Local vanadium release from a calcium sulfate carrier accelerates fracture healing

This study evaluated the efficacy of using calcium sulfate (CaSO₄) as a carrier for intramedullary delivery of an organic vanadium salt, vanadyl acetylacetonate (VAC) after femoral fracture. VAC can act as an insulin‐mimetic and can be used to accelerate fracture healing in rats. A heterogenous mixture of VAC and CaSO₄ was delivered to the fracture site of BB Wistar rats, and mechanical testing, histomorphometry, micro‐computed tomography (micro‐CT) were performed to measure healing. At 4 weeks after fracture, maximum torque to failure, effective shear modulus, and effective shear stress were all significantly higher (p < 0.05) in rats treated with 0.25 mg/kg VAC–CaSO₄ as compared to carrier control rats. Histomorphometry found a 71% increase in percent cartilage matrix (p < 0.05) and a 64% decrease in percent mineralized tissue (p < 0.05) at 2 weeks after fracture in rats treated with 0.25 mg/kg of VAC–CaSO₄. Micro‐CT analyses at 4 weeks found a more organized callus structure and higher trending maximum connected z‐ray. fraction for VAC–CaSO₄ groups. Evaluation of radiographs and serial histological sections at 12 weeks did not show any evidence of ectopic bone formation. As compared to previous studies, CaSO₄ was an effective carrier for reducing the dose of VAC required to accelerate femoral fracture healing in rats. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:727–734, 2014.     

Long‐term analysis of phase II studies of single‐agent lenalidomide in relapsed/refractory mantle cell lymphoma

Mantle cell lymphoma (MCL) is a type of non‐Hodgkin lymphoma (NHL) with aggressive disease characteristics resulting in multiple relapses after initial treatment. Lenalidomide is an immunomodulatory agent approved in the US for patients with relapsed/refractory MCL following bortezomib based on results from 3 multicenter phase II studies (2 including relapsed/refractory aggressive NHL and 1 focusing on MCL post‐bortezomib). The purpose of this report is to provide longer follow‐up on the MCL‐001 study (follow‐ups were 6.8 [NHL‐002], 7.6 [NHL‐003], and 52.2 [MCL‐001] months). The 206 relapsed MCL patients treated with single‐agent lenalidomide (25 mg/day PO, days 1 to 21 every 28‐days) had a median age of 67 years (63% ≥65 years), 91% with stage III/IV disease, and 50% with ≥4 previous treatment regimens. With a median follow‐up of X, the combined best overall response rate (ORR) was 33% (including 11% with complete remission [CR]/CR unconfirmed CRu). Lenalidomide produced rapid and durable responses with a median time to response of 2.2 months and median duration of response (DOR) of 16.6 months (95% CI: 11.1%‐29.8%). The safety profile was consistent and manageable; myelosuppression was the most common adverse event (AE). Overall, single‐agent lenalidomide showed consistent efficacy and safety in multiple phase II studies of heavily pretreated patients with relapsed/refractory MCL, including those previously treated with bortezomib.