MRSA colonisation and subsequent risk of infection despite effective eradication in orthopaedic elective surgery

The objective of this study was to determine the effectiveness of screening and successful treatment of methicillin-resistant Staphylococcus aureus (MRSA) colonisation in elective orthopaedic patients on the subsequent risk of developing a surgical site infection (SSI) with MRSA. We screened 5933 elective orthopaedic in-patients for MRSA at pre-operative assessment. Of these, 108 (1.8%) were colonised with MRSA and 90 subsequently underwent surgery. Despite effective eradication therapy, six of these (6.7%) had an SSI within one year of surgery. Among these infections, deep sepsis occurred in four cases (4.4%) and superficial infection in two (2.2%). The responsible organism in four of the six cases was MRSA. Further analysis showed that patients undergoing surgery for joint replacement of the lower limb were at significantly increased risk of an SSI if previously colonised with MRSA. We conclude that previously MRSA-colonised patients undergoing elective surgery are at an increased risk of an SSI compared with other elective patients, and that this risk is significant for those undergoing joint replacement of the lower limb. Furthermore, when an infection occurs, it is likely to be due to MRSA.     

Serum uric acid is associated with bone health in older men: A cross‐sectional population‐based study

Serum uric acid (UA) is a strong endogenous antioxidant. Since oxidative stress has been linked to osteoporosis, we examined the association between serum UA levels and bone mineral density (BMD), prevalent vertebral and nonvertebral fractures, and laboratory measures such as calcitropic hormones and bone turnover marker levels. This cross‐sectional analysis consisted of 1705 community‐dwelling men aged 70 years or over who participated in the baseline part of the Concord Health and Ageing in Men Project (CHAMP), a population‐based study of older men in Sydney, Australia. BMD at all sites was significantly higher among men with serum UA levels above the group median than among men with UA levels below the median. In multiple regression analyses adjusted for potential confounders, serum UA remained associated with BMD at all sites (β = 0.12 to 0.14, p < .001), serum calcium (β = 0.11, p = .001), parathyroid hormone (β = 0.09, p = .002), 25‐hydroxyvitamin D (β = 0.09, p = .005), and was negatively associated with urinary excretion amino‐terminal cross‐linked telopeptide of type 1 collagen (β = –0.09, p = .006). Overall, serum UA accounted for 1.0% to 1.44% of the variances in BMD (R² = 0.10 to 0.22). In multiple logistic regression analyses, above‐median serum UA levels were associated with a lower prevalence of osteoporosis at the femoral neck [odds ratio (OR) = 0.42, 95% confidence interval (CI) 0.22–0.81, p = .010) and lumbar spine (OR = 0.44, 95% CI 0.23–0.86, p = .016) and a lower prevalence of vertebral (OR = 0.62, 95% CI 0.43–0.91, p = .015) and nonvertebral (OR = 0.51, 95% CI 0.29–0.89, p = .018) fractures. In conclusion, higher serum UA levels are associated with higher BMD at all skeletal sites and with a lower prevalence of vertebral and nonvertebral fractures in older men. © 2011 American Society for Bone and Mineral Research.     

Early ultrastructural defects of axons and axon–glia junctions in mice lacking expression of Cnp1

Most axons in the central nervous system (CNS) are surrounded by a multilayered myelin sheath that promotes fast, saltatory conduction of electrical impulses. By insulating the axon, myelin also shields the axoplasm from the extracellular milieu. In the CNS, oligodendrocytes provide support for the long‐term maintenance of myelinated axons, independent of the myelin sheath. Here, we use electron microscopy and morphometric analyses to examine the evolution of axonal and oligodendroglial changes in mice deficient in 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase (CNP) and in mice deficient in both CNP and proteolipid protein (PLP/DM20). We show that CNP is necessary for the formation of a normal inner tongue process of oligodendrocytes that myelinate small diameter axons. We also show that axonal degeneration in Cnp1 null mice is present very early in postnatal life. Importantly, compact myelin formed by transplanted Cnp1 null oligodendrocytes induces the same degenerative changes in shiverer axons that normally are dysmyelinated but structurally intact. Mice deficient in both CNP and PLP develop a more severe axonal phenotype than either single mutant, indicating that the two oligodendroglial proteins serve distinct functions in supporting the myelinated axon. These observations support a model in which the trophic functions of oligodendrocytes serve to offset the physical shielding of axons by myelin membranes. © 2009 Wiley‐Liss, Inc.     

