Citations

Background Information on ice hockey injuries at the international level is very limited. The aim of the study was to analyse the incidence, type, mechanism and severity of ice hockey injuries in men's international ice hockey tournaments. Methods All the injuries in men's International Ice Hockey Federation World Championship tournaments over a 7-year period were analysed using a strict definition of injury, standardised reporting strategies and an injury diagnosis made by a team physician. Results 528 injuries were recorded in games resulting in an injury rate of 14.2 per 1000 player-games (52.1/1000 player-game hours). Additionally, 27 injuries occurred during practice. For WC A-pool Tournaments and Olympic Winter Games (OWG) the injury rate was 16.3/1000 player-games (59.6/1000 player-game hours). Body checking, and stick and puck contact caused 60.7% of the injuries. The most common types of injuries were lacerations, sprains, contusions and fractures. A laceration was the most common facial injury and was typically caused by a stick. The knee was the most frequently injured part of the lower body and the shoulder was the most common site of an upper body injury. Arenas with flexible boards and glass reduced the risk of injury by 29% (IRR 0.71, (95% CI 0.56 to 0.91)). Conclusions The incidence of injury during international ice hockey competition is relatively high. Arena characteristics, such as flexible boards and glass, appeared to reduce the risk of injury.

PurposeAdvanced systemic mastocytosis (SM), a fatal hematopoietic malignancy characterized by drug resistance, has no standard therapy. The effectiveness of allogeneic hematopoietic stem-cell transplantation (alloHCT) in SM remains unknown.Patients and MethodsIn a global effort to define the value of HCT in SM, 57 patients with the following subtypes of SM were evaluated: SM associated with clonal hematologic non–mast cell disorders (SM-AHNMD; n = 38), mast cell leukemia (MCL; n = 12), and aggressive SM (ASM; n = 7). Median age of patients was 46 years (range, 11 to 67 years). Donors were HLA-identical (n = 34), unrelated (n = 17), umbilical cord blood (n = 2), HLA-haploidentical (n = 1), or unknown (n = 3). Thirty-six patients received myeloablative conditioning (MAC), and 21 patients received reduced-intensity conditioning (RIC).ResultsResponses in SM were observed in 40 patients (70%), with complete remission in 16 patients (28%). Twelve patients (21%) had stable disease, and five patients (9%) had primary refractory disease. Overall survival (OS) at 3 years was 57% for all patients, 74% for patients with SM-AHNMD, 43% for those with ASM, and 17% for those with MCL. The strongest risk factor for poor OS was MCL. Survival was also lower in patients receiving RIC compared with MAC and in patients having progression compared with patients having stable disease or response.ConclusionAlloHCT was associated with long-term survival in patients with advanced SM. Although alloHCT may be considered as a viable and potentially curative therapeutic option for advanced SM in the meantime, given that this is a retrospective analysis with no control group, the definitive role of alloHCT will need to be determined by a prospective trial.

