Impact of Hamstring Graft Diameter on Tendon Strength: A Biomechanical Study.

PURPOSE: The purpose of this study was to compare the tensile strength of hamstring grafts of varying combined pull-through diameters within the clinically relevant range of 6 to 9 mm. METHODS: We tested 44 non-irradiated allograft hamstring grafts (11 per group). Combined looped semitendinosus and gracilis grafts were allocated to the 6-, 7-, 8-, or 9-mm group based on the smallest-diameter lumen that the graft could be "pulled through" using a surgical sizing instrument. Testing was performed on an Instron materials testing machine (Instron, Norwood, MA). Samples were secured with cryoclamps, prestressed, and pulled to failure at a rate of 10% gauge length per second. RESULTS: The mean load to failure was 2,359 ± 474 N, 3,263 ± 677 N, 3,908 ± 556 N, and 4,360 ± 606 N for the 6-, 7-, 8-, and 9-mm grafts, respectively. Minimum failure loads were as low as 1,567 N, 2,288 N, 2,874 N, and 3,720 N for each group, respectively. There were statistically significant differences between the 6- and 7-mm, 6- and 8-mm, 6- and 9-mm, and 7- and 9-mm groups (P = .01). CONCLUSIONS: Statistically different increasing tensile strength was seen as graft diameter increased. Significant variability exists in the strength of multi-stranded hamstring allografts within the diameter range of 6 to 9 mm that often falls well below the commonly accepted value of 4,000 N for a hamstring graft. CLINICAL RELEVANCE: Recent evidence suggests a higher early failure rate of hamstring autografts in subsets of patients with graft diameters of 8 mm or less. This study may increase awareness that hamstring grafts may not be nearly as strong as previously appreciated and that increasing tendon diameters by 1 to 2 mm may dramatically affect graft strength. These data may be helpful in preoperative discussions regarding variable hamstring size, strength, and potential intraoperative augmentation options.

ATM inhibitor KU-55933 increases the TMZ responsiveness of only inherently TMZ sensitive GBM cells.

Ataxia telangiectasia mutated (ATM) kinase is critical in sensing and repairing DNA double-stranded breaks (DSBs) such as those induced by temozolomide (TMZ). ATM deficiency increases TMZ sensitivity, which suggests that ATM inhibitors may be effective TMZ sensitizing agents. In this study, the TMZ sensitizing effects of 2 ATM specific inhibitors were studied in established and xenograft-derived glioblastoma (GBM) lines that are inherently sensitive to TMZ and derivative TMZ-resistant lines. In parental U251 and U87 glioma lines, the addition of KU-55933 to TMZ significantly increased cell killing compared to TMZ alone [U251 survival: 0.004 ± 0.0015 vs. 0.08 ± 0.01 (p < 0.001), respectively, and U87 survival: 0.02 ± 0.005 vs. 0.04 ± 0.002 (p < 0.001), respectively] and also elevated the fraction of cells arrested in G2/M [U251 G2/M fraction: 61.8 ± 1.1 % vs. 35 ± 0.8 % (p < 0.001), respectively, and U87 G2/M fraction 25 ± 0.2 % vs.18.6 ± 0.4 % (p < 0.001), respectively]. In contrast, KU-55933 did not sensitize the resistant lines to TMZ, and neither TMZ alone or combined with KU-55933 induced a G2/M arrest. While KU-55933 did not enhance TMZ induced Chk1/Chk2 activation, it increased TMZ-induced residual γ-H2AX foci in the parental cells but not in the TMZ resistant cells. Similar sensitization was observed with either KU-55933 or CP-466722 combined with TMZ in GBM12 xenograft line but not in GBM12TMZ, which is resistant to TMZ due to MGMT overexpression. These findings are consistent with a model where ATM inhibition suppresses the repair of TMZ-induced DSBs in inherently TMZ-sensitive tumor lines, which suggests an ATM inhibitor potentially could be deployed with an improvement in the therapeutic window when combined with TMZ.

Prevalence of postamputation pain and its subtypes: a meta-analysis with meta-regression.

INTRODUCTION: The inconsistent use of standardized approaches for classifying postamputation pain (PAP) has been a barrier to establishing its prevalence. OBJECTIVES: The primary objective of this systematic review and meta-analysis is to determine the prevalence of nontraumatic lower-extremity PAP using an established taxonomy. The secondary objective is to determine the prevalence of PAP subtypes, including phantom limb pain and residual limb pain (RLP). METHODS: An a priori protocol was registered, and a database search was conducted by a reference librarian. Randomized trials and uncontrolled studies were eligible for inclusion. The risk of bias was assessed using a tool developed for uncontrolled studies. A total of 2679 studies were screened, and 13 studies met inclusion criteria (n = 1063). RESULTS: The sources of risk of bias included selection bias and, to a lesser extent, whether the outcome was adequately ascertained. Two studies reported the prevalence of PAP and the pooled prevalence was 61% (95% confidence interval [CI], 33%-86%) with high heterogeneity (I2 = 93%). Thirteen studies reported the prevalence of phantom limb pain and the pooled prevalence was 53% (95% CI, 40%-66%) with high heterogeneity (I2 = 93%). Eight studies reported the prevalence of RLP and the pooled prevalence was 32% (95% CI 24%-41%) with high heterogeneity (I2 = 76%). Clinical subtypes of RLP were not reported. CONCLUSIONS: The prevalence of PAP is high in patients with nontraumatic lower-extremity amputations. Ongoing research that uses a taxonomy for PAP is needed to fully delineate the prevalence of PAP subtypes.