Long-term changes in blood metal ion levels in patients with hip resurfacing implants: implications for patient surveillance after 10 years follow-up.

BACKGROUND: Studies investigating changes in blood metal ion levels during the second decade of the implant lifetime in MoM hip resurfacing patients are scarce. METHODS: Patients implanted with either Birmingham Hip Resurfacing (BHR) or Articular Surface Replacement (ASR) hip resurfacings with >10 years follow-up and repeated blood metal ion measurements were identified at 2 large specialist European arthroplasty centres. After excluding patients with initial metal ion levels >7 ppb, the proportion of patients with an increase in blood metal ion levels above previously validated implant-specific thresholds (cobalt 2.15 ppb for unilateral implants, cobalt or chromium 5.5 ppb for bilateral) was assessed. RESULTS: We included 2743 blood metal ion measurements from 457 BHR patients (555 hips) and 216 ASR patients (263 hips). Of patients with initial metal ion levels below implant specific thresholds, increases in cobalt or chromium level, respectively, to above these thresholds during the second decade were seen as follows: unilateral BHR (cobalt = 15.6%), unilateral ASR (cobalt = 13.8%), bilateral BHR (cobalt = 8.2%, chromium = 11.8%), bilateral ASR (cobalt = 8.5%, chromium = 4.3%). Measurement-to-measurement changes exceeding +2.15 ppb or +5.5 ppb were, however, uncommon during the second decade. Subgroup results with small diameter (<50 mm) implants were similar. CONCLUSIONS: We recommend less frequent blood metal ion measurements are needed (every 3 to 5 years) for hip resurfacing patients if initial values were below 7ppb.

How much does a Medical and Healthcare Products Regulatory Agency medical device alert for metal-on-metal hip arthroplasty patients really cost?

BACKGROUND: Many worldwide regulatory authorities recommend regular surveillance of metal-on-metal hip arthroplasty patients given high failure rates. However, concerns have been raised about whether such regular surveillance, which includes asymptomatic patients, is evidence-based and cost-effective. We determined: (1) the cost of implementing the 2015 MHRA surveillance in "at-risk" Birmingham Hip Resurfacing (BHR) patients; and (2) how many asymptomatic hips with adverse reactions to metal debris (ARMD) would have been missed without patient recall. METHODS: All BHR patients eligible for the 2015 MHRA recall (all females, and males with head sizes ⩽46 mm, regardless of symptoms) at one centre were invited for review (hips = 707; patients = 593). All patients were investigated (Oxford Hip Score, radiographs, blood metal ions, and targeted cross-sectional imaging) and managed accordingly. Surveillance costs were calculated using finance department data. RESULTS: The surveillance cost £105,921.79 (range £147.76-£257.50/patient). Radiographs (£39,598) and nurse practitioner time/assistance (£23,618) accounted for 60% of overall costs. 31 hips had ARMD on imaging (12 revised; 19 under surveillance). All revisions were symptomatic. 7 hips with ARMD under surveillance were asymptomatic and remain under regular review. The number needed to treat to avoid missing one asymptomatic ARMD case was 101 patients, representing a cost of £18,041 to avoid one asymptomatic case. CONCLUSIONS: Implementing MHRA surveillance for "at-risk" BHR patients was extremely costly. The risk of asymptomatic ARMD was low with the BHR (1%), suggesting recommended follow-up in asymptomatic patients is not cost efficient. This raises concerns about the increasingly intensive surveillance recommended in the 2017 MHRA guidance for metal-on-metal hip patients.

Has the threshold for revision surgery for adverse reactions to metal debris changed in metal-on-metal hip arthroplasty patients? A cohort study of 239 patients using an adapted risk-stratification algorithm.

