The Role of One-Stage Exchange for Prosthetic Joint Infection

Purpose of Review

In an era of increasing numbers of hip and knee replacements, strategies to manage prosthetic joint infection (PJI) that are effective at infection control with good patient-reported outcomes and cost containment for health systems are needed. Interest in single-stage exchange for PJI is rising and we assess evidence from the last 5 years related to this treatment strategy.

Recent Findings

Only five series for total knee replacement and ten series for total hip replacement have been reported in the last five years. More review articles and opinion pieces have been written. Reinfection rates in these recent studies range from 0 to 65%, but a meta-analysis and systematic review of all studies showed a reinfection rate of 7.6% (95% CI 3.4–13.1) and 8.8% (95% CI 7.2–10.6) for single-stage and two-stage revisions respectively. There is emerging evidence to support single-stage revision in the setting of significant bony deficiency and atypical PJIs such as fungal infections.

Summary

Prospective randomised studies are recruiting and are necessary to guide the direction of single-stage revision selection criteria. The onus of surgical excellence in mechanical removal of implants, necrotic tissue, and biofilms lies with the arthroplasty surgeon and must remain the cornerstone of treatment. Single-stage revision may be considered the first-line treatment for all PJIs unless the organism is unknown, the patient is systemically septic, or there is a poor tissue envelope.

     

Ultra‐deep T cell receptor sequencing reveals the complexity and intratumour heterogeneity of T cell clones in renal cell carcinomas

The recognition of cancer cells by T cells can impact upon prognosis and be exploited for immunotherapeutic approaches. This recognition depends on the specific interaction between antigens displayed on the surface of cancer cells and the T cell receptor (TCR), which is generated by somatic rearrangements of TCR α‐ and β‐chains (TCRb). Our aim was to assess whether ultra‐deep sequencing of the rearranged TCRb in DNA extracted from unfractionated clear cell renal cell carcinoma (ccRCC) samples can provide insights into the clonality and heterogeneity of intratumoural T cells in ccRCCs, a tumour type that can display extensive genetic intratumour heterogeneity (ITH). For this purpose, DNA was extracted from two to four tumour regions from each of four primary ccRCCs and was analysed by ultra‐deep TCR sequencing. In parallel, tumour infiltration by CD4, CD8 and Foxp3 regulatory T cells was evaluated by immunohistochemistry and correlated with TCR‐sequencing data. A polyclonal T cell repertoire with 367–16 289 (median 2394) unique TCRb sequences was identified per tumour region. The frequencies of the 100 most abundant T cell clones/tumour were poorly correlated between most regions (Pearson correlation coefficient, –0.218 to 0.465). 3–93% of these T cell clones were not detectable across all regions. Thus, the clonal composition of T cell populations can be heterogeneous across different regions of the same ccRCC. T cell ITH was higher in tumours pretreated with an mTOR inhibitor, which could suggest that therapy can influence adaptive tumour immunity. These data show that ultra‐deep TCR‐sequencing technology can be applied directly to DNA extracted from unfractionated tumour samples, allowing novel insights into the clonality of T cell populations in cancers. These were polyclonal and displayed ITH in ccRCC. TCRb sequencing may shed light on mechanisms of cancer immunity and the efficacy of immunotherapy approaches. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Chronically elevated depressive symptoms interact with acute increases in inflammation to predict worse neurocognition among people with HIV

Journal of NeuroVirology - We examined the joint effects of depressive symptoms (Beck Depression Inventory-II (BDI-II)) and systemic inflammation (plasma C-reactive protein (CRP)) on longitudinal...     

Advances in antiepileptic drug treatments. A rational basis for selecting drugs for older patients with epilepsy

Incidence of epilepsy increases rapidly after age 65; recent studies indicate that approximately 10% of nursing home residents are being treated with antiepileptic drugs (AEDs). Almost all are being treated with first generation AEDs. The average nursing home patient receives six medications, has age-related changes in protein binding, decreases in hepatic and renal clearance, and may have alterations in gastrointestinal absorption. AEDs that do not have drug-drug interactions, are not metabolized by the liver, and are readily absorbed may offer benefits in this population. New studies are demonstrating that the first generation AEDs have a number of shortcomings for treating older patients, whereas some of the newer AEDs may overcome these limitations. This paper reviews the present knowledge base and compares properties of the first generation AEDs with newer agents to develop a more rational approach for drug selection in older adults.