Risk factors for wound infection in surgery for spinal metastasis

Wound infection rates are generally higher in patients undergoing surgery for spinal metastasis. Risk factors of wound infection in these patients are poorly understood. Purpose To identify demographic and clinical variables that may be associated with patients experiencing a higher wound infection rate. Study design Retrospective study with prospectively collected data of spinal metastasis patients operated consecutively at a University Teaching Hospital, adult spine division which is a tertiary referral centre for complex spinal surgery. Patient sample Ninety-eight patients were all surgically treated, consecutively from January 2009 to September 2011. Three patients had to be excluded due to inadequate data. Outcome measures Physiological measures, with presence or absence of microbiologically proven infection. Methods Various demographic and clinical data were recorded, including age, serum albumin level, blood total lymphocyte count, corticosteroid intake, Malnutrition Universal Screening Tool (MUST) score, neurological disability, skin closure material used, levels of surgery and administration of peri-operative corticosteroids. No funding was received from any sources for this study and as far as we are aware, there are no potential conflict of interest-associated biases in this study. Results Higher probabilities of infection were associated with low albumin level, seven or more levels of surgery, use of delayed/non-absorbable skin closure material and presence of neurological disability. Of these factors, levels of surgery were found to be statistically significant at the 5 % significance level. Conclusion Risk of infection is high (17.9 %) in patients undergoing surgery for spinal metastasis. Seven or more vertebral levels of surgery increase the risk of infection significantly (p < 0.05). Low albumin level and presence of neurological disability appear to show a trend towards increased risk of infection. Use of absorbable skin closure material, age, low lymphocyte count, peri-operative administration of corticosteroids and MUST score do not appear to influence the risk of infection

The effect of malnutrition on patients undergoing elective joint arthroplasty.

Malnutrition has been linked to serious complications in patients undergoing elective total joint arthroplasty (TJA). This study prospectively evaluated 2,161 patients undergoing elective TJA for malnutrition as defined by either an abnormal serum albumin or transferrin. The overall incidence of malnutrition was 8.5% (184 of 2,161) and the rate of overall complications in the malnourished group was 12% as compared to 2.9% in patients with normal parameters (P55years-old undergoing TJA and is associated with a significant increase in post-operative complications

Recurrence of Diabetic Pedal Ulcerations Following Tendo-Achilles Lengthening

Foot and ankle surgeons are frequently challenged by the devastating systemic consequences of diabetes mellitus manifested through neuropathy, integumentary and joint breakdown, delayed healing, decreased ability to fight infection, and fragile tendon/ligaments. Diabetic neuropathic pedal ulcerations lead to amputations at an alarming rate and also carry a high mortality rate. This article will discuss causes of diabetic pedal ulcerations that persist or recur after tendo-Achilles lengthening and will highlight areas that need to be addressed by the practitioner such as infection, vascular and nutritional status, glucose control, off-loading, biomechanics, and patient compliance

Enhancement of Tumour-Specific Immune Responses In Vivo by ‘MHC Loading-Enhancer’ (MLE)

BACKGROUND:Class II MHC molecules (MHC II) are cell surface receptors displaying short protein fragments for the surveillance by CD4+ T cells. Antigens therefore have to be loaded onto this receptor in order to induce productive immune responses. On the cell surface, most MHC II molecules are either occupied by ligands or their binding cleft has been blocked by the acquisition of a non-receptive state. Direct loading with antigens, as required during peptide vaccinations, is therefore hindered. PRINCIPAL FINDINGS:Here we show, that the in vivo response of CD4+ T cells can be improved, when the antigens are administered together with 'MHC-loading enhancer' (MLE). MLE are small catalytic compounds able to open up the MHC binding site by triggering ligand-release and stabilizing the receptive state. Their enhancing effect on the immune response was demonstrated here with an antigen from the influenza virus and tumour associated antigens (TAA) derived from the NY-ESO-1 protein. The application of these antigens in combination with adamantane ethanol (AdEtOH), an MLE compound active on human HLA-DR molecules, significantly increased the frequency of antigen-specific CD4+ T cells in mice transgenic for the human MHC II molecule. Notably, the effect was evident only with the MLE-susceptible HLA-DR molecule and not with murine MHC II molecules non-susceptible for the catalytic effect of the MLE. CONCLUSION:MLE can specifically increase the potency of a vaccine by facilitating the efficient transfer of the antigen onto the MHC molecule. They may therefore open a new way to improve vaccination efficacy and tumour-immunotherapy

