Background: Postoperative complications and substantial loss of physical function are common after musculoskeletal trauma. We conducted a prospective randomized controlled trial to assess the impact of conditionally essential amino acid (CEAA) supplementation on complications and skeletal muscle mass in adults after operative fixation of acute fractures.Methods: Adults who sustained pelvic and extremity fractures that were indicated for operative fixation at a level-I trauma center were enrolled. The subjects were stratified based on injury characteristics (open fractures and/or polytrauma, fragility fractures, isolated injuries) and randomized to standard nutrition (control group) or oral CEAA supplementation twice daily for 2 weeks. Body composition (fat-free mass [FFM]) was measured at baseline and at 6 and 12 weeks postoperatively. Complications were prospectively collected. An intention-to-treat analysis was performed. The relative risk (RR) of complications for the control group relative to the CEAA group was determined, and linear mixed-effects models were used to model the relationship between CEAA supplementation and changes in FFM.Results: Four hundred subjects (control group: 200; CEAA group: 200) were enrolled. The CEAA group had significantly lower overall complications than the control group (30.5% vs. 43.8%; adjusted RR = 0.71; 95% confidence interval [CI] = 0.55 to 0.92; p = 0.008). The FFM decreased significantly at 6 weeks in the control subjects (-0.9 kg, p = 0.0205), whereas the FFM was maintained at 6 weeks in the CEAA subjects (20.33 kg, p = 0.3606). This difference in FFM was not seen at subsequent time points. Conclusions:Our results indicate that CEAA supplementation has a protective effect against common complications and early skeletal muscle wasting after operative fixation of extremity and pelvic fractures. Given the potential benefits of this inexpensive, low-risk intervention, multicenter prospective studies in focused trauma populations are warranted.Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence. Despite continued advances in surgical management of extremity and pelvic fractures, complications and prolonged loss of function continue to adversely impact clinical outcomes 1-5 . In the musculoskeletal trauma population, malnutrition is common, and when diagnosed by a registered dietitian, it is associated with a 3-fold greater complication rate 6 . Malnutrition is a potentially modifiable risk factor for mortality, fracture nonunion, wound complications, and increased length of stay [6][7][8][9] .Baseline malnutrition is further compounded by inadequate calorie and protein intake following trauma and subsequent surgery 10,11 . An already poor diet is further suppressed by pain, medication side effects, and nausea, leading to worsening nutrition deficiencies and limiting healing potential. These deficiencies, in combination with the detrimental effects of prolonged immobilization, result in a catabolic state with d...

Adjuvant arthritis (AA) in rats is susceptible to cell-mediated passive transfer. Collagen-induced arthritis (CIA) in rats is susceptible to passive transfer with antibody to type II collagen. We report here the development of strikingly severe arthritis in Lewis rats as the result of synergy between passively transferred antibody to type II collagen from rats with CIA and concanavalin A (Con A)-stimulated lymph node or spleen cells from syngeneic rats with AA. Similar synergy was seen in rats with AA given anticollagen antibody, in rats with CIA given Con A-stimulated adjuvant spleen cells, and in rats actively immunized with CII and complete Freund's adjuvant. The synergistic process caused a very severe polyarthritis, characterized by marked swelling and erythema in all the joints of the distal extremities, with histologic and radiographic evidence of early, extensive erosion of articular cartilage. Synergy was apparent if the lymphoid cells from AA rats were given up to 1 mo after a single injection of anticollagen antibody. No synergy was seen when normal rat immunoglobulin or anti-ovalbumin antibody was substituted for anticollagen antibody, when Con A-stimulated lymphoid cells from normal rats or donors with CIA were used, or when Con A-stimulated AA lymphoid cells were irradiated before transfer. Synergy between separate immune effector mechanisms may represent a general phenomenon in the pathogenesis of inflammatory joint disease.

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A novel buprenorphine (BUP) extended-release formulation (BUP-XR) produced as a lipid-encapsulated, low viscosity BUP suspension for SC injection to control pain was evaluated for pharmacokinetics and safety in Sprague–Dawley rats given either 0.65 mg/kg (low dose) or 1.30 mg/kg (high dose). The 2 dosage groups each contained 6 male and 6 female rats to determine whether BUP-XR behaved differently in male or female animals. Blood samples were obtained from each animal before BUP-XR administration and at 6, 24, 48, 72, 96, and 168 h after administration. For necropsy and injection-sitehistopathology evaluation, 3 animals of each sex from each test group were euthanized on day 8, with the remaining animals euthanized on day 15. Mean plasma BUP concentration peaked from 6 to 24 h in all test groups, then declined in a linear fashion. Quantifiable plasma BUP was measured in all male rats at all time points except for one low dose group sample taken at 168 h. Female rats had quantifiable plasma BUP at all time points except for 1 low dose group sample at 72 and 96 h, and 2 low dose group samples at 168 h. The low dose groups, whether male or female, had lower mean plasma BUP levels at all time points as compared with their high dose counterparts, and female rats had lower mean plasma BUP levels than male rats at all time points. Results indicate that a single BUP-XR dose at either dose concentration can reliably provide plasma levels of BUP reported in the literature to be therapeutically relevant for up to 72 h, although lower plasma BUP levels can be anticipated in female rats compared with male counterparts. Mild to moderate injection-site granulomatous inflammation was observed in 6 of 12 rats in the low dose group and 7 of 12 in the high dose group. This reaction is characteristic of lipid material designed to persist in situ.