AIM:To suggest infliximab(IFX) is effective for acute severe ulcerative colitis,from real-life clinical practice.METHODS:All patients receiving IFX for the treatment of acute severe ulcerative colitis in a single cent...AIM:To suggest infliximab(IFX) is effective for acute severe ulcerative colitis,from real-life clinical practice.METHODS:All patients receiving IFX for the treatment of acute severe ulcerative colitis in a single centre were included.Data were extracted from clinical records in order to assess response to IFX therapy.The primary endpoint was colectomy-free survival,and secondary outcomes included glucocorticosteroid-free remission and safety,which was evaluated by recording deaths and adverse events.Demographic and clinical characteristics of those who underwent colectomy and those who were colectomy-free,both at discharge from their index admission,and during follow-up after an initial response to IFX were compared.RESULTS:Forty-four patients(16 females,mean age 36 years) received IFX between May 2006 and January 2012 for acute severe ulcerative colitis.The median duration of follow-up post-first infusion was 396 d(interquartile range = 173-828 d).There were 21(47.7%) patients with < 1 year of follow-up,10(22.7%) with 1 years to 2 years of follow-up,and 13(29.5%) with > 2 years of follow-up post-first infusion of IFX.Overall,35(79.5%) responded to IFX,avoiding colectomy during their index admission,29(65.9%) were colectomyfree at last point of follow-up(median follow-up 396 d),and 25(56.8%) were in glucocorticosteroid-free remission at end of follow-up.There was one death from post-operative sepsis,20 d after a single IFX infusion.Colectomy rates were generally lower among those "bridging" to thiopurine.Of 18 patients "bridged" to thiopurine therapy,17(94.4%) were colectomyfree,and 15(83.3%) were in glucocorticosteroid-free remission at study end.No predictors of response were identified.CONCLUSION:IFX is effective for acute severe ulcerative colitis in real-life clinical practice.Two-thirds of patients avoided colectomy,and more than 50% were in glucocorticosteroid-free remission.展开更多
Background: Nine proteins were identified as putative profibrotic biomarkers in systemic sclerosis (SSc) and an unrelated fibrotic disease in a previously published proteomic study. As the majority of these proteins w...Background: Nine proteins were identified as putative profibrotic biomarkers in systemic sclerosis (SSc) and an unrelated fibrotic disease in a previously published proteomic study. As the majority of these proteins were orphans of commercially available antibodies, the nine proteins were investigated to determine whether binding peptide aptamers of the Stefin A quadruple mutant-Tracy variant (referred to as “affimers”) could be validated by enzyme linked immunosorbant assay (ELISA) to allow the quantification of these candidate biomarkers in the sera of SSc patients. Materials and Methods: Candidate biomarker peptides were analysed by high throughput affimer microarray to identify binding affimers. Two candidate biomarkers were prioritised, and binding affimers were expressed from genetically modified BL21 competent E. coli strains and purified. These affimers were used in indirect ELISA, and then sandwich ELISA formats against the candidate biomarker recombinant proteins osteonectin and pigment epi-thetlium-derived factor (PEDF). Results: 39 affimers were identified as binders for eight of the nine candidate biomarker peptides were by affimer microarray;six for osteonectin and eleven for PEDF. Two of the six and all eleven were able to recognize physiological concentrations (5 and 1 μg·ml﹣1) of osteonectin and PEDF, respectively by indirect ELISA. In sandwich ELISA format: two affimers were able to detect recombinant PEDF;however, the two affimers identified in indirect ELISA were unable to recognise recombinant osteonectin, and were thus hypothesised to bind to osteonectin at the same binding site. Discussion: SSc is currently an orphan of fully validated biomarkers, which is required for the development of stratified medicine in this field. This approach has laid the groundwork for an affimer based on multiplexed assay, to validate biomarkers in the sera of SSc patients in the future.展开更多
Unlike bone marrow(BM)mesenchymal stem cells(MSCs),whose in vivo identity has been actively explored in recent years,the biology of MSCs in the synovium remains poorly understood.Synovial MSCs may be of great importan...Unlike bone marrow(BM)mesenchymal stem cells(MSCs),whose in vivo identity has been actively explored in recent years,the biology of MSCs in the synovium remains poorly understood.Synovial MSCs may be of great importance to rheumatology and orthopedics because of the direct proximity and accessibility of the synovium to cartilage,ligament,and meniscus.Their excellent chondrogenic capabilities and suggested transit through the synovial fluid,giving unhindered access to the joint surface,further support a pivotal role for synovial MSCs in homeostatic joint repair.This review highlights several unresolved issues pertaining to synovial MSC isolation,topography,and their relationship with pericytes,synovial fibroblasts,and synovial fluid MSCs.Critically reviewing published data on synovial MSCs,we also draw from our experience of exploring the in vivo biology of MSCs in the BM to highlight key differences.Extending our knowledge of synovial MSCs in vivo could lead to novel therapeutic strategies for arthritic diseases.展开更多
