215 results on '"Nilsson AC"'
Search Results
2. A population-based prospective study of optic neuritis
- Author
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Soelberg, K, primary, Jarius, S, additional, Skejoe, HPB, additional, Engberg, H, additional, Mehlsen, JJ, additional, Nilsson, AC, additional, Madsen, JS, additional, Reindl, M, additional, Wildemann, B, additional, Grauslund, J, additional, Kyvik, KO, additional, Smith, TJ, additional, Lillevang, ST, additional, Paul, F, additional, Weinshenker, BG, additional, and Asgari, N, additional
- Published
- 2017
- Full Text
- View/download PDF
3. Molecular pathophysiology of L-DOPA-induced dyskinesia
- Author
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Nilsson, AC
- Published
- 2024
- Full Text
- View/download PDF
4. Predictive values of anti-cyclic citrullinated peptide antibodies and rheumatoid factor in relation to serological aspects of the ACR/EULAR 2010 classification criteria for rheumatoid arthritis.
- Author
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Tenstad, HB, Nilsson, AC, Dellgren, CD, Lindegaard, HM, Rubin, KH, Lillevang, ST, Tenstad, H B, Nilsson, A C, Dellgren, C D, Lindegaard, H M, Rubin, K H, and Lillevang, S T
- Subjects
- *
RHEUMATOID factor , *RHEUMATOID arthritis , *IMMUNOGLOBULIN M , *CLINICAL immunology , *IMMUNOGLOBULINS , *SOCIAL security numbers - Abstract
Objective: In this retrospective population-based register study, we wanted to determine the positive predictive values (PPVs) of immunoglobulin M rheumatoid factor (IgM RF) and anti-citrullinated protein antibodies (ACPAs) at 3 × upper normal limit (UNL), since they are weighted equally in the American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) 2010 criteria for rheumatoid arthritis (RA).Methods: Test results, ordering unit, test date, and patient social security number were collected from the Department of Clinical Immunology at Odense University Hospital from 2007 to 2016 and merged with patient diagnosis from the Danish National Patient Registry.Results: The PPV of IgM RF at 3 × UNL was 14%, compared to a PPV of 43% for ACPAs at 3 × UNL.Conclusion: The PPV of ACPAs is higher than the PPV of IgM RF at 3 × UNL. These findings are not reflected in the ACR/EULAR 2010 classification criteria for RA. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
5. Effects of inogatran, a new low-molecular-weight thrombin inhibitor, in rat models of venous and arterial thrombosis, thrombolysis and bleeding time
- Author
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Börjesson I, Teger-Nilsson Ac, David Gustafsson, Margareta Elg, and Lenfors S
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Male ,Pathology ,medicine.medical_specialty ,Bleeding Time ,medicine.medical_treatment ,Glycine ,Arginine ,Antithrombins ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Thrombin ,Fibrinolytic Agents ,Piperidines ,Bleeding time ,Internal medicine ,Fibrinolysis ,Antithrombotic ,medicine ,Animals ,Thrombolytic Therapy ,Thrombus ,Sulfonamides ,medicine.diagnostic_test ,Aspirin ,business.industry ,Heparin ,Thrombosis ,Hematology ,General Medicine ,Thrombophlebitis ,medicine.disease ,Rats ,Molecular Weight ,Venous thrombosis ,Disease Models, Animal ,chemistry ,Pipecolic Acids ,Cardiology ,Inogatran ,business ,Platelet Aggregation Inhibitors ,medicine.drug - Abstract
Inogatran (MW 439 Da), a new, selective, active site inhibitor of thrombin, was evaluated in three rat models of thrombosis. In the venous thrombosis model, inogatran dose-dependently inhibited thrombus formation with a80% antithrombotic effect at a plasma concentration of 0.45 mumol l-1. In the arterial thrombosis model, inogatran dose-dependently inhibited thrombus formation, preserved vessel patency and the mean blood flow. Acetylsalicylic acid (ASA) potentiated the effects of low plasma concentrations of inogatran in the arterial thrombosis model. In the model of rt-PA-induced thrombolysis of a thrombus in the carotid artery, inogatran improved the patency time and the cumulative blood flow during the two hour thrombolysis period more than rt-PA alone. At high therapeutic plasma concentration of inogatran, there was only a moderate prolongation of bleeding time compared with the control value. It is concluded that inogatran is an effective antithrombotic agent both in the venous and arterial thrombosis models and also as adjuvant to rt-PA in the thrombolysis model.
- Published
- 1996
6. Molecular pathophysiology of L-DOPA-induced dyskinesia
- Author
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Nilsson, AC, primary
- Published
- 2005
- Full Text
- View/download PDF
7. Inogatran, a novel direct low molecular weight thrombin inhibitor, given with, but not after, tissue-plasminogen activator, improves thrombolysis.
- Author
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Chen, L, Nichols, WW, Mattsson, C, Teger-Nilsson, AC, Saldeen, Tom, Mehta, JL, Chen, L, Nichols, WW, Mattsson, C, Teger-Nilsson, AC, Saldeen, Tom, and Mehta, JL
- Published
- 1996
8. Kvaliteten i Socialstyrelsens slutenvårdsregister för 1986
- Author
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Nilsson, AC, Carsjö, K, Smedby, B, Spetz, CL, Nilsson, AC, Carsjö, K, Smedby, B, and Spetz, CL
- Published
- 1992
9. Early activation of humoral proteolytic systems in patients with multiple trauma
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Risberg B, Teger-Nilsson Ac, A Medegård, Odén M, Gyzander E, Heideman M, and Bundsen P
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Adult ,Male ,medicine.medical_specialty ,Resuscitation ,Adolescent ,medicine.medical_treatment ,Alpha (ethology) ,Carboxypeptidases ,Critical Care and Intensive Care Medicine ,Fibrinolysis ,Humans ,Medicine ,Aged ,Disseminated intravascular coagulation ,business.industry ,Antithrombin ,Complement C4 ,Complement C3 ,Kallikrein ,Disseminated Intravascular Coagulation ,medicine.disease ,Blood Coagulation Factors ,Carboxypeptidase B ,Surgery ,Intensive Care Units ,Blood pressure ,Coagulation ,Anesthesia ,Wounds and Injuries ,Female ,business ,medicine.drug - Abstract
Coagulation, fibrinolytic, kallikrein, and complement systems were studied in 20 patients with multiple trauma. Three of four patients with a trauma score less than 10 on hospital arrival died, compared to one of 16 with a score over 10. Five patients developed disseminated intravascular coagulation. Signs of activated cascade systems were evident in most patients on hospital arrival. Changes were not related to trauma score, but patients with an arterial pressure below 110 mm Hg had significantly lower levels of antithrombin III and alpha 2-antiplasmin than those with higher BP. This study confirms that the cascade systems are activated very soon after multiple trauma.
- Published
- 1986
10. Thrombosis after hip replacement: Relationship to the fibrinolytic system
- Author
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Erika Gyzander, Bo Risberg, Elsa Eriksson, Bengt I. Eriksson, and Teger-Nilsson Ac
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Male ,medicine.medical_specialty ,Deep vein ,medicine.medical_treatment ,Antithrombin III ,Fibrinogen uptake test ,Tissue plasminogen activator ,Plasminogen Activators ,Postoperative Complications ,Hip replacement ,Fibrinolysis ,medicine ,Humans ,alpha-Macroglobulins ,Orthopedics and Sports Medicine ,cardiovascular diseases ,Antigens ,Aged ,Glycoproteins ,alpha-2-Antiplasmin ,business.industry ,Fibrinogen ,Plasminogen ,Thrombophlebitis ,medicine.disease ,Thrombosis ,Surgery ,Plasminogen Inactivators ,medicine.anatomical_structure ,Tissue Plasminogen Activator ,Female ,Hip Joint ,Hip Prosthesis ,business ,Complication ,Plasminogen activator ,medicine.drug - Abstract
Twenty-nine patients were operated on with the Charnley hip prosthesis. All the patients were given dextran 70 as thrombosis prophylaxis. Deep vein thrombosis (DVT) was diagnosed in 10 patients with the radioactive fibrinogen uptake test and phlebography. Variables of coagulation and fibrinolysis were studied before and after surgery. Tissue plasminogen activator (t-PA) activity in the plasma without venous occlusion decreased postoperatively, but there was no correlation with DVT. The t-PA activity in venous occlusion plasma was not reduced after surgery. Plasminogen activator inhibitor (PAI-1) levels were raised immediately postoperatively. There was a significant correlation between preoperative PAI-1 activity and development of postoperative DVT (P less than 0.05). Patients developing DVT had higher levels of PAI-1 postoperatively than patients not developing DVT. A defective fibrinolytic system, as defined by high PAI-1 activity, thus predisposed to postoperative DVT.
- Published
- 1989
11. Haemostatic Clot Formation at Anastomosis of Synthetic Venous Graft in Defibrinogenated Dogs: A Scanning Electron Microscopic Study
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G. William-Olsson, Hans-Arne Hansson, Shin Ishimaru, Teger-Nilsson Ac, and Berglin E
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Pathology ,medicine.medical_specialty ,biology ,Scanning electron microscope ,business.industry ,Batroxobin ,Hematology ,Anastomosis ,Fibrinogen ,Inferior vena cava ,Fibrin ,Surgery ,medicine.vein ,medicine ,biology.protein ,Platelet ,business ,medicine.drug ,Venous graft - Abstract
SummaryA segment of the inferior vena cava was replaced by an expanded polytetrafluoroethylene graft in 13 dogs. Five of them served as a control group, while the other 8 were moderately or severely defibrinogenated with subcutaneous batroxobin. Plasma fibrinogen decreased to extremely low values throughout the experiment in the defibrinogenated dogs except in the moderately treated group in which it temporarily rose to 0.72-0.87 g/1 on the first postoperative day.Scanning electron microscopic observations of the haemostatic clot formed at the anastomoses of the graft revealed no significant morphological differences in platelet adhesion and/or aggregation between the three groups. These findings confirmed that platelets play a key role in primary haemostasis during defibrinogenation.The fibrin network was slightly diminished and only short fibrin filaments could be seen in the moderately and severely defibrinogenated groups respectively. These differences in composition of the clots are discussed in relation to their haemostatic capacity.
