A Link Between the Tribology and Corrosive Degradation of Metal-on-Metal THRs

The degradation of Metal-on-Metal (MoM) Total Hip Replacements (THRs) is a complex mix of tribological, corrosive phenomena and their synergistic processes. Previous links between the corrosion of these devices and their sliding conditions over a cycle have been observed in simulator studies instrumented with a three-electrode electrochemical cell. This study further quantifies that link; demonstrating clear repeating periodicity in the anodic current transients of a 28 mm diameter MoM bearing under a standard ISO-14242 walking profile. A simplified 2D model and an expression of the Hamrock-Dowson equation was utilised to estimate the Theoretical Minimum Film Thickness (hmin) over a cycle, which was shown to match closely to the measured anodic current in both shape and magnitude

Tribocorrosion of hard-on-hard total hip replacements with metal and ceramic counterfaces under standard and adverse loading conditions

28 mm Metal-on-Metal (MoM) and Metal-on-Ceramic (MoC) Total Hip Replacements were articulated to 1 million cycles under both Standard Gait and Microseparation conditions. The hip simulator was fully instrumented with a three-electrode electrochemical cell to facilitate monitoring of corrosive degradation. The estimated volume loss from corrosion at the bearing surface was seen to increase by nearly an order of magnitude for both devices, representing as much as 17% of total degradation. Anodic current transients also displayed near order of magnitude increases in the peak current for both bearing couples. An adverse loading scenario could cause as much as an order of magnitude increase in the metallic ions released into the joint capsule as well as an increased volume of wear debris

Adverse loading effects on tribocorrosive degradation of 28 mm metal-on-metal hip replacement bearings

Following the high clinical failure rates of metal-on-metal total hip replacements much work has been undertaken to investigate their poor performance. So called adverse loading scenarios such as acetabular inclination and microseparation have been attributed to indicators for failure of the implants. The ISO hip simulation standards (ISO 14242:1) still rely on gravimetric and ex situ analysis, considering only the total wear during articulation. Live in situ sensing can provide valuable insight into the degradation mechanisms of metallic interfaces under such scenarios. Clinical 28 mm diameter metal-on-metal components were articulated in a full-ISO hip simulator. The bearings were subjected to increasing angles of acetabular inclination and retroversion over short-term periods of articulation. Corrosive degradation was monitored during sliding by means of an in situ three-electrode cell. Changing acetabular inclination from 30° to 50° resulted in greater cathodic shifts in OCP upon the initiation of sliding; from −50 mV to as much as −150 mV. Under anodic polarisation (0 mV vs. Ag/AgCl) the resultant currents at the initiation of sliding also increased significantly with inclination; from approximately 4–10 µA to over 120 µA. Increased retroversion of 20° also resulted in increased anodic currents of 55–60 µA. Changing the nature of articulation demonstrated increased corrosive material loss compared to a standard ISO 14242 profile. The sole use of gravimetric assessment to determine a wear rate for hip replacement bearings under simulation can therefore neglect important degradation mechanisms, such as tribocorrosive loss in devices with metal sliding interfaces

Importance of surgical assembly technique on the engagement of 12/14 modular tapers

Fretting-corrosion at the modular taper junction in total hip replacements (THR), leading to implant failure, has been identified as a clinical concern and has received increased interest in recent years. There are many parameters thought to affect the performance of the taper junction, with the assembly process being one of the few consistently identified to have a direct impact. Despite this, the assembly process used by surgeons during THR surgery differs from a suggested ‘ideal’ process. For example, taper junctions of cutting tools should be pushed together rather than impacted, while ensuring as much concentricity as possible between the male and female taper and loading axis. This study devised six simple assembly methodologies to investigate how surgical variations affect the success of the compressive fit achieved at the taper interface compared to a controlled assembly method, designed to represent a more ‘ideal’ scenario. Key findings from this study suggest that a more successful and repeatable engagement can be achieved by quasi-statically loading the male and female taper concentrically with the loading axis. This was shown by a greater disassembly to assembly force ratio of 0.626 ± 0.07 when assembled using the more ‘ideal’ process, compared to 0.480 ± 0.05 when using a method closer to that used by a surgeon intraoperatively. Findings from this study can be used to help inform new surgical instrumentation and an improved surgical assembly method

Fretting–corrosion at the modular tapers interface: Inspection of standard ASTM F1875-98

Interest in the degradation mechanisms at the modular tapers interfaces has been renewed due to increased reported cases of adverse reactions to metal debris and the appearance of wear and corrosion at the modular tapers interfaces at revision. Over the past two decades, a lot of research has been expended to understand the degradation mechanisms, with two primary implant loading procedures and orientations used consistently across the literature. ASTM F1875-98 is often used as a guide to understand and benchmark the tribocorrosion processes occurring within the modular tapers interface. This article presents a comparison of the two methods outlined in ASTM F1875-98 as well as a critique of the standard considering the current paradigm in pre-clinical assessment of modular tapers

The Potential Influence of Common Viral Infections Diagnosed during Hospitalization among Critically Ill Patients in the United States

