    Stanford University, Stanford, USA.
    Christle, Jeffrey W.
    Stanford University, Stanford, USA.
    Patti, Alessandro
    Stanford University, Stanford, USA; Univ Padua, Italy.
    Ashley, Euan
    Stanford University, Stanford, USA.
    Hadley, David
    Cardiac Insight Inc, WA USA.
    Haddad, Francois
    Stanford University, Stanford, USA.
    Froelicher, Victor
    Stanford University, Stanford, USA.
    Limitations of Electrocardiography for Detecting Left Ventricular Hypertrophy or Concentric Remodeling in Athletes2020In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 133, no 1, p. 123-132.e8Article in journal (Refereed)
    Abstract [en]

    Background

    Electrocardiography (ECG) is used to screen for left ventricular hypertrophy (LVH), but common ECG-LVH criteria have been found less effective in athletes. The purpose of this study was to comprehensively evaluate the value of ECG for identifying athletes with LVH or a concentric cardiac phenotype.

    Methods

    A retrospective analysis of 196 male Division I college athletes routinely screened with ECG and echocardiography within the Stanford Athletic Cardiovascular Screening Program was performed. Left-ventricular mass and volume were determined using echocardiography. LVH was defined as left ventricular mass (LVM) > 102 g/m²; a concentric cardiac phenotype as LVM-to-volume (M/V) ≥ 1.05 g/mL. Twelve-lead electrocardiograms including high-resolution time intervals and QRS voltages were obtained. Thirty-seven previously published ECG-LVH criteria were applied, of which the majority have never been evaluated in athletes. C-statistics, including area under the receiver operating curve (AUC) and likelihood ratios were calculated.

    Results

    ECG lead voltages were poorly associated with LVM (r = 0.18-0.30) and M/V (r = 0.15-0.25). The proportion of athletes with ECG-LVH was 0%-74% across criteria, with sensitivity and specificity ranging between 0% and 91% and 27% and 99.5%, respectively. The average AUC of the criteria in identifying the 11 athletes with LVH was 0.57 (95% confidence interval [CI] 0.56-0.59), and the average AUC for identifying the 8 athletes with a concentric phenotype was 0.59 (95% CI 0.56-0.62).

    Conclusion

    The diagnostic capacity of all ECG-LVH criteria were inadequate and, therefore, not clinically useful in screening for LVH or a concentric phenotype in athletes. This is probably due to the weak association between LVM and ECG voltage.

  • 6.
    Kaveckyte, Vaiva
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Univ Hosp, Sweden.
    Persson, Linda
    Swedish Radiat Safety Author, Sweden.
    Malusek, Alexandr
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Benmakhlouf, Hamza
    Karolinska Univ Hosp, Sweden.
    Alm Carlsson, Gudrun
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Carlsson Tedgren, Åsa
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Karolinska Univ Hosp, Sweden.
    Investigation of a synthetic diamond detector response in kilovoltage photon beams2020In: Medical physics (Lancaster), ISSN 0094-2405Article in journal (Refereed)
    Abstract [en]