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- 1981
12. Defibrinogenation as an alternative to heparinization during prolonged extracorporeal circulation in the dog
- Author
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Berglin E, Hans-Arne Hansson, Teger-Nilsson Ac, and G. William-Olsson
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Blood Platelets ,Extracorporeal Circulation ,medicine.medical_specialty ,Membrane oxygenator ,Dogs ,medicine ,Animals ,Platelet ,Blood Coagulation ,Oxygenator ,Oxygenators, Membrane ,Heparin ,business.industry ,Extracorporeal circulation ,Batroxobin ,Fibrinogen ,Hematology ,Capillary bleeding ,Surgery ,Hemoglobinometry ,Microscopy, Electron, Scanning ,Blood Coagulation Tests ,business ,Peptide Hydrolases ,medicine.drug - Abstract
A comparison has been made between Defibrase and heparin during prolonged extracorporeal circulation with a membrane oxygenator in dogs. There was less capillary bleeding and less accumulation of platelets in lungs and on oxygenator membranes in defibrinogenated dogs. It was concluded that defibrinogenation is a superior anticoagulation alternative to heparinization under these experimental conditions.
- Published
- 1976
13. Administration of plasma to dogs defibrinogenated with defibraseR
- Author
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G. William-Olsson, Svalander C, Teger-Nilsson Ac, and Berglin E
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Blood Pressure ,Pulmonary Artery ,Fibrinogen ,Fibrin Fibrinogen Degradation Products ,Dogs ,Oxygen Consumption ,Renal Artery ,Internal medicine ,Fibrinolysis ,medicine ,Animals ,Cardiac Output ,Pulse ,Adverse effect ,Kidney ,Lung ,Chemistry ,Batroxobin ,Hematology ,Carbon Dioxide ,Afibrinogenemia ,Oxygen ,medicine.anatomical_structure ,Endocrinology ,Coagulation ,Anesthesia ,Arterial pO2 ,Increased pulmonary artery pressure ,Blood Flow Velocity ,Peptide Hydrolases ,medicine.drug - Abstract
Blood or plasma with a known fibrinogen content was given to 2 groups of dogs defibrinogenated with an excess amount of DefibraseR. One group received a smaller volume corresponding to 0.05 g fibrinogen/kg bw and the other a larger volume corresponding to 0.08 g/kg bw during 1 hour. Circulation, lung and kidney functions were studied: coagulation and fibrinolysis variables were followed. The group receiving the smaller amount of fibrinogen did not show any adverse reactions. The other group showed decreasing arterial pO2, increased pulmonary artery pressure and decreased oxygen consumption. It is concluded that it is possible to give without adverse effects limited amounts of fibrinogen to dogs treated with an excess amount of DefibraseR.
- Published
- 1978
14. A sensitive assay for tissue plasminogen activator activity in plasma, using adsorption on lysine-sepharose
- Author
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Elsa Eriksson, Erika Gyzander, and Teger-Nilsson Ac
- Subjects
Urokinase ,Chromatography ,Activator (genetics) ,Chemistry ,Plasmin ,Sepharose ,medicine.medical_treatment ,Hematology ,Tissue plasminogen activator ,Plasminogen Activators ,Biochemistry ,Fibrinolysis ,Blood plasma ,Methods ,medicine ,Humans ,Adsorption ,Plasminogen activator ,medicine.drug - Abstract
Tissue plasminogen activator (t-PA) in plasma was separated from inhibitors by adsorption on lysine-Sepharose. It was then determined indirectly by measuring the plasmin generated from plasminogen with poly-lysine as stimulator, in a chromogenic, parabolic rate assay. The reaction proceeded with tissue plasminogen activator and plasmin(ogen) adsorbed on the gel, and followed the kinetics described for similar parabolic rate assays in soluble systems. The assay was standardized against melanoma plasminogen activator (m-PA) and had the sensitivity range of 0.001-0.020 IU (4-80 pg). Anti-m-PA IgG quenched the activity generated in plasma on venous occlusion and part of the activity in pre-occlusion plasma. The method was sensitive to purified urokinase. The basic plasma values in resting normal individuals were: mean 0.08, range 0.01-0.26 X 10(3) IU/l (n = 19), and after 20 min of venous occlusion: mean 2.48, range 0.24-4.34 X 10(3) IU/l (n = 10). The assay correlates well with a fibrin plate method, r = 0.96.
- Published
- 1984
15. Determination of Fast-Acting Plasmin Inhibitor (α2-Antiplasmin) in Plasma from Patients with Tendency to Thrombosis and Increased Fibrinolysis
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Rolf Olsson, Helge Myrwold, Teger-Nilsson Ac, Henry Noppa, Erika Gyzander, and Leif Wallmo
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medicine.medical_specialty ,Plasmin ,Chromogenic ,Chemistry ,Increased fibrinolysis ,medicine.medical_treatment ,Hematology ,Tripeptide ,medicine.disease ,Thrombosis ,Surgery ,Endocrinology ,α2 antiplasmin ,Physiology (medical) ,Internal medicine ,Fibrinolysis ,medicine ,In patient ,medicine.drug - Abstract
The physiologically important α2-antiplasmin has been measured by aid of a chromogenic tripeptide substrate. Low values in patients’ plasmas are found in situations with increased fibrinolysis such as streptokinase therapy and liver cirrhosis, whereas high values are found postoperatively, postpartum and after an acute thrombosis.
- Published
- 1978
16. Activity of the alpha 2-macroglobulin-plasmin complex on the plasmin specific substrate H-D-Val-Leu-Lys-p-nitroanilide
- Author
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Teger-Nilsson Ac and Erika Gyzander
- Subjects
Time Factors ,Plasmin ,Stereochemistry ,medicine.medical_treatment ,Michaelis–Menten kinetics ,Fibrin ,Mole ,medicine ,Humans ,alpha-Macroglobulins ,Fibrinolysin ,Incubation ,Protease ,biology ,Chemistry ,Hematology ,Tosylarginine Methyl Ester ,Hydrogen-Ion Concentration ,Macroglobulin ,Biochemistry ,Ionic strength ,biology.protein ,Immunoelectrophoresis, Two-Dimensional ,Oligopeptides ,circulatory and respiratory physiology ,medicine.drug - Abstract
An α 2 -macroglobulin-plasmin complex was prepared by incubation of plasmin with an excess of purified α 2 -macroglobulin. The conditions for complex formation were analysed, and formation of a complex was confirmed by crossed immunoelectrophoresis and by activity measurements on fibrin and p-tosyl-L-arginine methyl ester. The experiments indicated binding of no more than one mole of plasmin per mole of α 2 -macroglobulin. The activity of the α 2 -macroglobulin-plasmin complex and free plasmin on the plasmin specific substrate H-D-Val-Leu-Lys-p-nitroanilid was investigated under various conditions. The activity of the complex was found to be about 50% of that of free plasmin. An increase in ionic strength increased the activity of free plasmin, while the activity of the complex was essentially unaffected. There were no differences in pH-optima or Michaelis constant for free and α 2 -macroglobulin-bound plasmin.
- Published
- 1980
17. Studies during rapid defibrinogenation followed by intra-arterial infusion of plasma on the pulmonary and renal function in dogs
- Author
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Berglin E, Nilsson F, G. William-Olsson, Teger-Nilsson Ac, and Shin Ishimaru
- Subjects
medicine.medical_specialty ,Cardiac output ,Time Factors ,Blood Pressure ,Kidney ,Fibrin ,Fibrin Fibrinogen Degradation Products ,Plasma ,Dogs ,Internal medicine ,medicine ,Animals ,Cardiac Output ,Pulse ,biology ,business.industry ,Platelet Count ,Central venous pressure ,Fibrinogen ,Hematology ,Blood pressure ,medicine.anatomical_structure ,Injections, Intra-Arterial ,Renal blood flow ,Circulatory system ,Ventricular pressure ,biology.protein ,Cardiology ,Blood Gas Analysis ,business ,Glomerular Filtration Rate - Abstract
Mongrel dogs were rapidly defibrinogenated with Defibrase R . During defibrinogenation, changes in the blood coagulation and fibrinolytic systems were followed and the circulatory, pulmonary and renal functions were studied. Besides the expected decrease in the fibrinogen concentration and an increase in fibrin(ogen) degradation products, there was a decreased cardiac output and right ventricular systolic pressure. The dogs were then given plasma intraarterially during one hour in a volume corresponding to 0.08 g fibrinogen/kg b.w. and the same recordings were repeated. The fibrinogen degradation products increased and there were measurable fibrin monomers in the plasma. While the pulmonary and renal functions remained unaffected, the cardiac output, right ventricular pressure, renal artery flow and central venous pressure were increased. It is concluded that plasma can be infused intra-arterially without disturbances in the renal and pulmonary function.
- Published
- 1980
18. TOTAL HIP REPLACEMENT AND DEEP VEIN THROMBOSIS - RELATIONSHIP TO THE FIBRINOLYTIC SYSTEM
- Author
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E Eriksson, B Riseberg, Teger-Nilsson Ac, Erika Gyzander, and B Eriksson
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medicine.medical_specialty ,medicine.anatomical_structure ,business.industry ,Deep vein ,medicine ,Total hip replacement ,medicine.disease ,business ,Thrombosis ,Surgery - Abstract
Reduced fibrinolytic activity increases the risk of recurrent thromboembolism and it has been suggested thatit also plays a role in postoperative thrombosis.Material and methods. Fibrinolytic parameters were analysed in 29 patients submitted to total hip replacement. Dextran 70 was given as thrombosis prophylaxis. Blood samples weretaken pre operatively, one day and oneweek postoperatively. Venous occlusion test was done in all patients.125 I-fibrinogen test was used for deep vein thrombosis (DVT) screening.Positive test was confirmed with phlebography. Fibrinolytic activity was measured on fibrin plates. Tissueplasminogen activator (t-PA) and itsspecific inhibitor (PAI) were analysed with photometric and immunologicalmethods.Results. The first postoperative dayt-PA activity decreased and PAI increased significantly. One week after operation only PAI showed significatdifference from preoperative values.10 of the patients developed DVT.The PAI level significantly higher in DVT patients preoperatively. Thisdifference in PAI level was significant compared with non-DVT patients also one day and one week postoperatively.Conclusion. The recently discovered t-PA inhibitor (PAI) seems to be correlated to postoperative thrombosis in total hip surgery.
