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Bergquist, Maria
Publications (10 of 22) Show all publications
Lipcsey, M., Bergquist, M., Sirén, R., Larsson, A., Huss, F., Pravda, J., . . . Janols, H. (2022). Urine Hydrogen Peroxide Levels and Their Relation to Outcome in Patients with Sepsis, Septic Shock, and Major Burn Injury. Biomedicines, 10(4), Article ID 848.
Open this publication in new window or tab >>Urine Hydrogen Peroxide Levels and Their Relation to Outcome in Patients with Sepsis, Septic Shock, and Major Burn Injury
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2022 (English)In: Biomedicines, E-ISSN 2227-9059, Vol. 10, no 4, article id 848Article in journal (Refereed) Published
Abstract [en]

Hydrogen peroxide (H2O2) and oxidative stress have been suggested as possible instigators of both the systemic inflammatory response and the increased vascular permeability associated with sepsis and septic shock. We measured H2O2 concentrations in the urine of 82 patients with severe infections, such as sepsis, septic shock, and infections not fulfilling sepsis-3 criteria, in patients with major burn injury with associated systemic inflammation, and healthy subjects. The mean concentrations of H2O2 were found to be lower in patients with severe infections compared to burn injury patients and healthy subjects. Patients with acute kidney injury (AKI), vs. those without AKI, in all diagnostic groups displayed higher concentrations of urine H2O2 (p < 0.001). Likewise, urine concentrations of H2O2 were higher in non-survivors as compared to survivors (p < 0.001) at day 28 in all diagnostic groups, as well as in patients with severe infections and burn injury (p < 0.001 for both). In this cohort, increased H2O2 in urine is thus associated with mortality in patients with sepsis and septic shock as well as in patients with burn injury.

Place, publisher, year, edition, pages
MDPI AG, 2022
Keywords
AKI, H2O2, TBSA, burn injury, hydrogen peroxide, hypermetabolism, mortality, sepsis, shock
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-473359 (URN)10.3390/biomedicines10040848 (DOI)000785106400001 ()35453598 (PubMedID)
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2022-04-26 Created: 2022-04-26 Last updated: 2024-02-20Bibliographically approved
Norin, U., Rintisch, C., Meng, L., Forster, F., Ekman, D., Tuncel, J., . . . Holmdahl, R. (2021). Endophilin A2 deficiency protects rodents from autoimmune arthritis by modulating T cell activation. Nature Communications, 12(1), Article ID 610.
Open this publication in new window or tab >>Endophilin A2 deficiency protects rodents from autoimmune arthritis by modulating T cell activation
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2021 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 12, no 1, article id 610Article in journal (Refereed) Published
Abstract [en]

The introduction of the CTLA-4 recombinant fusion protein has demonstrated therapeutic effects by selectively modulating T-cell activation in rheumatoid arthritis. Here we show, using a forward genetic approach, that a mutation in the SH3gl1 gene encoding the endocytic protein Endophilin A2 is associated with the development of arthritis in rodents. Defective expression of SH3gl1 affects T cell effector functions and alters the activation threshold of autoreactive T cells, thereby leading to complete protection from chronic autoimmune inflammatory disease in both mice and rats. We further show that SH3GL1 regulates human T cell signaling and T cell receptor internalization, and its expression is upregulated in rheumatoid arthritis patients. Collectively our data identify SH3GL1 as a key regulator of T cell activation, and as a potential target for treatment of autoimmune diseases.

Place, publisher, year, edition, pages
Springer NatureSpringer Nature, 2021
National Category
Rheumatology and Autoimmunity Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-441388 (URN)10.1038/s41467-020-20586-2 (DOI)000614500600010 ()33504785 (PubMedID)
Available from: 2021-05-03 Created: 2021-05-03 Last updated: 2024-01-15Bibliographically approved
Larsson, A., Tydén, J., Johansson, J., Lipcsey, M., Bergquist, M., Kultima, K. & Mandic-Havelka, A. (2020). Calprotectin is superior to procalcitonin as a sepsis marker and predictor of 30-day mortality in intensive care patients. Scandinavian Journal of Clinical and Laboratory Investigation, 80(2), 156-161
Open this publication in new window or tab >>Calprotectin is superior to procalcitonin as a sepsis marker and predictor of 30-day mortality in intensive care patients
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2020 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 80, no 2, p. 156-161Article in journal (Refereed) Published
Abstract [en]

