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- Badholm, M, et al.
(författare)
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Cerebrospinal fluid cell count variability is a major confounding factor in external ventricular drain-associated infection surveillance diagnostics: a prospective observational study
- 2021
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Ingår i: Critical care (London, England). - : Springer Science and Business Media LLC. - 1466-609X .- 1364-8535. ; 25:1, s. 291-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundExternal ventricular drain (EVD)-related infections (EVDIs) are feared complications that are difficult to rapidly and correctly diagnose, which can lead to unnecessary treatment with broad-spectrum antibiotics. No readily available diagnostic parameters have been identified to reliably predict or identify EVDIs. Moreover, intraventricular hemorrhage is common and affect cerebrospinal fluid (CSF) cellularity. The relationship between leukocytes and erythrocytes is often used to identify suspected infection and triggers the use of antibiotics pending results of cultures, which may take days. Cell count based surveillance diagnostics assumes a homogeneous distribution of cells in the CSF. Given the intraventricular sedimentation of erythrocytes on computed tomography scans this assumption may be erroneous and could affect diagnostics.AimsTo evaluate the consistency of cell counts in serially sampled CSF from EVDs, with and without patient repositioning, to assess the effect on infection diagnostics.MethodsWe performed a prospective single-center study where routine CSF sampling was followed by a second sample after 10 min, allocated around a standard patient repositioning, or not. Changes in absolute and pairwise cell counts and ratios were analyzed, including mixed regression models.ResultsData from 51 patients and 162 paired samples were analyzed. We observed substantial changes in CSF cellularity as the result of both resampling and repositioning, with repositioning found to be an independent predictor of bidirectional cellular change. Glucose and lactate levels were affected, however clinically non-significant. No positive CSF cultures were seen during the study. Thirty percent (30%) of patients changed suspected EVDI status, as defined by the cell component of local and national guidelines, when resampling after repositioning.ConclusionsCSF cell counts are not consistent and are affected by patient movement suggesting a heterogeneity in the intraventricular space. The relationship between leukocytes and erythrocytes was less affected than absolute changes. Importantly, cell changes are found to increase with increased cellularity, often leading to changes in suspected EVDI status. Faster and more precise diagnostics are needed, and methods such as emerging next generation sequencing techniques my provide tools to more timely and accurately guide antibiotic treatment.Trial RegistrationNCT04736407, Clinicaltrials.gov, retrospectively registered 2nd February 2021.
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- Tobola, Felix, et al.
(författare)
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Engineering the Ligand Specificity of the Human Galectin-1 by Incorporation of Tryptophan Analogues
- 2022
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Ingår i: ChemBioChem. - : Wiley. - 1439-4227 .- 1439-7633. ; 23:5
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Tidskriftsartikel (refereegranskat)abstract
- Galectin-1 is a β-galactoside-binding lectin with manifold biological functions. A single tryptophan residue (W68) in its carbohydrate binding site plays a major role in ligand binding and is highly conserved among galectins. To fine tune galectin-1 specificity, we introduced several non-canonical tryptophan analogues at this position of human galectin-1 and analyzed the resulting variants using glycan microarrays. Two variants containing 7-azatryptophan and 7-fluorotryptophan showed a reduced affinity for 3’-sulfated oligosaccharides. Their interaction with different ligands was further analyzed by fluorescence polarization competition assay. Using molecular modeling we provide structural clues that the change in affinities comes from modulated interactions and solvation patterns. Thus, we show that the introduction of subtle atomic mutations in the ligand binding site of galectin-1 is an attractive approach for fine-tuning its interactions with different ligands.
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