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- Aradottir, Sigridur Sunna, et al.
(författare)
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Factor D Inhibition Blocks Complement Activation Induced by Mutant Factor B Associated With Atypical Hemolytic Uremic Syndrome and Membranoproliferative Glomerulonephritis
- 2021
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Complement factor B (FB) mutant variants are associated with excessive complement activation in kidney diseases such as atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy and membranoproliferative glomerulonephritis (MPGN). Patients with aHUS are currently treated with eculizumab while there is no specific treatment for other complement-mediated renal diseases. In this study the phenotype of three FB missense variants, detected in patients with aHUS (D371G and E601K) and MPGN (I242L), was investigated. Patient sera with the D371G and I242L mutations induced hemolysis of sheep erythrocytes. Mutagenesis was performed to study the effect of factor D (FD) inhibition on C3 convertase-induced FB cleavage, complement-mediated hemolysis, and the release of soluble C5b-9 from glomerular endothelial cells. The FD inhibitor danicopan abrogated C3 convertase-associated FB cleavage to the Bb fragment in patient serum, and of the FB constructs, D371G, E601K, I242L, the gain-of-function mutation D279G, and the wild-type construct, in FB-depleted serum. Furthermore, the FD-inhibitor blocked hemolysis induced by the D371G and D279G gain-of-function mutants. In FB-depleted serum the D371G and D279G mutants induced release of C5b-9 from glomerular endothelial cells that was reduced by the FD-inhibitor. These results suggest that FD inhibition can effectively block complement overactivation induced by FB gain-of-function mutations.
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| 2. |
- Kristoffersson, Emelie, et al.
(författare)
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The accuracy of digital templating in cementless total hip arthroplasty in dysplastic hips
- 2021
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Ingår i: BMC Musculoskeletal Disorders. - : BioMed Central. - 1471-2474. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Total hip arthroplasty (THA) for developmental dysplasia of the hip (DDH) is a complex procedure due to associated anatomical abnormalities. We studied the extent to which preoperative digital templating is reliable when performing cementless THA in patients with DDH.Methods: We templated and compared the pre- and postoperative sizes of the acetabular and femoral components and the center of rotation (COR), and analysed the postoperative cup coverage, leg length discrepancy (LLD), and stem alignment in 50 patients (56 hips) with DDH treated with THA.Results: The implant size exactly matched the template size in 42.9% of cases for the acetabular component and in 38.2% of cases for the femoral component, whereas the templated ±1 size was used in 80.4 and 81.8% of cases for the acetabular and femoral components, respectively. There were no statistically significant differences between templated and used component sizes among different DDH severity levels (acetabular cup: p = 0.30 under the Crowe classification and p = 0.94 under the Hartofilakidis classification; femoral stem: p = 0.98 and p = 0.74, respectively). There were no statistically significant differences between the planned and postoperative COR (p = 0.14 horizontally and p = 0.52 vertically). The median postoperative LLD was 7 (range 0–37) mm.Conclusion: Digital preoperative templating is reliable in the planning of cementless THA in patients with DDH.
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