Sepsis is the most frequent cause of death in the intensive care unit (ICU). A rapid and correct diagnosis and initiation of therapy is crucial for improving patient outcomes. The aim of this study was to compare the performance of calprotectin with the more widely used sepsis biomarker procalcitonin (PCT) in ICU patients. The performance of calprotectin and PCT as sepsis and prognostic markers for 30-d mortality was compared in a prospective, observational study in an eight-bed ICU. We investigated concentrations of the biomarkers in plasma collected at admission from all ICU patients admitted during a year (2012-2013, n = 271) together with simplified acute physiology 3 scores (SAPS3) and sequential organ failure assessment (SOFA) scores. The receiver operating characteristic (ROC) analysis showed a higher area under the curve (AUC) value for calprotectin (0.79) than for PCT (0.49) when used as a sepsis marker. The calprotectin concentrations at admission were higher in non-survivors than in survivors at day 30. In our study, calprotectin was superior to PCT for distinguishing between ICU patients with sepsis and non-sepsis patients. Calprotectin also had higher predictive ability regarding 30-d mortality.

Place, publisher, year, edition, pages
Informa UK Limited, 2020
Keywords
Calprotectin, SAPS3, SOFA, intensive care, procalcitonin, sepsis
National Category
Medical and Health Sciences Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-400065 (URN)10.1080/00365513.2019.1703216 (DOI)000502497900001 ()31841042 (PubMedID)
Available from: 2019-12-18 Created: 2019-12-18 Last updated: 2021-03-29Bibliographically approved
Andersson, S. E. M., Lange, E., Kucharski, D., Svedlund, S., Önnheim, K., Bergquist, M., . . . Gjertsson, I. (2020). Moderate- to high intensity aerobic and resistance exercise reduces peripheral blood regulatory cell populations in older adults with rheumatoid arthritis. Immunity & Ageing, 17, Article ID 12.
Open this publication in new window or tab >>Moderate- to high intensity aerobic and resistance exercise reduces peripheral blood regulatory cell populations in older adults with rheumatoid arthritis
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2020 (English)In: Immunity & Ageing, E-ISSN 1742-4933, Vol. 17, article id 12Article in journal (Refereed) Published
Abstract [en]

Objective: Exercise can improve immune health and is beneficial for physical function in patients with rheumatoid arthritis (RA), but the immunological mechanisms are largely unknown. We evaluated the effect of moderate- to high intensity exercise with person-centred guidance on cells of the immune system, with focus on regulatory cell populations, in older adults with RA.

Methods: Older adults (>= 65 years) with RA were randomized to either 20-weeks of moderate - to high intensity aerobic and resistance exercise (n = 24) or to an active control group performing home-based exercise of light intensity (n = 25). Aerobic capacity, muscle strength, DAS28 and CRP were evaluated. Blood samples were collected at baseline and after 20 weeks. The frequency of immune cells defined as adaptive regulatory populations, CD4 + Foxp3 + CD25 + CD127- T regulatory cells (Tregs) and CD19 + CD24hiCD38hi B regulatory cells (Bregs) as well as HLA-DR-/lowCD33 + CD11b + myeloid derived suppressor cells (MDSCs), were assessed using flow cytometry.

Results: After 20 weeks of moderate- to high intensity exercise, aerobic capacity and muscle strength were significantly improved but there were no significant changes in Disease Activity Score 28 (DAS28) or CRP. The frequency of Tregs and Bregs decreased significantly in the intervention group, but not in the active control group. The exercise intervention had no effect on MDSCs. The reduction in regulatory T cells in the intervention group was most pronounced in the female patients.

Conclusion: Moderate- to high intensity exercise in older adults with RA led to a decreased proportion of Tregs and Bregs, but that was not associated with increased disease activity or increased inflammation.

Place, publisher, year, edition, pages
BMC, 2020
Keywords
Rheumatoid arthritis, Aging, Exercise, Treg cells, T cells, Breg cells, IL-10
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-414306 (URN)10.1186/s12979-020-00184-y (DOI)000536120000001 ()32467712 (PubMedID)
Funder
Region Västra Götaland, ALFGBG-4636751Swedish Rheumatism Association, R-663361
Available from: 2020-07-27 Created: 2020-07-27 Last updated: 2024-03-06Bibliographically approved
Bergquist, M., Samuelsson, L., Larsson, A., Tydén, J., Johansson, J. & Lipcsey, M. (2020). TNFR1, TNFR2, neutrophil gelatinase-associated lipocalin and heparin binding protein in identifying sepsis and predicting outcome in an intensive care cohort. Scientific Reports, 10(1), Article ID 15350.
Open this publication in new window or tab >>TNFR1, TNFR2, neutrophil gelatinase-associated lipocalin and heparin binding protein in identifying sepsis and predicting outcome in an intensive care cohort
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2020 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1, article id 15350Article in journal (Refereed) Published
Abstract [en]

