Plate-assisted Lengthening of the Femur and Tibia in Pediatric Patients.

BACKGROUND: Limb lengthening over a percutaneous plate can be used during pediatric distraction osteogenesis to decrease the time of external fixation. METHODS: A retrospective, consecutive 2-surgeon experience of pediatric femoral and tibial lengthenings with a plate-assisted lengthening (PAL) technique was performed. The plate was placed at the time of index corticotomy. The primary outcome measures of external fixation index, consolidation index, and complications were assessed for each lengthening. RESULTS: From 2005 to 2012, 38 lengthenings (23 femur, 15 tibia) in 30 patients were performed by a PAL technique. All patients experienced successful distraction and consolidation. The average achieved lengthening was 3.80±0.98 cm (range, 2.2 to 6.4) with an average consolidation index of 27 days/cm and a mean external fixation index of 13.1±4.29 days/cm (range, 7.8 to 30). Patients returned to full weight-bearing activity after an average of 98.3±28.5 days. There were an average of 1.08±1.05 total complications and 0.39±0.75 severe complications per lengthening. Complications were encountered most commonly during femoral lengthening, including procurvatum and varus deformity through the regenerate. These deformities were usually corrected by frame adjustment before removal. CONCLUSIONS: PAL is a safe technique that minimizes time of external fixation, accelerates rehabilitation and weight-bearing, and can be successfully used on the femur or tibia. The most common complications are angular deformities of the regenerate that can be treated with adjustment before or at the time of plate locking. LEVEL OF EVIDENCE: Level IV-retrospective case series.

Progressive loss of implant fixation in a preclinical rat model of cemented knee arthroplasty.

Aseptic loosening of total knee arthroplasty continues to be a challenging clinical problem. The progression of the loosening process, from the initial well-fixed component, is not fully understood. In this study, loss of fixation of cemented hemiarthroplasty was explored using 9-month-old Sprague-Dawley rats with 0, 2, 6, 12, 26 week end points. Morphological and cellular changes of cement-bone fixation were determined for regions directly below the tibial tray (epiphysis) and distal to the tray (metaphysis). Loss of fixation, with a progressive increase in cement-bone gap volume was found in the epiphysis (0.162 mm3 /week), but did not progress appreciably in the metaphysis (0.007 mm3 /week). In the epiphysis, there was an early and sustained elevation of osteoclasts adjacent to the cement border and development of a fibrous tissue layer between the cement and bone. There was early formation of bone around the cement in the metaphysis, resulting in a condensed bone layer without osteoclastic bone resorption or development of a fibrous tissue layer. Implant positioning was also an important factor in the cement-bone gap formation, with greater gap formation for implants that were placed medially on the tibial articular surface. Loss of fixation in the rat model mimicked patterns found in human arthroplasty where cement-bone gaps initiate under the tibial tray, at the periphery of the implant. This preclinical model could be used to study early biological response to cemented fixation and associated contributions of mechanical instability, component alignment, and periprosthetic inflammation.

Preserved Activity of CD20-Specific Chimeric Antigen Receptor-Expressing T Cells in the Presence of Rituximab.

CD20 is an attractive immunotherapy target for B-cell non-Hodgkin lymphomas, and adoptive transfer of T cells genetically modified to express a chimeric antigen receptor (CAR) targeting CD20 is a promising strategy. A theoretical limitation is that residual serum rituximab might block CAR binding to CD20 and thereby impede T cell-mediated anti-lymphoma responses. The activity of CD20 CAR-modified T cells in the presence of various concentrations of rituximab was tested in vitro and in vivo CAR-binding sites on CD20(+) tumor cells were blocked by rituximab in a dose-dependent fashion, although at 37°C blockade was incomplete at concentrations up to 200 µg/mL. T cells with CD20 CARs also exhibited modest dose-dependent reductions in cytokine secretion and cytotoxicity, but not proliferation, against lymphoma cell lines. At rituximab concentrations of 100 µg/mL, CAR T cells retained ≥50% of baseline activity against targets with high CD20 expression, but were more strongly inhibited when target cells expressed low CD20. In a murine xenograft model using a rituximab-refractory lymphoma cell line, rituximab did not impair CAR T-cell activity, and tumors were eradicated in >85% of mice. Clinical residual rituximab serum concentrations were measured in 103 lymphoma patients after rituximab therapy, with the median level found to be only 38 µg/mL (interquartile range, 19-72 µg/mL). Thus, despite modest functional impairment in vitro, the in vivo activity of CD20-targeted CAR T cells remains intact at clinically relevant levels of rituximab, making use of these T cells clinically feasible. Cancer Immunol Res; 4(6); 509-19. ©2016 AACR