Microporous titanium and hydroxyapatite improve fixation of the tibial wall in unicompartmental knee replacement.

PURPOSE: Cementless Oxford unicompartmental knee replacement (OUKR) is associated with less pain than cemented OUKR 5 years postoperatively. This may be due to improved fixation at the tibial wall, which transmits tension and reduces stress in the bone below the tibial component. This study compares tibial wall fixation with three different types of fixation: cemented, cementless with hydroxyapatite (HA) and cementless with a microporous titanium coat and HA (HA + MPC). METHODS: Three consecutive cohorts were identified (n = 221 cemented in 2005-2007, n = 118 HA in 2014-2015, n = 125 HA + MPC in 2016-2017). Analysis was performed on anterior-posterior radiographs aligned on the tibial component taken 1-2 years postoperatively. Aligned radiographs are needed to see narrow radiolucencies adjacent to the wall. Alignment was assessed with rotation ratio (RR = wall width/internal wall height). Perfect RR is 0.3, and a maximum threshold of 0.5 was used. Quality of fixation to the wall was assessed with fixation ratio (FR = bone wall contact height/total wall height). Notable radiographic features at the tibial wall were also recorded. RESULTS: A total of 33 knees with cement, 37 knees with cementless with HA and 57 knees cementless with HA + MPC had adequately aligned radiographs. Fixation was significantly better with HA compared with cement (55% vs. 25%, p = 0.0016). The microporous coat further improved fixation (81% vs. 55%, p < 0.0001). FR > 80% was achieved in 3% of the cemented implants, 32% of HA and 68% of HA + MPC. In cementless cohorts, features suggestive of a layer of bone that had delaminated from the wall were seen in 8 (22%) HA and 3 (5%) HA + MPC knees. CONCLUSION: Radiographic tibial wall fixation in OUKR is poor with cement. It improves with an HA coating and improves further with an intermediary MPC. Improved tibial wall fixation may explain the lower levels of pain observed with cementless rather than cemented fixation described in the literature, but further clinical correlation is needed. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Polyethylene bearing wear is comparable for cemented and cementless Oxford unicompartmental knee replacements: Ten-year results of a randomized controlled trial.

PURPOSE: There is concern that using cementless components may increase polyethylene wear of the Oxford unicompartmental knee replacement (OUKR). Therefore, this study aimed to measure bearing wear at 10 years in patients from a randomized trial comparing Phase 3 cemented and cementless OUKRs and to investigate factors that may affect wear. It was hypothesized that there would be no difference in wear rate between cemented and cementless OUKRs. METHODS: Bearing thickness was determined using radiostereometric analysis at postoperative, 3-month, 6-month, 1-year, 2-year, 5-year and 10-year timepoints. As creep occurs early, wear rate was calculated using linear regression between 6 months and 10 years for 39 knees (20 cemented, 19 cementless). Associations between wear and implant, surgical and patient factors were analysed. RESULTS: The linear wear rate of the Phase 3 OUKR was 0.06 mm/year with no significant difference (p = 0.18) between cemented (0.054 mm/year) and cementless (0.063 mm/year) implants. Age, Oxford Knee Score, component size and bearing thickness had no correlation with wear. A body mass index ≥ 30 was associated with a significantly lower wear rate (p = 0.007) as was having ≥80% femoral component contact area on the bearing (p = 0.003). Bearings positioned ≥1.5 mm from the tibial wall had a significantly higher wear rate (p = 0.002). CONCLUSIONS: At 10 years, the Phase 3 OUKR linear wear rate is low and not associated with the fixation method. To minimize the risk of wear-related bearing fracture in the very long-term surgeons should consider using 4 mm bearings in very young active patients and ensure that components are appropriately positioned, which is facilitated by the current instrumentation. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

A Comparison of the Periprosthetic Fracture Rate of Cemented and Cementless Mobile Bearing Unicompartmental Knee Arthroplasties: An Analysis of Data From the National Joint Registry for England, Wales, Northern Ireland, and the Isle of Man.

BACKGROUND: Periprosthetic fractures are rare but serious complications of unicompartmental knee arthroplasty (UKA). Although cementless UKA has a lower risk of loosening than cemented, there are concerns that tibial fracture risk may be higher given the reliance on interference fit for primary stability. The risk of fracture and the effect of surgical fixation are currently unknown. We compared the periprosthetic fracture rate following cemented and cementless UKA surgery. METHODS: A total of 14,122 medial mobile-bearing UKAs (7,061 cemented and 7,061 cementless) from the National Joint Registry and Hospital Episodes Statistics database were propensity score-matched. Cumulative fracture rates were calculated and Cox regressions were used to compare fixation groups. RESULTS: The three-month periprosthetic fracture rates were similar (P = .80), being 0.10% in the cemented group and 0.11% in the cementless group. The fracture rates were highest during the first three months postoperatively, but then decreased and remained constant between one and 10 years after surgery. The one-year cumulative fracture rates were 0.2% (confidence interval [CI]: 0.1 to 0.3) for cemented and 0.2% (CI: 0.1 to 0.3) for cementless cases. The 10-year cumulative fracture rates were 0.8% (CI: 0.2 to 1.3) and 0.8% (CI: 0.3 to 1.3), respectively. The hazard ratio during the whole study period was 1.06 (CI: 0.64 to 1.77; P = .79). CONCLUSIONS: The periprosthetic fracture rate following mobile bearing UKA surgery is low, being about 1% at 10 years. There were no significant differences in fracture rates between cemented and cementless implants after matching. We surmise that surgeons are aware of the higher theoretical risk of early fracture with cementless components and take care with tibial preparation. LEVELS OF EVIDENCE: III.

