Lower Risk of Revision With 32- and 36-Millimeter Femoral Heads Compared With 28-mm Heads in Primary Total Hip Arthroplasty: A Comparative Single-Center Study (10,104 Hips).

BACKGROUND: We aimed to compare the clinical outcomes of different head sizes (28-, 32-, and 36- millimeter) in primary total hip arthroplasty (THA) at mean 6 years follow-up (range, 1 to 17.5 years). METHODS: This was a retrospective consecutive study of primary THA at our institution (2003 to 2019). Demographic and surgical data were collected. The primary outcome measures were all-cause revision, revision for dislocation, and all-cause revision excluding dislocation. Continuous descriptive statistics used means, median values, ranges, and 95% confidence intervals, where appropriate. Kaplan-Meier survival curves were used to estimate time to revision. Cox proportional hazard regression analyses were used to compare revision rates between the femoral head size groups. Adjustments were made for age at surgery, sex, primary diagnosis, American Society of Anesthesiologists score, articulation type, and fixation methods. There were 10,104 primary THAs included; median age was 69 years (range, 13 to 101) with 61.5% women. A posterior approach was performed in 71.6%. There were 3,295 hips with 28-mm heads (32.6%), 4,858 (48.1%) with 32-mm heads, and 1,951 (19.3%) with 36-mm heads. RESULTS: Overall rate of revision was 1.7% with the lowest rate recorded for the 36-mm group (2.7 versus 1.3 versus 1.1%). Cox regression analyses showed a decreased risk of all-cause revision for 32 and 36-mm head sizes as compared to 28-mm; this was statistically significant for the 32-mm group (P = .01). Risk of revision for dislocation was significantly reduced in both 32-mm (P = .03) and 36-mm (P = .03) head sizes. Analysis of all cause revision excluding dislocation showed no significant differences between head sizes. CONCLUSIONS: We found a significantly reduced risk of revision for all causes, but particularly revision for dislocation with larger head sizes. Concerns regarding increased risk of early revision for aseptic loosening, polyethylene wear, or taper corrosion with larger heads appear to be unfounded in this cohort of 10,104 patients with up to 17 years follow-up.

Overcoming insecticide resistance through computational inhibitor design.

Insecticides allow control of agricultural pests and disease vectors and are vital for global food security and health. The evolution of resistance to insecticides, such as organophosphates (OPs), is a serious and growing concern. OP resistance often involves sequestration or hydrolysis of OPs by carboxylesterases. Inhibiting carboxylesterases could, therefore, restore the effectiveness of OPs for which resistance has evolved. Here, we use covalent virtual screening to produce nano-/picomolar boronic acid inhibitors of the carboxylesterase αE7 from the agricultural pest Lucilia cuprina as well as a common Gly137Asp αE7 mutant that confers OP resistance. These inhibitors, with high selectivity against human acetylcholinesterase and low to no toxicity in human cells and in mice, act synergistically with the OPs diazinon and malathion to reduce the amount of OP required to kill L. cuprina by up to 16-fold and abolish resistance. The compounds exhibit broad utility in significantly potentiating another OP, chlorpyrifos, against the common pest, the peach-potato aphid (Myzus persicae). These compounds represent a solution to OP resistance as well as to environmental concerns regarding overuse of OPs, allowing significant reduction of use without compromising efficacy.

High Survivorship of Short-Cemented Femoral Stems in Condylar Revision Total Knee Arthroplasty Without Significant Metaphyseal Bone Loss: Minimum 5-Year Follow-Up.