Viruses are the most common source of infection among immunocompetent individuals, yet they are not considered a clinically meaningful risk factor among the critically ill. This work examines the association of viral infections diagnosed during the hospital stay or not documented as present on admission to the outcomes of ICU patients with no evidence of immunosuppression on admission. This is a population-based retrospective cohort study of University HealthSystem Consortium (UHC) academic centers in the U.S. from the years 2006 to 2009. The UHC is an alliance of over 90% of the non-profit academic medical centers in the U.S. A total of 209,695 critically ill patients were used in this analysis. Eight hospital complications were examined. Patients were grouped into four cohorts: absence of infection, bacterial infection only, viral infection only, and bacterial and viral infection during same hospital admission. Viral infections diagnosed during hospitalization significantly increased the risk of all complications. There was also a seasonal pattern for viral infections. Specific viruses associated with poor outcomes included influenza, RSV, CMV, and HSV. Patients who had both viral and bacterial infections during the same hospitalization had the greatest risk of mortality RR 6.58, 95% CI (5.47, 7.91); multi-organ failure RR 8.25, 95% CI (7.50, 9.07); and septic shock RR 271.2, 95% CI (188.0, 391.3). Viral infections may play a significant yet unrecognized role in the outcomes of ICU patients. They may serve as biological markers or play an active role in the development of certain adverse complications by interacting with coincident bacterial infection

Validation of the Tetracycline Regulatable Gene Expression System for the Study of the Pathogenesis of Infectious Disease

Understanding the pathogenesis of infectious disease requires the examination and successful integration of parameters related to both microbial virulence and host responses. As a practical and powerful method to control microbial gene expression, including in vivo, the tetracycline-regulatable system has recently gained the favor of many investigative groups. However, some immunomodulatory effects of the tetracyclines, including doxycycline, could potentially limit its use to evaluate host responses during infection. Here we have used a well-established murine model of disseminated candidiasis, which is highly dependent on both the virulence displayed by the fungal cells and on the host immune status, to validate the use of this system. We demonstrate that the pathogenesis of the wild type C. albicans CAF2-1 strain, which does not contain any tet-regulatable element, is not affected by the presence of doxycycline. Moreover levels of key cytokines, chemokines and many other biomarkers, as determined by multi-analyte profiling, remain essentially unaltered by the presence of the antibiotic during infection. Our results indicate that the levels of doxycycline needed to control the tetracycline regulatable promoter gene expression system have no detectable effect on global host responses during candidiasis. Because tet-regulatable systems are now being increasingly used in a variety of pathogenic microorganisms, these observations have wide implications in the field of infectious diseases

The third signal cytokine IL-12 rescues the anti-viral function of exhausted HBV-specific CD8 T cells.

Optimal immune activation of naïve CD8 T cells requires signal 1 mediated by the T cell receptor, signal 2 mediated by co-stimulation and signal 3 provided by pro-inflammatory cytokines. However, the potential for signal 3 cytokines to rescue anti-viral responses in functionally exhausted T cells has not been defined. We investigated the effect of using third signal cytokines IL-12 or IFN-α to rescue the exhausted CD8 T cell response characteristic of patients persistently infected with hepatitis B virus (HBV). We found that IL-12, but not IFN-α, potently augmented the capacity of HBV-specific CD8 T cells to produce effector cytokines upon stimulation by cognate antigen. Functional recovery mediated by IL-12 was accompanied by down-modulation of the hallmark inhibitory receptor PD-1 and an increase in the transcription factor T-bet. PD-1 down-regulation was observed in HBV but not CMV-specific T cells, in line with our finding that the highly functional CMV response was not further enhanced by IL-12. IL-12 enhanced a number of characteristics of HBV-specific T cells important for viral control: cytotoxicity, polyfunctionality and multispecificity. Furthermore, IL-12 significantly decreased the pro-apoptotic molecule Bim, which is capable of mediating premature attrition of HBV-specific CD8 T cells. Combining IL-12 with blockade of the PD-1 pathway further increased CD8 functionality in the majority of patients. These data provide new insights into the distinct signalling requirements of exhausted T cells and the potential to recover responses optimised to control persistent viral infections

Real-time fretting loop regime transition identification using acoustic emissions

© 2020 Elsevier Ltd Acoustic emission (AE) has been successfully used to investigate the damage mechanisms of fretting contacts within different regimes. This study investigated the transition between fretting regimes using the relationship between AE and the mechanical response of a dry, steel-on-steel, ball-on-flat contact under different tangential displacements achieving the partial slip regime, mixed fretting regime and gross slip regime. Increased AE response occurred during gross-slip events and there was strong positive correlation between AE and fretting energy ratio. The relationship was strongest when gross sliding was experienced allowing identification of transition from the partial slip to the gross slip regime. This makes AE a good candidate to detect regime transition in-situ due to ease of integration and its non-destructive nature

Differential expression of regulator of G-protein signalling transcripts and in vivo migration of CD4(+) naïve and regulatory T cells

The immune response of T lymphocytes to pathogens is initiated in draining secondary lymphoid organs, and activated cells then migrate to the site of infection. Thus, control of naïve and regulatory CD4(+) T-cell migration is crucial; however, it is poorly understood in physiological and pathological conditions. We found that CD4(+) subpopulations displayed characteristic regulator of G-protein signalling (RGS) gene expression profiles. Regulatory T cells express higher levels of RGS1, RGS9 and RGS16 than naïve cells. These genes are up-regulated upon cell activation and their level of expression correlates with in vivo cell migration. Using parabiosis, we showed that regulatory T lymphocytes migrate less than naïve T cells and that migrant naïve T cells express even lower RGS levels than their static counterparts. Our results show an inverse correlation between the capacity to migrate and the levels of RGS1, RGS9 and RGS16 for both naïve and regulatory T cells. Taken together, these results suggest a role for RGS molecules in chemokine-induced lymphocyte migration and demonstrate the peculiarity of regulatory T cells in terms of phenotype and migration ability, providing new insights into their function