| 1. |
- Huang, Shan, et al.
(författare)
-
Cathepsin g Degrades Both Glycosylated and Unglycosylated Regions of Lubricin, a Synovial Mucin
- 2020
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Lubricin (PRG4) is a mucin type protein that plays an important role in maintaining normal joint function by providing lubrication and chondroprotection. Improper lubricin modification and degradation has been observed in idiopathic osteoarthritis (OA), while the detailed mechanism still remains unknown. We hypothesized that the protease cathepsin G (CG) may participate in degrading lubricin in synovial fluid (SF). The presence of endogenous CG in SF was confirmed in 16 patients with knee OA. Recombinant human lubricin (rhPRG4) and native lubricin purified from the SF of patients were incubated with exogenous CG and lubricin degradation was monitored using western blot, staining by Coomassie or Periodic Acid-Schiff base in gels, and with proteomics. Full length lubricin (∼300 kDa), was efficiently digested with CG generating a 25-kDa protein fragment, originating from the densely glycosylated mucin domain (∼250 kDa). The 25-kDa fragment was present in the SF from OA patients, and the amount was increased after incubation with CG. A CG digest of rhPRG4 revealed 135 peptides and 72 glycopeptides, and confirmed that the protease could cleave in all domains of lubricin, including the mucin domain. Our results suggest that synovial CG may take part in the degradation of lubricin, which could affect the pathological decrease of the lubrication in degenerative joint disease. © 2020, The Author(s).
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Persson, A., et al.
(författare)
-
EPOS trial: The effect of air filtration through a plasma chamber on the incidence of surgical site infection in orthopaedic surgery: A study protocol of a randomised, double-blind, placebo-controlled trial
- 2022
-
Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 12:2
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction There is controversy regarding the importance of air-transmitted infections for surgical site infections (SSIs) after orthopaedic surgery. Research has been hindered by both the inability in blinding the exposure, and by the need for recruiting large enough cohorts. The aim of this study is to investigate whether using a new form of air purifier using plasma air purification (PAP) in operating rooms (ORs) lowers the SSI rate or not. Methods and analysis Multicentre, double-blind, cluster-randomised, placebo-controlled trial conducted at seven hospitals in 2017-2022. All patients that undergo orthopaedic surgery for minimum 30 min are included. Intervention group: patients operated in OR with PAP devices turned on. Control group: patients operated in OR with PAP devices turned off. Randomisation: each OR will be randomised in periods of 4 weeks, 6 weeks or 8 weeks to either have the devices on or off. Primary outcome: any SSI postoperatively defined as a composite endpoint of any of the following: use of isoxazolylpenicillin, clindamycin or rifampicin for 2 days or more, International Classification of Diseases codes or Nordic Medico-Statistical Committee codes indicating postoperative infection. In a second step, we will perform a chart review on those patients with positive indicators of SSI to further validate the outcome. Secondary outcomes are described in the Methods section. Power: we assume an SSI rate of 2%, an SSI reduction rate of 25% and we need approximately 45 000 patients to attain a power of 80% at a significance level of 0.05. Ethics and dissemination The study is approved by the Swedish Ethical Review Authority. The interim analysis results from the study will be presented only to the researchers involved unless the study thereafter is interrupted for whatever reason. Publication in a medical journal will be presented after inclusion of the last patient. Trial registration number NCT02695368. © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
- Flowers, Sarah A., et al.
(författare)
-
Lubricin binds cartilage proteins, cartilage oligomeric matrix protein, fibronectin and collagen II at the cartilage surface
- 2017
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Lubricin, a heavily O-glycosylated protein, is essential for boundary lubrication of articular cartilage. Strong surface adherence of lubricin is required given the extreme force it must withstand. Disulfide bound complexes of lubricin and cartilage oligomeric matrix protein (COMP) have recently been identified in arthritic synovial fluid suggesting they may be lost from the cartilage surface in osteoarthritis and inflammatory arthritis. This investigation was undertaken to localise COMP-lubricin complexes within cartilage and investigate if other cartilage proteins are involved in anchoring lubricin to the joint. Immunohistochemical analysis of human cartilage biopsies showed lubricin and COMP co-localise to the cartilage surface. COMP knockout mice, however, presented with a lubricin layer on the articular cartilage leading to the further investigation of additional lubricin binding mechanisms. Proximity ligation assays (PLA) on human cartilage biopsies was used to localise additional lubricin binding partners and demonstrated that lubricin bound COMP, but also fibronectin and collagen II on the cartilage surface. Fibronectin and collagen II binding to lubricin was confirmed and characterised by solid phase binding assays with recombinant lubricin fragments. Overall, COMP, fibronectin and collagen II bind lubricin, exposed on the articular cartilage surface suggesting they may be involved in maintaining essential boundary lubrication.
|
|
| 12. |
|
|
| 13. |
- Jin, Chunsheng, et al.
(författare)
-
Human Synovial Lubricin Expresses Sialyl Lewis x Determinant and Has L-selectin Ligand Activity
- 2012
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 287:43, s. 35922-35933
-
Tidskriftsartikel (refereegranskat)abstract
- Lubricin (or proteoglycan 4 (PRG4)) is an abundant mucin-like glycoprotein in synovial fluid (SF) and a major component responsible for joint lubrication. In this study, it was shown that O-linked core 2 oligosaccharides (Gal beta 1-3(GlcNAc beta 1-6)GalNAc alpha 1-Thr/Ser) on lubricin isolated from rheumatoid arthritis SF contained both sulfate and fucose residues, and SF lubricin was capable of binding to recombinant L-selectin in a glycosylation-dependent manner. Using resting human polymorphonuclear granulocytes (PMN) from peripheral blood, confocal microscopy showed that lubricin coated circulating PMN and that it partly co-localized with L-selectin expressed by these cells. In agreement with this, activation-induced shedding of L-selectin also mediated decreased lubricin binding to PMN. It was also found that PMN recruited to inflamed synovial area and fluid in rheumatoid arthritis patients kept a coat of lubricin. These observations suggest that lubricin is able to bind to PMN via an L-selectin-dependent and -independent manner and may play a role in PMN-mediated inflammation.
|
|
| 14. |
- Malchau, Henrik, 1951, et al.