Background and purpose - A risk-stratification algorithm for metal-on-metal hip arthroplasty (MoMHA) patients was devised by US experts to help clinicians make management decisions. However, the proposed algorithm did not cover all potential patient or surgical abnormalities. Therefore we adapted the US risk-stratification algorithm in MoMHA patients revised for adverse reactions to metal debris (ARMD) to determine the variability in the revision threshold, and also whether high-risk patients had inferior outcomes following revision.Patients and methods - We analysed 239 MoMHA revisions for ARMD between 2001 and 2016 from 2 centres with pre-revision blood metal ions and imaging. Patients were stratified (low risk, moderate risk, high risk) using pre-revision factors (implant, radiographic, blood metal ions, cross-sectional imaging) by adapting a published algorithm. The risk categories for each factor were assessed against revision year, revision centre, and post-revision outcomes (re-revision surgery, and any poor outcome).Results - Compared with hips revised before 2012, hips revised from 2012 onwards included more high-risk implants (44% vs. 17% pre-2012), high-risk radiographic features (85% vs. 69% pre-2012), and low-risk metal ions (41% vs. 19% pre-2012). 1 centre more frequently revised patients with high-risk implants (48% vs. 14%) and low-risk blood metal ions (45% vs. 15%) compared with the other. All these comparisons were statistically significant (p < 0.05). With the limited sample size available, implant, radiographic, blood metal ion, and cross-sectional imaging risk groups did not statistically significantly affect the rates of re-revision surgery or frequency of poor outcomes post-revision.Interpretation - When applying the adapted risk-stratification algorithm the threshold for ARMD revision changed over time, presumably due to increasing evidence, patient surveillance, and investigation since 2012. Lower blood metal ion thresholds were used from 2012 for ARMD revisions; however, there was evidence that centres attached different importance to metal ions when managing patients. High-risk patients did not have inferior outcomes following ARMD revision.

No Threshold Exists for Recommending Revision Surgery in Metal-on-Metal Hip Arthroplasty Patients With Adverse Reactions to Metal Debris: A Retrospective Cohort Study of 346 Revisions.

BACKGROUND: Surgeons currently have difficulty when managing metal-on-metal hip arthroplasty (MoMHA) patients with adverse reactions to metal debris (ARMD). This stems from a lack of evidence, which is emphasized by the variability in the recommendations proposed by different worldwide regulatory authorities for considering MoMHA revision surgery. We investigated predictors of poor outcomes following MoMHA revision surgery performed for ARMD to help inform the revision threshold and type of reconstruction. METHODS: We retrospectively studied 346 MoMHA revisions for ARMD performed at 2 European centers. Preoperative (metal ions/imaging) and intraoperative (findings, components removed/implanted) factors were used to predict poor outcomes. Poor outcomes were postoperative complications (including re-revision), 90-day mortality, and poor Oxford Hip Score. RESULTS: Poor outcomes occurred in 38.5%. Shorter time (under 4 years) to revision surgery was the only preoperative predictor of poor outcomes (odds ratio [OR] = 2.12, confidence interval [CI] = 1.00-4.46). Prerevision metal ions and imaging did not influence outcomes. Single-component revisions (vs all-component revisions) increased the risk of poor outcomes (OR = 2.99, CI = 1.50-5.97). Intraoperative modifiable factors reducing the risk of poor outcomes included the posterior approach (OR = 0.22, CI = 0.10-0.49), revision head sizes ≥36 mm (vs <36 mm: OR = 0.37, CI = 0.18-0.77), ceramic-on-polyethylene revision bearings (OR vs ceramic-on-ceramic = 0.30, CI = 0.14-0.66), and metal-on-polyethylene revision bearings (OR vs ceramic-on-ceramic = 0.37, CI = 0.17-0.83). CONCLUSION: No threshold exists for recommending revision in MoMHA patients with ARMD. However postrevision outcomes were surgeon modifiable. Optimal outcomes may be achieved if surgeons use the posterior approach, revise all MoMHA components, and use ≥36 mm ceramic-on-polyethylene or metal-on-polyethylene articulations.

The effectiveness of blood metal ions in identifying bilateral metal-on-metal total hip arthroplasty patients at risk of adverse reactions to metal debris.

We investigated whether blood metal ions could effectively identify bilateral metal-on-metal total hip arthroplasty (THA) patients at risk of adverse reactions to metal debris (ARMD). Whole blood metal ions were sampled in 50 patients with bilateral 36mm Corail-Pinnacle THAs. Patients were divided into ARMD (n=10) and non-ARMD groups (n=40), with optimal ion thresholds for identifying ARMD determined using receiver operating characteristic analysis. Maximum cobalt or chromium produced the highest area under the curve (71.8%). The optimal ion threshold for distinguishing between patients with and without ARMD was 4.0µg/l (90.0%=sensitivity, 65.0%=specificity, 39.1%=positive predictive value, 96.3%=negative predictive value). Fixed regulatory authority thresholds missed more patients with ARMD (10%-12% missed) compared to our threshold (2% missed). Bilateral THA patients with blood metal ions below our threshold were at low-risk of ARMD. Compared to currently recommended fixed authority thresholds, our threshold appears preferable for managing patients with these particular implants.

