Causes of failure of ceramic-on-ceramic and metal-on-metal hip arthroplasties.

BACKGROUND: Few large series of hard bearing surfaces have reported on reasons for early failure. A number of unique mechanisms of failure, including fracture, squeaking, and adverse tissue reactions, have been reported with these hard bearing surfaces. However, the incidence varies among the published studies. QUESTIONS/PURPOSES: To confirm the incidences, we identified the etiologies of early failures of hard-on-hard bearing surfaces for ceramic-on-ceramic and metal-on-metal THAs. METHODS: We retrospectively reviewed records of 2907 THAs with hard-on-hard bearing surfaces implanted between 1996 and 2009; 1697 (58%) had ceramic-on-ceramic and 1210 (42%) had metal-on-metal bearing surfaces. We recorded bearing-related complications and compared them to nonspecific reasons for revision THA. The minimum followup of the ceramic-on-ceramic and metal-on-metal cohorts was 6 months (mean, 48 months; range, 6-97 months) and 24 months (mean, 60 months; range, 24-178 months), respectively. RESULTS: The overall revision rate for ceramic-on-ceramic THA was 2.2% (38 of 1697), with aseptic loosening accounting for 55% of revisions (femur or acetabulum). The bearing accounted for 13% of the revisions in the ceramic-on-ceramic THA cohort. The overall metal-on-metal revision rate was 5.4% (65 of 1210), 17 involving adverse tissue reactions related to the metal-on-metal bearing surface (17 of 1210, 1.4% of cases; 17 of 65, 26% of revisions). CONCLUSIONS: Twenty-six percent of the revisions from metal-on-metal and 13% of ceramic-on ceramic were bearing related. The overall short- to medium-term revision rate was 2.2% and 5.4% for ceramic-on-ceramic and metal-on-metal, respectively. The most common etiology of failure was loosening of the femoral or acetabular components. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of level of evidence

The fate of the unexpected positive intraoperative cultures after revision total knee arthroplasty

Of a consecutive series of 692 revision total knees at 3 centers, intraoperative cultures were unexpectedly found to be positive in 41 cases (5.9%). Of the 41, 29 (71%) cases had a single positive intraoperative culture and were determined to be a probable false positive based on absence of any other evidence of infection, of which 5 were treated with extended course of intravenous antibiotics after hospital discharge and the remaining 24 received no further treatment. None of these 24 patients manifested any sign of infection at follow-up, averaging 46 months (range, 24-74 months). Twelve patients were determined to have probable type 1 periprosthetic infection, 11 of which were treated with a course of antibiotics. Two of these patients became reinfected within a year. A single positive intraoperative culture after revision total knee arthroplasty does not mandate further treatment in the absence of any other signs of infection

Castration-resistant prostate cancer: Androgen receptor inactivation induces telomere DNA damage, and damage response inhibition leads to cell death

Telomere stability is important for cell viability, as cells with telomere DNA damage that is not repaired do not survive. We reported previously that androgen receptor (AR) antagonist induces telomere DNA damage in androgen-sensitive LNCaP prostate cancer cells; this triggers a DNA damage response (DDR) at telomeres that includes activation of ATM, and blocking ATM activation prevents telomere DNA repair and leads to cell death. Remarkably, AR antagonist induces telomere DNA damage and triggers ATM activation at telomeres also in 22Rv1 castration-resistant prostate cancer (CRPC) cells that are not growth inhibited by AR antagonist. Treatment with AR antagonist enzalutamide (ENZ) or ATM inhibitor (ATMi) by itself had no effect on growth in vitro or in vivo, but combined treatment with ENZ plus ATMi significantly inhibited cell survival in vitro and tumor growth in vivo. By inducing telomere DNA damage and activating a telomere DDR, an opportunity to inhibit DNA repair and promote cell death was created, even in CRPC cells. 22Rv1 cells express both full-length AR and AR splice variant AR-V7, but full-length AR was found to be the predominant form of AR associated with telomeres and required for telomere stability. Although 22Rv1 growth of untreated 22Rv1 cells appears to be driven by AR-V7, it is, ironically, expression of full-length AR that makes them sensitive to growth inhibition by combined treatment with ENZ plus ATMi. Notably, this combined treatment approach to induce telomere DNA damage and inhibit the DDR was effective in inducing cell death also in other CRPC cell lines (LNCaP/AR and C4-2B). Thus, the use of ENZ in combination with a DDR inhibitor, such as ATMi, may be effective in prolonging disease-free survival of patients with AR-positive metastatic CRPC, even those that co-express AR splice variant

Class III β-tubulin expression as a predictor of docetaxel-resistance in metastatic castration-resistant prostate cancer