Low polyethylene creep and wear following mobile-bearing unicompartmental knee replacement.

PURPOSE: The Oxford unicompartmental knee replacement (UKR) has a fully congruent mobile bearing to minimise wear. However, with younger higher demand patients, wear remains a concern. The aim of this study was to quantify the wear rate of Phase 3 Oxford UKR bearings over the course of 5 years and to identify the factors that influence it. METHODS: 40 medial Oxford UKRs recruited for a randomised study of cemented and cementless fixation were studied with Radiostereometric analysis (RSA) at 1 week, 3 months, 6 months, 1 year, 2 years, and 5 years post-operatively and bearing thickness was calculated. Penetration, defined as the change in thickness compared to the 1-week measurement, was determined. Creep (early penetration) and wear (late penetration at a constant rate) were calculated. The influence of demographic factors, Oxford Knee Score (OKS), Tegner score, fixation and bearing overhang (determined by RSA) on wear was analysed. RESULTS: After 6 months the penetration rate was constant, indicating that wear alone was occurring. The wear rate was 0.07 mm/year (SD 0.03). The creep was 0.06 mm with about 95% occurring during the first 3 months. There was no significant relationship between fixation (cemented/cementless), age, component size, OKS and Tegner score with wear rate. Increasing BMI was associated with decreasing wear (p = 0.042). 37/40 bearings overhung the tibia to some extent and 23/40 overhung the tibia medially. An increase in the area of overhang (p = 0.036), amount of medial overhang (p = 0.028) and distance between the bearing and tibial wall (p = 0.019) were associated with increased wear. Bearings that did not overhang (0.06 mm/year) had less wear (p = 0.025) than those that did (0.08 mm/year). There was no relationship (p = 0.6) between the femoral contact area and wear. CONCLUSION: During the first three to six months after implantation, the bearing becomes 0.06 mm thinner due to creep. The combined wear rate of the upper and lower surfaces of the bearing is constant (0.07 mm/year). The wear is lower if the bearing does not overhang the tibia so surgeons should aim for the bearing to be close to the tibial wall. The orientation of the femoral component does not influence wear. LEVEL OF EVIDENCE: Retrospective Study, Level III.

Ten-year clinical and radiographic results of 1000 cementless Oxford unicompartmental knee replacements.

PURPOSE: Unicompartmental knee replacement (UKR) has substantial benefits over total knee replacement (TKR) but has higher revision rates. The cementless Oxford UKR was introduced to address this but there are concerns about fixation and tibial plateau fractures. The first long-term study of the device with clinical and radiographic outcomes is reported. METHODS: The first 1000 medial cementless Oxford UKR were prospectively identified and followed up by independent physiotherapists. Survival was calculated using the endpoints reoperation, revision, revision to TKR, major revision requiring revision TKR components and patient mortality. The Oxford Knee Score (OKS), Tegner Activity Score and American Knee Society Score (AKSS) were recorded and radiographs analysed. RESULTS: The ten year survival was 96.6% (CI 94.8-97.8), 97.5% (CI 95.7-98.5), 98.9% (CI 97.7-99.4) and 99.6% (CI 98.8-99.9) using reoperation, revision, revision to TKR and major revision as the endpoint, respectively. Commonest causes for revision were bearing dislocation (n = 7, 0.7%), disease progression (n = 4, 0.4%) and pain (n = 2, 0.2%). There was one lateral tibial plateau fracture and one femoral component loosening. At 10 years, the mean OKS was 41.2 (SD 9.8), Tegner 2.8 (SD 1.3), AKSS-O 89.1 (SD 13.0) and AKSS-F 80.4 (SD 14.6). There were no pathological radiolucencies or complete radiolucent lines. There were no implant-related deaths. CONCLUSIONS: The cementless Oxford UKR is a safe procedure with excellent long-term clinical results. Our results suggest that reliable fixation was achieved with only one (0.1%) revision for loosening (femoral), no radiographic evidence of loosening in the remaining cases and no fractures related to implantation. LEVEL OF EVIDENCE: III.

Comparison of the 10-year outcomes of cemented and cementless unicompartmental knee replacements: data from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man.

