Auto-Allo Graft Parallel Juxtaposition for Improved Neuroregeneration in Peripheral Nerve Reconstruction Based on Acellular Nerve Allografts.

INTRODUCTION: Nerve repair poses a significant surgical challenge, and much research on this topic for improvement in reconstruction of segmental defects is ongoing. The aims of the study were to reconfirm the accuracy and safety of a previously described nerve decellularization method on a larger experimental population of rabbits, as well as on human nerves, and to establish in vivo the efficacy of a new-concept mixed graft, comprising autologous and acellular nerve allograft components within the same graft. METHODS: Acellular nerve allografts were implanted into tibial nerve defects of 5 rabbits (group A), autografts were implanted, representing the criterion standard, in other 5 animals (group B), and the innovative technique was used in the remaining 5 (group C). Twelve weeks postoperatively, nerve conduction evaluations were performed; animals were euthanatized, and grafts were harvested and morphologically, histomorphometrically, and immunohistochemically analyzed. Eventually, a preliminary in vitro validation of the decellularization method was performed on human nerves from a cadaver. RESULTS: No clinical adverse effect was revealed during all the experimental times. No tissue reaction was observed, and in all groups, regenerated fascicles and bundles were shown by histology. However, both histology and histomorphometry demonstrated a better regenerative efficiency in group C. The morphological evaluation of the human nerve treated with the novel method showed complete decellularization. CONCLUSION: The microsurgical combined model demonstrated a better neuroregeneration than did pure autografts and acellular nerve allografts. The decellularization method seemed effective also on human nerves. Deeper investigations are necessary to further validate and transfer this new encouraging protocol to the clinical arena.

Biological effects of metal degradation in hip arthroplasties.

Metals and metal alloys are the most used materials in orthopedic implants. The focus is on total hip arthroplasty (THA) that, though well tolerated, may be associated with local and remote adverse effects in the medium-long term. This review aims to summarize data on the biological consequences of the metal implant degradation that have been attributed predominantly to metal-on-metal (MoM) THA. Local responses to metals consist of a broad clinical spectrum ranging from small asymptomatic tissue lesions to severe destruction of bone and soft tissues, which are designated as metallosis, adverse reactions to metal debris (ARMD), aseptic lymphocytic vasculitis associated lesion (ALVAL), and pseudotumors. In addition, the dissemination of metal particles and ions throughout the body has been associated with systemic adverse effects, including organ toxicity, cancerogenesis, teratogenicity, and immunotoxicity. As proved by the multitude of studies in this field, metal degradation may increase safety issues associated with THA, especially with MoM hip systems. Data collection regarding local, systemic and long-term effects plays an essential role to better define any safety risks and to generate scientifically based recommendations.

Effects of hypoxia on osteogenic differentiation of mesenchymal stromal cells used as a cell therapy for avascular necrosis of the femoral head.

BACKGROUND AIMS: Avascular necrosis of the femoral head (AVN) occurs as common result of various conditions or develops as a primary entity, with a high freqency in young adults. Because of its tendency toward osteoarthritis requiring total hip arthroplasty, alternative treatments are being advocated, including cell therapy with mesenchymal stromal cells (MSCs). Because osteonecrotic bone is a severely hypoxic tissue, with a 1-3% oxygen tension, the survival and function of multipotent cells is questionable. METHODS: In this study, the proliferative, immunophenotypic and osteogenic properties of bone marrow (BM)-derived MSCs from a clinical series of patients with AVN were evaluated under in vitro conditions mimicking the hypoxic milieu of AVN to verify the rationale for cell therapy. MSCs retrieved from the iliac crest (BM-MSC) were isolated, expanded and induced to osteogenic differentiation under a 2% pO2 atmosphere (hypoxia) in comparison with the standard 21% pO2 (normoxia) that is routinely used in cell culture assays. RESULTS: Both proliferation and colony-forming ability were significantly enhanced in hypoxia-exposed BM-MSCs compared with BM-MSCs under normoxia. The expression of bone-related genes, including alkaline phosphatase, Type I collagen, and osteocalcin was significantly increased under hypoxia. Moreover, mineral deposition after osteogenic induction was not hampered, but in some cases even enhanced under low oxygen tension. CONCLUSIONS: These findings support autologous cell therapy as an effective treatment to stimulate bone healing in the hypoxic microenvironment of AVN.