About half of the patients treated with docetaxel in the setting of metastatic castration-resistant prostate cancer (CRPC) are non-responders. Therefore, a marker of response would be beneficial for clinical decision-making. We evaluated class III β-tubulin (βIII-tubulin) expression as a predictor of resistance in this setting, which previously has been correlated with lack of response to taxanes in other cancers. Patients with CRPC were included if they were treated with at least 3 cycles of docetaxel between 1990 and 2011. βIII-tubulin expression was assessed by immunostaining, which was performed in tissue samples obtained either via biopsy or prostatectomy at the time of diagnosis. Rates of prostate-specific antigen (PSA) response and overall survival (OS) following docetaxel treatment were compared between patients with high (2+ or 3+ staining) vs. low (0 or 1+ staining) βIII-tubulin expression. Of 73 patients, 26 (35%) had a high expression of βIII-tubulin. A PSA decline of 10% or greater occurred in 65% of patients with a high βIII-tubulin expression vs. 89% with a low βIII-tubulin expression (p = 0.0267). The median OS for patients with a high βIII-tubulin expression was 17.4 (95% CI 8.7-21.0) months vs. 19.8 (95% CI 16.6-23.6) months for patients with a low expression (p = 0.039). Our results show that a high βIII-tubulin expression is a negative prognostic factor in metastatic CRPC patients treated with docetaxel

Lumbopelvic Stability During a Single Leg Step Down Predicts Elbow Varus Torque During Baseball Pitching

During a baseball pitch, energy is transferred from the lower extremities through the lumbopelvic junction to produce ball velocity. Reduced lumbopelvic stability has been associated with elbow injury in pitchers, and commonly ulnar collateral ligament (UCL) tears. The primary biomechanical mechanism of UCL tears is high elbow varus torque. Understanding how decreased lumbopelvic stability influences the development of elbow varus torque could identify risk factors of UCL elbow injury. PURPOSE: Characterize the predictive ability of lumbopelvic stability on elbow varus torque during a baseball pitch. METHODS: NCAA Division 1 baseball players (N=44; 19.6+1.3yrs) participated. Pitchers threw ten fastballs from a mound to a catcher over regulation distance. Elbow varus torque was recorded using an inertial measurement unit and ball velocity was recorded with a radar gun. Pitchers also completed a single leg step down (SLSD) task. Triplanar kinematics were recorded for both legs, pelvis and trunk using inertial measurement units. Statistical analysis consisted of a cluster analysis, principal component analysis (PCA), and a multivariate logistic regression model to determine the relationship between lumbopelvic stability and elbow varus torque. RESULTS: Cluster analysis revealed 2 subgroups of pitchers: Low Torque-High Velocity and High Torque-Low Velocity. PCA analysis indicated 4 patterns of SLSD motion variability (principal components): 1-sagittal plane, 2-transverse plane, 3-frontal plane trail limb, and 4-frontal plane lead limb. Increased transverse plane motion of the trunk and pelvis predicted higher odds of belonging to the High Torque-Low Velocity cluster; trunk [Odds Ratio=2.9 (95%CI:1.1,8.0), p=0.036] and pelvis [Odds Ratio=2.6 (95%CI:1.1,6.0), p=0.031]. CONCLUSIONS: Lumbopelvic motion assessed during the SLSD in pitchers can identify deficits that predict high elbow varus torque and low ball velocity during the baseball pitch. Specifically, higher pelvis and trunk transverse plane motion was associated with pitchers in the High Torque-Low Velocity cluster. The SLSD provides an easily accessible method for coaches and clinicians to identify a potential risk factor related to increased elbow varus torque and UCL injury in pitchers

The effects of laterality on obstacle crossing performance in unilateral trans-tibial amputees

yesBackground Unilateral trans-tibial amputees have bilaterally reduced toe clearance, and an increased risk of foot contact, while crossing obstacles compared to the able-bodied. While the able-bodied tend to lead with a ‘preferred’ limb it is equivocal whether amputees prefer to lead with the intact or prosthetic limb. This study determined the effects of laterality, compared to side of amputation, on amputees' obstacle crossing performance. To help understand why laterality could affect performance we also assessed knee proprioception for both limbs. Methods Foot placement and toe clearance parameters were recorded while nine amputees crossed obstacles of varying heights leading with both their intact and prosthetic limbs. Joint-position sense was also assessed. Participants self-reported which limb was their preferred (dominant) limb. Findings There were no significant differences in foot placements or toe clearance variability across lead-limb conditions. There were no significant differences in toe clearance between intact and prosthetic lead-limbs (p = 0.28) but toe clearance was significantly higher when amputees led with their preferred compared to non-preferred limb (p = 0.025). There was no difference in joint-position sense between the intact and residual knees (p = 0.34) but joint-position sense tended to be more accurate for the preferred, compared to non-preferred limb (p = 0.08). Interpretation Findings suggest that, despite the mechanical constraints imposed by use of a prosthesis, laterality may be as important in lower-limb amputees as it is in the able bodied. This suggests that amputees should be encouraged to cross obstacles leading with their preferred limb.Engineering and Physical Sciences Research Counci