Roberto Rotini

Effects of metal ions on white blood cells of patients with failed total joint arthroplasties.

In this study twenty-two patients who had revision surgery for aseptic loosening of joint prostheses were examined. The concentration in serum of soluble products of corrosion from the implant, that is, chromium (Cr), cobalt (Co), and nickel (Ni) ions, and the number of white blood cells (leucocytes, myeloid cells, lymphocyte subpopulations) were measured. Twenty patients with no implants were used as controls. The patients who had revision surgery showed normal Ni concentration whereas by statistical analysis that same patient group was shown to have serum Cr and Co levels significantly higher than those of the control. By flow cytometry, a significant decrease of leucocytes, myeloid cells, lymphocytes, and CD16 populations as found in patients versus controls whereas CD3, CD4, CD8, and CD20 positive cells were decreased, but not significantly. In the arthroplasty patients the Cr concentrations were inversely correlated with some of the immunologic parameters while no significant correlation was found between Co levels and decreased lymphocyte subpopulations. Only in revision surgery patients with high Cr concentrations did we find a significant decrease of lymphocytes, namely of CD4 and CD16 positive cells; revision surgery patients with normal Cr concentrations did not show a significant decrease of lymphocyte subpopulations. These data suggest that the presence of metal ions, especially chromium, released from prosthesis components could be associated with changes of lymphocyte subpopulations in patients with loosening of joint prostheses.

Bone-resorbing cytokines in serum of patients with aseptic loosening of hip prostheses

Our aim was to determine if the serum levels of bone-resorbing cytokines (IL-1beta, TNF-alpha, IL-6, GM-CSF) are altered in patients with aseptic loosening of a total hip prosthesis, and if such levels are influenced by the type of implant. We determined cytokine levels in sera from 35 patients before revision for failed total hip arthroplasty and compared them with those in 25 healthy donors. We also assessed the soluble receptor of interleukin-2 (sIL-2r) in serum as an indication of a specific immune reaction against the implant. Our findings showed that the sIL-2r and TNF-alpha serum level did not change. The IL-6 level was not significantly altered, but was higher in patients with TiAIV prostheses than in those with a CrCoMo implant and in patients with cemented prostheses. The IL-1beta level was found to be higher in those with a TiAIV cemented prosthesis than in the control group (p=0.0001) and other groups of patients (p=0.003 v uncemented TiAIV, p=0.01 v cemented CrCoMo, p=0.001 v uncemented CrCoMo). The GM-CSF level significantly increased in patients compared with healthy subjects (p=0.008), and it was higher in those with cemented than with uncemented implants (p=0.01). Only patients with cementless CrCoMo prostheses had levels of GM-CSF similar to those of the control group. The highest GM-CSF concentrations were observed in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs) in the last months before revision (p=0.04). In addition, when massive osteolysis was observed, the level of GM-CSF tended to decrease to that of the control group.

Differences in ion release after ceramic-on-ceramic and metal-on-metal total hip replacement: MEDIUM-TERM FOLLOW-UP

Modern metal-on-metal bearings produce less wear debris and osteolysis, but have the potential adverse effect of release of ions. Improved ceramic-on-ceramic bearings have the lowest wear of all, but the corrosion process has not been analysed. Our aim was to measure the serum ion release (ng/ml) in 23 patients having stable hip prostheses with a ceramic-on-ceramic coupling (group A) and to compare it with the release in 42 patients with a metal-on-metal bearing (group B) in the medium term. Reference values were obtained from a population of 47 healthy subjects (group C). The concentrations of chromium, cobalt, aluminium and titanium were measured. There was a significant increase of cobalt, chromium and aluminium levels (p < 0.05) in group B compared with groups A and C. Group A did not differ significantly from the control group. Despite the apparent advantage of a metal-on-metal coupling, especially in younger patients with a long life expectancy, a major concern arises regarding the extent and duration of ion exposure. For this reason, the low corrosion level in a ceramic-on-ceramic coupling could be advantageous.

Immunological changes in patients with primary osteoarthritis of the hip after total joint replacement

We aimed to assess whether the immunological abnormalities which have been observed in patients with loose total hip replacements (THRs) are present in patients with a well-fixed prosthesis. We examined blood samples from 39 healthy donors, 22 patients before THR and 41 with well-fixed THRs of different types (15 metal-on-metal, 13 metal-on-polyethylene, 13 ceramic-on-ceramic). Before THR, the patients showed a decrease in leukocytes and myeloid cells in comparison with healthy donors, and a prevalence of type-1 T lymphocytes, which was confirmed by the increase in ratio of interferon-gamma to interleukin 4. Moreover, patients with metal-on-metal or metal-on-polyethylene implants showed a significant decrease in the number of T lymphocytes and a significant increase in the serum level of chromium and cobalt, although no significant correlation was observed with the immunological changes. In the ceramic-on-ceramic group, leukocytes and lymphocyte subsets were not significantly changed, but a significant increase in type-2 cytokines restored the ratio of interferon-gamma to interleukin 4 to normal values. We conclude that abnormalities of the cell-mediated immune response may be present in patients with a well-fixed THR, and that the immunological changes are more evident in those who have at least one metal component in the articular coupling.

