The main objective of this study is to evaluate the systemic impact of salting out of trace elements (TE) by metallic and nonmetallic implantable medical devices (IMD) and in particular the immune response of the organism to these trace elements and of their target organs, and to identify circulating protein biomarkers which might indicate an evolution of inflammation caused by an IMD.
As secondary objectives, the study aims: * to establish the norms of concentrations of free TE and nanoparticles for some forty of elements (in particular Chrome, Cobalt, Nickel, Titanium, Tantalum, Zirconium, Tungsten, Gold, Silver, Mercury, Molybdenum, Strontium ...) in different materials (blood, urine, hair and the viscera), with non-IMD holder subjects, before and after mineralization of these materials (dead patients and autopsied non-IMD holder subjects and subjects before placement of IMD. * to evaluate the distribution of concentrations of metals in the same materials and in peri-prothetic environment with IMD holder subjects (dead autopsied patients), more often with no inflammatory sign, with possibility of some probably inflammatory IMD. * to evaluate the parameters of distributions of concentrations of metals in same materials (with the exception of the viscera) with living IMD holder patients, with inflammatory reaction (during revision surgery). * to define the most suitable material (accessibility, concentrations, absence of contamination) for follow-up and evolution of inflammation in order to determinate norms of studied metals concentration. * to determinate proportion between different forms of circulation: particulate form (analysis after full mineralization) or free form (analysis without mineralization, permitting measurement of free forms), trace elements in organism.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
159
All inpatient subjects: following samples will be collected during hospitalization: Twice blood and urine collections: 1. at the beginning of hospitalization: 10 ml of blood + 5 ml of urine; 2. at the end of hospitalization: 5 ml of blood + 5 ml of urine. Synovial fluid collection: 1 ml Peri-prosthetic tissue collection: about 1 cm3 Hair collection: a single hair of 0.5 cm diameter
Dead patients will be autopsied: hair, urine, blood, peri-prosthetic tissue and viscera (liver, kidney, spleen, brain, heart, lung) sampling for each autopsy.
Service de Chirurgie orthopédique, Hôpital Raymond Poincaré
Garches, Hauts-des-Seine, France
Immunophenotyping of inflammatory cells activated in contact with trace element nanoparticles
Demonstration of systemic inflammation induced by the trace elements existing in IMD with blood and tissue criteria: 1/ A measure by flow cytometry to identify hyperactivated circulating mononuclear cells (macrophages, dendritic cells, T and B lymphocytes), in contact with trace element nanoparticles and thus, to highlight an immunophenotype of this inflammation.
Time frame: through study completion, an average of 2 years
Identification of specific circulating proteins (biomarkers) of inflammation related to trace element release
Demonstration of systemic inflammation induced by the trace elements existing in IMD with blood and tissue criteria: 2/ A measure by multiplex LuminexTM (Bio-plex ProTM human inflammation panel, Bio-rad) to identify specific circulating proteins such as TNF, IFN, cytokines, chemokines, metalloproteins, related to activation of the cells of inflammation throughout release of particles and salting out of trace elements by IMD
Time frame: through study completion, an average of 2 years
Macroscopic characterization of tissue inflammation of autopsied patients
Demonstration of systemic inflammation induced by the trace elements existing in IMD with blood and tissue criteria: \- 3/ A macroscopic study of organs to determine the possible presence of tumor foci
Time frame: through study completion, an average of 2 years
Microscopic characterization of tissue inflammation of autopsied patients
Demonstration of systemic inflammation induced by the trace elements existing in IMD with blood and tissue criteria: \- 4/ Cytopathological analysis on slides, after sampling, fixation, inclusion and staining with hematoxylin-eosin-saffron to evaluate semi-quantitatively the type of inflammation (chronic if mononuclear cells or acute if neutrophils) and degree according to the number of inflammatory cells
Time frame: through study completion, an average of 2 years
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Trace elements dosing in liquids and tissues
Trace elements dosing in liquids and tissue by high resolution ICP mass spectrometry in studied sub-population (autopsied IMD holder and non-holder dead subjects, IMD holder living patients with inflammatory reaction and will undergo re-intervention) and in each analyzed material in non-mineralized form, in order to determinate concentrations of free trace elements and after full mineralization to determinate the concentrations of trace elements in nanoparticle form.
Time frame: through study completion, an average of 2 years
Comparison of concentrations of 40 analyzed trace elements
Comparison of concentrations of 40 analyzed trace elements in different materials, depending on the groups.
Time frame: through study completion, an average of 2 years