High expression of interleukin-1β in the corneal epithelium of MRL/lpr mice is under the control of their genetic background

MRL/Mp mice bearing the Fas deletion mutant gene, lpr (MRL/lpr), spontaneously develop polyarthritis, sialoadenitis and dacryoadenitis, resembling rheumatoid arthritis (RA), and also corneal involvement such as keratopathy and scleritis, which is a major complication in RA patients. In this study, we found that the expression levels of IL-1β and MMP-1 mRNAs in cornea were high in both MRL/lpr and MRL/Mp-+/+ strains of mice at an age younger than when they develop any inflammatory lesions. This was not true of other inbred strains, even those bearing the lpr gene, and also not of (NZB × NZW) F1 lupus mice. There was no significant difference in the expression of IL-1α and TGFβ in cornea in these strains. Using crosses between MRL/lpr and C3H/HeJ-lpr/lpr (C3H/lpr) mice, at least the expression of IL-1β was found to be under the control of the MRL genetic background, likely with a recessive mode of inheritance. Considering that IL-1β in cornea was detected particularly in the epithelial layer, the high expression of IL-1β in cornea is most likely involved in the genetic predisposition for corneal involvement and possibly also for arthritis in an MRL strain of mice

International Survey: Factors Associated With Operative Treatment of Distal Radius Fractures and Implications for the American Academy of Orthopaedic Surgeons' Appropriate Use Criteria

Objectives: Through an international survey, we assessed whether deciding to operatively treat an intra-articular distal radius fracture (DRF) is guided by identifiable patient and surgeon factors. In addition, we compared surgeons' treatment decisions with the American Academy of Orthopaedic Surgeons' Appropriate Use Criteria (AUC) treatment recommendations. Methods: This cross-sectional survey asked 224 surgeons to operatively or nonoperatively treat 28 hypothetical patients with radiographs of an intra-articular DRF. We randomized patient age (50/70 years), gender, mechanism of injury, activity level, and OTA/AO fracture type. We classified 6 fractures as “nonclinically significant displacement” and 22 as “potentially clinically significant displacement.” Multilevel logistic regression analysis was performed. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported. Statistical significance was P < 0.05. Results: Patient factors independently associated with surgery included younger age (OR 6.7, P = 0.003), clinically significant fracture displacement (type B: OR 122, CI, 20–739, P < 0.001; type C: OR 59, CI, 12–300, P < 0.001), normal activity level (OR 5.0, P < 0.001), and high-energy mechanisms (OR 1.3, P = 0.002). Surgeon factors associated with recommending surgery included practicing outside the United States (Europe: OR 2.6, P < 0.001; “other”: OR 4.8, P < 0.001). Hand surgeons most often selected surgery, as compared to orthopaedic trauma surgeons (OR 2.3, P = 0.001) and “other orthopaedists” (OR 2.2, P = 0.022). Thirty-seven percent of treatment decisions for patients with normal activity levels were rated by AUC recommendations as “rarely appropriate,” which included 91% disagreement for 70-year-olds with nonclinically significant displacement. Conclusions: Surgeons use patient age and fracture displacement to make treatment recommendations for intra-articular DRF. We recommend that the AUC be updated to include these clinical factors as essential components in its algorithm. Level of Evidence: Therapeutic Level V. See Instructions for Authors for a complete description of levels of evidence