- Published
- 1987
19. Intrapleural instillation of streptokinase. Effects on systemic fibrinolysis
- Author
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Berglin E, Ekroth R, Teger-Nilsson Ac, and G. William-Olsson
- Subjects
Pulmonary and Respiratory Medicine ,Adult ,Male ,Streptokinase ,medicine.medical_treatment ,Thrombin time ,Fibrinogen ,Fibrin ,Fibrinolysis ,Medicine ,Humans ,Infusions, Parenteral ,Empyema ,Aged ,Hemothorax ,biology ,medicine.diagnostic_test ,business.industry ,Acute-phase protein ,Venous blood ,Middle Aged ,medicine.disease ,Anesthesia ,biology.protein ,Pleura ,Surgery ,Female ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
Ten consecutive patients aged 25 to 75 with postoperative empyema or hemothorax conventionally treated with drainage without sufficient effect were given intrapleural instillations of streptokinase (Kabikinase, 250,000 IE) for 4 hours). The effects on systemic fibrinolysis were studied. Venous blood samples for determination of fibrinolytic activity on fibrin plates, plasminogen, alpha 2-antiplasmin, alpha 2-macroglobulin, fibrinogen, fibrin(ogen) degradation products (FDP) and thrombin time were taken before instillation, after instillation and then after 24 hours. Preinstillation values were compared to the values 4 and 24 hours after instillation with Student's paired t-test. There were no differences in fibrinolytic activity, alpha 2-macroglobulin and thrombin time. There was a slight increase in plasminogen, alpha 2-antiplasmin and fibrinogen, probably due to an acute phase reaction. Fibrin degradation products showed an increase with border line significance. These changes are not consistent with generalized fibrinolysis, and it is concluded that intrapleural instillations of streptokinase can be given safely in the early posttraumatic or postoperative period.
- Published
- 1981
20. Platelet reactivity, fibrinogen and smoking
- Author
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Hans Wadenvik, Teger-Nilsson Ac, Annika Dotevall, Lars Wilhelmsen, and Jack Kutti
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Blood Platelets ,Male ,medicine.medical_specialty ,Platelet Aggregation ,Plasma factor ,Fibrinogen ,Platelet Factor 4 ,Platelet reactivity ,Fibrinogen levels ,chemistry.chemical_compound ,Internal medicine ,medicine ,Humans ,Platelet ,Blood Coagulation ,Factor VIII ,business.industry ,Smoking ,Hematology ,General Medicine ,beta-Thromboglobulin ,Thromboxane B2 ,Endocrinology ,Coagulation ,chemistry ,Immunology ,behavior and behavior mechanisms ,business ,Platelet factor 4 ,medicine.drug - Abstract
40 young healthy male volunteers (20 habitual smokers and 20 non-smokers) were investigated with respect to platelet reactivity, plasma fibrinogen and coagulation factor VIII. Smokers had significantly lower systolic blood pressures and higher venous platelet counts. The results for ADP-induced platelet aggregation, plasma concentrations for the 2 alpha-granule proteins, beta-thromboglobulin and platelet factor 4, did not differ between the 2 study groups involved; nor was there any difference between serum thromboxane B2 formation or plasma factor VIII:C activity. However, as compared to non-smokers, plasma fibrinogen levels were significantly higher among the smokers.
- Published
- 1987
21. Anticoagulation During Six Hours of Extracorporeal Perfusion. Comparison between Heparinization and Defibrinogenation
- Author
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Hans-Arne Hansson, Berglin E, Williams-Olsson G, and Teger-Nilsson Ac
- Subjects
Extracorporeal perfusion ,business.industry ,Anesthesia ,Medicine ,business - Abstract
Four dogs were given heparin and four other dogs were defibrinogenated with Defibrase®. The dogs were then perfused for six hours with a membrane oxygenator. Capillary bleeding tendency was measured with a standardized skin-flap technique. Platelet accumulation in the lungs and on the oxygenator membranes was examined with 51Cr-labelled platelets and with scanning electron microscopy. Fibrin deposits on the oxygenator membranes were examined with immunoelectrophoresis after plasmic degradation. Pump flow, gas transfer across the oxygenator membrane and coagulation data were followed.Capillary bleeding from the skin-flap was more pronounced in the dogs treated with heparin than in the defibrinogenated dogs. The 51Cr-labelled platelets accumulated in the lungs and on the membranes of both groups, but more pronounced in the heparinized animals. Scanning electron microscopy confirmed the findings for oxygenator membranes. Both groups of animals had fibrin deposits on the membranes with wide individual variations. There was no difference between the two groups concerning gas exchange across the oxygenation membranes. The pump flow was higher in the defibrinogenated dogs (mean flow 38-64 ml/min and kg bw) than in the heparinized ones (mean flow 22-40 ml/min and kg bw).Anticoagulation with Defibrase® might be an alternative to heparin during prolonged extracorporeal perfusion.
- Published
- 1975
22. Acute hepatitis non-A, non-B following administration of factor VIII concentrates
- Author
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Gert Frösner, Gunnar Norkrans, Widell A, Iwarson S, Kjellman H, and Teger-Nilsson Ac
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Adult ,medicine.medical_specialty ,Adolescent ,Hepatitis, Viral, Human ,Attack rate ,Haemophilia ,Hemophilia A ,Gastroenterology ,Von willebrand ,Mild hemophilia A ,hemic and lymphatic diseases ,Internal medicine ,Blood plasma ,medicine ,Humans ,Aged ,Hepatitis ,Factor VIII ,business.industry ,Hematology ,General Medicine ,Hepatitis B ,Middle Aged ,medicine.disease ,Hepatitis C ,von Willebrand Diseases ,Immunology ,Acute Disease ,business ,Acute hepatitis - Abstract
A retrospective survey on clinical hepatitis in patients with bleeding disorders was performed. Nine episodes of hepatitis non-A, non-B occurred in 8 out of 20 patients (40%) with mild hemophilia A or von Willebrand's disease, who had been treated with commercial factor VIII concentrates. Only two episodes of hepatitis B occurred during the study period. The non-A, non-B attack rate after the first treatment was 40 % with factor VIII concentrate obtained from large plasma pools (=2,000 donors) including professional plasma donors as compared to 8 % after treatment with factor VIII concentrate obtained from smaller (100–250 donors) plasma pools from Scandinavian donors.
- Published
- 1981
23. Pseudoendothelium formation in expanded polytetrafluoroethylene grafts implanted in the inferior vena cava of normal and defibrinogenated dogs
- Author
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Teger-Nilsson Ac, G. William-Olsson, Hans-Arne Hansson, Eva Berglin W-O, and Shin Ishimaru
- Subjects
medicine.medical_specialty ,Time Factors ,Endothelium ,Biomedical Engineering ,Medicine (miscellaneous) ,Bioengineering ,Vena Cava, Inferior ,Expanded polytetrafluoroethylene ,Anastomosis ,Structural difference ,Fibrinogen ,Inferior vena cava ,Fibrin ,Biomaterials ,Dogs ,medicine ,Animals ,Polytetrafluoroethylene ,biology ,business.industry ,Graft Survival ,Batroxobin ,Thrombosis ,General Medicine ,Surgery ,Blood Vessel Prosthesis ,medicine.anatomical_structure ,medicine.vein ,cardiovascular system ,biology.protein ,business ,medicine.drug - Abstract
The outgrowth of endothelial cells in an expanded polytetrafluoroethylene graft implanted in the canine inferior vena cava was studied by scanning electron microscopy. The adjacent endothelial cells of the vena cava started to invade the anastomotic area three days after the implantation and reached approximately the central part of the 2-cm-long graft after 21 days. There was no obvious difference in the process of endothelialization between the control group and the moderately defibrinogenated group, in which the fibrinogen concentration was at most 0.72-0.87 gm/L. A slight delay in the outgrowth of endothelial cells was noted within the first seven days in the severely defibrinogenated group, in which the fibrinogen concentration was below 0.40 gm/L. After 70 days, all grafts were completely covered by endothelial cells. The structural difference of the mural thrombus resulting from reduced fibrin formation might be a major factor influencing the endothelium formation.
- Published
- 1981
24. A comparison between effects of estradiol valerate and low dose ethinyl estradiol on haemostasis parameters
- Author
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Lindberg, UB, primary, Crona, N, additional, Stigendal, L, additional, Teger-Nilsson, AC, additional, and Silfverstolpe, G, additional
- Published
- 1989
- Full Text
- View/download PDF
25. Clinical severity of Mycoplasma pneumoniae (MP) infection is associated with bacterial load in oropharyngeal secretions but not with MP genotype.
- Author
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Nilsson AC, Björkman P, Welinder-Olsson C, Widell A, Persson K, Nilsson, Anna C, Björkman, Per, Welinder-Olsson, Christina, Widell, Anders, and Persson, Kenneth
- Abstract
Background: Disease severity in Mycoplasma pneumoniae (MP) infection could potentially be related to bacterial factors such as MP genotype (MP1 or MP2; distinguished by different adhesions proteins) or bacterial load in airway secretions. We have compared these parameters in patients who were hospitalized for MP pneumonia, with outpatients with mild MP disease.Methods: MP bacterial load was measured by real-time PCR in 45 in- and outpatients ("clinical study group") in whom MP DNA had been detected in oropharyngeal secretions by PCR. In addition, genotype and phylogenetic relationships were determined. The phylogenetical assessment was done by partial DNA sequencing of the P1 gene on isolates from 33 patients in the clinical study-group where sufficient DNA was available. The assessment was further extended to isolates from 13 MP-positive family members and 37 unselected MP positive patients from the two subsequent years and two different geographical locations. In total 83 strains were molecular characterized.Results: Mean MP loads were significantly higher in 24 hospitalized patients than in 21 outpatients (1600 vs. 170 genomic equivalents/microL, p = 0.009). This difference remained significant after adjustment for age and days between disease onset and sampling. Hospitalized patients also had higher C-reactive protein levels. Mean levels were 188 vs 20 mg/L (p = 0,001). The genotype assessment showed MP genotype 1 in 17 of the 33 sequenced strains from the clinical study-group, and type 2 in 16 of these patients. Within each genotype, sequence differences were minimal. No association between disease severity and MP genotype was observed. In the extended genotype assessment, MP1 was found in similar proportions. In family contacts it was found in 53% and among patients from the two subsequent years 53% and 40%.Conclusions: A higher MP bacterial load in throat secretions at diagnosis was associated with more advanced respiratory disease in patients, but MP genotype did not influence disease severity. Both MP genotypes co-circulated during recent outbreaks in Sweden. [ABSTRACT FROM AUTHOR]- Published
- 2010
- Full Text
- View/download PDF
26. 'Does this fecal microbiota transplant work?' Quality assurance of capsule based fecal microbiota transplant production.
