A Retrospective Analysis Comparing Post-Operative Bleeding with Various Doses of Aspirin after Lower Extremity Joint Arthroplasty or Revision.

STUDY OBJECTIVE: Previous studies have shown that aspirin is noninferior to other anticoagulation therapies in preventing postoperative venous thromboembolism following lower extremity arthroplasty or revision; however, its optimal dosing for this indication is less clear. This study aims to compare the odds of bleeding between different aspirin dosages following lower extremity joint arthroplasty or revision. DESIGN: This is a 3-year retrospective multi-center cohort study across the United States and its territories. SETTING: This study included patients admitted for total hip or knee arthroplasty or revision and were treated with prophylactic aspirin. PATIENTS, INTERVENTION, MEASUREMENTS: Patients were assigned to groups based on a total daily aspirin dose of 81, 162, 325, or 650 mg. Data were analyzed for postsurgical bleeding and thromboembolism events occurring during the initial admission and up to 40 days following surgery. Other exploratory variables included type of surgery, hip or knee arthroplasty, length of stay, and patient demographic data. MAIN RESULTS: Among 53,848 patients receiving aspirin, 3922 received a total daily dose of 81 mg, 19,341 received a total daily dose of 162 mg, 5256 received a total daily dose of 325 mg, and 25,329 received a total daily dose of 650 mg. Bleeding occurred in 466 (0.87%) patients and venous thromboembolism (VTE) in 209 patients (0.39%). The odds of bleeding were compared using logistic regression, with the 650-mg dose as the reference group. None were statistically significant for bleeding between all studied aspirin doses: 81 mg (OR 1.12, 95% CI 0.83-1.51, p = 0.451), 162 mg (OR 0.83, 95% CI 0.67-1.03, p = 0.097), and 325 mg (OR 0.83, 95% CI 0.59-1.13, p = 0.245). The odds of VTE were also not statistically significant: 81 mg (OR 0.71, 95% CI 0.40-1.17, p = 0.181), 162 mg (OR 0.75 95% CI 0.54-1.03, p = 0.072), and 325 mg (OR 1.00, 95% CI 0.64-1.53, p = 0.989). CONCLUSIONS: There were no significant differences in the odds of bleeding or venous thromboembolism among all studied aspirin dosages in patients receiving aspirin for thromboprophylaxis following lower extremity joint arthroplasty or revision.

Increased survival of tumor-bearing mice by the delta opioid SNC 80.

Opioids represent a major source of relief from pain. However, opioid abuse may cause immunosuppression and cancer. We have recently reported results on novel non-peptidic delta- and mu-selective opioids that induced immunopotentiation of T cell and macrophage functions in vitro and ex vivo. In the present study, the effects of the delta-opioid receptor agonist and potent analgesic (+)-4-((alpha R)-alpha-((2S, 5R)-4-allyl-2, 5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N, N-diethyl-benzamide (SNC80) on in vitro and in vivo tumor cell growth were investigated using the L5178Y-R murine model. SNC80 marginally, but significantly (p < 0.05), inhibited (up to 14%) the in vitro growth of L5178Y-R tumor cells. However, in vivo intratumor administration of SNC80 (2 and 4 mg/kg) reduced up to 60% L5178Y-R tumor-bearing Balb/c mice death, and significantly (p < 0.05) reduced tumor weights (up to 73% reduction) in these animals. This study may support the evaluation of SNC80 in preclinical and clinical studies.

Potentiation of rat lymphocyte proliferation by novel non-peptidic synthetic opioids.

Opioids represent a major source of relief for acute and chronic, moderate to severe nonmalignant pain. However, opioid abuse may cause immunosuppression leading to infections and cancer development. Recently we reported results on novel non-peptidic delta- and mu-selective opioids that induced immunopotentiation in vitro and ex vivo. In the present study, we investigated the effects of the delta agonist SNC 80, and mu agonists, naltrindole and naltrexone derivatives for their capacity to alter lymphoproliferation in vitro. They were observed to stimulate lymphoproliferation at concentrations ranging from 10(-10) to 10(-5) M. SNC 80 significantly (p<0.05) stimulated (43-311%) proliferation of resident and concanavalin A (Con A)-treated lymphocytes; the naltrindole derivatives 9332 and 9333 caused significant (p<0.05) 26-47% and 13-43%, respectively, stimulation of Con A-treated lymphoproliferation; whereas the naltrexone derivatives 9334 and 9336 significantly (p<0.05) stimulated 9-40% and 15-69%, respectively, proliferation of resident and Con A-treated lymphocytes. These novel opioid ligands could serve as immunotherapeutic agents by increasing the pool of lymphocytes with potential use in the treatment of infectious diseases including AIDS. This study provides evidence of the relationship structure/function of opioids on lymphoproliferation, and supports further evaluation of opioids with immunomodulatory potential in preclinical and clinical studies.