Benign and malignant tumors of the foot and ankle.

Pain and focal masses in the foot and ankle are frequently encountered and often initiate a workup including imaging. It is important to differentiate benign lesions from aggressive benign or malignant lesions. In this review, multiple examples of osseous and soft tissue tumors of the foot and ankle will be presented. Additionally, the compartmental anatomy of the foot and ankle will be discussed in terms of its relevance for percutaneous biopsy planning and eventual surgery. Finally, a general overview of the surgical management of benign, benign aggressive and malignant tumors of the foot and ankle will be discussed.

Abdominopelvic hemorrhage: correlation of CT positivity with the subsequent decision to perform blood transfusion.

The purpose of this study is to determine the role of computed tomography (CT) on the decision to administer blood transfusions in patients with abdominopelvic hemorrhage (trauma, surgery, invasive procedure, and spontaneous) and to determine the clinical parameters most likely to influence the decision to administer blood transfusions in patients with spontaneous abdominopelvic hemorrhage. In this IRB approved and HIPPA compliant study, retrospective analysis was performed on 298 patients undergoing abdominal and pelvic CT for suspected abdominopelvic hemorrhage and the CT reports and electronic medical records were reviewed. Odds ratios and 95% CI were calculated to compare the odds of abdominopelvic hemorrhage and transfusion for categorical and continuous predictors. The presence of abdominopelvic hemorrhage by CT was significantly associated with blood transfusions for trauma patients (p-value <0.0001) only. 106 patients with suspected spontaneous abdominopelvic hemorrhage had the lowest CT positivity rate (n = 23, 21.7%) but the highest blood transfusion rate (n = 62, 58.5%) compared to the patients with abdominopelvic hemorrhage from known preceding causes. In patients with spontaneous abdominopelvic hemorrhage, low hemoglobin and hematocrit levels immediately prior to obtaining the CT study were more predictive for receiving a blood transfusion (p-value <0.0001) than the presence of hemorrhage by CT. CT positivity is strongly correlated with the decision to administer blood transfusions for patients with abdominopelvic hemorrhage from trauma, indicating that CT studies play a significant role in determining the clinical management of trauma patients. For patients with spontaneous abdominopelvic hemorrhage, the decision to transfuse depends not on the CT study but on the patient's hemoglobin and hematocrit levels. CT studies should therefore not be performed for the sole purpose of determining the need for blood transfusion in patients with spontaneous abdominopelvic hemorrhage.

The comparative immunogenicity of human and porcine factor VIII in haemophilia A mice.

Inhibitory antibodies to factor VIII (FVIII inhibitors) are the most significant complication in the management of haemophilia A. The immunogenicity of FVIII may be driven in part by structural determinants within the FVIII molecule itself. Regions of nonidentity between human and porcine FVIII possibly could drive differential immune responses. The goal of this study was to compare the overall antibody response and levels of antibodies to the individual FVIII domains in naïve haemophilia A mice immunised with human or porcine FVIII. Haemophilia A mice were immunised with human or porcine FVIII using a protocol that mimics human clinical use. Inhibitor and total anti-FVIII antibody titers were measured and the domain-specificity of antibodies from 1,759 anti-FVIII hybridomas was determined. The overall immunogenicity of human and porcine FVIII was similar but significant differences in domain recognition were discovered. Anti-A2 and anti-C2 antibodies constituted the majority of inhibitors in both the human and porcine FVIII groups, similar to inhibitors that develop in humans. The proportions of anti-A2 or anti-C2 antibodies were not significantly different between the two groups. However, the specific inhibitory activity of anti-A2 antibodies was higher in the human FVIII group. Additionally, proportion of anti-C1 antibodies was significantly higher in the human FVIII group. In contrast, anti-A3 antibodies were more common in the porcine FVIII group. The differential immune response to human and porcine FVIII suggests that it may be possible to reduce the immunogenicity of FVIII by mutagenesis of the A2, A3 and C1 domains.

Adherence of recombinant pneumococcal surface adhesin A (rPsaA)-coated particles to human nasopharyngeal epithelial cells for the evaluation of anti-PsaA functional antibodies.

Pneumococcal surface adhesin A (PsaA) is a pneumococcal vaccine candidate. In this study, we detect functional antibodies to PsaA by using carboxylate-modified fluospheres coated with either recombinant non-lipidated PsaA (rPsaA) or synthetic peptides with relevant epitopes of PsaA. Peptides P1-P3 were derived from phage display sequences; peptides P4-P7 were homologous to rPsaA. P1- and P4-coated fluospheres had similar adherence to Detroit 562 nasopharyngeal cells when compared to rPsaA-coated fluospheres. Homologous and heterologous competitive inhibitions with peptides in solution determined the specificity of the adherence. There was no significant difference (P=0.25) between the inhibition of adherence of rPsaA- and P4-coated fluospheres. This study indicates that P1 and P4 contain a functional epitope(s) for the adherence of PsaA to nasopharyngeal cells making them suitable targets for the measurement of functional antibodies to PsaA.