Long-term systemic metal distribution in patients with stainless steel spinal instrumentation: a case-control study.

STUDY DESIGN: Case-control study. OBJECTIVE: To verify whether metal ions in the serum of patients bearing spinal stainless steel instrumentation were elevated over the long-term period after implantation of stainless steel prostheses and to determine whether these levels could predict potential unfavorable outcomes. SUMMARY OF BACKGROUND DATA: Instrumented spinal arthrodesis, the standard procedure to correct scoliosis, routinely remains in situ for the lifetime of the patient. Elevated metal ion levels have been reported at short-term follow-up, but the long-term status, possibly related to systemic toxic effects, is unknown. METHODS: Twenty-two patients treated for scoliosis with posterior spinal arthrodesis using stainless steel instrumentation were included. Minimum follow-up was 10 years. Oswestry Disability Index and visual analog scale were recorded. Chromium (Cr) and nickel (Ni) levels were measured (ng/mL) and compared with levels in a control group including 30 healthy subjects. A receiver-operating characteristic curve was calculated on the basis of the clinical assessment (pain and disability) and the x-ray picture; the cutoff values for the parameters were settled, and the ion-testing potential was considered as a surrogate marker for failure. RESULTS: The level of Cr was significantly increased in patients, compared with controls (P=0.018). A remarkable Cr release without any clinical-radiologic sign was recorded in some female patients. A high specificity (93%), positive likelihood ratio (7.00), and overall accuracy (77%) were calculated for Cr; these indicate a high risk of failure when the levels exceeded the cutoff value, which was 0.6 ng/mL. No significant difference between the groups was found for Ni (P=0.7). CONCLUSIONS: Cr testing is suggested as a reliable marker for the malfunctioning assessment and as a support for standard procedures, especially with doubtful diagnosis. Furthermore, high levels of Cr ions were observed in female patients. This finding deserves attention especially when counseling young fertile women.

How do metal ion levels change over time in hip resurfacing patients? A cohort study.

Metal-on-metal hip resurfacing (MOM-HR) is offered as an alternative to traditional hip arthroplasty for young, active adults with advanced osteoarthritis. Nevertheless, concerns remain regarding wear and corrosion of the bearing surfaces and the resulting increase in metal ion levels. We evaluated three cohorts of patients with Birmingham hip resurfacing (BHR) at an average follow-up of 2, 5, and 9 years. We asked whether there would be differences in ion levels between the cohorts and inside the gender. Nineteen patients were prospectively analyzed. The correlation with clinical-radiographic data was also performed. Chromium, cobalt, nickel, and molybdenum concentrations were measured by atomic absorption spectrophotometry. Chromium and cobalt levels demonstrated a tendency to decrease over time. Such tendency was present only in females. An inverse correlation between chromium, implant size, and Harris hip score was present at short term; it disappeared over time together with the decreased ion levels. The prospective analysis showed that, although metal ion levels remained fairly constant within each patient, there was a relatively large variation between subjects, so mean data in this scenario must be interpreted with caution. The chronic high exposure should be carefully considered during implant selection, particularly in young subjects, and a stricter monitoring is mandatory.

Do ion levels in metal-on-metal hip resurfacing differ from those in metal-on-metal THA at long-term followup?