BACKGROUND: We aimed to evaluate the outcomes of hybrid fixation technique in condylar revision total knee arthroplasty (rTKA) using cementless metaphyseal tibial sleeves and short-cemented femoral stems with a rotating platform articulation. METHODS: Retrospective consecutive study of all condylar rTKAs with a cemented femoral stem between 2009 and 2016 was conducted. Patients were identified using a local prospective database and linkable data obtained from the National Joint Registry for rTKA. Demographic, clinical, and surgical data were collected from patients' electronic health records. The primary outcome measure was mechanical failure and implant survivorship using a nationally collected data, complications, re-operations, and "any-cause revision" were also recorded. RESULTS: There were 72 consecutive patients (72 knees) with minimum 5-year follow-up: 33 (45.8%) females and 39 (54.2%) males with a median age of 70 years (range 47-88). The indication for revision surgery was aseptic loosening (n = 34, 47.2%), instability (n = 17, 23.6%), infection (n = 14, 19.5%) with 10 patients having 2-stage approach and 4 patients with single-stage approach, stiffness (n = 4, 5.6%), and malalignment (n = 3, 4.1%). At mean follow-up of 6.87 years (median 6.7; range 5-11.8), only 2 patients required revision for infection. Using "any-cause implant revision" as an end point, implant survivorship for this construct was 97.2% at median 6.7 years. To date, none of the femoral stems have been revised for mechanical failure. CONCLUSION: In rTKA with good femoral condylar bone stock, we have shown excellent survivorship with a short-cemented femoral stem, in conjunction with a mobile-bearing and a tibial sleeve. This has the advantage of reducing the length of the revision construct of this complex surgery. LEVEL OF EVIDENCE: Level IV.

Septic Revision Total Knee Arthroplasty Is Associated With Significantly Higher Mortality Than Aseptic Revisions: Long-Term Single-Center Study (1254 Patients).

BACKGROUND: The aim of this study is to examine the differences in long-term mortality rates between septic and aseptic revision total knee arthroplasty (rTKA) in a single specialist center over 17-year period. METHODS: Retrospective consecutive study of all patients who underwent rTKA at our tertiary center between 2003 and 2019 was carried out. Revisions were classified as septic or aseptic. We identified patients' age, gender, American Society of Anesthesiologists grade, and body mass index. The primary outcome measure was all-cause mortality at 5 years, 10 years, and over the whole study period of 17 years. Death was identified through both local hospital electronic databases and linked data from the National Joint Registry/NHS Personal Demographic Service. Kaplan-Meier survival curves were used to estimate time to death. RESULTS: In total, 1298 consecutive knee revisions were performed on 1254 patients (44 bilateral revisions) with 985 aseptic revisions in 945 patients (75.4%) and 313 septic revisions in 309 patients (24.6%). Average age was 70.6 years (range 27-95) with 720 females (57.4%). Septic revisions had higher mortality rates; patients' survivorship for septic vs aseptic revisions was 77.6% vs 89.5% at 5 years, 68.7% vs 80.2% at 10 years, and 66.1% vs 75.0% at 17 years; these differences were all statistically significant (P < .0001). The unadjusted 10-year risk ratio of death after septic revision was 1.59 (95% confidence interval 1.29-1.96) compared to aseptic revisions. CONCLUSION: rTKA performed for infection is associated with significantly higher long-term mortality at all time points compared with aseptic revision surgery. LEVEL OF EVIDENCE: Level IV.

Metaphyseal Sleeves in Revision Total Knee Arthroplasty Provide Reliable Fixation and Excellent Medium to Long-Term Implant Survivorship.

BACKGROUND: Addressing bone loss and securing implant fixation can be challenging in revision total knee arthroplasty (TKA). We present the results of a large series of revision TKAs using a metaphyseal sleeve. METHODS: We retrospectively analyzed 319 revision TKAs with the use of a metaphyseal sleeve that had been followed up for at least 2 years, using a prospectively collected database. The mean follow-up was 91 months, and 73 patients were followed up for more than 10 years. RESULTS: Implant survivorship was 99.1% at 3 years, 98.7% at 5 years, and 97.8% at 10 years. No metaphyseal sleeve was revised for aseptic loosening. Final radiographic review showed that there were radiolucent lines present in 2.8% of tibial sleeves and 2.7% of femoral sleeves; none of these had progressed and none were revised. About 3.7% of tibial sleeves subsided more than 1 mm compared with the immediate postoperative X-ray but all stabilized and none were revised. CONCLUSION: Use of a metaphyseal sleeve in revision TKA is associated with excellent survivorship and radiographic outcome in the medium to long term.

Is there an increased revision rate due to early tibial component loosening with a modern total knee arthroplasty design? A retrospective analysis from a large volume arthroplasty centre.