The Effectiveness of Blood Metal Ions in Identifying Patients with Unilateral Birmingham Hip Resurfacing and Corail-Pinnacle Metal-on-Metal Hip Implants at Risk of Adverse Reactions to Metal Debris.

BACKGROUND: We investigated whether blood metal ions could effectively identify patients with metal-on-metal hip implants with two common designs (Birmingham Hip Resurfacing [BHR] and Corail-Pinnacle) who were at risk of adverse reactions to metal debris. METHODS: This single-center, prospective study involved 598 patients with unilateral hip implants (309 patients with the BHR implant and 289 patients with the Corail-Pinnacle implant) undergoing whole blood metal ion sampling at a mean time of 6.9 years. Patients were classified into two groups, one that had adverse reactions to metal debris (those who had to undergo revision for adverse reactions to metal debris or those with adverse reactions to metal debris on imaging; n = 46) and one that did not (n = 552). Three metal ion parameters (cobalt, chromium, and cobalt-chromium ratio) were compared between groups. Optimal metal ion thresholds for identifying patients with adverse reactions to metal debris were determined using receiver operating characteristic analysis. RESULTS: All ion parameters were significantly higher (p < 0.0001) in the patients who had adverse reactions to metal debris compared with those who did not. Cobalt maximized the area under the curve for patients with the BHR implant (90.5%) and those with the Corail-Pinnacle implant (79.6%). For patients with the BHR implant, the area under the curve for cobalt was significantly greater than that for the cobalt-chromium ratio (p = 0.0005), but it was not significantly greater than that for chromium (p = 0.8483). For the patients with the Corail-Pinnacle implant, the area under the curve for cobalt was significantly greater than that for chromium (p = 0.0004), but it was similar to that for the cobalt-chromium ratio (p = 0.8139). Optimal blood metal ion thresholds for identifying adverse reactions to metal debris varied between the two different implants. When using cobalt, the optimal threshold for identifying adverse reactions to metal debris was 2.15 µg/L for the BHR group and 3.57 µg/L for the Corail-Pinnacle group. These thresholds had good sensitivities (88.5% for the BHR group and 80.0% for the Corail-Pinnacle group) and specificities (84.5% for the BHR group and 76.2% for the Corail-Pinnacle group), high negative predictive values (98.8% for the BHR group and 98.1% for the Corail-Pinnacle group), and low positive predictive values (34.3% for the BHR group and 20.0% for the Corail-Pinnacle group). The authority thresholds proposed by the United States (3 µg/L and 10 µg/L) and the United Kingdom (7 µg/L) missed more patients with adverse reactions to metal debris at 2.0% to 4.7% (twelve to twenty-eight patients) compared with our implant-specific thresholds at 1.2% (seven patients missed). CONCLUSIONS: Patients who underwent metal-on-metal hip arthroplasty performed with unilateral BHR or Corail-Pinnacle implants and who had blood metal ions below our implant-specific thresholds were at low risk of adverse reactions to metal debris. These thresholds could be used to rationalize follow-up resources in asymptomatic patients. Analysis of cobalt alone is acceptable. Implant-specific thresholds were more effective than currently recommended fixed authority thresholds for identifying patients at risk of adverse reactions to metal debris requiring further investigation. LEVEL OF EVIDENCE: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Predicting high blood metal ion concentrations following hip resurfacing.

