Is there evidence for accelerated polyethylene wear in uncemented compared to cemented acetabular components? A systematic review of the literature

Joint arthroplasty registries show an increased rate of aseptic loosening in uncemented acetabular components as compared to cemented acetabular components. Since loosening is associated with particulate wear debris, we postulated that uncemented acetabular components demonstrate a higher polyethylene wear rate than cemented acetabular components in total hip arthroplasty. We performed a systematic review of the peer-reviewed literature, comparing the wear rate in uncemented and cemented acetabular components in total hip arthroplasty. Studies were identified using MEDLINE (PubMed), EMBASE and the Cochrane Central Register of Controlled Trials. Study quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The search resulted in 425 papers. After excluding duplicates and selection based on title and abstracts, nine studies were found eligible for further analysis: two randomised controlled trials, and seven observational studies. One randomised controlled trial found a higher polyethylene wear rate in uncemented acetabular components, while the other found no differences. Three out of seven observational studies showed a higher polyethylene wear in uncemented acetabular component fixation; the other four studies did not show any differences in wear rates. The available evidence suggests that a higher annual wear rate may be encountered in uncemented acetabular components as compared to cemented components

Population-Based Rates of Revision of Primary Total Hip Arthroplasty: A Systematic Review

Background: Most research on failure leading to revision total hip arthroplasty (THA) is reported from single centers. We searched PubMed between January 2000 and August 2010 to identify population- or community-based studies evaluating ten-year revision risks. We report ten-year revision risk using the Kaplan-Meier method, stratifying by age and fixation technique. Results: Thirteen papers met the inclusion criteria. Cemented prostheses had Kaplan-Meier estimates of revision-free implant survival of ten years ranging from 88 % to 95%; uncemented prostheses had Kaplan-Meier estimates from 80 % to 85%. Estimates ranged from 72 % to 86 % in patients less than 60 years old and from 90 to 96 % in older patients. Conclusion: Data reported from national registries suggest revision risks of 5 to 20 % ten years following primary THA. Revision risks are lower in older THA recipients. Uncemented implants may have higher ten-year rates of revision, regardless of age

A High Through-Put Reverse Genetic Screen Identifies Two Genes Involved in Remote Memory in Mice

Previous studies have revealed that the initial stages of memory formation require several genes involved in synaptic, transcriptional and translational mechanisms. In contrast, very little is known about the molecular and cellular mechanisms underlying later stages of memory, including remote memory (i.e. 7-day memory). To identify genes required for remote memory, we screened randomly selected mouse strains harboring known mutations. In our primary reverse genetic screen, we identified 4 putative remote memory mutant strains out of a total of 54 lines analyzed. Additionally, we found 11 other mutant strains with other abnormal profiles. Secondary screens confirmed that mutations of integrin β2 (Itgβ2) and steryl-O-acyl transferase 1 (Soat1) specifically disrupted remote memory. This study identifies some of the first genes required for remote memory, and suggests that screens of targeted mutants may be an efficient strategy to identify molecular requirements for this process

Influence of surgical approach on component positioning in primary total hip arthroplasty

Background: Minimal invasive surgery (MIS) has gained growing popularity in total hip arthroplasty (THA) but concerns exist regarding component malpositioning. The aim of the present study was to evaluate femoral and acetabular component positioning in primary cementless THA comparing a lateral to a MIS anterolateral approach. Methods: We evaluated 6 week postoperative radiographs of 52 hips with a minimal invasive anterolateral approach compared to 54 hips with a standard lateral approach. All hips had received the same type of implant for primary cementless unilateral THA and had a healthy hip contralaterally. Results: Hip offset was equally restored comparing both approaches. No influence of the approach was observed with regard to reconstruction of acetabular offset, femoral offset, vertical placement of the center of rotation, stem alignment and leg length discrepancy. However, with the MIS approach, a significantly higher percentage of cups (38.5 %) was malpositioned compared to the standard approach (16.7 %) (p = 0.022). Conclusions: The MIS anterolateral approach allows for comparable reconstruction of stem position, offset and center of rotation compared to the lateral approach. However, surgeons must be aware of a higher risk of cup malpositioning for inclination and anteversion using the MIS anterolateral approach