BACKGROUND: The Attune TKR was introduced in 2011 as a successor to its predicate design The PFC Sigma. However, following reports of early failures, there are ongoing concerns related to increased loosening rates. Given the concerns, this study aimed to compare revision rates of the Attune implant to an established predicate, and other implant designs used in a high-volume arthroplasty center. METHODS: We identified 10,202 patients who underwent primary cemented TKR at our institution with a minimum of 1 year follow-up, involving 2406 Attune TKR (557 S +), 4642 PFC TKR, 3154 other designs. Primary outcomes were revision for all-causes, aseptic loosening of any component, and aseptic tibial loosening. Kaplan-Meier survival and Cox regression models were used to compare groups. Matched cohorts were selected for radiographic analysis. RESULTS: 308 knees were revised. The Attune cohort had the lowest risk of revision, with a rate of 2.98 per 1000 implant-years while the PFC and All Other Implant groups had a rate of 3.15 and 4.4 respectively. Aseptic loosing was the most common cause for revision, with 76% (65/88) involving the tibia. Survival analysis showed no significant differences between the Attune and other cohorts. Radiolucent lines were detected in 7.1% of the Attune S + group, 6.8% of the standard Attune group, and 6.3% of the PFC group, with no significant differences found between them. CONCLUSION: This study represents the largest non-registry review of the Attune TKR in comparison to a predicate and other designs. There was no significant increased revision rate for all-cause revision or aseptic loosening, or peri-implant radiolucencies. It appears that increased loosening may not be as concerning as originally thought. LEVEL OF EVIDENCE: Level III.

Satisfactory medium- to long-term outcomes of cemented rotating hinge prosthesis in revision total knee arthroplasty.

Aims: The aim of this study was to evaluate medium- to long-term outcomes and complications of the Stanmore Modular Individualised Lower Extremity System (SMILES) rotating hinge implant in revision total knee arthroplasty (rTKA) at a tertiary unit. It is hypothesized that this fully cemented construct leads to satisfactory clinical outcomes. Methods: A retrospective consecutive study of all patients who underwent a rTKA using the fully cemented SMILES rotating hinge prosthesis between 2005 to 2018. Outcome measures included aseptic loosening, reoperations, revision for any cause, complications, and survivorship. Patients and implant survivorship data were identified through both prospectively collected local hospital electronic databases and linked data from the National Joint Registry/NHS Personal Demographic Service. Kaplan-Meier survival analysis was used at ten years. Results: Overall, 69 consecutive patients (69 knees) were included with a median age of 78 years (interquartile range 69 to 84), and there were 46 females (66.7%). Indications were septic revisions in 26 (37.7%), and aseptic aetiology in the remining 43 (62.3%). The mean follow-up was 9.7 years (4 to 18), and the overall complication was rate was 7.24%, all with patellofemoral complications. Failure rate with 'any cause revision' was 5.8%. There was one case of aseptic loosening of the femoral component. At ten years, 17/69 patients (24.63%) had died, and implant survivorship was 92.2%. Conclusion: In our experience, the SMILES rotating hinge prosthesis achieves satisfactory long-term outcomes with ten-year implant survivorship of 92.2% and a patellofemoral complication rate of 7.24%.

The impact of a revision arthroplasty network on patient outcomes.

Aims: Revision total knee arthroplasty (rTKA) and revision total hip arthroplasty (rTHA) are complex procedures with higher rates of re-revision, complications, and mortality compared to primary TKA and THA. We report the effects of the establishment of a revision arthroplasty network (the East Midlands Specialist Orthopaedic Network; EMSON) on outcomes of rTKA and rTHA. Methods: The revision arthroplasty network was established in January 2015 and covered five hospitals in the Nottinghamshire and Lincolnshire areas of the East Midlands of England. This comprises a collaborative weekly multidisciplinary meeting where upcoming rTKA and rTHA procedures are discussed, and a plan agreed. Using the Hospital Episode Statistics database, revision procedures carried out between April 2011 and March 2018 (allowing two-year follow-up) from the five network hospitals were compared to all other hospitals in England. Age, sex, and mean Hospital Frailty Risk scores were used as covariates. The primary outcome was re-revision surgery within one year of the index revision. Secondary outcomes were re-revision surgery within two years, any complication within one and two years, and median length of hospital stay. Results: A total of 57,621 rTHA and 33,828 rTKA procedures were performed across England, of which 1,485 (2.6%) and 1,028 (3.0%), respectively, were conducted within the network. Re-revision rates within one year for rTHA were 7.3% and 6.0%, and for rTKA were 11.6% and 7.4% pre- and postintervention, respectively, within the network. This compares to a pre-to-post change from 7.4% to 6.8% for rTHA and from 11.7% to 9.7% for rTKA for the rest of England. In comparative interrupted time-series analysis for rTKA there was a significant immediate improvement in one-year re-revision rates for the revision network compared to the rest of England (p = 0.024), but no significant change for rTHA (p = 0.504). For the secondary outcomes studied, there was a significant improvement in trend for one- and two-year complication rates for rTHA for the revision network compared to the rest of England. Conclusion: Re-revision rates for rTKA and complication rates for rTHA improved significantly at one and two years with the introduction of a revision arthroplasty network, when compared to the rest of England. Most of the outcomes studied improved to a greater extent in the network hospitals compared to the rest of England when comparing the pre- and postintervention periods.

