ABSTRACT
Ankylosing spondylitis (AS) is a prototypical sero-negative autoimmune disease that affects millions worldwide. Single nucleotide polymorphisms in the Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) gene have been linked to AS via GWAS studies, however, the exact mechanism as to how ERAP1 contributes to pathogenesis of AS is not understood. We undertook µCT imaging and histologic analysis to evaluate bone morphology of the axial skeletons of ERAP1-/- mice and discovered the hallmark skeletal features of AS in these mice, including spinal ankylosis, osteoporosis, and spinal inflammation. We also confirmed the presence of spontaneous intestinal dysbiosis and increased susceptibility to Dextran Sodium Sulfate (DSS)-induced colitis in ERAP1-/- mice, however the transfer of healthy microbiota from wild type mice via cross-fostering experiments did not resolve the skeletal phenotypes of ERAP1-/- mice. Immunological analysis demonstrated that while ERAP1-/- mice had normal numbers of peripheral Foxp3+ Tregs, they had reduced numbers of both "Tr1-like" regulatory T cells and tolerogenic dendritic cells, which are important for Tr1 cell differentiation. Together, our data suggests that ERAP1-/- mice may serve as a useful animal model for studying pathogenesis of intestinal, skeletal, and immunological manifestations of Ankylosing Spondylitis.
Subject(s)
Aminopeptidases/genetics , Genetic Predisposition to Disease/genetics , Minor Histocompatibility Antigens/genetics , Polymorphism, Single Nucleotide/genetics , Spondylitis, Ankylosing/genetics , Spondylitis, Ankylosing/immunology , T-Lymphocytes, Regulatory/immunology , Aminopeptidases/immunology , Animals , Colitis/genetics , Colitis/immunology , Dysbiosis/genetics , Dysbiosis/immunology , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/immunology , Inflammation/genetics , Inflammation/immunology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Minor Histocompatibility Antigens/immunology , Phenotype , Polymorphism, Single Nucleotide/immunologyABSTRACT
CONTEXT: The purpose of this study was to assess the effectiveness of topical pre-closure application of tranexamic acid (TXA) to reduce postoperative blood loss and blood transfusion rates in primary total hip and knee arthroplasty (THA and TKA) in a private, high-volume orthopedic specialty hospital setting. METHODS: This was a retrospective study examining 140 consecutive patients undergoing primary hip or knee arthroplasty at the sample setting by a single surgeon. The first 70 patients did not receive topical TXA (2 gm./20ml.), the final 70 did receive topical TXA. We compared the postoperative hemoglobin levels of both sample subgroups at postoperative days 1, 2, and 3. RESULTS: Overall, the postoperative hemoglobin levels were significantly higher in the TXA group on postoperative days 1, 2, and 3 (p < 0.05). When patients who underwent THA (n = 70) were investigated separately, the hemoglobin levels were significantly higher on postoperative days 1, 2, and 3 in the group that received TXA. In the TKA group (n = 70), there was not a significantly higher hemoglobin level in patients who received TXA. There were no blood transfusions in the entire study cohort. Possibly due to the more restrictive transfusion criteria employed in this study, the total estimated prospective cost savings from use of TXA was calculated at about $116 per patient. CONCLUSIONS: Based on these results from a high volume orthopedic specialty hospital, pre-closure topical TXA application may prove effective in reducing postoperative blood loss for some patients but have a relatively small impact on cost outcomes.