PURPOSE: To determine whether gender, femoral head size, acetabular inclination, and time since surgery predicted high blood metal ion concentrations following Birmingham Hip Resurfacing (BHR). METHODS: BHR patients with unilateral bearings at one specialist centre with blood cobalt and chromium concentrations measured up to May 2013 were included. This comprised a mixed (at-risk) group including symptomatic patients and asymptomatic individuals with specific clinical and/or radiological findings. Blood sampling was at a mean of 7.5 years (range 1-15.4 years) postoperatively. RESULTS: Of 319 patients (mean age 49.3 years; 53% male), blood metal ions greater than 7 µg/l were observed in 9% (n = 28). Blood metal ions were significantly higher in females (p<0.001), femoral head sizes ≤48 mm (p<0.01), and cup inclinations >55° (p<0.001). Linear regression demonstrated femoral head size was responsible for the highest proportion of variance in blood metal ions (cobalt p<0.001, R2 = 8%; chromium p<0.001, R2 = 11%). Analysis of femoral head size and inclination together demonstrated 36% of BHRs with head sizes of 38-44 mm and inclination >55° had blood metal ions >7 µg/l. BHR 10-year survival for this at-risk group was 91% (95% confidence intervals 86.0%-95.0%) with 30 hips revised. CONCLUSIONS: If blood metal ions are used to screen hip resurfacing patients for adverse reactions to metal debris it is recommended those with small femoral head sizes (38-44 mm) and high acetabular inclinations (>55°) are targeted. These findings require validation in other cohorts as they may not be applicable to all hip resurfacing devices given the differences in radial clearance, coverage arc, and metallurgy.

Influence of implant design on blood metal ion concentrations in metal-on-metal total hip replacement patients.

PURPOSE: Most factors considered to affect blood metal ions following metal-on-metal hip replacement are based on hip resurfacing patients. The study aims were to determine which factors affect blood metal ion concentrations following metal-on-metal total hip replacement (MoM THR). METHODS: All unilateral MoM THR patients at one centre with whole-blood cobalt (Co) and chromium (Cr) concentrations measured up to May 2013 were included. Blood sampling was at a mean of 4.5 years (range 1.1-11.8 years) postoperatively. RESULTS: Of 496 patients (mean age 59.1 years; 52.8% male), blood metal ions >7 µg/l were observed in 9.7% (n = 48). Large femoral head sizes (≥38 mm) had significantly higher (p < 0.0001) blood metal ions than smaller sizes (28/36 mm). Corail-Pinnacle implants produced significantly lower blood metal ions compared to other implant designs (p < 0.01 Co and Cr). Univariate linear regression demonstrated the only significant predictors of both blood Co and Cr concentrations were femoral head size (R(2) = 8.6% Co and R(2) = 3.3% Cr, both p < 0.0001) and implant design (R(2) = 8.8%, p = 0.005 Co and R(2) = 5.1%, p = 0.003 Cr). When the three THR implant design groups (Corail-Pinnacle, Synergy, Other) were analysed separately, femoral head size no longer significantly affected blood metal ions in any of the three implant design groups. CONCLUSIONS: Implant design was the most important factor affecting blood metal ion concentrations. We recommend the regularity of follow-up be tailored to survival rates of various MoM THR designs rather than according to femoral head size.

Revision of metal-on-metal hip replacements and resurfacings for adverse reaction to metal debris: a systematic review of outcomes.

PURPOSE: This systematic review assessed evidence on outcomes following revision of MoM hip resurfacings (HRs) and total hip replacements (THRs) for adverse reaction to metal debris (ARMD). METHODS: Four electronic databases were searched between January 2009 and July 2013 to identify studies reporting clinical outcomes following revision of MoM HRs and THRs for ARMD. Only studies reporting cohorts with more than 10 metal-on-metal (MoM) hips revised for ARMD were included. Outcomes of interest following ARMD revision were: (1) complication rates; (2) re-revision rates; (3) surgical intervention other than re-revision; (4) functional outcome. RESULTS: Of 148 unique studies identified, six studies were eligible for inclusion containing 216 MoM hips (197 HRs and 19 THRs) revised for ARMD. Mean follow-up time from ARMD revision ranged between 21-61 months. Complication rates were 4%-50% for HR and 68% for THR. Re-revision rates were 3%-38% for HR and 21% for THR. Dislocation (n = 14), ARMD recurrence (n = 11), and acetabular loosening (n = 9) were the three commonest complications and indications for re-revision. All six studies reported between one and three cases of ARMD recurrence during follow-up. One study specifically reported on performing procedures other than re-revision with 26% requiring closed reductions for dislocated THRs. Functional outcomes following ARMD revision were good or satisfactory in all but two studies. CONCLUSIONS: Limited evidence exists regarding outcomes following revision of MoM hips for ARMD, especially for THRs. This should be addressed in future studies and may be important when counselling asymptomatic individuals in whom revision is considered for raised blood metal ions.

