Sex differences in the morphological failure patterns following hip resurfacing arthroplasty

<p>Abstract</p> <p>Background</p> <p>Metal-on-metal hybrid hip resurfacing arthroplasty (with a cementless acetabular component and a cemented femoral component) is offered as an alternative to traditional total hip arthroplasty for the young and active adult with advanced osteoarthritis. Although it has been suggested that women are less appropriate candidates for metal-on-metal arthroplasty, the mechanisms of prosthesis failure has not been fully explained. While specific failure patterns, particularly osteonecrosis and delayed type hypersensitivity reactions have been suggested to be specifically linked to the sex of the patient, we wished to examine the potential influence of sex, clinical diagnosis, age of the patient and the size of the femoral component on morphological failure patterns in a large cohort of retrieved specimens following aseptic failure of hip resurfacing arthroplasty.</p> <p>Methods</p> <p>Femoral remnants retrieved from 173 hips with known patient's sex were morphologically analyzed for the cause of failure. The results were compared with the control group of the remaining 31 failures from patients of unknown sex. The odds ratios (OR) and 95% confidence intervals (CI) of the following morphologically defined variables were calculated using logistic regression analysis: periprosthetic fractures (n = 133), osteonecrosis (n = 151), the presence of excessive intraosseous lymphocyte infiltration (n = 11), and interface hyperosteoidosis (n = 30). Logistic regression analysis was performed both unadjusted and after adjustment for sex, age, the size of the femoral component, and preoperative clinical diagnosis.</p> <p>Results</p> <p>Femoral remnants from female patients had a smaller OR for fracture (adjusted OR: 0.29, 95% CI 0.11, 0.80, <it>P </it>for difference = 0.02) and for the presence of osteonecrosis (adjusted OR: 0.16, 95% CI 0.04, 0.63, <it>P </it>for difference = 0.01). However, women had a higher OR for both the presence of excessive intraosseous lymphocyte infiltration (adjusted OR: 10.22, 95% CI 0.79, 132.57, <it>P </it>for difference = 0.08) and interface hyperosteoidosis (adjusted OR: 4.19, 95% CI 1.14, 15.38, <it>P </it>for difference = 0.03).</p> <p>Conclusions</p> <p>Within the limitations of this study, we demonstrated substantial sex differences in distinct failure patterns of metal-on-metal hip resurfacing. Recognition of pathogenically distinct failure modes will enable further stratification of risk factors for certain failure mechanisms and thus affect future therapeutic options for selected patient groups.</p

Molecular and functional characterization of VDAC2 purified from mammal spermatozoa

International audienceVDAC (Voltage Dependent Anion selective Channel) is the pore-forming protein located in the outer mitochondrial membrane. In higher eukaryotes three genes encode for VDAC. Nevertheless the knowledge of VDAC isoforms is mainly restricted to VDAC1, the only isoform characterized from living tissues until now. We have highly enriched the isoform VDAC2 using as starting material bovine spermatozoa. VDAC2 was obtained in the hydroxyapatite/celite pass-through of sperm proteins solubilized with Triton X-100. This fraction showed in SDS-PAGE two major and one-faint bands in the Mr range of 30-35 kDa. Two-dimensional electrophoresis resolved these bands in ten spots with various Coomassie staining intensities. Western blot analysis with antibodies monospecific for each isoform and MS peptide sequencing showed that the main protein resolved in electrophoresis was VDAC2 with minor contaminations of the other isoforms. Proteomic analysis of the higher Mw VDAC2 protein allowed the coverage of the whole protein with the exception of the tri-peptide A24AR26. In the same material it was revealed the presence of two possible amino acid substitutions (T88 to L88 and A97 to Q97). Reconstitution of VDAC2 pores in planar lipid bilayers showed typical features of mitochondrial porins. Step-wise increases in membrane conductance were observed with a predominant conductance of about 3.5 nS in 1 M KCl. Very often small short-lived fluctuations were observed with single-channel conductance of about 1.5 nS. Bovine spermatozoa VDAC2 was anion-selective and showed voltage dependence. This is the first work reporting the purification and characterization of VDAC2 from a mammalian tissue

Factors Influencing Choice of Rituximab Versus an Alternative Tumor Necrosis Factor Inhibitor Following Tumor Necrosis Factor Inhibitor Failure in Patients with Rheumatoid Arthritis: Sub-Analysis of a Global, Observational Comparative Effectiveness Study

Rituximab is more effective to treat rheumatoid arthritis compared to a second anti-TNFalpha blockers

p53 overexpression is a prognosticator of poor outcome in esophageal cancer

Immunohistochemistry studies on p53 inactivation in esophageal cancer are available with inconclusive results. Data on the combined effect of p53 protein accumulation and TP53 genomic deactivation in large scale studies for esophageal cancer are currently lacking. A tissue microarray with 691 esophageal cancer samples was analyzed by p53 immunohistochemistry and fluorescence in situ hybridization (FISH). Nuclear p53 accumulation was observed in 45.9% of patients with adenocarcinoma (AC) and in 40.0% in squamous cell carcinoma (SCC). Heterozygous TP53 deletions occurred in 40.9% in AC and in 19.4% in SCC. Homozygous deletions did not occur at all. High-level p53 immunostaining was associated with shortened overall survival in AC and SCC while TP53 deletions alone showed no correlation with survival. High-level p53 immunostaining in patients with AC was associated with advanced tumor (P=0.019) and Union for International Cancer Control stages (P=0.004), grading (P=0.027) and the resection margin status (P=0.006). Associations between p53 immunostaining and SCC were not found. TP53 deletions were found to be associated with advanced tumor stages (P=0.028) and the presence of lymph node metastasis (P=0.009) in SCC. In conclusion, strong p53 immunostaining, but not TP53 deletion alone, is associated with unfavorable outcomes and may therefore represent a clinically useful molecular marker in esophageal cancer