Background and purpose - Unicompartmental knee replacement (UKR) offers advantages over total replacement but has higher revision rates, particularly for aseptic loosening. The cementless Oxford UKR was introduced to address this. We undertook a registry-based matched comparison of cementless and cemented UKRs.Patients and methods - From 40,552 Oxford UKRs identified by the National Joint Registry for England, Wales, Northern Ireland and Isle of Man (NJR) we propensity score matched, based on patient, surgical, and implant factors, 7,407 cemented and 7,407 cementless UKRs (total = 14,814).Results - The 10-year cumulative implant survival rates for cementless and cemented UKRs was 93% (95% CI 90-96) and 90% (CI 88-92) respectively, with this difference being significant (HR 0.76; p = 0.002). The risk of revision for aseptic loosening was less than half (p < 0.001) in the cementless (0.42%) compared with the cemented group (1.00%), and the risk of revision also decreased for unexplained pain (to 0.46% from 0.74%; p = 0.03) and lysis (to 0.04% from 0.15%; p = 0.03). However, the risk of revision for periprosthetic fracture increased significantly (p = 0.01) in the cementless (0.26%) compared with the cemented group (0.09%). 10-year patient survival rates were similar (HR 1.2; p = 0.1).Interpretation - The cementless UKR has improved 10-year implant survival compared with the cemented UKR, independent of patient, implant, and surgical factors. This improved survival in the cementless group was primarily the result of lower revision rate for aseptic loosening, unexplained pain, and lysis, suggesting the fixation of the cementless was superior. However, there was a small increased risk of revision for periprosthetic fracture with the cementless implant.

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.

Liposomal bupivacaine infiltration at the surgical site for the management of postoperative pain.

BACKGROUND: Despite multi-modal analgesic techniques, acute postoperative pain remains an unmet health need, with up to three quarters of people undergoing surgery reporting significant pain. Liposomal bupivacaine is an analgesic consisting of bupivacaine hydrochloride encapsulated within multiple, non-concentric lipid bi-layers offering a novel method of sustained-release analgesia. OBJECTIVES: To assess the analgesic efficacy and adverse effects of liposomal bupivacaine infiltration at the surgical site for the management of postoperative pain. SEARCH METHODS: On 13 January 2016 we searched CENTRAL, MEDLINE, MEDLINE In-Process, Embase, ISI Web of Science and reference lists of retrieved articles. We obtained clinical trial reports and synopses of published and unpublished studies from Internet sources, and searched clinical trials databases for ongoing trials. SELECTION CRITERIA: Randomised, double-blind, placebo- or active-controlled clinical trials in people aged 18 years or over undergoing elective surgery, at any surgical site, were included if they compared liposomal bupivacaine infiltration at the surgical site with placebo or other type of analgesia. DATA COLLECTION AND ANALYSIS: Two review authors independently considered trials for inclusion, assessed risk of bias, and extracted data. We performed data analysis using standard statistical techniques as described in the Cochrane Handbook for Systematic Reviews of Interventions, using Review Manager 5.3. We planned to perform a meta-analysis and produce a 'Summary of findings' table for each comparison however there were insufficient data to ensure a clinically meaningful answer. As such we have produced two 'Summary of findings' tables in a narrative format. Where possible we assessed the quality of evidence using GRADE. MAIN RESULTS: We identified nine studies (10 reports, 1377 participants) that met inclusion criteria. Four Phase II dose-escalating/de-escalating trials, designed to evaluate and demonstrate efficacy and safety, presented pooled data that we could not use. Of the remaining five parallel-arm studies (965 participants), two were placebo controlled and three used bupivacaine hydrochloride local anaesthetic infiltration as a control. Using the Cochrane tool, we judged most studies to be at unclear risk of bias overall; however, two studies were at high risk of selective reporting bias and four studies were at high risk of bias due to size (fewer than 50 participants per treatment arm).Three studies (551 participants) reported the primary outcome cumulative pain intensity over 72 hours following surgery. Compared to placebo, liposomal bupivacaine was associated with a lower cumulative pain score between the end of the operation (0 hours) and 72 hours (one study, very low quality). Compared to bupivacaine hydrochloride, two studies showed no difference for this outcome (very low quality evidence), however due to differences in the surgical population and surgical procedure (breast augmentation versus knee arthroplasty) we did not perform a meta-analysis.No serious adverse events were reported to be associated with the use of liposomal bupivacaine and none of the five studies reported withdrawals due to drug-related adverse events (moderate quality evidence).One study reported a lower mean pain score at 12 hours associated with liposomal bupivacaine compared to bupivacaine hydrochloride, but not at 24, 48 or 72 hours postoperatively (very low quality evidence).Two studies (382 participants) reported a longer time to first postoperative opioid dose compared to placebo (low quality evidence).Two studies (325 participants) reported the total postoperative opioid consumption over the first 72 hours: one study reported a lower cumulative opioid consumption for liposomal bupivacaine compared to placebo (very low quality evidence); one study reported no difference compared to bupivacaine hydrochloride (very low quality evidence).Three studies (492 participants) reported the percentage of participants not requiring postoperative opioids over initial 72 hours following surgery. One of the two studies comparing liposomal bupivacaine to placebo demonstrated a higher number of participants receiving liposomal bupivacaine did not require postoperative opioids (very low quality evidence). The other two studies, one versus placebo and one versus bupivacaine hydrochloride, found no difference in opioid requirement (very low quality evidence). Due to significant heterogeneity between the studies (I2 = 92%) we did not pool the results.All the included studies reported adverse events within 30 days of surgery, with nausea, constipation and vomiting being the most common. Of the five parallel-arm studies, none performed or reported health economic assessments or patient-reported outcomes other than pain.Using GRADE, the quality of evidence ranged from moderate to very low. The major limitation was the sparseness of data for outcomes of interest. In addition, a number of studies had a high risk of bias resulting in further downgrading. AUTHORS' CONCLUSIONS: Liposomal bupivacaine at the surgical site does appear to reduce postoperative pain compared to placebo, however, at present the limited evidence does not demonstrate superiority to bupivacaine hydrochloride. There were no reported drug-related serious adverse events and no study withdrawals due to drug-related adverse events. Overall due to the low quality and volume of evidence our confidence in the effect estimate is limited and the true effect may be substantially different from our estimate.