- Author
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Jochumsen EA, Kragsnaes MS, Nilsson AC, Rasmussen KF, Ellingsen T, Juul MA, Kjeldsen J, and Holm DK
- Subjects
- Humans, Female, Male, Middle Aged, Capsules, Aged, Quality Assurance, Health Care, Colonoscopy, Treatment Outcome, Clostridioides difficile, Feces microbiology, Adult, Aged, 80 and over, Administration, Oral, Fecal Microbiota Transplantation, Clostridium Infections therapy
- Abstract
Background: Fecal Microbiota Transplant (FMT) is an effective treatment for recurring Clostridioides Difficile Infections (rCDI). FMT administered via oral capsules (caFMT) offers several practical advantages to conventional liquid FMT. We began using caFMT in 2021 imported from an external institution. Based on similar production methods, we began our own caFMT production in 2022. We aimed to evaluate the quality of our caFMT., Study Design and Methods: We created a database of all FMT treatments ( n = 180) provided by our institution. Quality of all FMT was evaluated by treatment success rates. We compared our caFMT to the imported caFMT., Results: Our caFMT yielded similar success rates compared to that of the imported caFMT, 65% (CI 95% 58-72%) and 72% (CI 95% 66-79%) respectively. FMT administered via colonoscopy had a significantly higher success rate, 79% (CI 95% 73-85%) than own our caFMT and other routes of administration. The combined success rate of treatments increased notably for all routes of administration when repeating FMT after prior failure., Discussion: The fact that our caFMT compared similarly to the imported caFMT was viewed as a success in terms of quality assurance. Our caFMT had a slightly lower success rates compared to data from other studies, but could be affected by several other factors than our FMT-production methods. A lower success rate of caFMT compared to FMT via colonoscopy is acceptable due to the practical advantages offed by caFMT. Our study serves as a practical example, proving that of the standardization of caFMT production is indeed viable.
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- 2024
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27. Humoral and cellular immune response from first to fourth SARS-CoV-2 mRNA vaccination in anti-CD20-treated multiple sclerosis patients-a longitudinal cohort study.
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Novak F, Nilsson AC, Christensen EB, Stougaard CL, Barnkob MB, Holm DK, Witt AH, Byg KE, Johansen IS, Nielsen C, and Sejbaek T
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- Humans, Male, Female, Adult, Middle Aged, Longitudinal Studies, COVID-19 Vaccines immunology, Antibodies, Monoclonal, Humanized therapeutic use, Spike Glycoprotein, Coronavirus immunology, Antigens, CD20 immunology, Vaccination, Immunoglobulin G blood, Immunoglobulin G immunology, Breakthrough Infections, COVID-19 immunology, COVID-19 prevention & control, Immunity, Humoral, SARS-CoV-2 immunology, BNT162 Vaccine immunology, Immunity, Cellular, Antibodies, Viral blood, Antibodies, Viral immunology, Multiple Sclerosis immunology, Multiple Sclerosis drug therapy
- Abstract
Background: This study examines the humoral and cellular response in multiple sclerosis (MS) patients on anti-CD20 therapy before and after the 1st to 4th BNT162b2 mRNA SARS-CoV-2 vaccination and the relationship with breakthrough infection., Methods: Participants with McDonald 2017 MS that were treated with ocrelizumab were included. The study duration was throughout the COVID-19 pandemic until four months after fourth mRNA SARS-CoV-2 vaccination (BNT162b2). Longitudinal blood samples were analysed for: IgG antibodies of SARS-CoV-2 spike anti-receptor binding domain (anti-RBD), nucleocapsid IgG antibodies (anti-N) and activation induced marker expressing CD4+, CD8+ T-cells and concentration of ocrelizumab and anti-drug antibodies. Incidences of breakthrough infection were confirmed with SARS-CoV-2 PCR tests., Results: The rate of anti-RBD positive participants increased substantially between the third and fourth vaccination from 22.2% to 55.9% (median 54.7 BAU/mL; IQR: 14.5 - 221.2 BAU/mL and 607.7 BAU/mL; IQR: 29.4 - 784.6 BAU/mL, respectively). Within the same period 75% of participants experienced breakthrough infection. The fourth vaccination resulted in an additional increase in seropositive individuals (64.3%) (median 541.8 BAU/mL (IQR: 19.1-1007 BAU/mL). Breakthrough infection did not influence the cellular response without a significant change after the fourth vaccination. During the study period two participants had detectable anti-N, both after the fourth vaccination. No correlation was found between serum concentration of ocrelizumab and the humoral and cellular response., Discussion: Low levels or absence of specific anti-RBD following vaccination, with a significant increase after breakthrough infections and boosted by the fourth vaccination. T-cell reactivity remained sustained and unaffected by breakthrough infections., Competing Interests: FN served on advisory boards for Sanofi and received travel grants from Sanofi and Merck. MB has receiving consulting honorariums from Roche and Kite/Gilead, unrelated to this work. TS has received travel grants from Biogen, Merck, Novartis, Roche, and Sanofi, has received research grants from Biogen, and has served on advisory boards for Biogen, Merck, Novartis, and Sanofi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Novak, Nilsson, Christensen, Stougaard, Barnkob, Holm, Witt, Byg, Johansen, Nielsen and Sejbaek.)
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- 2024
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28. Outcomes of Adjunctive Corticosteroid Treatment on Hypoxemic Adults Hospitalised for Mycoplasma pneumoniae Pneumonia: a Retrospective Cohort Study.
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Hagman K, Nilsson AC, Hedenstierna M, and Ursing J
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Background: Corticosteroids appears to be beneficial for severe Mycoplasma pneumoniae pneumonia in children but data in adults are limited. This study investigated effects of adjunctive corticosteroids in hypoxemic adults with M. pneumoniae pneumonia., Methods: Adults admitted 2013-2017 with verified M. pneumoniae pneumonia and hypoxemia (SpO2<93% or oxygen treatment) were included in a cohort. Treatment was defined as receipt of at least one glucocorticoid dose.Primary outcome was time to regression of hypoxemia, analysed with a multivariable Cox regression. Secondary outcomes included fever duration, length of stay, and complications., Results: Corticosteroids were given to 31% (122/388) during hypoxemia. Median age was 44 (IQR 34-57) years. Median time to start of corticosteroid treatment was 1.9 (IQR 0.6-3.6) days from admission. Median cumulative dose was equivalent to 15 (IQR 10-19) mg betamethasone. Treatment duration was 5 (IQR 3-6) days. Patients treated with corticosteroids had more severe respiratory disease, longer symptom duration and were more often treated with fluoroquinolones.Time to regression of hypoxemia (HR 0.92 [95% CI 0.72-1.19], P = 0.53) and length of stay (HR 0.91 [95% CI 0.71-1.16], P = 0.44) were not significantly different between corticosteroid treated and controls. Corticosteroid treatment was associated to shorter fever duration (HR 1.44 [95% CI 1.00-2.06], P = 0.046). Complications did not differ significantly between treatment groups., Conclusion: Adjunctive corticosteroids were not associated with reduced time to regression of hypoxemia in adults with M. pneumoniae pneumonia. However, duration of fever was shorter and no increase in complications was seen., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2024
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29. Sotrovimab lost neutralization efficacy against SARS-CoV-2 subvariants but remained clinically effective: Were monoclonal antibodies against COVID-19 rejected too early?
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Bang LL, Madsen LW, Pedersen RM, Nilsson AC, Johansen IS, and Andersen TE
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- Humans, COVID-19 Drug Treatment, SARS-CoV-2 immunology, COVID-19 immunology, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Neutralizing blood, Antibodies, Neutralizing therapeutic use, Antibodies, Viral blood, Antibodies, Monoclonal therapeutic use
- Abstract
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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- 2024
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30. Prolonged Fatigue and Mental Health Challenges in Critical COVID-19 Survivors.
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Hultgren M, Didriksson I, Håkansson A, Andertun S, Frigyesi A, Mellerstedt E, Nelderup M, Nilsson AC, Reepalu A, Spångfors M, Friberg H, and Lilja G
- Abstract
Background: The aim of this study was to investigate the development of fatigue and mental illness between 3 and 12 months after critical COVID-19 and explore risk factors for long-lasting symptoms. Study Design and Methods: A prospective, multicenter COVID-19 study in southern Sweden, including adult patients (≥18 years) with rtPCR-confirmed COVID-19 requiring intensive care. Survivors were invited to a follow-up at 3 and 12 months, where patient-reported symptoms were assessed using the Modified Fatigue Impact Scale (MFIS), the Hospital Anxiety and Depression Scale (HADS) and the Posttraumatic Stress Disorder Checklist version 5 (PCL-5). The development between 3 and 12 months was described by changes in relation to statistical significance and suggested values for a minimally important difference (MID). Potential risk factors for long-lasting symptoms were analyzed by multivariable logistic regression. Results: At the 3-month follow-up, 262 survivors (87%) participated, 215 (72%) returned at 12 months. Fatigue was reported by 50% versus 40%, with a significant improvement at 12 months (MFIS; median 38 vs. 33, P < .001, MID ≥4). There were no significant differences in symptoms of mental illness between 3 and 12 months, with anxiety present in 33% versus 28%, depression in 30% versus 22%, and posttraumatic stress disorder in 17% versus 13%. A worse functional outcome and less sleep compared to before COVID-19 were risk factors for fatigue and mental illness at 12 months. Conclusions: Fatigue improved between 3 and 12 months but was still common. Symptoms of mental illness remained unchanged with anxiety being the most reported. A worse functional outcome and less sleep compared to before COVID-19 were identified as risk factors for reporting long-lasting symptoms., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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31. Staphylococcus aureus carriage and prevalence of skin and soft tissue infections among people who inject drugs: a longitudinal study.