    Purpose An important characteristic of radiation dosimetry detectors is their energy response which consists of absorbed-dose and intrinsic energy responses. The former can be characterized using Monte Carlo (MC) simulations, whereas the latter (i.e., detector signal per absorbed dose to detector) is extracted from experimental data. Such a characterization is especially relevant when detectors are used in nonrelative measurements at a beam quality that differs from the calibration beam quality. Having in mind the possible application of synthetic diamond detectors (microDiamond PTW 60019, Freiburg, Germany) for nonrelative dosimetry of low-energy brachytherapy (BT) beams, we determined their intrinsic and absorbed-dose energy responses in 25-250 kV beams relative to a Co-60 beam, which is usually the reference beam quality for detector calibration in radiotherapy. Material and Methods Three microDiamond detectors and, for comparison, two silicon diodes (PTW 60017) were calibrated in terms of air-kerma free in air in six x-ray beam qualities (from 25 to 250 kV) and in terms of absorbed dose to water in a Co-60 beam at the national metrology laboratory in Sweden. The PENELOPE/penEasy MC radiation transport code was used to calculate the absorbed-dose energy response of the detectors (modeled based on blueprints) relative to air and water depending on calibration conditions. The MC results were used to extract the relative intrinsic energy response of the detectors from the overall energy response. Measurements using an independent setup with a single ophthalmic BEBIG I25.S16 I-125 BT seed (effective photon energy of 28 keV) were used as a qualitative check of the extracted intrinsic energy response correction factors. Additionally, the impact of the thickness of the active volume as well as the presence of extra-cameral components on the absorbed-dose energy response of a microDiamond detector was studied using MC simulations. Results The relative intrinsic energy response of the microDiamond detectors was higher by a factor of 2 in 25 and 50 kV beams compared to the Co-60 beam. The variation in the relative intrinsic energy response of silicon diodes was within 10% over the investigated photon energy range. The use of relative intrinsic energy response correction factors improved the agreement among the absorbed dose to water values determined using microDiamond detectors and silicon diodes, as well as with the TG-43 formalism-based calculations for the I-125 seed. MC study of microDiamond detector design features provided a possible explanation for inter-detector response variation at low-energy photon beams by differences in the effective thickness of the active volume. Conclusions MicroDiamond detectors had a non-negligible variation in the relative intrinsic energy response (factor of 2) which was comparable to that in the absorbed-dose energy response relative to water at low-energy photon beams. Silicon diodes, in contrast, had an absorbed-dose energy dependence on photon energy that varied by a factor of 6, whereas the intrinsic energy dependence on beam quality was within 10%. It is important to decouple these two responses for a full characterization of detector energy response especially when the user and reference beam qualities differ significantly, and MC alone is not enough.

  • 7.
    Nasr, Patrik
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Fredrikson, Mats
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences, Forum Östergötland.
    Ekstedt, Mattias
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Kechagias, Stergios
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    The Amount of Liver Fat Predicts Mortality and Development of Type 2 Diabetes in Non-alcoholic Fatty Liver Disease.2020In: Liver international (Print), ISSN 1478-3223, E-ISSN 1478-3231Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is a risk factor for development of type 2 diabetes mellitus (T2DM). We aimed to evaluate whether conventional histological grading of steatosis and accurate quantification of fat content in liver biopsies using stereological point counting (SPC) can predict mortality and future development of T2DM in NAFLD patients.

    METHODS: 129 patients with biopsy proven NAFLD, enrolled between 1988 and 1992, were re-evaluated on two occasions, after 13.7 (±1.5) and 23.2 (±6.8) years. In patients accepting to undergo the procedure, repeat liver biopsies were performed on each follow-up and were evaluated with conventional histopathological methodology and SPC.

    RESULTS: Of the 106 patients without T2DM at baseline, 66 (62%) developed T2DM during a mean follow-up of 23.2 (± 6.8) years. Steatosis grade and liver fat measured with SPC independently (adjusted for age, BMI, fibrosis stage) predicted development of T2DM with an aHR of 1.60 per grade and 1.03 for each SPC percentage increase, respectively. Overall mortality and development of T2DM was more common in patients with grade 3 steatosis compared to lower grades of steatosis. Liver fat measured with SPC was significant for overall mortality (aHR 1.04). In patients that underwent repeat biopsy, reduction of liver fat measured with SPC was associated with decreased risk of developing T2DM (aHR 0.91 for each SPC percentage decrease).

    CONCLUSION: Steatosis grade and liver fat measured with SPC predict mortality and the risk of developing T2DM in NAFLD. Reduction of liver fat decreases the risk of developing T2DM.

  • 8.
    Nelzén, Oskar
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Skoog, Johan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Öster, Malin
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Zachrisson, Helene
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Impact on venous haemodynamics after treatment of great saphenous vein incompetence using plethysmography and duplex ultrasound2020In: Phlebology, ISSN 0268-3555, E-ISSN 1758-1125, article id 0268355519898952Article in journal (Refereed)
    Abstract [en]

    Objectives

    To evaluate postoperative venous haemodynamics and quality of life after treatment of great saphenous vein (GSV) incompetence.