The Interaction of Caseload and Usage in Determining Outcomes of Unicompartmental Knee Arthroplasty: A Meta-Analysis.

BACKGROUND: Outcomes after unicompartmental knee arthroplasty (UKA) are variable and influenced by caseload (UKA/y) and usage (percentage of knee arthroplasty that are UKA), which relates to indications. This meta-analysis assesses the relative importance of these factors. METHODS: MEDLINE (Ovid), Embase (Ovid), and Web of Science (ISI) were searched for consecutive series of cemented Phase 3 Oxford medial UKA. The primary outcome was revision rate/100 observed component years (% pa) with subgroup analysis based on caseload and usage. RESULTS: Forty-six studies (12,520 knees) with an annual revision-rate ranging from 0% to 4.35% pa, mean 1.21% pa (95% confidence interval [CI], 0.97-1.47), were identified. In series with mean follow-up of 10-years, the revision-rate was 0.63% pa (95% CI, 0.46-0.83), equating to a 94% (95% CI, 92%-95%) 10-year survival. Aseptic loosening, lateral arthritis, bearing dislocation, and unexplained pain were the predominant failure mechanisms with revision for patellofemoral problems and polyethylene wear exceedingly rare. The lowest revision-rates were achieved with caseload >24 UKA/y (0.88% pa; 95% CI, 0.63-1.61) and usage >30% (0.69% pa; 95% CI, 0.50-0.90). Usage was more important than caseload; with high usage (≥20%), the revision-rate was low, whether the caseload was high (>12 UKA/y) or low (≤12 UKA/y; (0.94% pa; 95% CI, 0.69-1.23 and 0.85% pa; 95% CI, 0.65-1.08), respectively); with low usage (<20%), the revision-rate was high, whether the caseload was high or low (1.58% pa; 95% CI, 0.57-3.05 and 1.76% pa; 95% CI, 1.21-2.41, respectively). CONCLUSION: To achieve optimum results, surgeons, whether high or low caseload, should adhere to the recommended indications such that ≥20%, or ideally >30% of their knee arthroplasties are UKA. If they do this, then they can expect to achieve results similar to those of the long-term series, which all had high usage (>20%) and an average 10-year survival of 94%.

Liposomal bupivacaine peripheral nerve block for the management of postoperative pain.

BACKGROUND: Postoperative pain remains a significant issue with poor perioperative pain management associated with an increased risk of morbidity and mortality. Liposomal bupivacaine is an analgesic consisting of bupivacaine hydrochloride encapsulated within multiple, non-concentric lipid bi-layers offering a novel method of sustained release. OBJECTIVES: To assess the analgesic efficacy and adverse effects of liposomal bupivacaine infiltration peripheral nerve block for the management of postoperative pain. SEARCH METHODS: We identified randomised trials of liposomal bupivacaine peripheral nerve block for the management of postoperative pain. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 1), Ovid MEDLINE (1946 to January Week 1 2016), Ovid MEDLINE In-Process (14 January 2016), EMBASE (1974 to 13 January 2016), ISI Web of Science (1945 to 14 January 2016), and reference lists of retrieved articles. We sought unpublished studies from Internet sources, and searched clinical trials databases for ongoing trials. The date of the most recent search was 15 January 2016. SELECTION CRITERIA: Randomised, double-blind, placebo- or active-controlled clinical trials of a single dose of liposomal bupivacaine administered as a peripheral nerve block in adults aged 18 years or over undergoing elective surgery at any surgical site. We included trials if they had at least two comparison groups for liposomal bupivacaine peripheral nerve block compared with placebo or other types of analgesia. DATA COLLECTION AND ANALYSIS: Two review authors independently considered trials for inclusion in the review, assessed risk of bias, and extracted data. We performed analyses using standard statistical techniques as described in the Cochrane Handbook for Systematic Reviews of Interventions, using Review Manager 5. We planned to perform a meta-analysis, however there were insufficient data to ensure a clinically meaningful answer; as such we have produced a 'Summary of findings' table in a narrative format, and where possible we assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation). MAIN RESULTS: We identified seven studies that met inclusion criteria for this review. Three were recorded as completed (or terminated) but no results were published. Of the remaining four studies (299 participants): two investigated liposomal bupivacaine transversus abdominis plane (TAP) block, one liposomal bupivacaine dorsal penile nerve block, and one ankle block. The study investigating liposomal bupivacaine ankle block was a Phase II dose-escalating/de-escalating trial presenting pooled data that we could not use in our analysis.The studies did not report our primary outcome, cumulative pain score between 0 and 72 hours, and secondary outcomes, mean pain score at 12, 24, 48, 72, or 96 hours. One study reported no difference in mean pain score during the first, second, and third postoperative 24-hour periods in participants receiving liposomal bupivacaine TAP block compared to no TAP block. Two studies, both in people undergoing laparoscopic surgery under TAP block, investigated cumulative postoperative opioid dose, reported opposing findings. One found a lower cumulative opioid consumption between 0 and 72 hours compared to bupivacaine hydrochloride TAP block and one found no difference during the first, second, and third postoperative 24-hour periods compared to no TAP block. No studies reported time to first postoperative opioid or percentage not requiring opioids over the initial 72 hours. No studies reported a health economic analysis or patient-reported outcome measures (outside of pain). The review authors sought data regarding adverse events but none were available, however there were no withdrawals reported to be due to adverse events.Using GRADE, we considered the quality of evidence to be very low with any estimate of effect very uncertain and further research very likely to have an important impact on our confidence in the estimate of effect. All studies were at high risk of bias due to their small sample size (fewer than 50 participants per arm) leading to uncertainty around effect estimates. Additionally, inconsistency of results and sparseness of data resulted in further downgrading of the quality of the data. AUTHORS' CONCLUSIONS: A lack of evidence has prevented an assessment of the efficacy of liposomal bupivacaine administered as a peripheral nerve block. At present there is a lack of data to support or refute the use of liposomal bupivacaine administered as a peripheral nerve block for the management of postoperative pain. Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Adverse reactions to metal debris occur with all types of hip replacement not just metal-on-metal hips: a retrospective observational study of 3340 revisions for adverse reactions to metal debris from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man.