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Jörgensen J, Dahlman D, Alanko Blomé M, Janson H, Riesbeck K, and Nilsson AC
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- Humans, Male, Longitudinal Studies, Female, Adult, Prevalence, Staphylococcal Skin Infections epidemiology, Staphylococcal Skin Infections microbiology, Middle Aged, Staphylococcal Infections epidemiology, Staphylococcal Infections microbiology, Risk Factors, Soft Tissue Infections epidemiology, Soft Tissue Infections microbiology, Staphylococcus aureus isolation & purification, Substance Abuse, Intravenous complications, Substance Abuse, Intravenous epidemiology, Carrier State epidemiology, Carrier State microbiology
- Abstract
People who inject drugs are frequently colonized with Staphylococcus aureus and have an increased risk for skin and soft tissue infections. This longitudinal study aims to describe S. aureus carriage in this group and the risk for infections during a 1-year follow-up. We included 61 participants from the Malmö Needle Exchange Program. Mapping of S. aureus carriage was conducted by screening cultures every third month and S. aureus growth was semi-quantified. Data regarding infections and living conditions were collected from structured interviews. Statistics included univariate analysis with the Fischer's exact test, univariate logistic regression and multivariate logistic regression. S. aureus carriage was detected in 46-63% of participants, and 75% reported one or more infections during the study period. Self-reported infections were associated with carriage in perineum (OR 5.08 [95% CI 1.45-17.73]), in skin lesions (OR 1.48 [95% CI 1.21-1.81]), and unstable housing situation (OR 12.83 [95% CI 1.56-105.81]). Thus, people who inject drugs are frequent carriers of S. aureus and report a surprisingly high prevalence of skin and soft tissue infections. Homeless people and those with skin carriage seem to be at highest risk. Effective clinical interventions are needed, aiming at preventing infections in this vulnerable group., (© 2024. The Author(s).)
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- 2024
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32. Initial screening for neuronal autoantibodies and their putative impact on survival in patients with small-cell lung cancer.
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Mikkelsen AW, Nilsson AC, Tenstad HB, Lillevang ST, and Asgari N
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- Humans, Male, Female, Aged, Middle Aged, Retrospective Studies, Aged, 80 and over, Adult, Prognosis, Neurons pathology, Neurons immunology, Autoantibodies blood, Autoantibodies immunology, Small Cell Lung Carcinoma immunology, Small Cell Lung Carcinoma mortality, Small Cell Lung Carcinoma blood, Lung Neoplasms mortality, Lung Neoplasms immunology
- Abstract
Introduction: Small-cell lung cancer (SCLC) may be associated with neuronal autoantibodies and paraneoplastic neurological syndromes. It has been suggested that neuronal autoantibodies, especially antineuronal nuclear antibody type 1 (Hu) autoantibodies, are associated with longer survival of patients with SCLC. The objective of this study was to determine the frequency and distribution of neuronal autoantibodies at the time of diagnosis of SCLC patients and assess survival rates in relation to autoimmunity., Methods: In this retrospective study, serum from 40 patients with biopsy-proven SCLC at the time of diagnosis was studied prior to treatment. The sera originated from a cancer registry at the Oncology Department, Vejle Hospital from 2007 to 2010. The sera were analyzed blindly to clinical status for the presence of neuronal autoantibodies. Medical records were reviewed for neurological symptoms., Results: Neuronal autoantibodies were detected in 22/40 (55%) of the SCLC patients. A broad range of neurological symptoms was recorded in 28/40 (70%) patients, of which 14/28 (50%) were positive for neuronal autoantibodies. The most frequently detected autoantibodies were Hu (7/40, 17.5%) followed by GAD65 (6/22, 15.0%). Striational and P/Q- or N-type voltage-gated calcium channel antibodies were less common, with each found in five patients (12.5%). Eight patients (20%) had coexisting autoantibodies. Autoantibody-positivity was not associated with survival., Conclusion: Neuronal autoantibodies were at time of diagnosis found in approximately half of the treatment-naïve SCLC patients. Neither autoantibody positivity at diagnosis nor neurological manifestations correlated with survival and their clinical importance requires further studies in larger, prospective cohorts., (© 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)
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- 2024
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33. SARS-CoV-2 Antibodies in Breastmilk Three and Six Months Postpartum in Relation to the Trimester of Maternal SARS-CoV-2 Infection-An Exploratory Study.
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Fich L, Christiansen AH, Nilsson AC, Lindman J, Juul-Larsen HG, Hansen CB, la Cour Freiesleben N, Khalil MR, and Nielsen HS
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- Infant, Newborn, Pregnancy, Humans, Female, Child, Male, SARS-CoV-2, Milk, Human, Prospective Studies, Postpartum Period, Antibodies, Viral, Immunoglobulin G, Mothers, Immunoglobulin A, COVID-19
- Abstract
The immune system of neonates is immature and therefore knowledge of possible early-life protection against SARS-CoV-2 infection, such as breastfeeding, is of great importance. Few studies have investigated the presence and duration of SARS-CoV-2 antibodies in breastmilk in relation to the trimester of maternal infection during pregnancy, and none with successful participation from all three trimesters. This study has dual objectives (1) in relation to the trimester of infection to examine the frequency, concentration and duration of IgA and IgG antibodies in breastmilk and blood serum in the third and sixth month post-partum in former SARS-CoV-2-infected mothers and (2) to examine the association in pediatric emergency admission of children within the first six months of life compared to children of non-SARS-CoV-2-infected women. The first objective is based on a prospective cohort and the second is based on a nested case-control design. The study participants are women with a former SARS-CoV-2 infection during pregnancy, whose serology IgG tests at delivery were still positive. Maternal blood and breastmilk samples were collected at three and six months postpartum. Serum IgA frequency three months pp was 72.7% (50%, 90% and 60% in the first, second and third trimester) and 82% six months pp (67%, 91% and 82% in the first, second and third trimester). Breastmilk IgA frequency three months pp was 27% (16.6%, 36% and 20% in first, second and third trimester) and 28% six months pp (0%, 38% and 28% in the first, second and third trimester). The highest IgA concentration in breastmilk was found six months post-partum with infection in the third trimester. Serum IgA was detectable more than 400 days post infection, and serum IgG above threshold was found 430 days after date of infection. We found no correlation between serum IgA and breastmilk IgA, nor between serum IgG and breastmilk IgA regardless of the trimester of infection.
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- 2024
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34. Mortality of the Danish Nationwide AQP4 Antibody-Seropositive Neuromyelitis Optica Spectrum Disorder Patient Cohort.
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Papp V, Magyari M, Möller S, Sellebjerg F, Battistini JL, Svendsen KB, Søndergaard HB, Nilsson AC, and Illes Z
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- Humans, Aquaporin 4, Antibodies, Denmark epidemiology, Autoantibodies, Neuromyelitis Optica diagnosis, Multiple Sclerosis complications
- Abstract
Background and Objectives: We aimed to evaluate the mortality of patients with AQP4 antibody-seropositive (AQP4-Ab+) neuromyelitis optica spectrum disorder (NMOSD) in Denmark compared with that in the general population., Methods: We identified patients with AQP4-Ab+ NMOSD fulfilling the 2015 International Panel for Neuromyelitis Optica Diagnosis (IPND) criteria from multiple sources (laboratories and the Danish Multiple Sclerosis Registry). We obtained detailed information about patients from hospital records and about the general population matched on age, sex, and calendar year from Statistics Denmark. We calculated standardized mortality ratio (SMR), excess number of deaths per 1,000 person-years (EDR), and life expectancies compared with those of the matched general population. We examined predictive factors of mortality and the cause of death., Results: Of 66 patients with AQP4-Ab+ NMOSD between 2008 and 2020, 15 died. Overall, the SMR was 2.54 (95% CI 1.47-4.09), and the EDR was 16.8 (95% CI 4.6-34.3). The median life expectancy for patients with AQP4-Ab+ NMOSD was 64.08 years (95% CI 53.02-83.9), compared with 83.07 years for the general population. Risk of death over time was increased in the patient population with a hazard ratio (HR) of 2.22 (1.34-3.68; p = 0.002). The cause of death was directly related to NMOSD in 93% of the cases. The age at disease onset was an independent predictor of death (HR 1.042; 95% CI 1.006-1.079; p = 0.02)., Discussion: AQP4-Ab+ NMOSD is associated with increased mortality and shorter life expectancy compared with that in the general population, underlining the need for highly effective treatment approaches.
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- 2024
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35. Tick-borne encephalitis as a trigger for anti-N-Methyl-d-aspartate receptor encephalitis.
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Gaist TA, Nilsson AC, Nissen MS, Ryding MAJ, Nielsen SL, and Blaabjerg M
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- Male, Humans, Middle Aged, Europe epidemiology, Asia, Encephalitis, Tick-Borne epidemiology, Anti-N-Methyl-D-Aspartate Receptor Encephalitis complications, Encephalitis Viruses, Tick-Borne
- Abstract
Tick Borne Encephalitis (TBE) is endemic to an increasing number of countries and is a common cause of meningoencephalitis in Europe and Asia making any potential complications of the disease increasingly relevant to clinicians. We present, what is to our knowledge, the second reported case of N-methyl-d-aspartate receptor (NMDAR) encephalitis following Tick Borne Encephalitis (TBE) in a 47-year-old Lithuanian man. The case provides further evidence of TBE being a possible trigger of NMDAR encephalitis and highlights the importance of being aware of symptoms of autoimmune encephalitis in patients with infectious encephalitis., (Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.)
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- 2024
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36. Dynamics of inflammation-associated plasma proteins following faecal microbiota transplantation in patients with psoriatic arthritis and healthy controls: exploratory findings from the FLORA trial.