BACKGROUND: Metal-on-metal hip resurfacing arthroplasty (MOM HR) has become an established alternative to traditional metal-on-metal total hip arthroplasty (MOM THA) for younger, more active patients. Nevertheless, concerns remain regarding wear and corrosion of the bearing surfaces and the resulting systemic metal ion distribution. QUESTIONS/PURPOSES: We therefore asked whether (1) serum ion concentrations in patients with MOM HR at the time of long-term followup were higher than concentrations in a control population with no hip implants; (2) the ion concentrations in patients with MOM HR were different from those in patients with MOM THA; and (3) sex would influence ion levels with regard to implant type. METHODS: The MOM HR and MOM THA groups consisted of 25 patients (evaluated at a minimum of 96 months) and 16 patients (evaluated at a minimum of 106 months), respectively. Forty-eight healthy donors were recruited for reference values. Cobalt, chromium, nickel, and molybdenum were measured by furnace graphite atomic absorption spectrophotometry. RESULTS: Ion concentrations of cobalt, chromium, and molybdenum in MOM HR were higher than in controls. Chromium and cobalt release were higher in MOM HR than in MOM THA. The sex-based analysis showed the difference was because women had higher concentrations in the MOM HR group than in the MOM THA group, whereas there was no difference between the men in the two groups. CONCLUSIONS: In MOM HR, high metal ion release persists for the long term. Consequently, it is important to implement strict biomonitoring for patients who have received these implants. The sustained high levels of chromium in females within the MOM HR group are concerning and merits strong consideration when choosing implants in this patient group.

Relevance of deep decortication and vascularization in a case of post-traumatic femoral non-union treated with grafts, platelet gel and bone marrow stromal cells.

PURPOSE: A male patient suffering from non-union of the femoral diaphysis after a traumatic fracture was treated with deep decortication and grafted with lyophilized bone, platelet gel (PG) and autologous bone marrow stromal cells (BMSCs). After 40 days from surgery, he was re-operated, due to fracture secondary displacement, caused by inappropriate load during sports activity. In addition to radiographs, two bone biopsies were retrieved: this allowed for a histological evaluation of the early response of host bone to the graft. To our knowledge, there is no report describing such early tissue response. METHODS: A clinical-radiographic evaluation of the patient and a histomorphometric analysis of the bone biopsies were performed. RESULTS: An early reparative bone formation was observed adjacent to the osteointegrated graft. Non-resorbed bone chips and large islands of non-vital bone particles, surrounded by fibrous tissue, were observed in a zone of sclerotic diaphyseal bone, that is the process was delayed despite decortication. CONCLUSIONS: These findings support the concept, until now evidenced only by imaging, that bone chips added with PG and BMSCs are effective in shortening the healing time in fracture non-union. The clinical relevance of deep decortication and vascularization is emphasized. LEVEL OF EVIDENCE: Therapeutic studies-investigating the results of treatment, Level V.

Pre-operative diagnosis of infection in total knee arthroplasty: an algorithm.

The aim of our study was to construct an algorithm for the pre-operative diagnosis of infection in total knee arthroplasty. We analyzed the currently used parameters in a consecutive series of 31 patients with failed implants. An outcome of at least 2 years was prospectively considered to validate our algorithm. Patient history, imaging, laboratory studies, histology, pre- and intra-operative cultures were considered. The optimal cutoffs of the inflammation tests for diagnosing infection were determined by constructing the receiver operating-characteristic curves. Sensitivity, specificity and accuracy of these tests as infection markers were determined. The combination of at least two tests with values higher than the cutoffs is reliable for predicting the infection. Scintigraphy, needle-aspirate cell count and culture can integrate the pre-operative evaluation. Doubtful cases can be clarified by microbiological and histological analyses. As a result an algorithm helpful to identify the cause of loosening has been developed. In our opinion, adherence to this algorithm could contribute to preoperatively define a rational surgical and antibiotic treatment strategy.

Is wear debris responsible for failure in alumina-on-alumina implants?