BACKGROUND: Adverse reactions to metal debris (ARMD) have resulted in the high short-term failure rates observed with metal-on-metal hip replacements. ARMD has recently been reported in non-metal-on-metal total hip replacements (non-MoM THRs) in a number of small cohort studies. However the true magnitude of this complication in non-MoM THRs remains unknown. We used a nationwide database to determine the risk of ARMD revision in all non-MoM THRs, and compared patient and surgical factors associated with ARMD revision between non-MoM and MoM hips. METHODS: We performed a retrospective observational study using data from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man. All primary hip replacements undergoing revision surgery for ARMD were included (n = 3,340). ARMD revision risk in non-MoM THRs was compared between different commonly implanted bearing surfaces and femoral head sizes (Chi-squared test). Differences in patient and surgical factors between non-MoM hips and MoM hips revised for ARMD were also analysed (Chi-squared test and unpaired t-test). RESULTS: Of all ARMD revisions, 7.5% (n = 249) had non-MoM bearing surfaces. The relative risk of ARMD revision was 2.35 times (95% CI 1.76-3.11) higher in ceramic-on-ceramic bearings compared with hard-on-soft bearings (0.055 vs. 0.024%; p < 0.001), and 2.80 times (95% CI 1.74-4.36) higher in 36 mm metal-on-polyethylene bearings compared to 28 mm and 32 mm metal-on-polyethylene bearings (0.058 vs. 0.021%; p < 0.001). ARMD revisions were performed earlier in non-MoM hips compared to MoM hips (mean 3.6-years vs. 5.6-years; p < 0.0001). Non-MoM hips had more abnormal findings at revision (63.1 vs. 35.7%; p < 0.001), and more intra-operative adverse events (6.4 vs. 1.6%; p < 0.001) compared to MoM hips. CONCLUSIONS: Although the overall risk of ARMD revision surgery in non-MoM THRs appears low, this risk is increasing, and is significantly higher in ceramic-on-ceramic THRs and 36 mm metal-on-polyethylene THRs. ARMD may therefore represent a significant clinical problem in non-MoM THRs.

The John Charnley Award: Highly crosslinked polyethylene in total hip arthroplasty decreases long-term wear: a double-blind randomized trial.

BACKGROUND: The use of highly crosslinked polyethylene (HXLPE) is now commonplace for total hip arthroplasty. Hip simulator studies and short-term in vivo measurements suggest that the wear rate of some types of HXLPE is significantly less than conventional ultrahigh-molecular-weight polyethylene (UHMWPE). However, there are few long-term data to support its use. QUESTIONS/PURPOSES: The aim of this study was to measure the long-term steady-state wear of HXLPE compared with UHMWPE liners in a prospective, double-blind, randomized controlled trial using radiostereometric analysis. METHODS: Fifty-four patients were randomized to receive hip arthroplasties with either UHMWPE liners or HXLPE liners. Complete followup was available on 39 of these patients (72%). All patients received the same cemented stem and an uncemented acetabular component. Three-dimensional penetration of the head into the socket was determined at 10 years using a radiostereometric analysis system, which has an in vivo accuracy of <0.1 mm. Oxford Hip Scores were compared between the groups. RESULTS: At 10 years there was significantly less wear of HXLPE (0.003 mm/year; 95% confidence interval [CI], ±0.010; SD 0.023; range, -0.057 to 0.074) compared with UHMWPE (0.030 mm/year; 95% CI, ±0.012; p<0.001; SD 0.0.27; range, -0.001 to 0.164). The volumetric penetration from 1 to 10 years for the UHMWPE group was 98 mm3 (95% CI, ±46 mm3; SD 102 mm3; range, -4 to 430 mm3) compared with 14 mm3 (95% CI, ±40 mm3; SD 91 mm3; range, -189 to 242 mm3) for the HXLPE group (p=0.01). CONCLUSIONS: This study demonstrates that HXLPE has little detectable steady-state in vivo wear. This may result in fewer reoperations from loosening; however, careful clinical followup into the second decade still needs to be performed. LEVEL OF EVIDENCE: Level I, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

A Matched Comparison of Implant and Functional Outcomes of Cemented and Cementless Unicompartmental Knee Replacements: A Study from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man and the Hospital Episode Statistics Patient Reported Outcome Measures Database.