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Kragsnaes MS, Jensen JRB, Nilsson AC, Malik MI, Munk HL, Pedersen JK, Horn HC, Kruhøffer M, Kristiansen K, Mullish BH, Marchesi JR, Kjeldsen J, Röttger R, and Ellingsen T
- Subjects
- Humans, Fecal Microbiota Transplantation adverse effects, Interleukin-6, Treatment Outcome, Inflammation etiology, Tumor Necrosis Factor-alpha, Antigens, Neoplasm, Cell Adhesion Molecules, Arthritis, Psoriatic therapy, Arthritis, Psoriatic etiology
- Abstract
Objectives: The gut microbiota can mediate both pro and anti-inflammatory responses. In patients with psoriatic arthritis (PsA), we investigated the impact of faecal microbiota transplantation (FMT), relative to sham transplantation, on 92 inflammation-associated plasma proteins., Methods: This study relates to the FLORA trial cohort, where 31 patients with moderate-to-high peripheral PsA disease activity, despite at least 3 months of methotrexate treatment, were included in a 26-week, double-blind, randomised, sham-controlled trial. Participants were allocated to receive either one gastroscopic-guided healthy donor FMT (n=15) or sham (n=16). Patient plasma samples were collected at baseline, week 4, 12 and 26 while samples from 31 age-matched and sex-matched healthy controls (HC) were collected at baseline. Samples were analysed using proximity extension assay technology (Olink Target-96 Inflammation panel)., Results: Levels of 26 proteins differed significantly between PsA and HC pre-FMT (adjusted p<0.05), of which 10 proteins were elevated in PsA: IL-6, CCL20, CCL19, CDCP1, FGF-21, HGF, interferon-γ (IFN-γ), IL-18R1, monocyte chemotactic protein 3, and IL-2. In the FMT group, levels of 12 proteins changed significantly across all timepoints (tumour necrosis factor (TNF), CDCP1, IFN-γ, TWEAK, signalling lymphocytic activation molecule (SLAMF1), CD8A, CD5, Flt3L, CCL25, FGF-23, CD6, caspase-8). Significant differences in protein levels between FMT and sham-treated patients were observed for TNF (p=0.002), IFN-γ (p=0.011), stem cell factor (p=0.024), matrix metalloproteinase-1 (p=0.038), and SLAMF1 (p=0.042). FMT had the largest positive effect on IFN-γ, Axin-1 and CCL25 and the largest negative effect on CCL19 and IL-6., Conclusions: Patients with active PsA have a distinct immunological plasma protein signature compared with HC pre-FMT. FMT affects several of these disease markers, including sustained elevation of IFN-γ., Trial Registration Number: NCT03058900., Competing Interests: Competing interests: BHM has received consultancy fees from Finch Therapeutics Group, outside of the submitted work. JRM has received consultancy fees from Cultech Ltd., and Enterobiotix Ltd., outside of the submitted work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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37. Pathophysiological Effects of Autoantibodies in Autoimmune Encephalitides.
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Ryding M, Mikkelsen AW, Nissen MS, Nilsson AC, and Blaabjerg M
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- Humans, Autoantibodies, Consensus, Encephalitis, Hashimoto Disease, Autoimmune Diseases of the Nervous System
- Abstract
The heterogeneity of autoantibody targets in autoimmune encephalitides presents a challenge for understanding cellular and humoral pathophysiology, and the development of new treatment strategies. Thus, current treatment aims at autoantibody removal and immunosuppression, and is primarily based on data generated from other autoimmune neurological diseases and expert consensus. There are many subtypes of autoimmune encephalitides, which now entails both diseases with autoantibodies targeting extracellular antigens and classical paraneoplastic syndromes with autoantibodies targeting intracellular antigens. Here, we review the current knowledge of molecular and cellular effects of autoantibodies associated with autoimmune encephalitis, and evaluate the evidence behind the proposed pathophysiological mechanisms of autoantibodies in autoimmune encephalitis.
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- 2023
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38. Humoral antibody response following mRNA vaccines against SARS-CoV-2 in solid organ transplant recipients; a status after a fifth and bivalent vaccine dose.
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Christophorou E, Nilsson AC, Petersen I, Lindvig SO, Davidsen JR, Abazi R, Poulsen MK, Pedersen RM, Justesen US, Johansen NE, Bistrup C, Madsen LW, and Johansen IS
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- Humans, Antibody Formation, BNT162 Vaccine, Breakthrough Infections, Immunoglobulin G, mRNA Vaccines, Prospective Studies, SARS-CoV-2, Vaccines, Combined, COVID-19 prevention & control, COVID-19 Vaccines adverse effects, Organ Transplantation adverse effects
- Abstract
Background: In solid organ transplant (SOT) recipients, the humoral response following COVID-19 vaccination is reduced, as a result of their immunosuppressed treatment. In this study, we investigated antibody concentrations after booster vaccinations until the fifth dose, the latter by monovalent or bivalent BA1 or BA4/5 vaccines. In addition, we evaluated the efficacy of vaccination by recording breakthrough infections, hospitalizations, and deaths., Method: This prospective cohort study included 438 SOT recipients (>18 years) vaccinated with mRNA vaccines against COVID-19 from January 2021 until March 2023. Blood samples were drawn before and after each vaccination and tested for SARS-CoV-2 spike RBD IgG antibodies with the lowest and highest cut-off at 7.1 and 5,680 BAU/mL, respectively. Vaccine information, breakthrough infections, and hospitalizations were collected from the medical records., Results: Most participants received BNT162b2 and 61.4% received five vaccine doses. The response proportion in SOT recipients increased from 86.7% after the fourth dose to 93.0% following the fifth dose. Antibody concentration decreased with 142.7 BAU/mL between the third and fourth dose (median 132 days, Quartile 1: 123, Quartile 3: 148) and 234.3 BAU/mL between the fourth and fifth (median 250 days, Quartile 1: 241, Quartile 3: 262) dose among those without breakthrough infection (p=0.34). When comparing the Omicron BA.1 or Omicron BA.4/BA.5 adapted vaccines, no significant differences in antibody concentration were found, but 20.0% of SOT recipients receiving a monovalent fifth vaccine dose had a breakthrough infection compared to 4.0% and 7.9% among those who received BA.1 and BA.4/BA.5 adapted vaccines, respectively (p=0.04). Since January 2021, 240 (54.8%) participants had a breakthrough infection, and 22 were hospitalized, but no deaths were observed., Conclusions: The fifth COVID-19 vaccine dose raised antibody response to 93.0% of the study population. Additional booster doses, as well as bivalent vaccines, led to higher levels of antibody concentration in SOT recipients. We found a lower incidence of breakthrough infections among SOT recipients after receiving a bivalent vaccine as a fifth dose compared to those receiving a monovalent dose. Antibody concentrations did not wane when the time between doses was prolonged from four to eight months., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Christophorou, Nilsson, Petersen, Lindvig, Davidsen, Abazi, Poulsen, Pedersen, Justesen, Johansen, Bistrup, Madsen and Johansen.)
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- 2023
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39. Small Intestinal Permeability and Metabolomic Profiles in Feces and Plasma Associate With Clinical Response in Patients With Active Psoriatic Arthritis Participating in a Fecal Microbiota Transplantation Trial: Exploratory Findings From the FLORA Trial.
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Kragsnaes MS, Miguens Blanco J, Mullish BH, Serrano-Contreras JI, Kjeldsen J, Horn HC, Pedersen JK, Munk HL, Nilsson AC, Salam A, Lewis MR, Chekmeneva E, Kristiansen K, Marchesi JR, and Ellingsen T
- Abstract
Objective: We investigated intestinal permeability and fecal, plasma, and urine metabolomic profiles in methotrexate-treated active psoriatic arthritis (PsA) and how this related to clinical response following one sham or fecal microbiota transplantation (FMT)., Methods: This exploratory study is based on the FLORA trial cohort, in which 31 patients with moderate-to-high peripheral PsA disease activity, despite at least 3 months of methotrexate-treatment, were included in a 26-week, double-blind, 1:1 randomized, sham-controlled trial. Participants were randomly allocated to receive either one healthy donor FMT (n = 15) or sham (n = 16) via gastroscopy. The primary trial end point was the proportion of treatment failures through 26 weeks. We performed a lactulose-to-mannitol ratio (LMR) test at baseline (n = 31) and at week 26 (n = 26) to assess small intestinal permeability. Metabolomic profiles in fecal, plasma, and urine samples collected at baseline, weeks 4, 12, and 26 were measured using
1 H Nuclear Magnetic Resonance., Results: Trial failures (n = 7) had significantly higher LMR compared with responders (n = 19) at week 26 (0.027 [0.017-0.33]) vs. 0.012 [0-0.064], P = 0.013), indicating increased intestinal permeability. Multivariate analysis revealed a significant model for responders (n = 19) versus failures (n = 12) at all time points based on their fecal (P < 0.0001) and plasma (P = 0.005) metabolomic profiles, whereas urine metabolomic profiles did not differ between groups (P = 1). Fecal N-acetyl glycoprotein GlycA correlated with Health Assessment Questionnaire Disability Index (coefficient = 0.50; P = 0.03) and fecal propionate correlated with American College of Rheumatology 20 response at week 26 (coefficient = 27, P = 0.02)., Conclusion: Intestinal permeability and fecal and plasma metabolomic profiles of patients with PsA were associated with the primary clinical trial end point, failure versus responder., (© 2023 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)- Published
- 2023
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40. Low protection from breakthrough SARS-CoV-2 infection and mild disease course in ocrelizumab-treated patients with multiple sclerosis after three mRNA vaccine doses.