BACKGROUND AND PURPOSE: Ceramic-on-ceramic articulation is an attractive alternative to metal-on-polyethylene (PE) bearings, but little is known about the in vivo effects induced by dissemination of alumina wear debris in the periprosthetic tissues. We hypothesized that wear debris is not the main factor responsible for loosening and failure of the implant but that mechanical problems caused by incorrect surgical technique, prosthetic design, or trauma, may cause instability of the implants and result in production of wear debris. PATIENTS AND METHODS: Clinical, radiographic, laboratory, and microbiological data from 30 consecutive patients with failed alumina-on-alumina arthroplasties, 19 with screwed socket and 11 with press-fit socket, were systematically collected and evaluated. Retrieved peri-implant tissues and prosthesis wear were also analyzed. RESULTS AND INTERPRETATION: Loosening was due to malpositioning, primary mechanical instability, trauma, or infection. Bone stock was generally preserved, even if screwed implants showed higher levels of osteolysis. Variable implant wear and tissue macrophage reaction were present but activation of giant cells/osteoclasts was not induced, and no correlation between histocytic reaction and the level of osteolysis was found. These findings indicate that, in contrast to the situation with metal-on-PE bearings, wear debris and occasional osteolysis were the effect rather than the cause of failure of ceramic-on-ceramic implants, and that press-fit socket fixation was the socket fixation design of preference.

Evaluation of restorative materials using a new perfusion system.

PURPOSE: 1) To test a new perfusion device able to alternate demineralizing/nondemineralizing solutions, as an acid attack system, and 2) to standardize the dentin demineralization procedure, in order to define the in vitro secondary caries inhibiting potential of different restorative materials. MATERIALS AND METHODS: A fluoride-containing adhesive/composite resin (group A), an experimental adhesive/composite resin (group B), and a glass-ionomer cement (group C) were used to restore 24 Class II cavities in extracted molars. Optimal conditions to obtain dentin demineralization inside the perfusion device were identified and applied to restored teeth. Dentin demineralization after perfusion was analyzed by microradiography. The output parameters were lesion morphology, dentin mineral volume percentage, and integrated mineral loss (Delta Z, % volume x microm) of the exposed (outer lesions) and marginal (inner lesions or caries inhibition zones, CIZs) dentin. RESULTS: Demineralization increased as follows: group A < group B < group C. Group A behaved better than group B, probably due to fluoride content, as indicated by Delta-Z values, higher number of CIZs, and few inner lesions. Group C showed a marginal protective effect, demonstrated by the frequent CIZs and Delta-Z positive values. This effect, however, was unable to reduce the high demineralization, probably due to the critical handling characteristics, inducingthe worst marginal adaptation. CONCLUSION: A new dynamic perfusion device was tested and a reproducible procedure was standardized in order to achieve in vitro conditions that could better simulate the pH changes of oral environment. A limited fluoride protective effect was demonstrated by using the perfusion system, whereas a perfect marginal adaptation was shown as a paramount factor to prevent restoration failure.

Pseudotumor due to metallosis after total elbow arthroplasty.

The incidence of primary total elbow arthroplasty (TEA) in young patients is increasing. The indications for revision surgery are also rising. Here, we report a rare case of pseudotumor detected in a patient 16 years after TEA. Intraoperative findings revealed a necrotic mass characterized by a conspicuous metallosis in the soft tissues around the prosthesis, which caused ulnar nerve dislocation. Due to this anatomical change, a lesion of the nerve was accidentally produced during revision surgery. The case report emphasizes that the indications for elbow replacement, as well as the patient education about the permanent physical limitations, should be carefully considered. Moreover, the high risks of complications related to the revision procedure and pseudotumor removal need to be addressed before surgery. The technique should be done carefully and a preliminary thorough imaging should be performed, since a newly formed mass can cause significant distortion of the anatomy.

Does chronic raise of metal ion levels induce oxidative DNA damage and hypoxia-like response in patients with metal-on-metal hip resurfacing?