Caloric Restriction Suppresses Microglial Activation and Prevents Neuroapoptosis Following Cortical Injury in Rats

Traumatic brain injury (TBI) is a widespread cause of death and a major source of adult disability. Subsequent pathological events occurring in the brain after TBI, referred to as secondary injury, continue to damage surrounding tissue resulting in substantial neuronal loss. One of the hallmarks of the secondary injury process is microglial activation resulting in increased cytokine production. Notwithstanding that recent studies demonstrated that caloric restriction (CR) lasting several months prior to an acute TBI exhibits neuroprotective properties, understanding how exactly CR influences secondary injury is still unclear. The goal of the present study was to examine whether CR (50% of daily food intake for 3 months) alleviates the effects of secondary injury on neuronal loss following cortical stab injury (CSI). To this end, we examined the effects of CR on the microglial activation, tumor necrosis factor-α (TNF-α) and caspase-3 expression in the ipsilateral (injured) cortex of the adult rats during the recovery period (from 2 to 28 days) after injury. Our results demonstrate that CR prior to CSI suppresses microglial activation, induction of TNF-α and caspase-3, as well as neurodegeneration following injury. These results indicate that CR strongly attenuates the effects of secondary injury, thus suggesting that CR may increase the successful outcome following TBI

Increased expression of inducible co-stimulator on CD4+ T-cells in the peripheral blood and synovial fluid of patients with failed hip arthroplasties

OBJECTIVES: T-cells are considered to play an important role in the inflammatory response causing arthroplasty failure. The study objectives were to investigate the composition and distribution of CD4+ T-cell phenotypes in the peripheral blood (PB) and synovial fluid (SF) of patients undergoing revision surgery for failed metal-on-metal (MoM) and metal-on-polyethylene (MoP) hip arthroplasties, and in patients awaiting total hip arthroplasty. METHODS: In this prospective case-control study, PB and SF were obtained from 22 patients (23 hips) undergoing revision of MoM (n = 14) and MoP (n = 9) hip arthroplasties, with eight controls provided from primary hip osteoarthritis cases awaiting arthroplasty. Lymphocyte subtypes in samples were analysed using flow cytometry. RESULTS: The percentages of CD4+ T-cell subtypes in PB were not different between groups. The CD4+ T-cells in the SF of MoM hips showed a completely different distribution of phenotypes compared with that found in the PB in the same patients, including significantly decreased CD4+ T-central memory cells (p < 0.05) and increased T-effector memory cells (p < 0.0001) in the SF. Inducible co-stimulator (ICOS) was the only co-stimulatory molecule with different expression on CD4+ CD28+ cells between groups. In PB, ICOS expression was increased in MoM (p < 0.001) and MoP (p < 0.05) cases compared with the controls. In SF, ICOS expression was increased in MoM hips compared with MoP hips (p < 0.05). CONCLUSIONS: Increased expression of ICOS on CD4+ T-cells in PB and SF of patients with failed arthroplasties suggests that these cells are activated and involved in generating immune responses. Variations in ICOS expression between MoM and MoP hips may indicate different modes of arthroplasty failure. Cite this article: Professor P. A. Revell. Increased expression of inducible co-stimulator on CD4+ T-cells in the peripheral blood and synovial fluid of patients with failed hip arthroplasties. Bone Joint Res 2016;5:52–60. DOI: 10.1302/2046-3758.52.200057

Morphological features of microglial cells in the hippocampal dentate gyrus of Gunn rat: a possible schizophrenia animal model