Clinical outcome following surgical intervention for periprosthetic hip fractures at a tertiary referral centre.

Complications following surgical intervention for periprosthetic hip fractures are not uncommon. We report the clinical outcome following definitive surgical intervention for this indication at a single tertiary referral centre. All patients admitted between 2003 and 2009 undergoing such treatment were included. Patient demographics, all surgical interventions, complications following definitive fracture treatment, and postoperative mortality were recorded. Radiographs were reviewed to determine the Vancouver classification for each fracture. There were 67 patients (mean age at revision 76.7 years; 61% female). Fractures occurred around primary total hip arthroplasties (43%), revision arthroplasties (34%), and hip hemiarthroplasties (23%). Mean time to fracture from the most recent arthroplasty performed was 7.0 years. Most fractures were Vancouver type B2 (49%). The majority of patients underwent revision total hip arthroplasty (96%), using long-stemmed prostheses or proximal femoral endoprostheses, with cables for fracture fixation. Wound infection and systemic complications were seen in 16% and 13% respectively. One or more further surgical interventions were performed in 12%. There were no deaths in-hospital or at 30-days, with 10 fatalities (15%) at a mean 2-year follow-up. Lower rates of re-intervention and mortality were observed when surgery for acute periprosthetic hip fractures was performed at a tertiary centre. Revision hip arthroplasty with or without fracture fixation proved an effective and safe treatment of periprosthetic hip fractures in a high-risk patient population.

Can a new design of pneumatic compression device reduce variations in delivered therapy for the mechanical prophylaxis of thromboembolic disease after total hip arthroplasty?

BACKGROUND: Compression devices have been shown to prevent thromboembolic disease. However, the pressures generated may not be the same as the ones recommended by the manufacturer. The purpose of this study is to investigate a new sequential compression device with feedback to maintain optimal therapy, and to determine whether therapy is improved with this new device. PATIENTS AND METHOD: A series of 50 patients undergoing elective total hip arthroplasty at a major tertiary-care hospital with a special interest in joint replacement were enrolled prospectively. In addition to pharmacological prophylaxis for thromboembolic disease, all patients received compression from a modified device. Maximum pressures generated and the rate of pressure rise in each of the 3 compartments within the device sleeves were measured and the results compared with data from historical controls. RESULTS: We considered therapy to be ideal when in a particular compression cycle all chambers of both right and left sleeves reach within 10% of their target pressures at within 10% of their target pressure rise rates. The average patient received this ideal therapy 88% of the time that the new trial sequential compression device was operating. This represents a dramatic improvement over previous devices. CONCLUSIONS: The new device allows dramatically improved pressures within the device because of a feedback loop that allows dynamic control of each chamber's pressure. Improved consistency of delivery should make it easier to accurately assess the true benefits of mechanical prophylaxis with a sequential compression device.

A pilot study of CODOX-M/IVAC in primary refractory or relapsed high-grade non-Hodgkin's lymphoma. A Scotland and Newcastle Lymphoma Group Study.

BACKGROUND AND OBJECTIVES: The prognosis in patients with primary refractory or relapsed high grade non-Hodgkin's lymphoma (NHL) is very poor--the 5-year survival being generally reported at 10%. DESIGN AND METHODS: Multiple salvage regimens have been investigated and, while response rates of 50-80% have been noted in selected patients, the long-term prognosis remains poor. Following the encouraging results in high risk Burkitt's and Burkitt-like lymphoma using the CODOX-M and IVAC protocols, we performed a pilot study using a similar regimen in patients with primary refractory or relapsed high grade NHL. RESULTS: The regimens were modified by a reduction in the intensity of intrathecal therapy. It was planned to mobilize peripheral blood stem cells following the IVAC cycle for use in subsequent autologous peripheral blood stem cell transplantation in chemosensitive patients. The initial plan was to recruit 50 patients, but the study was closed after 8 due to excessive toxicity. INTERPRETATION AND CONCLUSIONS: We conclude that the CODOX-M/IVAC regimen is too toxic for this group of patients and does not result in better response rates than those to currently available salvage regimens.