To date no biomarkers can aid diagnosing sepsis with adequate accuracy. We set out to assess the ability of Tumor necrosis factor receptor (TNFR) 1 and 2, Neutrophil gelatinase-associated lipocalin (NGAL) and Heparin binding protein (HBP) to discriminate sepsis from non-infected critically ill patients in a large ICU cohort, and to evaluate their value to predict mortality at 30 days. Adult patients admitted to the ICU with an arterial catheter were included. Clinical data and blood samples were prospectively recorded daily. Diagnoses were set retrospectively. Descriptive statistics and logistic regression models were used. NGAL, TNFR1 and TNFR2 were higher in sepsis patients compared to other diagnoses, as well as in non-survivors compared to survivors. In addition, these biomarkers increased with increasing stages of acute kidney injury. TNFR1 and TNFR2 performed similarly to NGAL and CRP in identifying sepsis patients, but they performed better than CRP in predicting 30-day mortality in this ICU cohort. Thus, TNFR1 and TNFR2 may be particularly useful in identifying high risk sepsis patients and facilitate relevant health care actions in this group of sepsis patients.

National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-420005 (URN)10.1038/s41598-020-72003-9 (DOI)000573753400006 ()32948801 (PubMedID)
Available from: 2020-09-21 Created: 2020-09-21 Last updated: 2022-09-15Bibliographically approved
Bergquist, M., Hastbacka, J., Glaumann, C., Fredén, F., Huss, F. & Lipcsey, M. (2019). The time-course of the inflammatory response to major burn injury and its relation to organ failure and outcome. Burns, 45(2), 354-363
Open this publication in new window or tab >>The time-course of the inflammatory response to major burn injury and its relation to organ failure and outcome
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2019 (English)In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 45, no 2, p. 354-363Article in journal (Refereed) Published
Abstract [en]

Burn injury causes major inflammatory activation and cytokine release, however, the temporal resolution of the acute and sub-acute inflammatory response has not yet been fully delineated. To this end, we have quantified 20 inflammatory mediators in plasma from 44 adult patients 0-21 days after burn injury and related the time course of these mediators to % total body surface area (TBSA) burned, clinical parameters, organ failure and outcome. Of the cytokines analyzed in these patients, interleukin 6 (IL-6), IL-8, IL-10 and monocyte chemoattractant protein 1 (MCP-1) correlated to the size of the injury at 24-48h after burn injury. In our study, the concentration of IL-10 had prognostic value in patients with burn injury both measured at admission and at 24-48h after injury. However, simple demographic data such as age, % burned TBSA, inhalation injury and their combination, the Baux score and modified Baux score, outperform most of the cytokines, with the exception of IL-8 and MCP1 levels on admission, in predicting death.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD, 2019
Keywords
Cytokines, Burns, Mortality, Multiple organ failure, Severity of illness index
National Category
Anesthesiology and Intensive Care Surgery
Identifiers
urn:nbn:se:uu:diva-380482 (URN)10.1016/j.burns.2018.09.001 (DOI)000461044900012 ()30274808 (PubMedID)
Available from: 2019-04-15 Created: 2019-04-15 Last updated: 2024-02-20Bibliographically approved
Bergquist, M., Huss, F., Fredén, F., Hedenstierna, G., Hästbacka, J., Rockwood, A. L., . . . Bergquist, J. (2016). Altered adrenal and gonadal steroids biosynthesis in patients with burn injury. Clinical Mass Spectrometry, 1, 19-26
Open this publication in new window or tab >>Altered adrenal and gonadal steroids biosynthesis in patients with burn injury
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2016 (English)In: Clinical Mass Spectrometry, ISSN 2213-8005, E-ISSN 2376-9998, Vol. 1, p. 19-26Article in journal (Refereed) Published
Abstract [en]

Introduction: Burn injury inevitably leads to changes in the endogenous production of cytokines, as well as adrenal and gonadal steroids. Previous studies have reported gender-related differences in outcome following burn injury, which suggests that gonadal steroids may play a role. The aim of this study was to assess alterations in concentration of endogenous steroids in patients with burn injury.

