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- Zdolsek, Markus, 1989-
(author)
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Volume effects of albumin infusion in humans
- 2023
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Doctoral thesis (other academic/artistic)abstract
- Background: The use of colloids when treating a patient for hypovolemia has been debated throughout the years. During the last decade, albumin solutions have become the colloids of choice in both operating theatres and intensive care settings when crystalloid fluids are insufficient. The volume effects of albumin infusion are explored in this thesis. Methods: Recruitment of fluid from the interstitial fluid compartment to the plasma was estimated in healthy volunteers who received 3 ml/kg of albumin 20% infusion over 30 min. The same infusion protocol was applied to burn patients to study whether significant inflammation changes the volume effect of an albumin infusion. The influence of the infusion rate of albumin 20% on plasma volume (PV) was evaluated in a crossover fashion in healthy volunteers. Additionally, two concentrations, 5% and 20%, with equivalent amounts of albumin, were given to healthy volunteers in a crossover fashion to determine if a difference in volume effect occurred. The volume effects in terms of PV expansion and capillary leakage of albumin were calculated by mass balance and volume kinetics based on repeated blood samples. Results: There was a 10–20 min delay after completion of the albumin 20% infusion until maximum PV expansion was reached. Extravascular fluid was recruited at a ratio of 3.4 times the infused albumin 20%. Both healthy volunteers and burn patients had a 15% increase in PV. Capillary leakage of albumin occurred at a similar rate in both groups. Rapid infusion resulted in a longer intravascular half-life for albumin and a larger initial PV expansion over time without long-term negative compensation. Albumin 20% increased the PV to twice the infused volume in contrast to albumin 5%, which only increased the PV by two-thirds of the infused volume. Conclusion: Albumin infusions provide long-lasting PV expansion in both burn patients and healthy volunteers. Albumin 20% induces the recruitment of extravascular fluid, amounting to three times the infused fluid volume. A rapid infusion rate is beneficial, as it results in a larger initial PV expansion over time and a longer intravascular persistence of albumin. Further, albumin 20% provides a three times more potent PV expansion than albumin 5%. The infused fluid volume of an albumin solution depends more on the amount of albumin infused than the infused volume; albumin 20% could be preferred over other fluids for its dehydrating effect in the prevention of oedema.
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- Hober, Sophia, Professor, 1965-, et al.
(author)
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Systematic evaluation of SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay
- 2021
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In: Clinical & Translational Immunology. - : Wiley. - 2050-0068. ; 10:7
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Journal article (peer-reviewed)abstract
- Objective. The COVID-19 pandemic poses an immense need for accurate, sensitive and high-throughput clinical tests, and serological assays are needed for both overarching epidemiological studies and evaluating vaccines. Here, we present the development and validation of a high-throughput multiplex bead-based serological assay. Methods. More than 100 representations of SARS-CoV-2 proteins were included for initial evaluation, including antigens produced in bacterial and mammalian hosts as well as synthetic peptides. The five best-performing antigens, three representing the spike glycoprotein and two representing the nucleocapsid protein, were further evaluated for detection of IgG antibodies in samples from 331 COVID-19 patients and convalescents, and in 2090 negative controls sampled before 2020. Results. Three antigens were finally selected, represented by a soluble trimeric form and the S1-domain of the spike glycoprotein as well as by the C-terminal domain of the nucleocapsid. The sensitivity for these three antigens individually was found to be 99.7%, 99.1% and 99.7%, and the specificity was found to be 98.1%, 98.7% and 95.7%. The best assay performance was although achieved when utilising two antigens in combination, enabling a sensitivity of up to 99.7% combined with a specificity of 100%. Requiring any two of the three antigens resulted in a sensitivity of 99.7% and a specificity of 99.4%. Conclusion. These observations demonstrate that a serological test based on a combination of several SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay.
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