文摘AIM:To suggest infliximab(IFX) is effective for acute severe ulcerative colitis,from real-life clinical practice.METHODS:All patients receiving IFX for the treatment of acute severe ulcerative colitis in a single centre were included.Data were extracted from clinical records in order to assess response to IFX therapy.The primary endpoint was colectomy-free survival,and secondary outcomes included glucocorticosteroid-free remission and safety,which was evaluated by recording deaths and adverse events.Demographic and clinical characteristics of those who underwent colectomy and those who were colectomy-free,both at discharge from their index admission,and during follow-up after an initial response to IFX were compared.RESULTS:Forty-four patients(16 females,mean age 36 years) received IFX between May 2006 and January 2012 for acute severe ulcerative colitis.The median duration of follow-up post-first infusion was 396 d(interquartile range = 173-828 d).There were 21(47.7%) patients with < 1 year of follow-up,10(22.7%) with 1 years to 2 years of follow-up,and 13(29.5%) with > 2 years of follow-up post-first infusion of IFX.Overall,35(79.5%) responded to IFX,avoiding colectomy during their index admission,29(65.9%) were colectomyfree at last point of follow-up(median follow-up 396 d),and 25(56.8%) were in glucocorticosteroid-free remission at end of follow-up.There was one death from post-operative sepsis,20 d after a single IFX infusion.Colectomy rates were generally lower among those "bridging" to thiopurine.Of 18 patients "bridged" to thiopurine therapy,17(94.4%) were colectomyfree,and 15(83.3%) were in glucocorticosteroid-free remission at study end.No predictors of response were identified.CONCLUSION:IFX is effective for acute severe ulcerative colitis in real-life clinical practice.Two-thirds of patients avoided colectomy,and more than 50% were in glucocorticosteroid-free remission.
文摘Background: Nine proteins were identified as putative profibrotic biomarkers in systemic sclerosis (SSc) and an unrelated fibrotic disease in a previously published proteomic study. As the majority of these proteins were orphans of commercially available antibodies, the nine proteins were investigated to determine whether binding peptide aptamers of the Stefin A quadruple mutant-Tracy variant (referred to as “affimers”) could be validated by enzyme linked immunosorbant assay (ELISA) to allow the quantification of these candidate biomarkers in the sera of SSc patients. Materials and Methods: Candidate biomarker peptides were analysed by high throughput affimer microarray to identify binding affimers. Two candidate biomarkers were prioritised, and binding affimers were expressed from genetically modified BL21 competent E. coli strains and purified. These affimers were used in indirect ELISA, and then sandwich ELISA formats against the candidate biomarker recombinant proteins osteonectin and pigment epi-thetlium-derived factor (PEDF). Results: 39 affimers were identified as binders for eight of the nine candidate biomarker peptides were by affimer microarray;six for osteonectin and eleven for PEDF. Two of the six and all eleven were able to recognize physiological concentrations (5 and 1 μg·ml﹣1) of osteonectin and PEDF, respectively by indirect ELISA. In sandwich ELISA format: two affimers were able to detect recombinant PEDF;however, the two affimers identified in indirect ELISA were unable to recognise recombinant osteonectin, and were thus hypothesised to bind to osteonectin at the same binding site. Discussion: SSc is currently an orphan of fully validated biomarkers, which is required for the development of stratified medicine in this field. This approach has laid the groundwork for an affimer based on multiplexed assay, to validate biomarkers in the sera of SSc patients in the future.
文摘Unlike bone marrow(BM)mesenchymal stem cells(MSCs),whose in vivo identity has been actively explored in recent years,the biology of MSCs in the synovium remains poorly understood.Synovial MSCs may be of great importance to rheumatology and orthopedics because of the direct proximity and accessibility of the synovium to cartilage,ligament,and meniscus.Their excellent chondrogenic capabilities and suggested transit through the synovial fluid,giving unhindered access to the joint surface,further support a pivotal role for synovial MSCs in homeostatic joint repair.This review highlights several unresolved issues pertaining to synovial MSC isolation,topography,and their relationship with pericytes,synovial fibroblasts,and synovial fluid MSCs.Critically reviewing published data on synovial MSCs,we also draw from our experience of exploring the in vivo biology of MSCs in the BM to highlight key differences.Extending our knowledge of synovial MSCs in vivo could lead to novel therapeutic strategies for arthritic diseases.