Metal-on-metal hip resurfacing (MOM-HR) represents a viable alternative to traditional arthroplasty. Nevertheless, in MOM coupling both metal nanoparticles and ions are released, whose toxicity remains a matter of concern. We investigated whether 'endogenous' chronic exposure to cobalt and chromium induced a state of oxidative stress, DNA damage and a hypoxia-like response in patients with well-functioning MOM-HR. Twenty-two patients with unilateral MOM-HR were recruited at long-term. Twenty-one osteoarthritic subjects were enrolled for comparison. Serum ion levels were measured and correlated with 8-hydroxydeoxyguanosine and circulating-free-DNA, as markers of oxidative DNA damage. Moreover, the hypoxia-inducible factor-1α, marker of hypoxic state, was evaluated. Ion concentrations were found to be 5-to-15 times higher in MOM-HR patients than in presurgery subjects (p < 0.001); circulating-free-DNA, 8-hydroxydeoxyguanosine, and hypoxia-inducible factor-1α levels were not significantly different between groups and did not correlate with ion levels. Analyzing the results according to gender, MOM-HR males had higher 8-hydroxydeoxyguanosine levels (p = 0.01) compared with MOM-HR females. Similarly, circulating-free-DNA values were higher in males than females, even if this difference did not reach statistical significance. This research is the first that attempted to investigate the long-term effects of ion dissemination in subjects with well-fixed MOM implants. A significant correlation between biomarkers increase and ion levels was not demonstrated. Nevertheless, both circulating-free-DNA and 8-hydroxydeoxyguanosine showed a tendency to increase in MOM-HR males. Further studies with a larger sample size should be performed to detect the clinical relevance of biomarkers increase especially in younger subjects, where a chronic moderately elevated exposure has to be faced. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 460-466, 2017.

Serum levels of osteoprotegerin and receptor activator of nuclear factor-kappaB ligand as markers of periprosthetic osteolysis.

BACKGROUND: Previous studies have suggested that the balance between receptor activator of nuclear factor-kappaB ligand (RANKL) and its decoy-receptor osteoprotegerin (OPG) in local tissue seems to play a crucial role in the loosening of the total hip replacement. The aim of this study was to evaluate whether the circulating levels of OPG and RANKL, as well as their ratio, could be different in patients with aseptic loosening compared with patients with stable implants. METHODS: One hundred and twenty-eight subjects were recruited. They included thirty-nine patients with osteoarthritis who had not yet undergone total hip arthroplasty, thirty-three patients who had undergone total hip arthroplasty and had clinically and radiographically stable implants, thirty-six patients with aseptic loosening of total hip arthroplasty components, and twenty healthy volunteers. Serum levels of OPG and RANKL were measured with use of an immunoenzymatic method, and in each individual the OPG-to-RANKL ratio was calculated. RESULTS: In every group, a significant correlation was detected between OPG concentration and age (r = 0.58, p < 0.0001), especially in individuals older than fifty years, while gender and underlying disease were not found to influence serum levels of the tested parameters. In comparison with the levels in healthy donors and patients with a stable total hip replacement, the serum levels of OPG were increased in the patients who had not yet had an arthroplasty, those with aseptic loosening of a total hip replacement, and those with a cemented total hip replacement. Moreover, the OPG serum level provided good diagnostic accuracy in detecting the implant failure. A correlation was found between the sum of the osteolytic areas seen radiographically around the femoral stem and the RANKL level (r = 0.38, p = 0.02) and the OPG-to-RANKL ratio (r = -0.29, p = 0.04). CONCLUSIONS: An increase in OPG levels may reflect a protective mechanism of the skeleton to compensate for the osteolytic activity that occurs in severe osteoarthritis and in aseptic loosening. Prospective studies are needed to determine whether serum OPG levels could be used as markers for monitoring the stability of the implant, as well as for predicting aseptic loosening. LEVEL OF EVIDENCE: Diagnostic study, Level III. See Instructions to Authors for a complete description of levels of evidence.