(författare)
-
Presidential guest address: the Swedish Hip Registry: increasing the sensitivity by patient outcome data
- 2005
-
Ingår i: Clin Orthop Relat Res. - 0009-921X. ; 441, s. 19-29
-
Tidskriftsartikel (refereegranskat)abstract
- The Swedish Hip Register was initiated in 1979. The mission of the register is to improve the outcome of THA. The hypothesis is that feedback of data stimulates participating clinics to reflect and improve. In addition to revision surgery, patient-based outcome measures and radiographic results are included to improve sensitivity. All patients who have a total hip arthroplasty answer a questionnaire preoperatively and again after 1, 6, and 10 years postoperatively. The questionnaire includes the Charnley classification, EQ-5D and visual analog scales concerning pain and overall satisfaction and is used by 31 of 81 units. Average costs for the procedure ($11,000) are obtained from a national database. The mean gain in the EQ-5D index after 1 year for 3900 patients was 0.37, giving a low cost of $3000 per quality adjusted life year. Patient satisfaction and pain amelioration generally was high. The national average 7-year survival (revision as endpoint), has improved from 93.5% (+/- 0.15) to 95.8 (+/- 0.15) between the two periods 1979 to 1991 and 1992 to 2003. National implant registers define the epidemiology of primary and revision surgery. In conjunction with individual subjective patient data and radiography they contribute to development of evidence-based THA surgery.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Persson, A., et al.
(författare)
-
Increased mortality after total hip prosthetic joint infection is mainly caused by the comorbidities rather than the infection itself
- 2023
-
Ingår i: Acta Orthopaedica. - 1745-3674 .- 1745-3682. ; 94, s. 484-489
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purpose - Periprosthetic joint infection (PJI) is a feared complication of arthroplasty surgery. There is controversy as to whether PJI also correlates with increased mortality. Our aim was to investigate in a nation-wide cohort if PJI is an independent risk factor for dying. Patients and methods - We performed a retrospective cohort study based on data from the Swedish Hip Arthro-plasty Register (SHAR). All patients with a revision THA performed between 1998 and 2017 were included. The out-come is mortality; exposure is PJI according to SHAR. The control group was study participants who underwent aseptic revision. Confounders were age, sex, diagnosis, and comorbidity according to the Elixhauser index. The outcome was analyzed with a Cox proportional hazards model. Results - 4,943 PJI revisions and 12,529 non-infected revisions were included in the analysis. The median follow-up time was 4.1 years. In the PJI group, 1,972 patients died and in the control group, 4,512. The incidence rate ratio was 1.19 (95% confidence interval [CI] 1.13-1.25), the crude hazard ratio (HR) 1.19 (CI 1.13-1.25), and the adjusted HR 1.05 (CI 0.99-1.12) for the exposed versus the unexposed group. The strongest confounder was comorbidity. Conclusion - The increased mortality risk after revision due to PJI is mainly caused by the comorbidity of the patient, rather than by the infection itself.
|
|
| 18. |
- Rysinska, A., et al.
(författare)
-
Aseptic loosening after total hip arthroplasty and the risk of cardiovascular disease: A nested case-control study
- 2018
-
Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 13:11
-
Tidskriftsartikel (refereegranskat)abstract
- Background Patients with surgically treated osteoarthritis of the hip have an increased risk of cardiovascular morbidity and mortality many years after the operation compared with controls. Our hypothesis is that this increased risk after total hip arthroplasty (THA) is mediated by development of periprosthetic osteolysis leading to aseptic loosening of the implant. Methods We conducted a nation-wide, nested, case-control study consisting of patients receiving a cemented THA due to osteoarthritis between the years 1992 and 2005. Our study population included a total of 14,430 subjects identified in the Swedish hip arthroplasty register and linked to the Swedish National Patient Register. The case group consisted of patients (n = 2,886) who underwent reoperation of the treated hip due to osteolysis or aseptic loosening at any time within five years after the index surgery. Each case was matched with four controls (n = 11,544) who had not undergone reoperation. The main outcomes were cardiovascular events i.e. myocardial infarction, heart failure and cerebral infarction according to ICD-codes and time to the first cardiovascular event during the exposure period. Outcomes were subgrouped into cardiac and cerebral events. We used regression models to calculate the incidence rates and adjusted our results for confounders. Findings Overall, 5.1% of patients had cardiac events, with slightly more overall cardiovascular events occurring in the control group (8.1% vs. 6.7%, odds ratio 0.8, 95% confidence interval (CI) 0.7 to 1.0). After adjusting for confounders, the case group had an increased relative risk of 1.3 (95% confidence interval (CI) 1.1 to 1.3) for total number of cardiovascular events. Similar effect sizes were observed for time to first event. Interpretation Patients with osteoarthritis who received THA and subsequently underwent a revision operation due to loosening had a higher relative risk of developing cardiovascular events than controls. Thus there is an association which could be explained by a common inflammatory disease pathway that requires further experimental research. Copyright: © 2018 Rysinska et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