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Novak F, Bajwa HM, Coia JE, Nilsson AC, Nielsen C, Holm DK, Østergaard K, Hvidt MVM, Byg KE, Johansen IS, Mittl K, Rowles W, Zamvil SS, Bove R, Sabatino JJ Jr, and Sejbaek T
- Subjects
- Humans, BNT162 Vaccine, SARS-CoV-2, Prospective Studies, Antibodies, Monoclonal, Humanized therapeutic use, Breakthrough Infections, Disease Progression, RNA, Messenger, Antibodies, Viral, mRNA Vaccines, COVID-19 prevention & control, Multiple Sclerosis complications, Multiple Sclerosis drug therapy
- Abstract
Background: Our study investigated the rate of breakthrough SARS-CoV-2 infection and clinical outcomes in a cohort of multiple sclerosis (MS) patients who were treated with the anti-CD20 monoclonal antibody (Ab), ocrelizumab, before first, second and third BNT162b2 mRNA vaccinations. To correlate clinical outcomes with the humoral and cellular response., Methods: The study was a prospective non-randomised controlled multicentre trial observational study. Participants with a diagnosis of MS who were treated for at least 12 months with ocrelizumab prior to the first BNT162b2 mRNA vaccination were prospectively followed up from January 2021 to June 2022., Results: Out of 54 participants, 32 (59.3%) developed a positive SARS-CoV-2 PCR test in the study period. Mild infection was observed in all infected participants. After the third vaccination, the non-infected participants had higher mean Ab levels compared to the infected participants (54.3 binding antibody unit (BAU)/mL vs 26.5 BAU/mL, p=0.030). The difference in reactivity between spike-specific CD4
+ and CD8+ T lymphocytes in the two groups was not significant., Conclusion and Relevance: The study results demonstrate rates of 59% in breakthrough infections after the third SARS-CoV-2 mRNA vaccination in ocrelizumab-treated patients with MS, without resulting in critical disease courses. These findings suggest the need for continuous development of prophylactic treatments when proved important in the protection of severe breakthrough infection., Competing Interests: Competing interests: HMB, ACN, K-EB, ISJ, CN, DKH, MVMH, KM and WR have nothing to disclose. RB received research support from Biogen, Roche Genentech and Novartis; personal consulting fees from Alexion, Biogen, EMD Serono, Novartis, Roche Genentech and Sanofi Genentech; and funding from Harry Weaver Award from the National Multiple Sclerosis Society and the National Institutes of Health. SZ received consulting honoraria from Alexion, Biogen-Idec, EMD-Serono, Genzyme, Novartis, Roche/Genentech and Teva Pharmaceuticals, Inc, and served on data safety monitoring boards for Lilly, BioMS, Teva and Therapeutics. JJS received research support from Novartis. TS received travel grants from Biogen, Merck, Novartis and Roche, and research grants from Biogen, and served on advisory boards for Biogen, Merck and Novartis. FN served on advisory boards for Sanofi and received travel grants from Sanofi and Merck., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2023
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41. SARS-CoV-2 and autoantibodies in the cerebrospinal fluid of COVID-19 patients: prospective multicentre cohort study.
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Nersesjan V, Amiri M, Nilsson AC, Wamberg C, Jensen VVS, Petersen CB, Hejl AM, Lebech AM, Theut AM, Jørgensen CS, Blaabjerg M, Benros ME, and Kondziella D
- Abstract
Disease mechanisms underlying neurological and neuropsychiatric symptoms after coronavirus disease 2019 (COVID-19), termed neuro-COVID, are poorly understood. Investigations of the cerebrospinal fluid (CSF) for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and antibodies, as well as autoantibodies against neuronal surface antigens, could improve our understanding in that regard. We prospectively collected CSF and blood from patients investigated by lumbar puncture for neurological or neuropsychiatric symptoms during or after COVID-19. Primary outcomes were the presence of (i) SARS-CoV-2 RNA in CSF via polymerase chain reaction (PCR), (ii) SARS-CoV-2 immunoglobulin G (IgG) anti-S receptor-binding-domain antibodies via the Euroimmun and Wantai assays and (iii) IgG autoantibodies against neuronal surface antigens using commercial cell- and tissue-based assays (Euroimmun). Secondary outcomes were (i) routine CSF investigations and (ii) correlation between SARS-CoV-2 antibody levels in CSF with serum levels, blood-brain barrier permeability and peripheral inflammation. We obtained CSF from 38 COVID-19 patients (mean age 56.5 ± 19.2 years, 53% women) who developed neurological and neuropsychiatric symptoms. CSF pleocytosis (>5 cells) was observed in 9/38 patients (23.7%), elevated CSF protein (>0.50 g/L) in 13/38 (34.2%) and elevated CSF/serum albumin ratio in 12/35 (34.3%). PCR for SARS-CoV-2 RNA in CSF was negative in all. SARS-CoV-2 CSF antibodies were detected in 15/34 (44.1%; Euroimmun assay) and 7/31 (22.6%; Wantai assay) individuals, but there were no signs of intrathecal SARS-CoV-2 IgG production. SARS-CoV-2 CSF antibodies were positively correlated with serum levels ( R = 0.93, P < 0.001), blood-brain barrier permeability ( R = 0.47, P = 0.006), peripheral inflammation ( R = 0.51, P = 0.002) and admission to the intensive care unit [odds ratio (OR) 17.65; 95% confidence interval (CI) 1.18-264.96; P = 0.04; n = 15]. Cell-based assays detected weakly positive NMDAR, LGI1 and CASPR2 antibodies in serum of 4/34 (11.8%) patients but not in CSF. The tissue-based assay showed anti-neuronal fluorescence in CSF from one individual, staining for Purkinje cells. In summary, whereas we did not detect active SARS-CoV-2 infection in the CSF, SARS-CoV-2 antibodies were prevalent. The absence of intrathecal antibody production points towards blood-brain barrier impairment as the origin of CSF SARS-CoV-2 antibodies. In contrast, CSF autoantibodies against neuronal surface antigens were rare. There was no evidence for a clinical correlate of these antibodies. We conclude that, rather than specific autoimmune neuronal injury, non-specific effects of critical illness including an impaired blood-brain barrier are more likely to contribute to neuro-COVID., Competing Interests: The authors report no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)
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- 2023
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42. Management of influenza - updated Swedish guidelines for antiviral treatment.
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Westin J, Andersson E, Bengnér M, Berggren A, Brytting M, Ginström Ernstad E, Nilsson AC, Wahllöf M, Westman G, and Furberg M
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- Child, Female, Humans, Pregnancy, Antiviral Agents therapeutic use, Infection Control, Sweden epidemiology, Vaccination, Influenza Vaccines, Influenza, Human drug therapy, Influenza, Human prevention & control, Influenza, Human epidemiology
- Abstract
Influenza causes seasonal epidemics of respiratory infection in all parts of the world. Manifestations of influenza range from mild upper to severe lower respiratory tract infection. Medical risk groups are defined by factors predisposing for development of severe disease and are recommended annual vaccination as a protective measure. The previous Swedish treatment guidelines for influenza were issued in 2011, and a review of current evidence was deemed relevant. An important reason to revisit the guidelines is the recent approval of a novel drug for influenza treatment, baloxavir. Updated Swedish evidence-based guidelines created by a group of experts from various research areas, for the management of influenza are presented here. The work has been made in collaboration with the Public Health Agency of Sweden and the Swedish Reference Group for AntiViral therapy (RAV). The updated guidelines include guidelines for diagnostics, treatment and prophylaxis in special groups, including management of pregnant women and children with influenza. A new section about infection control has been added. Pharmacological treatment is covered in detail with regards to indication and dosage. Additionally, drug resistance and environmental aspects are discussed.
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- 2023
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43. A pilot phase 2a, randomized, double-blind, placebo-controlled study to explore the antiviral activity, clinical outcomes, safety, and tolerability of rilematovir at two dose levels in non-hospitalized adults with respiratory syncytial virus infection.
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Nilsson AC, Pullman J, Napora P, Luz K, Gupta A, Draghi J, Guzman Romero AK, Aggarwal N, Petrova G, Ianus J, Vijgen L, Scott J, Sinha R, Rusch S, Huntjens D, Bertzos K, and Stevens M
- Subjects
- Adult, Humans, Antiviral Agents adverse effects, Double-Blind Method, RNA, Respiratory Syncytial Virus Infections drug therapy, Respiratory Syncytial Virus, Human
- Abstract
Objectives: To assess the antiviral effect, clinical outcomes, and safety of the respiratory syncytial virus (RSV) fusion inhibitor rilematovir in non-hospitalized RSV-infected adults., Methods: This phase 2a, double-blind, multicentre study randomly assigned RSV-positive adult outpatients ≤5 days from symptom onset 1:1:1 to receive rilematovir 500 mg, 80 mg, or placebo once-daily for 7 days. Antiviral effect was assessed by RSV RNA viral load (VL), measured by quantitative RT-PCR, and Kaplan-Meier (KM) estimates of time to undetectable VL. Clinical course was assessed by KM estimates of median time to resolution of key RSV symptoms assessed through patient-reported outcomes., Results: RSV-positive patients (n = 72) were randomly assigned; 66 had confirmed RSV infection and received rilematovir 500 mg (n = 23), 80 mg (n = 21) or placebo (n = 22). Differences versus placebo in mean RSV RNA VL area under the curve (90% CI) through days 3, 5 and 8, respectively, were 0.09 (-0.837; 1.011), -0.10 (-2.171; 1.963), and -1.03 (-4.746; 2.682) log
10 copies.day/mL for rilematovir 500 mg, and 1.25 (0.291; 2.204), 2.53 (0.430; 4.634), and 3.85 (0.097; 7.599) log10 copies.day/mL for rilematovir 80 mg. KM estimates of median (90% CI) time-to-first confirmed undetectable VL were 5.9 (3.85; 6.90), 8.0 (6.86; 12.80) and 7.0 (6.62; 10.88) days and 5.7 (2.93; 7.01), 8.1 (6.74; 12.80) and 7.9 (6.62; 11.74) days in patients with symptom onset ≤3 days, for rilematovir 500 mg, 80 mg, and placebo, respectively. KM estimates of median (90% CI) time to resolution of key RSV symptoms were 7.1 (5.03; 11.43), 7.6 (5.93; 8.32), and 9.6 (5.95; 14.00) days for rilematovir 500 mg, 80 mg, and placebo, respectively; and in patients with symptom onset ≤3 days, median 8.0, 7.6, and 11.8 days, respectively., Discussion: Rilematovir use, initiated early, suggests a potential clinical benefit in RSV-infected adults, with data supporting development of RSV therapeutic options., Trial Registration: This study is registered with clinicaltrials.gov (NCT03379675)., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)- Published
- 2023
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44. Response to: 'Correspondence on 'Safety and efficacy of faecal microbiota transplantation for active peripheral psoriatic arthritis: an exploratory randomised placebo-controlled trial'' by McGonagle et al .