New couplings, old problems: Is there a role for ceramic-on-metal hip arthroplasty?

Ceramic-on-metal (CoM) total hip arthroplasty (THA) theoretically combines both the advantages of ceramic-on-ceramic (CoC) and metal-on-metal (MoM) bearings: negligible rupture risk of the liner with a limited ion release. As primary endpoint, we asked whether serum cobalt, chromium and molybdenum concentrations in 20 CoM-THA patients at an average of 3-years follow-up were higher than those measured in the pre-operative population and correlate with clinical/radiological parameters. As secondary endpoint, we wanted to verify whether ion levels in CoM-THA patients were different from those obtained in a similar cohort of 29 MoM-THA patients at the same average follow-up. Ion values were measured by atomic absorption spectrometry. Functional outcome was assessed with Harris Hip Score and UCLA scale. Presence of radiographic radiolucencies around the implant, and acetabular inclination angle were evaluated. Chromium and cobalt levels in CoM-THA patients were significantly higher (p < 0.001) at 3-years follow-up than before surgery. Molybdenum concentrations were not significantly different (p = 0.45). No signs of implant loosening were recorded. Functional outcome was excellent with HHS and UCLA scale rising from 50 and 3.6 pre-operatively to 90.8 and 6.3, respectively at 3-years follow-up (p < 0.001). Chromium serum levels were significantly lower in CoM-THA than in MoM-THA group (p = 0.02) while cobalt values, even if lower, did not reach statistically significance (p = 0.054). Our results show that CoM-THA patients achieve excellent clinical outcome with a limited chromium release at 3-years follow-up.

Effect of four acrylic bone cements on transforming growth factor-beta1 expression by osteoblast-like cells MG63.

Based on the hypothesis that bone cements cause changes in the production of transforming growth factor-beta 1 (TGF-beta1) by bone cells, the effects of four acrylic bone cements (Sulfix-60, CMW 1, CMW 2 and CMW 3) were examined using the osteoblast-like cell line MG63. The extracts in MEM of the cements were tested, following 1 h- and 7 day-curing. MG63 cells seldom expressed mRNA specific for TGF-beta1 in basal conditions. The cultures expressed mRNA constantly after incubation with the extract of CMW 1 cured for 1 h. TGF-beta1 specific mRNA was seldom expressed after incubation with the other cement extracts. The release of TGF-beta1 into the conditioned medium was increased significantly by CMW 1 extract at 1 h-curing, but was not changed significantly by CMW 1 extract at 7 day-curing and by the extracts of the other cements, at both curing times. The stimulating effect of CMW 1 on the secretion of TGF-beta1, even with all the restrictions of an in vitro study of continuous cell lines, if confirmed in vivo, might favor the development of the synovial-like membrane around the implant, and therefore impair the chance of success of the prosthesis.

Effects of bone cement extracts on the cell-mediated immune response.

The aim of the study was to evaluate some aspects of the immunocompatibility of 10 acrylic bone cements. Mononuclear cells harvested from healthy individuals were cultured with cement extracts which were tested to assess their effect on the viability of lymphocytes, unstimulated and phytohaemoagglutinin (PHA)-stimulated, activating resting lymphocytes, and changing the reactivity of PHA-stimulated lymphocytes. After 24 h the extracts did not increase the percentage of dead cells in unstimulated or PHA-stimulated lymphocytes. The early apoptotic events of culture were evaluated after 4 and 24 h in PHA-stimulated lymphocytes: at 4 h three cements, namely Zimmer-dough type, Palacos R and CMW-1, increased significantly the percentage of apoptotic cells, while at 24 h no differences were found. Cement extracts did not activate the resting lymphocytes, whereas the response of the PHA-stimulated cells was significantly modified. All cements decreased the expression of the interleukin 2 receptor (CD25) and the lymphocyte proliferation, whereas only two materials (Zimmer-dough type, CMW 1) affected the expression of early activation antigen (CD69). These findings show that the products released from bone cement are not able, by themselves, to elicit a specific immune response; on the contrary they hamper the function of lymphocytes activated by an exogenous stimulus.