Characterization of Structural Features Controlling the Receptiveness of Empty Class II MHC Molecules

MHC class II molecules (MHC II) play a pivotal role in the cell-surface presentation of antigens for surveillance by T cells. Antigen loading takes place inside the cell in endosomal compartments and loss of the peptide ligand rapidly leads to the formation of a non-receptive state of the MHC molecule. Non-receptiveness hinders the efficient loading of new antigens onto the empty MHC II. However, the mechanisms driving the formation of the peptide inaccessible state are not well understood. Here, a combined approach of experimental site-directed mutagenesis and computational modeling is used to reveal structural features underlying “non-receptiveness.” Molecular dynamics simulations of the human MHC II HLA-DR1 suggest a straightening of the α-helix of the β1 domain during the transition from the open to the non-receptive state. The movement is mostly confined to a hinge region conserved in all known MHC molecules. This shift causes a narrowing of the two helices flanking the binding site and results in a closure, which is further stabilized by the formation of a critical hydrogen bond between residues αQ9 and βN82. Mutagenesis experiments confirmed that replacement of either one of the two residues by alanine renders the protein highly susceptible. Notably, loading enhancement was also observed when the mutated MHC II molecules were expressed on the surface of fibroblast cells. Altogether, structural features underlying the non-receptive state of empty HLA-DR1 identified by theoretical means and experiments revealed highly conserved residues critically involved in the receptiveness of MHC II. The atomic details of rearrangements of the peptide-binding groove upon peptide loss provide insight into structure and dynamics of empty MHC II molecules and may foster rational approaches to interfere with non-receptiveness. Manipulation of peptide loading efficiency for improved peptide vaccination strategies could be one of the applications profiting from the structural knowledge provided by this study

Anchor Side Chains of Short Peptide Fragments Trigger Ligand-Exchange of Class II MHC Molecules

Class II MHC molecules display peptides on the cell surface for the surveillance by CD4+ T cells. To ensure that these ligands accurately reflect the content of the intracellular MHC loading compartment, a complex processing pathway has evolved that delivers only stable peptide/MHC complexes to the surface. As additional safeguard, MHC molecules quickly acquire a ‘non-receptive’ state once they have lost their ligand. Here we show now that amino acid side chains of short peptides can bypass these safety mechanisms by triggering the reversible ligand-exchange. The catalytic activity of dipeptides such as Tyr-Arg was stereo-specific and could be enhanced by modifications addressing the conserved H-bond network near the P1 pocket of the MHC molecule. It affected both antigen-loading and ligand-release and strictly correlated with reported anchor preferences of P1, the specific target site for the catalytic side chain of the dipeptide. The effect was evident also in CD4+ T cell assays, where the allele-selective influence of the dipeptides translated into increased sensitivities of the antigen-specific immune response. Molecular dynamic calculations support the hypothesis that occupation of P1 prevents the ‘closure’ of the empty peptide binding site into the non-receptive state. During antigen-processing and -presentation P1 may therefore function as important “sensor” for peptide-load. While it regulates maturation and trafficking of the complex, on the cell surface, short protein fragments present in blood or lymph could utilize this mechanism to alter the ligand composition on antigen presenting cells in a catalytic way

Measuring Risk Attitudes Controlling for Personality Traits*

Abstract: This study measures risk attitudes using two paid experiments: the Holt and Laury (2002) procedure and a variation of the game show Deal or No Deal. The participants also completed a series of personality questionnaires developed in the psychology literature including the risk domains of Weber, Blais, and Betz (2002). As in previous studies risk attitudes vary within subjects across elicitation methods. However, this variation can be explained by individual personality traits. Specifically, subjects behave as though the Holt and Laury task is an investment decision while the Deal or No Deal task is a gambling decision