Allograft Extensor Mechanism Reconstruction in Salvage Revision Knee Arthroplasty: Surgical Technique.

Although extensor mechanism failure remains a catastrophic complication of knee arthroplasty, there are a number of contemporary techniques with reasonable outcomes that restore function. Chronic failures require advanced reconstruction techniques. Similar complication rates have been reported for the use of autografts, allografts, or mesh reconstructions. Here, we describe our surgical technique in allograft extensor mechanism reconstruction for chronic failures in salvage revision knee arthroplasty using a complete extensor mechanism allograft with a modified proximal fixation and case demonstrations.

Removal of Metaphyseal Sleeves in Revision Knee Arthroplasty: Surgical Technique.

The use of metaphyseal sleeves in revision total knee arthroplasty has gained popularity with numerous clinical series demonstrating excellent osseointegration and survivorship at medium- to long-term follow up. Once osseointegrated, sleeves provide excellent biological fixation and are difficult to remove. Here, we describe our surgical technique and sequence in removing metaphyseal sleeves in contemporary revision knee systems with case demonstrations.

High ten-year implant survivorship and low patellofemoral complication rate for S-ROM rotating-hinge implants in revision total knee arthroplasty : a single-centre study.

AIMS: The aim of this study was to evaluate medium-term outcomes and complications of the S-ROM NOILES Rotating Hinge Knee System (DePuy, USA) in revision total knee arthroplasty (rTKA) at a tertiary unit. METHODS: A retrospective consecutive study of all patients who underwent a rTKA using this implant from January 2005 to December 2018. Outcome measures included reoperations, revision for any cause, complications, and survivorship. Patients and implant survivorship data were identified through both local hospital electronic databases and linked data from the National Joint Registry/NHS Personal Demographic Service. Kaplan-Meier survival analysis was used at ten years. RESULTS: A total of 89 consecutive patients (89 knees) were included with 47 females (52.8%) and a median age of 74 years (interquartile range 66 to 79). The main indications were aseptic loosening with instability (39.4%; n = 35) and infection (37.1%; n = 33) with the majority of patients managed through two-stage approach. The mean follow-up was 7.4 years (2 to 16). The overall rate of reoperation, for any cause, was 10.1% (n = 9) with a rate of implant revision of 6.7% (n = 6). Only two cases required surgery for patellofemoral complications. Kaplan-Meier implant-survivorship analysis was 93.3% at ten years, using revision for any cause as an endpoint. CONCLUSION: This implant achieved high ten-year survivorship with a low complication rate, particularly patellofemoral complications. These can be avoided by ensuring central patella tracking and appropriate tension of the patellofemoral joint in this posterior hinge design. Cite this article: Bone Jt Open 2022;3(3):205-210.

Extensor mechanism failure in total knee arthroplasty.

Extensor mechanism failure in total knee arthroplasty (TKA) can present as quadriceps tendon rupture, patella fracture or patella tendon rupture.Component malrotation, excessive joint line elevation and previous lateral release are some of the risk factors contributing to extensor mechanism failure in TKA.Partial quadriceps tendon rupture and undisplaced patella fracture with intact extensor mechanism function can be treated conservatively.Extensor mechanism failure in TKA with disruption of the extensor mechanism function should be treated operatively as it is associated with poor function and extensor lag.It is recommended that acute repair of patella or quadriceps tendon rupture are augmented due to the high risk of re-rupture.Chronic ruptures of the extensor mechanism must be reconstructed as repair has a high failure rate. Reconstruction can be performed using autograft, allograft or synthetic graft. Cite this article: EFORT Open Rev 2021;6:181-188. DOI: 10.1302/2058-5241.6.200119.