Methods: For this single-center, prospective descriptive study, high-sensitivity liquid chromatography tandem mass spectrometry (LC-MS/MS)-based steroid quantification was used to determine longitudinal profiles of the concentrations of endogenous steroids in plasma from sixteen adult male patients with burn injury (14.5-72% of total body surface area). Steroids were extracted from plasma samples and analyzed using multiple reaction monitoring acquisition, with electrospray ionization on a triple quadruple mass spectrometer. Total protein concentration was measured in the samples using spectrophotometry.

Results: Steroid and total protein concentration distributions were compared to reference intervals characteristic of healthy adult men. Concentrations of the following steroids in plasma of burn injured patients were found to correlate positively to the area of the burn injury: cortisol (r = 0.84), corticosterone (r = 0.73), 11-deoxycortisol (r = 0.72), androstenedione (r = 0.72), 17OH-progesterone (r = 0.68), 17OH-pregnenolone (r = 0.64) and pregnenolone (r = 0.77). Concentrations of testosterone decreased during the acute phase and were up to ten-times lower than reference values for healthy adult men, while concentrations of estrone were elevated. By day 21 after injury, testosterone concentrations were increased in younger, but not older, patients. The highest concentrations of estrone were observed on day 3 after the injury and then declined by day 21 to concentrations comparable to those observed on the day of the injury.

Conclusion: Burn injury alters endogenous steroid biosynthesis, with decreased testosterone concentrations and elevated estrone concentrations, during the first 21 days after the injury. Concentrations of glucocorticoids, progestagens and androgen precursors correlated positively with the area of burn injury. The finding of increased estrone following burn injury needs to be confirmed in a larger hypothesis driven study.

Keywords
Burn, Trauma, Gonadal steroids, Sex steroids, Estrogen, Testosterone, DHEA, Androstenedione, LC-MS/MS
National Category
Anesthesiology and Intensive Care Surgery
Identifiers
urn:nbn:se:uu:diva-397419 (URN)10.1016/j.clinms.2016.10.002 (DOI)000510146700004 ()
Funder
Swedish Research Council, 621-2011-4423Swedish Research Council, 2015-4870
Available from: 2019-11-20 Created: 2019-11-20 Last updated: 2024-02-20Bibliographically approved
Bergquist, M., Huss, F., Hästbacka, J., Lindholm, C., Martijn, C., Rylander, C., . . . Fredén, F. (2016). Glucocorticoid receptor expression and binding capacity in patients with burn injury. Acta Anaesthesiologica Scandinavica, 60(2), 213-221
Open this publication in new window or tab >>Glucocorticoid receptor expression and binding capacity in patients with burn injury
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2016 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, no 2, p. 213-221Article in journal (Refereed) Published
Abstract [en]

Background

Burn injuries are associated with strong inflammation and risk of secondary sepsis which both may affect the function of the glucocorticoid receptor (GR). The aim of this study was to determine GR expression and binding capacity in leucocytes from patients admitted to a tertiary burn center.

Methods

Blood was sampled from 13 patients on admission and days 7, 14 and 21, and once from 16 healthy subjects. Patients were grouped according to the extent of burn and to any sepsis on day 7. Expression and binding capacity of GR were determined as arbitrary units using flow cytometry.

Results

GR expression and binding capacity were increased compared to healthy subjects in most circulating leucocyte subsets on admission irrespective of burn size. Patients with sepsis on day 7 displayed increased GR expression in T lymphocytes (51.8%, < 0.01) compared to admission. There was a negative correlation between GR binding capacity in neutrophils and burn size after 14 days (< 0.05).

Conclusions

GR expression and binding capacity are increased in most types of circulating leucocytes of severely burned patients on their admission to specialized burn care. If sepsis is present after 1 week, it is associated with higher GR expression in T lymphocytes and NK cells.

National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-229116 (URN)10.1111/aas.12604 (DOI)000368139700009 ()
Funder
Swedish Research Council, 5315
Available from: 2014-07-31 Created: 2014-07-31 Last updated: 2018-01-11
Bergquist, M., Lindholm, C., Strinnholm, M., Hedenstierna, G. & Rylander, C. (2015). Impairment of neutrophilic glucocorticoid receptor function in patients treated with steroids for septic shock. Intensive Care Medicine Experimental, 3(1), Article ID 23.
Open this publication in new window or tab >>Impairment of neutrophilic glucocorticoid receptor function in patients treated with steroids for septic shock
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2015 (English)In: Intensive Care Medicine Experimental, E-ISSN 2197-425X, Vol. 3, no 1, article id 23Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Glucocorticoid (GC) treatment has variable effect in sepsis. This may be explained by decreased expression or function of the glucocorticoid receptor (GR). The aim of this study was to determine GR expression and binding capacity in patients during and after sepsis.