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Kragsnaes MS, Kjeldsen J, Horn HC, Munk HL, Pedersen JK, Just SA, Ahlquist P, Davidsen JR, Nilsson AC, Röttger R, Kruhøffer M, Marchesi JR, Kristiansen K, Christensen R, and Ellingsen T
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Competing Interests: Competing interests: JRM has received a paid consultancy from Enterobiotix Ltd.
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- 2023
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45. Paraneoplastic neurologic syndromes.
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Nilsson AC, Ryding M, Poulsen CA, and Blaabjerg M
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- Humans, Autoantibodies, Paraneoplastic Syndromes, Paraneoplastic Syndromes, Nervous System diagnosis
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Diagnosis of paraneoplastic neurologic syndromes (PNS) requires an understanding of the clinical, immunologic and oncologic heterogeneity. The 2004 PNS criteria were partially outdated due to advances in the field, and updated consensus criteria for PNS have been proposed in 2021, including the PNS-Care score for assessment of PNS probability. Furthermore, knowledge on the limitations of autoantibody testing is crucial to ensure accurate interpretation. This review presents the updated diagnostic criteria for PNS, in a Danish context.
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- 2023
46. Immunogenicity and risk of disease flare after a three-dose regimen with SARS-CoV-2 vaccination in patients with systemic lupus erythematosus: results from the prospective cohort study COVAC-SLE.
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Larsen ES, Nilsson AC, Möller S, Voss AB, and Johansen IS
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- Adult, Humans, Antibodies, Viral, BNT162 Vaccine, Breakthrough Infections, Immunoglobulin G, Prospective Studies, SARS-CoV-2, Symptom Flare Up, Vaccination adverse effects, COVID-19 prevention & control, COVID-19 Vaccines adverse effects, Lupus Erythematosus, Systemic diagnosis, Lupus Erythematosus, Systemic drug therapy
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Objectives: To investigate the humoral immune response and risk of disease flare in systemic lupus erythematosus (SLE) patients following three-doses of SARS-CoV-2 vaccines., Methods: In adult patients with SLE, we measured SARS-CoV-2 spike IgG in blood samples drawn three weeks after the 1st dose (baseline), four and eight weeks after the 2nd dose and after the 3rd dose. A sufficient antibody response was ≥54BAU/mL. SLEDAI-2K, SLAQ and SDI were assessed at baseline and eight weeks after the 2nd dose along with adverse events. Demographic and treatment data were collected from hospital records., Results: Of 123 patients, 115 (93.5%) received the BNT162b2 vaccine, the remaining received the 1st dose of ChAdOx-1 followed by a 2nd and 3rd dose of mRNA-1273. After the 2nd dose 102 (83%) patients had a sufficient antibody response (median 559.2, IQR 288.8-1180.5 BAU/mL), increasing to 115 (93.5%) (median 2416.9, IQR 1289-4603.8 BAU/mL) patients after the 3rd dose. Eight weeks after the 2nd dose patients treated with high dose prednisolone (p=0.034) and DMARDs (p<0.001) had significantly lower antibodies; however, this difference was not significant following the 3rd dose. Disease activity and damage were stable during the study period. Adverse events were more frequent in patients with a sufficient response. Breakthrough infections were reported in 39 (31.7%) patients; all with mild symptoms., Conclusions: A 3rd dose improved the humoral response to SARS-CoV-2 vaccines in patients with SLE to the level of healthy individuals. Vaccination did not affect SLE disease activity. Subsequent breakthrough infections were mild and did not require hospitalisation.
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- 2023
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47. Serum Neutralization of Omicron BA.5, BA.2 and BA.1 in Triple Vaccinated Kidney Transplant Recipients.
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Pedersen RM, Bang LL, Tornby DS, Nilsson AC, Nielsen C, Madsen LW, Johansen IS, Sydenham TV, Jensen TG, Justesen US, Vitved L, Palarasah Y, Bistrup C, and Andersen TE
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- 2023
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48. Antineuronal antibodies in cerebrospinal fluid and serum of 104 patients with psychotic disorders compared to 104 individually matched healthy controls.
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Jeppesen R, Nilsson AC, Sørensen NV, Orlovska-Waast S, Christensen RHB, and Benros ME
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- Humans, Autoantibodies, Immunoglobulin G, Psychotic Disorders, Encephalitis, Hashimoto Disease
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Background: Antineuronal antibodies can cause psychotic symptoms, particularly NMDAR antibodies; however, studies on the prevalence of antineuronal antibodies in cerebrospinal fluid (CSF) and serum of patients with psychotic disorders compared to matched healthy controls are sparse., Methods: We included 104 patients with a first-time diagnosis of a psychotic disorder within one year prior to inclusion (50 % outpatients) and 104 individually matched healthy controls, all without any known immunological conditions. CSF and serum were tested for IgG antibodies (Abs) against NMDAR NR1-subunit, GAD65, LGI1, CASPR2, AMPAR1, AMPAR2 and GABAb-receptor B1/B2 using commercial fixed cell-based assays (CBAs) (Euroimmun). Positive samples were retested with CBA twice, and tested with tissue-based assays (TBA). Primary outcomes were the presence of any of the seven anti-neuronal antibodies in CSF or serum. Secondarily, we analyzed the prevalence of each autoantibody., Results: No antineuronal IgG antibodies were consistently found in any CSF sample and NMDAR-antibodies were not consistently present in any of the 208 participants, neither in CSF nor serum. CASPR2-Abs were consistently found in the serum of one patient and one control, and one healthy control, without diabetes, was seropositive for GAD65-Abs. CASPR2 borderline seropositivity was additionally found in one patient and two controls. All samples positive on CBA were negative on TBA., Conclusions: We found no significant differences between patients and controls. Antineuronal IgG antibodies are very rare when screening a broad group of individuals with recent-onset psychotic disorders without other indications of autoimmune encephalitis. Thus, much larger studies are needed to conclude on potential contrasts in prevalence compared to healthy controls., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2023
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49. Salivary gland ultrasound is associated with the presence of autoantibodies in patients with Sjögren's syndrome: A Danish single-centre study.
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Schmidt NS, Voss A, Nilsson AC, Terslev L, Just SA, and Lindegaard HM
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- Humans, Autoantibodies, Salivary Glands diagnostic imaging, Salivary Glands pathology, Ultrasonography, Parotid Gland diagnostic imaging, Antibodies, Antinuclear, Sjogren's Syndrome diagnosis
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Objectives: To investigate whether ultrasound findings of major salivary glands are correlated with serological markers, autoantibodies, patient- or doctor-reported disease activity in a Danish cohort of patients with primary Sjögren's Syndrome (pSS)., Methods: In all, 49 patients at Odense University Hospital with pSS diagnosed according to the 2002 American-European Consensus Group (AECG) classification criteria were included. Patients were characterized using the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI, score of systemic complications) and EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), serologic markers, Schirmer's test and salivary test. Salivary gland ultrasound (SGUS) was performed of the submandibular and parotid glands and scored according to the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) semi-quantitative scoring system., Results: More patients with abnormal SGUS had antinuclear antibodies (ANA) (p = 0.002), anti-Ro52 (p = 0.001), anti-Ro60 (p<0.001), anti-La (p<0.001) and IgM-RF (p<0.001). Titers for ANA (p = 0.02) and anti-Ro52 (p = 0.03) were higher in patients with abnormal SGUS. Twenty-three of the pSS patients had no pathological findings on SGUS. There was no correlation between SGUS severity and ESSDAI- or ESSPRI-scores., Conclusions: Abnormal SGUS findings are associated with autoantibodies of high specificity for pSS but not with ESSDAI, ESSPRI or inflammatory markers., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Schmidt et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2022
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50. Humoral immune response following a third SARS-CoV-2 mRNA vaccine dose in solid organ transplant recipients compared with matched controls.
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Balsby D, Nilsson AC, Petersen I, Lindvig SO, Davidsen JR, Abazi R, Poulsen MK, Holden IK, Justesen US, Bistrup C, and Johansen IS
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- Adult, Humans, Immunity, Humoral, COVID-19 Vaccines, SARS-CoV-2, BNT162 Vaccine, Case-Control Studies, Antibodies, Breakthrough Infections, mRNA Vaccines, COVID-19 prevention & control, Organ Transplantation adverse effects
- Abstract
Background: Solid organ transplant (SOT) recipients have shown suboptimal antibody response following COVID-19 vaccination. Several risk factors for the diminished response have been identified including immunosuppression and older age, but the influence of different comorbidities is not fully elucidated., Method: This case-control study consisted of 420 Danish adult SOT recipients and 840 sex- and age-matched controls, all vaccinated with a third homologous dose of either BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine. The primary outcome was differences in humoral immune response. The secondary outcome was breakthrough infections. Additionally, we looked for factors that could predict possible differences between the two groups., Results: Response rate increased from 186/382 (49%) to 275/358 (77%) in SOT recipients and remained on 781/790 (99%) to 601/609 (99%) in controls following a third vaccine dose. SOT recipients had significantly lower median antibody concentrations after third dose compared to controls (332.6 BAU/ml vs 46,470.0 BAU/ml, p <0.001). Lowest median antibody concentrations were seen in SOT recipients with liver disease (10.3 BAU/ml, IQR 7.1-319) and diabetes (275.3 BAU/ml, IQR 7.3-957.4). Breakthrough infections occurred similarly frequent, 150 (40%) among cases and 301 (39%) among controls (p = 0.80)., Conclusion: A third COVID-19 vaccine dose resulted in a significant increase in humoral immunogenicity in SOT recipients and maintained high response rate in controls. Furthermore, SOT recipients were less likely to produce antibodies with overall lower antibody concentrations and humoral immunity was highly influenced by the presence of liver disease and diabetes. The prevalence of breakthrough infections was similar in the two groups., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Balsby, Nilsson, Petersen, Lindvig, Davidsen, Abazi, Poulsen, Holden, Justesen, Bistrup and Johansen.)
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- 2022
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