Fatal mycotic aneurysms due to Scedosporium and Pseudallescheria infection

Angioinvasive complications of Scedosporium infections are rare. We report two cases of mycotic aneurysm, following apparent localized infection, due to Scedosporium apiospermum and Pseudallescheria boydii. The thoracoabdominal aorta was affected in one patient, and cerebral vessels were affected in the other. Despite voriconazole therapy and surgical resection, the patients died. Previously reported cases are reviewed.     

Insertional mutagenesis reveals progression genes and checkpoints in MYC/Runx2 lymphomas

In this study, we have exploited the power of insertional mutagenesis to elucidate tumor progression pathways in mice carrying two oncogenes (MYC/Runx2) that collaborate to drive early lymphoma development. Neonatal infection of these mice with Moloney murine leukemia virus resulted in accelerated tumor onset with associated increases in clonal complexity and lymphoid dissemination. Large-scale analysis of retroviral integration sites in these tumors revealed a profound bias towards a narrow range of target genes, including Jdp2 (Jundm2), D cyclin, and Pim family genes. Remarkably, direct PCR analysis of integration hotspots revealed that every progressing tumor consisted of multiple clones harboring hits at these loci, giving access to large numbers of independent insertion events and uncovering the contrasting mutagenic mechanisms operating at each target gene. Direct PCR analysis showed that high-frequency targeting occurs only in the tumor environment in vivo and is specific for the progression gene set. These results indicate that early lymphomas in MYC/Runx2 mice remain dependent on exogenous growth signals, and that progression can be achieved by constitutive activation of pathways converging on a cell cycle checkpoint that acts as the major rate-limiting step for lymphoma outgrowth.     

Accuracy and feasibility of point-of-care and continuous blood glucose analysis in critically ill ICU patients

Introduction  

To obtain strict glucose regulation, an accurate and feasible bedside glucometry method is essential. We evaluated three different types of point-of-care glucometry in seriously ill intensive care unit (ICU) patients. The study was performed as a single-centre, prospective, observational study in a 12-bed medical ICU of a university hospital.     

Monocytes mediate Salmonella Typhimurium-induced tumor growth inhibition in a mouse melanoma model

The use of bacteria as an alternative cancer therapy has been reinvestigated in recent years. SL7207: an auxotrophic Salmonella enterica serovar Typhimurium aroA mutant with immune-stimulatory potential has proven a promising strain for this purpose. Here, we show that systemic administration of SL7207 induces melanoma tumor growth arrest in vivo, with greater survival of the SL7207-treated group compared to control PBS-treated mice. Administration of SL7207 is accompanied by a change in the immune phenotype of the tumor-infiltrating cells toward pro-inflammatory, with expression of the T_H1 cytokines IFN-γ, TNF-α, and IL-12 significantly increased. Interestingly, Ly6C⁺MHCII⁺ monocytes were recruited to the tumors following SL7207 treatment and were pro-inflammatory. Accordingly, the abrogation of these infiltrating monocytes using clodronate liposomes prevented SL7207-induced tumor growth inhibition. These data demonstrate a previously unappreciated role for infiltrating inflammatory monocytes underlying bacterial-mediated tumor growth inhibition. This information highlights a possible novel role for monocytes in controlling tumor growth, contributing to our understanding of the immune responses required for successful immunotherapy of cancer.