Abstract Wee1 is a key regulator of both G2/M transition and DNA replication fork stability. In this study, the efficacy of the Wee1 inhibitor MK1775 was evaluated in the Mayo primary glioblastoma multiforme (GBM) xenograft model. Based on western blot expression of Wee1, GBM22, GBM12 and GBM6 were selected for study based on low, intermediate and high-level expression, respectively. Wee1-mediated phosphorylation of Y15-Cdc2 was robustly suppressed in vitro in both GBM22 and GBM6 at 300 nM MK1775. At this concentration, MK1775 had marked anti-proliferative effects on GBM22 with 80±2.5% suppression of absorbance in a CyQUANT cell proliferation assay, while similar treatment of GBM6 had minimal effect on growth (26±21% suppression of absorbance). In a similar primary neurosphere formation assay, 300 nM completely inhibited neurosphere formation in GBM22 and GBM12, while having no effect on GBM6 neurosphere formation. Consistent with the cytotoxicity data, single agent treatment of GBM22 with MK1775 resulted in a marked S-phase arrest 24 hours after treatment (60% vs. 40% cells in S with MK1775 vs. control, respectively) and subsequent accumulation of cells in G2/M 48 hours after treatment (95% vs. 9.5%, respectively). In contrast, relatively minimal cell cycle perturbations were observed with MK1775 in GBM6 (24 hour S-phase accumulation 27% vs. 21%, respectively). Combination studies with MK1775 and temozolomide (TMZ) in a neurosphere formation assay demonstrated enhancement of treatment benefit only in GBM22 and GBM12 but not GBM6 (relative neurosphere numbers for TMZ, MK1775, or combined treatment compared to untreated were 34%, 16% and 7%, respectively for GBM22, 41%, 95% and 15%, respectively, for GBM12; while the same combination had no effect on GBM6 neurosphere formation). In anticipation of evaluating treatment efficacy in animal models, pharmacokinetic modeling of MK1775 brain delivery was performed in nude mice. Following a single MK1775 dose of 50 mg/kg, time to maximum blood concentration was 1.0 hours, AUC was 29.8 microM·h, and Cmax was 7.8 microM in whole blood and 0.24 microM in brain parenchyma. To evaluate whether limitations in brain delivery affected efficacy, parallel in vivo GBM12 heterotopic and orthotopic xenograft efficacy studies were performed with a 5 day dosing regimen of TMZ and MK1775 repeated every 28 days for 3 cycles. In the orthotopic model, MK1775 provided no survival benefit with median survival being 16, 15, 88 and 92 days for placebo, MK1775 alone, TMZ alone, or MK1775 + TMZ treatment, respectively. In contrast, there is some suggestion of MK1775 efficacy in the flank tumor model with median time to reach 1000 mm3 being 45, 56, 101 and 112 days, respectively. Collectively, these data suggest that despite promising in vitro activity for MK1775, limited drug delivery into the brain may reduce the efficacy of MK1775 therapy in an orthotopic GBM xenograft model. Citation Format: Jenny Pokorny, Vincenzo Pucci, Stuart Shumway, Bennett Ma, Katrina Bakken, Mark Schroeder, Brett Carlson, Jann N. Sarkaria. Pre-clinical investigation of the Wee1 inhibitor, MK1775, in glioblastoma multiforme. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3240. doi:10.1158/1538-7445.AM2013-3240

AbstractPurposeThe purpose of this study was to review the results of patellofemoral arthroplasty (PFA) performed by a single surgeon at a single institution in order to determine factors associated with clinical outcomes and progression of tibiofemoral degenerative joint disease.MethodsSixty‐one patients with isolated patellofemoral osteoarthritis were treated with a PFA by a single surgeon between 2003 and 2009. Fifty‐nine patients were available for analysis with a mean follow‐up of 4 years (range 2–6 years). Patients were evaluated by measuring range of motion and with the use of the Knee Society clinical rating system, the Tegner Activity Level Scale, and the UCLA Activity Score. In addition, preoperative radiographs were evaluated for patellofemoral and tibiofemoral compartment osteoarthritis and presence of trochlear dysplasia, and post‐operative radiographs were reviewed for progression of tibiofemoral degenerative arthritis. Furthermore, multivariate statistical methods were applied to study factors that had potential to influence the final outcome.ResultsThere was no statistically significant association between age, gender, history of prior knee surgery, patellar height, patellofemoral osteoarthritis severity, patellar and femoral component size, or performance of lateral release with patient pain and function (as measured by the Knee Society scores) or progression of tibiofemoral joint osteoarthritis at final follow‐up. Increased preoperative body mass index (BMI) was associated with lower post‐operative Knee Society function scores (p = 0.03). Patients with preoperative trochlear dysplasia had significantly less radiographic evidence of tibiofemoral joint osteoarthritis progression compared with patients without trochlear dysplasia at final follow‐up (p < 0.0001).ConclusionIn this study, patients with preoperative radiographic evidence of trochlear dysplasia experienced less progression of tibiofemoral degenerative joint disease than patients without trochlear dysplasia at a mean follow‐up of 4 years.Level of evidenceIV.

Abstract Bag3, a nucleotide exchange factor of the heat shock protein Hsp70, has been implicated in cell signaling. Here, we report that Bag3 interacts with the SH3 domain of Src, thereby mediating the effects of Hsp70 on Src signaling. Using several complementary approaches, we established that the Hsp70–Bag3 module is a broad-acting regulator of cancer cell signaling by modulating the activity of the transcription factors NF-κB, FoxM1, Hif1α, the translation regulator HuR, and the cell-cycle regulators p21 and survivin. We also identified a small-molecule inhibitor, YM-1, that disrupts the Hsp70–Bag3 interaction. YM-1 mirrored the effects of Hsp70 depletion on these signaling pathways, and in vivo administration of this drug was sufficient to suppress tumor growth in mice. Overall, our results defined Bag3 as a critical factor in Hsp70-modulated signaling and offered a preclinical proof-of-concept that the Hsp70–Bag3 complex may offer an appealing anticancer target. Cancer Res; 74(17); 4731–40. ©2014 AACR.