Outcomes of Salvage Endoprostheses in Revision Total Knee Arthroplasty for Infection and Aseptic Loosening: Experience of a Specialist Centre.

BACKGROUND: We aimed to evaluate the clinical and radiographic outcomes of complex salvage knee revision arthroplasty (rTKA) using endoprostheses with segmental bone loss. METHODS: A consecutive study of patients who underwent salvage distal femoral replacement (DFR) or proximal tibial replacement (PTR) with a minimum 2- year follow-up (2005-2018). Patients who had acute DFR for periprosthetic fractures were excluded. Clinical outcomes, complications, reoperations, revision for any cause, loosening and mortality data were collected. Knee Society Score (KSS) at final follow up was used as a patient-reported-outcome-measure. RESULTS: Thirty three consecutive patients were included; average age 79.6 years (range 58-89); 15 males/18 females. All had AORI-III massive bone defects and were reconstructed using DFRs; 6 patients had concurrent PTRs. The indication for salvage rTKA was infection in 16/33 (48.5%) and aseptic-loosening in the remaining 17 patients (51.5%). Complications rate was 12.1%; two patients had significant extensor lag; 1 patella dislocation and one recurrent infection. Median follow-up was 5 years (range 2-15) with median arc of flexion- extension of 100° (range 60-120). KSS was available for 29/33 patients with an average of 73.2 (range 51-86). Patients with infection as their indication had poorer KSS scores (66.1 vs. 81.6; P < 0.0001). Eleven patients have died at median 4 years postoperatively (range 2-7) for unrelated causes, none of the components have been revised to date with overall 80% patients' survivorship at 5 years. CONCLUSIONS: The use of endoprostheses in salvage knee arthroplasty led to satisfactory medium-term clinical outcomes with an acceptable complication rate for this challenging group of patients with poorer functional scores for infection compared to aseptic loosening. LEVEL OF EVIDENCE: Level IV.

Distal Femoral Replacements for Acute Comminuted Periprosthetic Knee Fractures: Satisfactory Clinical Outcomes at Medium-Term Follow-up.

BACKGROUND: Fracture fixation techniques of comminuted periprosthetic distal femoral fractures have high risk of complications. The aim of this study was to evaluate short- to medium-term outcomes of comminuted periprosthetic distal femoral fractures treated with distal femoral replacements (DFR) at a tertiary arthroplasty unit. METHODS: Retrospective consecutive study of all patients who underwent DFR for periprosthetic fractures with minimum 2-year follow-up between 2010 and 2018. Clinical outcomes, surgical complications, revision for any cause, loosening, Knee Society Score and mortality data were collected at final follow-up. RESULTS: Thirty patients with average age 81 years (range, 65-90; 6 males and 24 females) were included. All had comminuted fractures (Rorabeck type-2/3). All patients had cemented DFRs. Three patients (10%) with multiple comorbidities died postoperatively. Average time from admission to being fit for discharge was 9 days (range, 3-14). Clinical outcomes and follow-up were available for 27 patients with a median follow-up duration of 4 years (2-13 years). Complication rate was 7.4% with one reoperation, change of polyethylene insert. None of the components have been revised to date. Average Knee Society Score at final follow-up was 78 (range, 57-92) with median arc of motion flexion-extension being 100° (range, 60°-125°). CONCLUSIONS: In our experience, DFRs for comminuted periprosthetic fractures allow immediate mobilization and rehabilitation leading to satisfactory clinical outcomes with low complication rate for this challenging group of patients. LEVEL OF EVIDENCE: level IV.

Role of metaphyseal sleeves in revision total knee arthroplasty: Rationale, indications and long-term outcomes.

Metaphyseal sleeves have become an integral part of surgeons' armamentarium in dealing with complex revision knee arthroplasty. They offer the advantages of addressing bone defects with biological fixation techniques, efficient surgical preparation providing a stable tibial platform which optimises joint line positioning and gap balancing leading to excellent long-term survivorship and clinical outcomes. Here, we review the concept of metaphyseal fixation, indications of metaphyseal sleeves and their limitations with our surgical tips on how to remove well-fixed sleeves. We also present our tertiary experience and review clinical outcome studies of metaphyseal sleeves in revision knee arthroplasty literature.

