ABSTRACT
Quorum sensing (QS) is a complex communication system in bacteria, directing their response to the environment. QS is also one of the main regulators of bacterial biofilms' formation, maturation and dispersion. Matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI) is a molecular imaging technique that allows the mapping of QS molecules in bacterial biofilms. Here, we highlight the latest advances in MALDI-MSI in recent years and how this technology can improve QS understanding at the molecular level.
ABSTRACT
In vitro and in vivo studies are critical for the preclinical efficacy assessment of novel therapies targeting musculoskeletal infections (MSKI). Many preclinical models have been developed and applied as a prelude to evaluating safety and efficacy in human clinical trials. In performing these studies, there is both a requirement for a robust assessment of efficacy, as well as a parallel responsibility to consider the burden on experimental animals used in such studies. Since MSKI is a broad term encompassing infections varying in pathogen, anatomical location, and implants used, there are also a wide range of animal models described modeling these disparate infections. Although some of these variations are required to adequately evaluate specific interventions, there would be enormous value in creating a unified and standardized criteria to animal testing in the treatment of MSKI. The Treatment Workgroup of the 2023 International Consensus Meeting on Musculoskeletal Infection was responsible for questions related to preclinical models for treatment of MSKI. The main objective was to review the literature related to priority questions and estimate consensus opinion after voting. This document presents that process and results for preclinical models related to (1) animal model considerations, (2) outcome measurements, and (3) imaging.
Subject(s)
Research Design , Animals , Humans , Consensus , Models, AnimalABSTRACT
BACKGROUND: Malalignment is often postulated as an important reason for the high failure rate of total ankle replacements (TARs). The correlation between TAR malalignment and clinical outcome, however, is not fully understood. Improving and expanding radiographic TAR alignment measurements in the clinic might lead to a better insight into the correlation between malalignment and the clinical outcome. This study aims to develop and validate a tool to semi-automatic measure TAR alignment, and to improve alignment measurements on radiographs in the clinic. METHODS: A tool to semi-automatically measure TAR alignment on anteroposterior and lateral radiographs was developed in MATLAB. Using the principle of edge contouring and the perpendicular relationship between the anteroposterior and lateral radiographs, the exact configuration of the TAR components can be found. Two observers validated the tool by measuring TAR alignment of ten patients using the tool. The Intraclass Coefficient (ICC) was calculated to assess the reliability of the developed method. The results obtained by the tool were compared to clinical results during radiographic follow-up in the past, and the accuracy of both methods was calculated using three-dimensional CT data. RESULTS: The tool showed an accuracy of 76% compared to 71% for the method used during follow-up. ICC values were 0.94 (p < 0.01) and higher for both inter-and intra-observer reliability. CONCLUSIONS: The tool presents a reproducible method to measure TAR alignment parameters. Three-dimensional alignment parameters are obtained from two-dimensional radiographs, and as the tool can be applied to most TAR designs, it offers a valuable addition in the clinic and for research purposes.
Subject(s)
Ankle Joint , Arthroplasty, Replacement, Ankle , Humans , Ankle Joint/diagnostic imaging , Reproducibility of Results , Arthroplasty, Replacement, Ankle/methods , RadiographyABSTRACT
INTRODUCTION: Malalignment of the Total Ankle Replacement (TAR) has often been postulated as the main reason for the high incidence of TAR failure. As the ankle joint has a small contact area, stresses are typically high, and malalignment may lead to non-homogeneous stress distributions, including stress peaks that may initiate failure. This study aims to elucidate the effect of TAR malalignment on the contact stresses on the bone-implant interface, thereby gaining more understanding of the potential role of malalignment in TAR failure. METHODS: Finite Element (FE) models of the neutrally aligned as well as malaligned CCI (Ceramic Coated Implant) Evolution TAR implant (Van Straten Medical) were developed. The CCI components were virtually inserted in a generic three-dimensional (3D) reconstruction of the tibia and talus. The tibial and talar TAR components were placed in neutral alignment and in 5° and 10° varus, valgus, anterior and posterior malalignment. Loading conditions of the terminal stance phase of the gait cycle were applied. Peak contact pressure and shear stress at the bone-implant interface were simulated and stress distributions on the bone-implant interface were visualized. RESULTS: In the neutral position, a peak contact pressure and shear stress of respectively 98.4 MPa and 31.9 MPa were found on the tibial bone-implant interface. For the talar bone-implant interface, this was respectively 68.2 MPa and 39.0 MPa. TAR malalignment increases peak contact pressure and shear stress on the bone-implant interface. The highest peak contact pressure of 177 MPa was found for the 10° valgus malaligned tibial component, and the highest shear stress of 98.5 MPa was found for the 10° posterior malaligned talar model. High contact stresses were mainly located at the edges of the bone-implant interface and the fixation pegs of the talar component. CONCLUSIONS: The current study demonstrates that TAR malalignment leads to increased peak stresses. High peak stresses could contribute to bone damage and subsequently reduced implant fixation, micromotion, and loosening. Further research is needed to investigate the relationship between increased contact stresses at the bone-implant interface and TAR failure.
