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- Aamodt, A. H., et al.
(författare)
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Blood neurofilament light concentration at admittance: a potential prognostic marker in COVID-19
- 2021
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 268, s. 3574-3583
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Tidskriftsartikel (refereegranskat)abstract
- Objective To test the hypotheses that blood biomarkers for nervous system injury, serum concentrations of neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAp) can serve as biomarkers for disease severity in COVID-19 patients. Methods Forty-seven inpatients with confirmed COVID-19 had blood samples drawn on admission for assessing serum biomarkers of CNS injury by Single molecule array (Simoa), NfL and GFAp. Concentrations of NfL and GFAp were analyzed in relation to symptoms, clinical signs, inflammatory biomarkers and clinical outcomes. We used multivariate linear models to test for differences in biomarker concentrations in the subgroups, accounting for confounding effects. Results In total, 21% (n = 10) of the patients were admitted to an intensive care unit, and the overall mortality rate was 13% (n = 6). Non-survivors had higher serum concentrations of NfL (p < 0.001) upon admission than patients who were discharged alive both in adjusted analyses (p = 2.6 x 10(-7)) and unadjusted analyses (p = 0.001). The concentrations of NfL in non-survivors increased over repeated measurements; whereas, the concentrations in survivors were stable. The GFAp concentration was also significantly higher in non-survivors than survivors (p = 0.02). Conclusion Increased concentrations of NfL and GFAp in COVID-19 patients on admission may indicate increased mortality risk. Measurement of blood biomarkers for nervous system injury can be useful to detect and monitor CNS injury in COVID-19.
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- Huber-Lang, Markus, et al.
(författare)
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Double blockade of CD14 and complement C5 abolishes the cytokine storm and improves morbidity and survival in polymicrobial sepsis in mice.
- 2014
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 192:11, s. 5324-5331
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Tidskriftsartikel (refereegranskat)abstract
- Sepsis and septic shock, caused by an excessive systemic host-inflammatory response, are associated with high morbidity and mortality. The complement system and TLRs provide important pattern recognition receptors initiating the cytokine storm by extensive cross-talk. We hypothesized that double blockade of complement C5 and the TLR coreceptor CD14 could improve survival of experimental polymicrobial sepsis. Mice undergoing cecal ligation and puncture (CLP)-induced sepsis were treated with neutralizing anti-CD14 Ab biG 53, complement C5 inhibitor coversin (Ornithodoros moubata C inhibitor), or a combination thereof. The inflammatory study (24-h observation) revealed statistically significant increases in 22 of 24 measured plasma biomarkers in the untreated CLP group, comprising 14 pro- and anti-inflammatory cytokines and 8 chemokines, growth factors, and granulocyte activation markers. Single CD14 or C5 blockade significantly inhibited 20 and 19 of the 22 biomarkers, respectively. Combined CD14 and C5 inhibition significantly reduced all 22 biomarkers (mean reduction 85%; range 54-95%) compared with the untreated CLP group. Double blockade was more potent than single treatment and was required to significantly inhibit IL-6 and CXCL1. Combined inhibition significantly reduced morbidity (motility and eyelid movement) and mortality measured over 10 d. In the positive control CLP group, median survival was 36 h (range 24-48 h). Combined treatment increased median survival to 96 h (range 24-240 h) (p = 0.001), whereas survival in the single-treatment groups was not significantly increased (median and range for anti-CD14 and anti-C5 treatment were 36 h [24-48 h] and 48 h [24-96 h]). Combined with standard intervention therapy, specific blockade of CD14 and C5 might represent a promising new therapeutic strategy for treatment of polymicrobial sepsis.
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- Wester, T., et al.
(författare)
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Assessment of skin and tongue microcirculation reveals major changes in porcine sepsis
- 2011
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Ingår i: Clinical Physiology and Functional Imaging. - : Blackwell. - 1475-0961 .- 1475-097X. ; 31:2, s. 151-158
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To examine the relation between central hemodynamics, clinical severity and microvascular findings in tongue and skin during sepsis. Materials and methods: Skin and tongue microcirculation was examined using laser Doppler and video microscopy techniques before and 200 min after inducing sepsis in pigs (n = 6) by inactivated Neisseria meningitides and in two control animals. Results: All infected pigs developed clinical signs of sepsis. Pericapillary bleedings developed in the tongue in the two pigs with the most severe disease. Capillary density increased in the groin skin in infected pigs after 200 min as compared to baseline (P < 0·02). In the same period, mean capillary flow velocity was reduced in groin skin and tongue in septic pigs (P < 0·02). At 200 min a fraction of capillaries had developed 'no flow' or 'brisk flow', patterns hardly seen at baseline. Laser Doppler perfusion was reduced in ear and tongue after 200 min (P < 0·02 for both). The described pathology was more pronounced in the pigs with the most severe sepsis. Conclusion: Capillary bleedings may be used as an early indication of severe sepsis. Examination of skin and tongue microcirculations may be used to characterize severity of sepsis and possibly to assess effect of treatment.
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