Outcomes of single- and two-stage revision total knee arthroplasty for chronic periprosthetic joint infection : long-term outcomes of changing clinical practice in a specialist centre.

AIMS: Single-stage revision total knee arthroplasty (rTKA) is gaining popularity in treating chronic periprosthetic joint infections (PJIs). We have introduced this approach to our clinical practice and sought to evaluate rates of reinfection and re-revision, along with predictors of failure of both single- and two-stage rTKA for chronic PJI. METHODS: A retrospective comparative cohort study of all rTKAs for chronic PJI between 1 April 2003 and 31 December 2018 was undertaken using prospective databases. Patients with acute infections were excluded; rTKAs were classified as single-stage, stage 1, or stage 2 of two-stage revision. The primary outcome measure was failure to eradicate or recurrent infection. Variables evaluated for failure by regression analysis included age, BMI, American Society of Anesthesiologists grade, infecting organisms, and the presence of a sinus. Patient survivorship was also compared between the groups. RESULTS: A total of 292 consecutive first-time rTKAs for chronic PJI were included: 82 single-stage (28.1%); and 210 two-stage (71.9%) revisions. The mean age was 71 years (27 to 90), with 165 females (57.4%), and a mean BMI of 30.9 kg/m2 (20 to 53). Significantly more patients with a known infecting organism were in the single-stage group (93.9% vs 80.47%; p = 0.004). The infecting organism was identified preoperatively in 246 cases (84.2%). At a mean follow-up of 6.3 years (2.0 to 17.6), the failure rate was 6.1% in the single-stage, and 12% in the two-stage groups. All failures occurred within four years of treatment. The presence of a sinus was an independent risk factor for failure (odds ratio (OR) 4.97; 95% confidence interval (CI) 1.593 to 15.505; p = 0.006), as well as age > 80 years (OR 5.962; 95% CI 1.156 to 30.73; p = 0.033). The ten-year patient survivorship rate was 72% in the single-stage group compared with 70.5% in the two-stage group. This difference was not significant (p = 0.517). CONCLUSION: Single-stage rTKA is an effective strategy with a high success rate comparable to two-stage approach in appropriately selected patients. Cite this article: Bone Joint J 2021;103-B(8):1373-1379.

A Systematic Review of Randomized Controlled Trials in Anterior Cruciate Ligament Reconstruction: Standard Techniques Are Comparable (299 Trials With 25,816 Patients).

PURPOSE: To provide an overview of all published randomized controlled trials (RCTs) in anterior cruciate ligament reconstruction (ACLR) summarizing the available evidence. METHODS: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched the Cochrane FIGCentral Register of Controlled Trials, Ovid MEDLINE, and Embase for RCTs of ACLR from their inception to August 26, 2020. Outcome measure was whether RCTs reported statistically significant findings. RCTs were then classified according to their intervention groups in a narrative synthesis of the evidence. RESULTS: In total, 299 RCTs met the inclusion criteria and were included with a total number of 25,186 patients. Only 30 RCTs (10%) reported significant differences between the intervention and the control groups. These included 101 RCTs on grafts, 20 RCTs on tunnel placements, 48 RCTs on graft fixation, 42 RCTs on single-bundle compared with double-bundle reconstructions, 11 RCTs on additional procedures, 11 RCTs on graft tensioning, 5 RCTs on timing of surgery, 25 RCTs on technical variations from standard techniques, 6 RCTs on ACL repair, 5 RCTs on navigation, 16 RCTs on perioperative management, and 9 RCTs on other aspects of ACLR. Only 14 RCTs (4.7%) reported outcomes beyond 10 years with greater allograft failures compared with autografts, high incidence of osteoarthritic changes in reconstructed knees (22%-100%), with no significant differences in outcomes between bioabsorbable or metal screws for graft fixation, patellar versus hamstrings or single- versus double-bundle reconstructions. CONCLUSIONS: The evidence indicates that a standard arthroscopic single- or double-bundle ACLR with hamstrings/patella autografts, transportal technique, and fixation techniques familiar to the surgeon leads to comparable results. This evidence offers surgeons the flexibility to use standard and cost-effective techniques and achieve comparable outcomes. LEVEL OF EVIDENCE: Level II; systematic review of Level I-II randomized controlled trials.