Expression of the CD69 activation antigen on lymphocytes of patients with hip prosthesis

The aim of the study was to evaluate the sensitization to metals in patients with Co-Cr hip prosthesis. Peripheral blood mononuclear cells (PBMC) were collected from 14 healthy donors and three groups of patients: 10 candidates for primary total joint replacements, 11 patients with well-fixed implant and 13 patients with aseptic loosening of the hip prosthesis. PBMCs were cultured with the metal ions employed for implant manufacturing and the expression of CD69 activation antigen on CD3/T lymphocytes was detected by flow cytometry. Chromium extract increased significantly the expression of CD3/CD69 phenotype in patients with loosening of hip prosthesis. The chromium-induced activation index was higher in patients with loosening of hip prosthesis than in healthy donors and in pre-implant patients. The cobalt-stimulated PBMC of patients with either well-fixed or loosened prosthesis had an activation index significantly higher than healthy donors. The activation index values were used to graduate the PBMC-response as normal (> or = 0.9 and < 2), low (< 0.9) and high (> or = 2): an high-activation index was observed only in chromium-exposed PBMC of patients with prosthesis. Our data show that chromium released from orthopedic implants could be responsible for the lymphocyte sensitization and flow cytometry is an easy and reliable method for monitoring the hypersensitivity state in patients with metal prostheses. Activated lymphocytes in the peri-implant tissue are likely to elicit a localized immune response and contribute to maintain the inflammatory process evolving in the implant failure.

Surgical treatment of proximal ulna nonunion.

We reviewed our experience in the surgical treatment of 12 cases of proximal ulna nonunion. The primary injuries were 2 fracture-dislocations of the olecranon, 6 Monteggia lesions and 3 isolated fractures of the proximal ulna. According to the type of primary injury and its anatomical site, the nonunions were classified into 2 groups, considering that the nonunions nearest to the humerus-ulna joint present a more disabling clinical profile and are more difficult to treat: group A (6 patients — nonunion within 5 cm from the olecranon tip of the olecranon) and group B (6 patients — nonunion between 5 and 10 cm from the olecranon tip of the olecranon). In all cases, after fibrous callus debridement and bone surface remodelling, fixation was performed with plate and screws and homoplastic cortical bone graft (orthogonal or parallel to the plate) and an intercalary bone cylinder when the bone defect was severe. In 3 patients (group A), where the defect was smaller than 1 cm, fixation of the ulna was combined with a resection of the radial neck. Clinical-radiographic healing was achieved in all patients followed for a mean of 27 months. Complications included a case of nonunion due to failure of the intercalary graft with plate breakage. The patient healed after a new surgery performed with same technique. The score, according to the Broberg-Morrey scoring system, was 78 in group A patients and 93 in group B patients. The use of homoplastic cortical bone graft represents an effective technique to improve the mechanical properties of the fixation and supports biological union, even when the bone defect is severe.

Plasma levels of coagulation inhibitors, fibrinolytic markers and platelet-derived growth factor-AB in patients with failed hip prosthesis.

We studied the plasma levels of coagulation inhibitors, of fibrinolysis and PDGF-AB, in patients with aseptic loosening of the hip replacement. 23 patients having loose hip prostheses were compared to patients having 15 stable hip prostheses, and 26 undergoing primary hip replacement. The levels of the coagulation inhibitors antithrombin III and protein C were determined by chromogenic assays. Fibrinolysis was evaluated by the changes in fibrin degradation products (D-dimer), determined by enzyme immunoassay, and in the plasminogen activator inhibitor-1 (PAI-1), by enzymatic assay. PDGF-AB was determined by enzyme immunoassay. In patients with failed prostheses, we found fibrinolysis activation, as shown by a statistically significant increase in D-dimer and a significant decrease of PAI-1. No significant differences were obseved in antithrombin III, protein C, and PDGF-AB. PAI-1 and D-dimer assays in failed prostheses may be useful for the pathogenetic evaluation, because the continuous inflammatory stimulus associated with fibrin deposition may also affect the systemic levels.