<p>Abstract</p> <p>Background</p> <p>Schizophrenia is a debilitating and complex mental disorder whose exact etiology remains unknown. There is growing amount of evidence of a relationship between neuroinflammation, as demonstrated by microglial activation, and schizophrenia. Our previous studies have proposed that hyperbilirubinemia plays a role in the pathophysiology of schizophrenia. Furthermore, we suggested the Gunn rat, an animal model of bilirubin encephalopathy, as a possible animal model of schizophrenia. However, the effects of unconjugated bilirubin on microglia, the resident immune cell of the CNS, in Gunn rats have never been investigated. In the present study, we examined how microglial cells respond to bilirubin toxicity in adult Gunn rats.</p> <p>Methods</p> <p>Using immunohistochemical techniques, we compared the distribution, morphology, and ultrastructural features of microglial cells in Gunn rats with Wistar rats as a normal control. We also determined the ratio of activated and resting microglia and observed microglia-neuron interactions. We characterized the microglial cells in the hippocampal dentate gyrus.</p> <p>Results</p> <p>We found that microglial cells showed activated morphology in the hilus, subgranular zone, and granular layer of the Gunn rat hippocampal dentate gyrus. There was no significant difference between cell numbers between in Gunn rats and controls. However, there was significant difference in the area of CD11b expression in the hippocampal dentate gyrus. Ultrastructurally, microglial cells often contained rich enlarged rich organelles in the cytoplasm and showed some phagocytic function.</p> <p>Conclusions</p> <p>We propose that activation of microglia could be an important causal factor of the behavioral abnormalities and neuropathological changes in Gunn rats. These findings may provide basic information for further assessment of the Gunn rat as an animal model of schizophrenia.</p

The impact of single and pairwise Toll-like receptor activation on neuroinflammation and neurodegeneration

Background Toll-like receptors (TLRs) enable innate immune cells to respond to pathogen- and host-derived molecules. The central nervous system (CNS) exhibits most of the TLRs identified with predominant expression in microglia, the major immune cells of the brain. Although individual TLRs have been shown to contribute to CNS disorders, the consequences of multiple activated TLRs on the brain are unclear. We therefore systematically investigated and compared the impact of sole and pairwise TLR activation on CNS inflammation and injury. Methods Selected TLRs expressed in microglia and neurons were stimulated with their specific TLR ligands in varying combinations. Cell cultures were then analyzed by immunocytochemistry, FlowCytomix, and ELISA. To determine neuronal injury and neuroinflammation in vivo, C57BL/6J mice were injected intrathecally with TLR agonists. Subsequently, brain sections were analyzed by quantitative real-time PCR and immunohistochemistry. Results Simultaneous stimulation of TLR4 plus TLR2, TLR4 plus TLR9, and TLR2 plus TLR9 in microglia by their respective specific ligands results in an increased inflammatory response compared to activation of the respective single TLR in vitro. In contrast, additional activation of TLR7 suppresses the inflammatory response mediated by the respective ligands for TLR2, TLR4, or TLR9 up to 24 h, indicating that specific combinations of activated TLRs individually modulate the inflammatory response. Accordingly, the composition of the inflammatory response pattern generated by microglia varies depending on the identity and combination of the activated TLRs engaged. Likewise, neuronal injury occurs in response to activation of only selected TLRs and TLR combinations in vitro. Activation of TLR2, TLR4, TLR7, and TLR9 in the brain by intrathecal injection of the respective TLR ligand into C57BL/6J mice leads to specific expression patterns of distinct TLR mRNAs in the brain and causes influx of leukocytes and inflammatory mediators into the cerebrospinal fluid to a variable extent. Also, the intensity of the inflammatory response and neurodegenerative effects differs according to the respective activated TLR and TLR combinations used in vivo. Conclusions Sole and pairwise activation of TLRs modifies the pattern and extent of inflammation and neurodegeneration in the CNS, thereby enabling innate immunity to take account of the CNS diseases’ diversity