Synthesis, binding and bioactivity of gamma-methylene gamma-lactam ecdysone receptor ligands: advantages of QSAR models for flexible receptors.

Nuclear hormone receptors, such as the ecdysone receptor, often display a large amount of induced fit to ligands. The size and shape of the binding pocket in the EcR subunit changes markedly on ligand binding, making modelling methods such as docking extremely challenging. It is, however, possible to generate excellent 3D QSAR models for a given type of ligand, suggesting that the receptor adopts a relatively restricted number of binding site configurations or 'attractors'. We describe the synthesis, in vitro binding and selected in vivo toxicity data for gamma-methylene gamma-lactams, a new class of high-affinity ligands for ecdysone receptors from Bovicola ovis (Phthiraptera) and Lucilia cuprina (Diptera). The results of a 3D QSAR study of the binding of methylene lactams to recombinant ecdysone receptor protein suggest that this class of ligands is indeed recognised by a single conformation of the EcR binding pocket.

A New Total Knee Arthroplasty Design Has Significantly Better Early Implant Survivorship than a Previous Gold-Standard Design-A Retrospective Analysis of 1,000 Cases.

This study examined whether a new total knee arthroplasty (TKA) prosthesis improved implant survivorship and reoperation rates compared with a gold-standard, established TKA. A retrospective analysis of the first 500 consecutive new TKAs was compared with a consecutive series of the last 500 currently available TKAs performed by a single senior surgeon in one center. The primary outcome measure was revision of the femoral, tibial, or patellar component. A secondary outcome was reoperation for any reason. The new-TKA group had a significantly reduced revision rate at up to 5 years follow-up (p = 0.02). Reoperation rates for any reason were similar (p = 0.3). The new TKA design has a significantly better early revision rate compared with a currently available gold-standard TKA. This is the largest study of 1,000 cases comparing a new TKA design with a currently available design with excellent midterm results. It demonstrates very favorable early clinical results for the new TKA design, providing reassurance for patients, surgeons, and regulatory bodies.

Influence of environmental factors on the detection of blood in sheep faeces using visible-near-infrared spectroscopy as a measure of Haemonchus contortus infection.

BACKGROUND: Existing diagnostic methods for the parasitic gastrointestinal nematode, Haemonchus contortus, are time consuming and require specialised expertise, limiting their utility in the field. A practical, on-farm diagnostic tool could facilitate timely treatment decisions, thereby preventing losses in production and flock welfare. We previously demonstrated the ability of visible-near-infrared (Vis-NIR) spectroscopy to detect and quantify blood in sheep faeces with high accuracy. Here we report our investigation of whether variation in sheep type and environment affect the prediction accuracy of Vis-NIR spectroscopy in quantifying blood in faeces. METHODS: Visible-NIR spectra were obtained from worm-free sheep faeces collected from different environments and sheep types in South Australia (SA) and New South Wales, Australia and spiked with various sheep blood concentrations. Spectra were analysed using principal component analysis (PCA), and calibration models were built around the haemoglobin (Hb) wavelength region (387-609 nm) using partial least squares regression. Models were used to predict Hb concentrations in spiked faeces from SA and naturally infected sheep faeces from Queensland (QLD). Samples from QLD were quantified using Hemastix® test strip and FAMACHA© diagnostic test scores. RESULTS: Principal component analysis showed that location, class of sheep and pooled versus individual samples were factors affecting the Hb predictions. The models successfully differentiated 'healthy' SA samples from those requiring anthelmintic treatment with moderate to good prediction accuracy (sensitivity 57-94%, specificity 44-79%). The models were not predictive for blood in the naturally infected QLD samples, which may be due in part to variability of faecal background and blood chemistry between samples, or the difference in validation methods used for blood quantification. PCA of the QLD samples, however, identified a difference between samples containing high and low quantities of blood. CONCLUSION: This study demonstrates the potential of Vis-NIR spectroscopy for estimating blood concentration in faeces from various types of sheep and environmental backgrounds. However, the calibration models developed here did not capture sufficient environmental variation to accurately predict Hb in faeces collected from environments different to those used in the calibration model. Consequently, it will be necessary to establish models that incorporate samples that are more representative of areas where H. contortus is endemic.