    Methods

    Radiofrequency ablation and high ligation and stripping were performed in 62 patients (65 limbs) and 58 (65 limbs), respectively. Phlebectomies were performed in both modalities. Strain-gauge plethysmography on the foot combined with superficial venous occlusion was used to measure refilling time after knee bends. Strain-gauge plethysmography, duplex ultrasound and quality of life were assessed before and one month after treatment.

    Results

    Duplex ultrasound displayed successful intervention in all but two limbs. Refilling time increased similar in radiofrequency ablation and high ligation and stripping after treatment (p < 0.001). Postoperatively, strain-gauge plethysmography detected remaining reflux in 71% of the patients. Multivariate analysis showed that two or more incompetent calf branches were associated with remaining reflux (OR 4.82 (95% CI: 1.33–17.5), p = 0.02). No difference in quality of life was seen in patients with remaining reflux.

    Conclusions

    Despite successful treatment, a majority of the limbs showed remaining reflux, in which incompetent calf branches appear to play an important role.

    Clinicaltials.gov: Lower Limb Venous Insufficiency and the Effect of Radiofrequency Treatment Versus Open Surgery. Nr: NCT02397226

  • 9.
    Törnudd, Mattias
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Ramström, Sofia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Orebro Univ, Sweden.
    Kvitting, John-Peder Escobar
    Oslo Univ Hosp, Norway.
    Alfredsson, Joakim
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Pihl, Richard
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Sci, Linkoping, Sweden; Linkoping Univ, Dept Clin Chem, Linkoping, Sweden; Linkoping Univ, Dept Clin and Expt Med, Linkoping, Sweden.
    Berg, Sören
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Protamine stimulates platelet aggregation in vitro with activation of the fibrinogen receptor and alpha-granule release, but impairs secondary activation via ADP and thrombin receptors2020In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635Article in journal (Refereed)
    Abstract [en]

    Heparin and protamine are fundamental in the management of anticoagulation during cardiac surgery. Excess protamine has been associated with increased bleeding. Interaction between protamine and platelet function has been demonstrated but the mechanism remains unclear. We examined the effect of protamine on platelet function in vitro using impedance aggregometry, flow cytometry, and thrombin generation. Platelets were exposed to protamine at final concentrations of 0, 20, 40, and 80 mu g/mL, alone or together with adenosine diphosphate (ADP) or thrombin PAR1 receptor-activating peptide (TRAP). We found that in the absence of other activators, protamine (80 mu g/mL) increased the proportion of platelets with active fibrinogen receptor (binding of PAC-1) from 3.6% to 97.0% (p amp;lt; .001) measured with flow cytometry. Impedance aggregometry also increased slightly after exposure to protamine alone. When activated with ADP or TRAP protamine at 80 mu g/mL reduced aggregation, from 73.8 +/- 29.4 U to 46.9 +/- 21.1 U (p amp;lt; .001) with ADP and from 126.4 +/- 16.1 U to 94.9 +/- 23.7 U (p amp;lt; .01) with TRAP. P-selectin exposure (a marker of alpha-granule release) measured by median fluorescence intensity (MFI) increased dose dependently with protamine alone, from 0.76 +/- 0.20 (0 mu g/mL) to 10.2 +/- 3.1 (80 mu g/mL), p amp;lt; .001. Protamine 80 mu g/mL by itself resulted in higher MFI (10.16 +/- 3.09) than activation with ADP (2.2 +/- 0.7, p amp;lt; .001) or TRAP (5.7 +/- 2.6, p amp;lt; .01) without protamine. When protamine was combined with ADP or TRAP, there was a concentration-dependent increase in the alpha-granule release. In conclusion, protamine interacts with platelets in vitro having both a direct activating effect and impairment of secondary activation of aggregation by other agonists.

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