METHODS: In this prospective, non-interventional clinical study, peripheral blood and clinical data were collected from 20 adult patients at five timepoints during sepsis and 5-13 months after recovery. GR expression and binding capacity were assessed by flow cytometry.

RESULTS: GR expression was higher in T lymphocytes from patients with septic shock compared to healthy subjects (p = 0.01). While there was no difference in GR expression between GC-treated and non-treated patients, GR binding capacity was lower in GC-treated patients at admission compared to healthy subjects (p ≤ 0.03). After the acute inflammation inflammatory phase, GR binding capacity was still lower in neutrophils of GC-treated patients, compared to healthy subjects (p = 0.01). On admission, GR binding capacity in T lymphocytes and neutrophils was inversely correlated with noradrenaline dose and lactate (p ≤ 0.03).

CONCLUSIONS: Our data suggest that GR expression is increased in T lymphocytes during septic shock regardless of GC treatment, while GR binding capacity is decreased in neutrophils in GC-treated patients. As neutrophils are the predominant circulating leucocyte in septic shock, their decreased GR binding capacity may impede the response to exogenous or endogenous glucocorticoids.

National Category
Medical and Health Sciences
Research subject
Biochemistry; Anaesthesiology and Intensive Care; Physiology
Identifiers
urn:nbn:se:uu:diva-264213 (URN)10.1186/s40635-015-0059-9 (DOI)26215823 (PubMedID)
Available from: 2015-10-07 Created: 2015-10-07 Last updated: 2020-11-18Bibliographically approved
Borges, J. B., Costa, E. L. V., Bergquist, M., Lucchetta, L., Widström, C., Maripuu, E., . . . Hedenstierna, G. (2015). Lung Inflammation Persists After 27 Hours of Protective Acute Respiratory Distress Syndrome Network Strategy and Is Concentrated in the Nondependent Lung. Critical Care Medicine, 43(5), E123-E132
Open this publication in new window or tab >>Lung Inflammation Persists After 27 Hours of Protective Acute Respiratory Distress Syndrome Network Strategy and Is Concentrated in the Nondependent Lung
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2015 (English)In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 43, no 5, p. E123-E132Article in journal (Refereed) Published
Abstract [en]

Objective: PET with [F-18]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which during lung inflammation mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. We aimed at studying the location and evolution of inflammation by PET imaging, relating it to morphology (CT), during the first 27 hours of application of protective-ventilation strategy as suggested by the Acute Respiratory Distress Syndrome Network, in a porcine experimental model of acute respiratory distress syndrome. Design: Prospective laboratory investigation. Setting: University animal research laboratory. Subjects: Ten piglets submitted to an experimental model of acute respiratory distress syndrome. Interventions: Lung injury was induced by lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. During 27 hours of controlled mechanical ventilation according to Acute Respiratory Distress Syndrome Network strategy, the animals were studied with dynamic PET imaging of [F-18]fluoro-2-deoxy-D-glucose at two occasions with 24-hour interval between them. Measurements and Main Results: [F-18]fluoro-2-deoxy-D-glucose uptake rate was computed for the total lung, four horizontal regions from top to bottom (nondependent to dependent regions) and for voxels grouped by similar density using standard Hounsfield units classification. The global lung uptake was elevated at 3 and 27 hours, suggesting persisting inflammation. In both PET acquisitions, nondependent regions presented the highest uptake (p = 0.002 and p = 0.006). Furthermore, from 3 to 27 hours, there was a change in the distribution of regional uptake (p = 0.003), with more pronounced concentration of inflammation in nondependent regions. Additionally, the poorly aerated tissue presented the largest uptake concentration after 27 hours. Conclusions: Protective Acute Respiratory Distress Syndrome Network strategy did not attenuate global pulmonary inflammation during the first 27 hours after severe lung insult. The strategy led to a concentration of inflammatory activity in the upper lung regions and in the poorly aerated lung regions. The present findings suggest that the poorly aerated lung tissue is an important target of the perpetuation of the inflammatory process occurring during ventilation according to the Acute Respiratory Distress Syndrome Network strategy.

Keywords
[F-18]fluoro-2-deoxy-D-glucose, acute pulmonary inflammation, acute respiratory distress syndrome, mechanical ventilation, positron emission tomography, ventilator-induced lung injury
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-252977 (URN)10.1097/CCM.0000000000000926 (DOI)000353061000001 ()25746507 (PubMedID)
Available from: 2015-05-19 Created: 2015-05-18 Last updated: 2018-11-12Bibliographically approved
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