BACKGROUND: Unicompartmental knee replacement (UKR) is an effective treatment for end-stage medial compartment osteoarthritis, but there can be problems with fixation. The cementless UKR was introduced to address this issue. It is unknown how its functional outcomes compare with those of the cemented version on a national scale. We performed a matched comparison of the clinical and functional outcomes of cementless and cemented UKRs. METHODS: Using the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man (NJR), 14,764 Oxford UKRs with linked data regarding patient-reported outcomes were identified. A total of 6,906 UKRs (3,453 cemented and 3,453 cementless) were propensity score matched on the basis of patient, surgical, and implant factors. RESULTS: The 10-year cumulative implant survival rate was 93.0% (95% confidence interval [CI], 90.0% to 95.1%) for cementless UKRs and 91.3% (95% CI, 89.0% to 93.0%) for cemented UKRs. The cementless UKR group had a significantly lower revision risk (hazard ratio [HR], 0.74; p = 0.02). Subgroup analyses showed a stronger effect size (HR, 0.66) among UKRs performed by high-caseload surgeons (i.e., surgeons performing ≥30 UKRs/year). In the overall cohort, the postoperative Oxford Knee Score (OKS) in the cementless group (mean and standard deviation, 39.1 ± 8.7) was significantly higher (p = 0.001) than that in the cemented group (38.5 ± 8.6). The cementless group gained a mean of 17.6 ± 9.3 points in the OKS postoperatively and the cemented group gained 16.5 ± 9.6 points, with a difference of 1.1 points between the groups (p < 0.001). The difference in OKS points gained postoperatively was highest among UKRs performed by high-caseload surgeons, with the cementless group gaining 1.8 points more (p < 0.001) than the cemented group. CONCLUSIONS: The cementless UKR demonstrated better 10-year implant survival and postoperative functional outcomes than the cemented UKR. The difference was largest among UKRs performed by high-caseload surgeons, with the cementless fixation group having an HR for revision of 0.66 and an approximately 2-point greater improvement in the OKS compared with the cemented fixation group. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Helping general dental practitioners use the Index of Orthodontic Treatment Need: an assessment of available educational apps.

Introduction The Index of Orthodontic Treatment Need (IOTN) defines who receives treatment on the NHS. The British Orthodontic Society developed the 'Easy IOTN' app to help the dental team use IOTN more effectively.Aim This study aims to investigate the quality of the 'Easy IOTN' app and any alternative mobile apps developed to aid a dentist's ability to use IOTN.Materials and methods The App Store and Google Play were searched to identify available apps which provide an educational resource for IOTN. Any app identified was assessed using the Mobile App Rating Scale (MARS) and the Royal College of Physicians' health informatics unit checklist. The 'Easy IOTN' app continuous professional development (CPD) section was assessed for accuracy using a focus group.Results Only the 'Easy IOTN' app was identified. It has a mean MARS score of 3.6. Significant inaccuracies were found within the CPD component of the 'Easy IOTN' app.Discussion A mean MARS score of 3.6 is deemed average and is comparable to the quality of other orthodontic apps which exist. Errors contained within the CPD component could confuse users and have a negative impact on IOTN skill development.Conclusions The educational component of the 'Easy IOTN' app is of an acceptable standard, but the CPD section is flawed.

The Effect of Body Mass Index on the Relative Revision Rates of Cemented and Cementless Unicompartmental Knee Replacements: An Analysis of Over 10,000 Knee Replacements from National Databases.