Thrombomodulin expression in endothelial cells after contact with bone cement.

The expression of thrombomodulin after contact with CMW 1 bone cement extracts was studied in human umbilical vein endothelial cells. Cement extracts after 1 h and 7-day curing induced no significant variations in thrombomodulin antigen levels and in mRNA expression. Significant increase of thrombomodulin was observed when endothelial cells were treated with all-trans retinoic acid (ATRA). ATRA induced the increase of thrombomodulin also in cells incubated with cement extracts. These results suggest that CMW 1 bone cement does not impair the expression of thrombomodulin in endothelial cells.

Bone cement extracts modulate the osteoprotegerin/osteoprotegerin-ligand expression in MG63 osteoblast-like cells.

The osteoprotegerin-ligand (OPG-L) has been identified as the essential factor required for osteoclastogenesis, and its effects are prevented by the osteoprotegerin (OPG). The OPG-L/OPG balance plays a crucial role in coordinating the sequence of osteoclast and osteoblast differentiation during the bone remodeling. The aim of the study was to investigate if polymethylmethacrylate-based cements are able to modulate the expression of OPG-L/OPG in MG63 cells, which are known to have high levels of OPG and inducible expression of OPG-L. Four radio-opaque cements. namely Sulfix-60, CMW1, CMW2 and CMW3, were polymerized for either 1 h or 7 d. MG63 were incubated for 24 h with culture medium only, cement extracts and 2 microg/ml of human recombinant IL-1beta as positive control. An RT-PCR was performed to detect the OPG and OPG-L expression, and the house-keeping gene, GAPDH, was used as a reference for the semi-quantitative analysis. An increase in the OPG-L band density was observed for all cements, and consequently, the OPG-L/OPG ratio also increased. The ability of bone cements to induce the expression of OPG-L could be a co-factor in the development of osteolysis at the bone-cement interface.

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.

Effect of acetabular cup design on metal ion release in two designs of metal-on-metal hip resurfacing.

The purpose of this observational prospective cohort study was to evaluate the serum concentrations of cobalt (Co), chromium (Cr), and nickel (Ni) at a 2-year follow-up in patients operated on with a novel design of hip resurfacing: Romax resurfacing system (RRS). RRS is characterized by the presence of an acetabular notch which theoretically provides a wider range of motion and a reduced incidence of groin pain. The presence of radiolucencies and functional outcome, assessed using the Harris hip score (HHS) and the University of California Activity scale (UCLA), were secondary endpoints. Moreover, these results were compared with those obtained in our previous study from a similar cohort of patients implanted using the Birmingham Hip Resurfacing (BHR) system. At a 2-year follow-up, the serum levels of Co in patients operated on using the RRS were five times higher (p = 0.0002) than those found before surgery (Co, means: 1.04 and 0.20 ng/mL, respectively); similarly, Cr levels were 13 times higher (p < 0.0001) at a 2-year follow-up than before surgery (Cr, means: 1.69 and 0.13 ng/mL, respectively). Ni concentrations (0.42 and 0.78 ng/mL) were not significantly different (p = 0.16), even if they increased 86% after surgery. In the RRS patients, an inverse correlation was found between Co and Cr concentrations and length of follow-up (Co: r = -0.64, p = 0.0096; Cr: r= -0.45, p = 0.08). The serum levels of Co and Cr were not significantly different between RRS (Co: 1.04 ng/mL and Cr: 1.69 ng/mL) and BHR (Co: 1.39 ng/mL and Cr: 2.30 ng/mL) patients at 2 years (p = 0.95 and 0.26 for Co and Cr, respectively). Our results showed that RRS patients achieved an excellent clinical outcome with limited metal ion release.