Survival of block and fascial-wrapped diced cartilage grafts: an experimental study in rabbits.

INTRODUCTION: Cartilage grafts have become an integral part in plastic surgery. Classic autogenous cartilage harvesting techniques are associated with significant donor- and recipient-site morbidity. The use of cartilage micrografts wrapped in a sleeve was first developed to decrease the complication rates of block cartilage grafts. The aim of this study was to compare the resorption rate of solid block cartilage graft and diced cartilage wrapped in fascia graft in rabbits. MATERIALS AND METHODS: In 12 rabbits, 1 solid block cartilage and 1 diced graft wrapped in fascia were implanted in subcutaneous pockets. By the end of the fourth month, the cartilage implants were dissected free and photographed and weighed exactly. Then specimens were stained with hematoxylin and eosin to determine their architectural characteristics. RESULTS: In the solid block cartilage graft group, the means ± standard deviation preimplant weight values were 5.34 ± 1.68. The weight was changed to 7.74 ± 3.26. The change was not statistically significant. In diced cartilage grafts wrapped in fascia, the means ± standard deviation preimplanted weight values were 8.13 ± 1.83. These values were changed to 2.79 ± 1.97, meaning statistically significant resorption of diced cartilage grafts wrapped in fascia (P < 0.001). In histologic examination, block cartilage grafts showed viable cartilage but diced cartilage grafts wrapped in fascia yielded fibrosis and inflammatory cell infiltration. CONCLUSION: The amplitude of resorption of the diced cartilage wrapped in fascia is considerable compared with one-piece block grafts. It may be anticipated that the enthusiasm for this technique will decline once the long-term results of pertaining clinical studies are available.

Safety and Clinical Activity of MEDI1873, a Novel GITR Agonist, in Advanced Solid Tumors.

PURPOSE: The safety and preliminary efficacy of MEDI1873, an agonistic IgG1 fusion protein targeting glucocorticoid-induced TNF receptor-related protein (GITR), were evaluated in an open-label, first-in-human, phase I, dose escalation study in previously treated patients with advanced solid tumors. PATIENTS AND METHODS: Two single-patient cohorts at 1.5 and 3 mg i.v. were followed by 3+3 dose escalation in six cohorts at 7.5, 25, 75, 250, 500, and 750 mg, all every 2 weeks, for up to 52 weeks. Primary endpoints were safety and tolerability, dose-limiting toxicities (DLT), and MTD. Secondary endpoints included antitumor activity, pharmacokinetics, immunogenicity, and pharmacodynamics. RESULTS: Forty patients received MEDI1873. Three experienced DLTs: grade 3 worsening tumor pain (250 mg); grade 3 nausea, vomiting, and headache (500 mg); and grade 3 non-ST segment elevation myocardial infarction (750 mg). An MTD was not reached and treatment was well tolerated up to 500 mg. Most common treatment-related adverse events were headache (25%), infusion-related reaction (17.5%), and decreased appetite (17.5%). MEDI1873 exposure was dose proportional. Antidrug-antibody incidence was low. MEDI1873 increased peripheral CD4+ effector memory T-cell proliferation as well as cytokines associated with effector T-cell activation at dose levels ≥75 mg. The best response was stable disease (SD) in 17 patients (42.5%), including 1 unconfirmed partial response. Eight patients (20.0%) had SD ≥24 weeks. CONCLUSIONS: MEDI1873 showed acceptable safety up to 500 mg i.v. every 2 weeks with pharmacodynamics activity, and prolonged SD in some patients. However, further development is not planned because of lack of demonstrated tumor response.

Randomized trial of physician alerts for thromboprophylaxis after discharge.

BACKGROUND: Many hospitalized Medical Service patients are at risk for venous thromboembolism in the months after discharge. We conducted a multicenter randomized controlled trial to test whether a hospital staff member's thromboprophylaxis alert to an Attending Physician before discharge will increase the rate of extended out-of-hospital prophylaxis and, in turn, reduce the incidence of symptomatic venous thromboembolism at 90 days. METHODS: From April 2009 to January 2010, we enrolled hospitalized Medical Service patients using the point score system developed by Kucher et al to identify those at high risk for venous thromboembolism who were not ordered to receive thromboprophylaxis after discharge. There were 2513 eligible patients from 18 study sites randomized by computer in a 1:1 ratio to the alert group or the control group. RESULTS: Patients in the alert group were more than twice as likely to receive thromboprophylaxis at discharge as controls (22.0% vs 9.7%, P <.0001). Based on an intention-to-treat analysis, symptomatic venous thromboembolism at 90 days (99.9% follow-up) occurred in 4.5% of patients in the alert group, compared with 4.0% of controls (hazard ratio 1.12; 95% confidence interval, 0.74-1.69). The rate of major bleeding at 30 days in the alert group was similar to that of the control group (1.2% vs 1.2%, hazard ratio 0.94; 95% confidence interval, 0.44-2.01). CONCLUSIONS: Alerting providers to extend thromboprophylaxis after hospital discharge in Medical Service patients increased the rate of prophylaxis but did not decrease the rate of symptomatic venous thromboembolism.