BACKGROUND: Unicompartmental knee replacements (UKRs) are being performed in an increasingly overweight population. There are concerns that cemented fixation will not last. Cementless fixation may offer a solution, but the relative performance in different body mass index (BMI) groups remains unknown. METHODS: Ten thousand, four hundred and forty cemented and cementless UKRs were propensity matched. Patients were stratified into 4 BMI groups: underweight (<18.5 kg/m 2 ), normal weight (18.5 to <25 kg/m 2 ), overweight (25 to <30 kg/m 2 ), and obese (≥30 kg/m 2 ). The effect of BMI on the relative performance of UKR fixation groups was studied. Cox regression was used to compare revision and reoperation rates. RESULTS: The revision rate per 100 component-years significantly increased (p < 0.001) with BMI for the cemented UKRs. Revision rates per 100 component-years for the normal, overweight, and obese groups were 0.92 (95% confidence interval [CI], 0.91 to 0.93), 1.15 (95% CI, 1.14 to 1.16), and 1.31 (95% CI, 1.30 to 1.33), respectively. This was not observed for the cementless UKR, with revision rates of 1.09 (95% CI, 1.08 to 1.11), 0.70 (95% CI, 0.68 to 0.71), and 0.96 (95% CI, 0.95 to 0.97), respectively. The 10-year implant survival rates for the matched cemented and cementless UKRs in the normal, overweight, and obese groups were 93.8% (95% CI, 89.1% to 96.5%) and 94.3% (95% CI, 90.9% to 96.5%) (hazard ratio [HR], 1.17; p = 0.63), 88.5% (95% CI, 84.2% to 91.7%) and 93.8% (95% CI, 90.2% to 96.2%) (HR, 0.61; p = 0.005), and 90.7% (95% CI, 88.2% to 92.6%) and 91.8% (95% CI, 88.9% to 94.0%) (HR, 0.74; p = 0.02), respectively. There were insufficient numbers in the underweight group for analysis (n = 13). Obese patients had less than half the rates of aseptic loosening (0.46% vs. 1.31%; p = 0.001) and pain (0.60% vs. 1.20%; p = 0.02) in the cementless group as compared with the cemented group. CONCLUSIONS: Higher-BMI groups had higher revision rates for the cemented UKRs but not for the cementless UKRs. Cementless fixation was associated with reduced long-term revision rates compared with cement fixation in the overweight and obese groups. In the obese group, the rates of aseptic loosening and pain were at least 50% lower in the cementless UKR group. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Efficacy of Liposomal Bupivacaine and Bupivacaine Hydrochloride vs Bupivacaine Hydrochloride Alone as a Periarticular Anesthetic for Patients Undergoing Knee Replacement: A Randomized Clinical Trial.

Importance: More than half of patients who undergo knee replacement surgery report substantial acute postoperative pain. Objective: To evaluate the efficacy and cost-effectiveness of periarticular liposomal bupivacaine for recovery and pain management after knee replacement. Design, Setting, and Participants: This multicenter, patient-blinded, pragmatic, randomized clinical superiority trial involved 533 participants at 11 institutions within the National Health Service in England. Adults undergoing primary unilateral knee replacement for symptomatic end-stage osteoarthritis were enrolled between March 29, 2018, and February 29, 2020, and followed up for 1 year after surgery. Follow-up was completed March 1, 2021. A per-protocol analysis for each coprimary outcome was performed in addition to the main intention-to-treat analysis. Interventions: Two hundred sixty-six milligrams of liposomal bupivacaine admixed with 100 mg of bupivacaine hydrochloride compared with 100 mg of bupivacaine hydrochloride alone (control) administered by periarticular injection at the time of surgery. Main Outcome and Measures: The coprimary outcomes were Quality of Recovery 40 (QoR-40) score at 72 hours and pain visual analog scale (VAS) score area under the curve (AUC) from 6 to 72 hours. Secondary outcomes included QoR-40 and mean pain VAS at days 0 (evening of surgery), 1, 2, and 3; cumulative opioid consumption for 72 hours; functional outcomes and quality of life at 6 weeks, 6 months, and 1 year; and cost-effectiveness for 1 year. Adverse events and serious adverse events up to 12 months after randomization were also assessed. Results: Among the 533 participants included in the analysis, the mean (SD) age was 69.0 (9.7) years; 287 patients were women (53.8%) and 246 were men (46.2%). Baseline characteristics were balanced between study groups. There was no difference between the liposomal bupivacaine and control groups in QoR-40 score at 72 hours (adjusted mean difference, 0.54 [97.5% CI, -2.05 to 3.13]; P = .64) or the pain VAS score AUC at 6 to 72 hours (-21.5 [97.5% CI, -46.8 to 3.8]; P = .06). Analyses of pain VAS and QoR-40 scores demonstrated only 1 statistically significant difference, with the liposomal bupivacaine arm having lower pain scores the evening of surgery (adjusted difference -0.54 [97.5% CI, -1.07 to -0.02]; P = .02). No difference in cumulative opioid consumption and functional outcomes was detected. Liposomal bupivacaine was not cost-effective compared with the control treatment. No difference in adverse or serious adverse events was found between the liposomal bupivacaine and control groups. Conclusions and Relevance: This study found no difference in postoperative recovery or pain associated with the use of periarticular liposomal bupivacaine compared with bupivacaine hydrochloride alone in patients who underwent knee replacement surgery. Trial Registration: isrctn.com Identifier: ISRCTN54191675.

Molecular mechanism of cholesterol- and polyphosphoinositide-mediated syntaxin clustering.

The neuronal acceptor SNARE complex that functions as the receptor for synaptic vesicle docking and fusion at the presynaptic membrane is composed of the single-span transmembrane protein syntaxin-1A and the palmitoylated soluble protein SNAP-25. Previously, we explored interactions that promote the formation of syntaxin-1A clusters in membranes. Cholesterol activates clustering in native and model membranes, and its depletion in neuroendocrine cells results in a homogeneous distribution of the protein. However, as little as 1 mol % phosphatidylinositol 4,5-bisphosphate (PI-4,5-P(2)) or 20 mol % phosphatidylserine was found to disperse syntaxin-1A clusters [Murray, D. H., and Tamm, L. K. (2009) Biochemistry 48, 4617-4625]. Strong evidence suggests that syntaxin-1A and its synaptic vesicle cognate synaptobrevin both interact directly with PI-4,5-P(2) and that this interaction activates fusion. However, the molecular details of this interaction and its relationship to the partial dispersion of syntaxin-1A clusters remain largely unexplored. Hence, we mutated the polybasic juxtamembrane motif of syntaxin-1A and found several residues that partially or fully abrogate the electrostatic interaction with PI-4,5-P(2). We further show that even in the presence of physiological concentrations of phosphatidylserine, the PI-4,5-P(2)-syntaxin interaction is sufficiently strong to disrupt syntaxin-1A clustering. The stereochemistry of PI-4,5-P(2) is not critical for this interaction as other polyphosphoinositides have similar effects. Forming an acceptor SNARE complex between syntaxin-1A and SNAP-25 weakens but does not abrogate cholesterol/PI-4,5-P(2)-controlled cluster formation. Potential consequences of these interactions with respect to synaptic vesicle fusion are discussed.

A Matched Comparison of the Long-Term Outcomes of Cemented and Cementless Total Knee Replacements: An Analysis from the National Joint Registry of England, Wales, Northern Ireland and the Isle of Man.

BACKGROUND: Total knee replacements (TKRs) can be implanted with or without the use of cement. It is currently uncertain how cemented and cementless TKRs compare overall and in different age groups of the population in the long term. METHODS: The National Joint Registry collects information on knee replacements inserted in England, Wales, Northern Ireland, and the Isle of Man and was linked for multiple confounders to the National Health Service Hospital Episode Statistics database. With use of propensity score matching techniques, 44,954 cemented and cementless TKRs were compared. Regression models were used to compare the outcomes of revision, reoperation, and mortality both overall and in different age strata. RESULTS: The 10-year implant survival rate with revision as the end point for cemented and cementless TKRs was 96.0% and 95.5%, respectively (hazard ratio [HR] = 1.14; p = 0.01). The 10-year survival rate with reoperation as the end point was 82.7% and 81.4%, respectively (HR = 1.08; p = 0.001). The rate of revision for pain was higher for cementless TKRs (0.5% [cemented] compared with 0.7% [cementless]; p = 0.002), but the rate of revision for infection was lower (0.7% [cemented] compared with 0.5% [cementless]; p = 0.003). No significant interactions with age existed for the outcomes of revision (p = 0.24), reoperation (p = 0.30), or mortality (p = 0.58). CONCLUSIONS: We found that matched cemented and cementless TKRs both have 10-year implant survival rates of >95%. Cementless TKRs had a higher revision rate (absolute difference, 0.5%) and reoperation rate (absolute difference, 1.3%). The rate of revision for infection was lower in the cementless group, although the rate of revision for pain was higher. Age did not significantly affect the relative performances. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Monitoring Ravulizumab effect on complement assays.

Ravulizumab is a new C5 inhibitor therapeutic monoclonal antibody with a longer half-life than eculizumab. Monitoring complete complement blockade by eculizumab has allowed personalized therapy in specific settings. Similar action is expected with ravulizumab. Ravulizumab has 4 different amino acids from eculizumab, which allow greater affinity for the FcRn immunoglobulin receptor and change the affinity of the molecule for C5. Here we investigate if clinical lab tests traditionally used to monitor complement blockade for eculizumab are appropriate for monitoring complement blockade caused by ravulizumab. De-identified serum samples with known normal complement activity were spiked with increasing amounts of ravulizumab, from zero to 1000 µg/mL. Measurement of classical pathway function (CH50) and C5 function using a liposome method (Wako Diagnostics) showed >50% complement inhibition starting with 50 µg/mL of ravulizumab, but inhibition >95% of complement activity was not achieved, with residual measurements of 11% at 700 µg/mL. In contrast, measurement of alternative pathway function using an ELISA (AH50, Wieslab) showed alternative pathway function inhibition of 80% at 50 µg/mL of ravulizumab and > 95% at 200 µg/mL, which is consistent with expected therapeutic concentrations of ravulizumab >175 µg/mL. If replicated in patient sera, AH50 could be a suitable therapeutic monitoring tool.

Citric acid functionalized nitinol stent surface promotes endothelial cell healing.

While drug-eluting stents containing anti-proliferative agents inhibit proliferation of smooth muscle cells (SMCs), they also delay the regrowth of the endothelial cells which can result in subsequent development of restenosis. Acidic extracellular environments promote cell anchorage and migration by inducing conformational change in integrins, the main cell adhesion proteins. This study addresses the feasibility of a citric acid (CA) functionalized nitinol stent for improving vascular biocompatibility, specifically enhancing endothelialization. CA functionalized nitinol vascular stents are compared to commercial bare metal (Zilver Flex) and paclitaxel eluting stents (Zilver PTX) in terms of re-endothelialization. To study the effect of stent coatings, a stent conditioned media methodology was developed in an attempt to represent in vivo conditions. Overall, distinct advantages of the CA functionalized nitinol stent over commercial Zilver PTX DES and Zilver Flex BMS stents in terms of endothelial cell adhesion, migration, and proliferation are reported. These novel findings indicate the potential of a CA functionalized stent to serve as a bioactive and therapeutic surface for re-endothelialization, perhaps in combination with a SMC proliferation inhibitor coating, to prevent restenosis.