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Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 52 - 52
1 Mar 2021
Harris A O'Grady C Sensiba P Vandenneucker H Huang B Cates H Christen B Hur J Marra D Malcorps J Kopjar B
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Patients ≤ 55 years have a high primary TKA revision rate compared to patients >55 years. Guided motion knee devices are commonly used in younger patients yet outcomes remain unknown. In this sub-group analysis of a large multicenter study, 254 TKAs with a second-generation guided motion knee implant were performed between 2011–2017 in 202 patients ≤ 55 years at seven US and three European sites. Revision rates were compared with Australian Joint Registry (AOANJRR) 2017 data. Average age 49.7 (range 18–54); 56.4% females; average BMI 34 kg/m2; 67.1% obese; patellae resurfaced in 98.4%. Average follow-up 4.2 years; longest follow-up six years; 27.5% followed-up for ≥ five years. Of eight revisions: total revision (one), tibial plate replacements (three), tibial insert exchanges (four). One tibial plate revision re-revised to total revision. Revision indications were mechanical loosening (n=2), infection (n=3), peri-prosthetic fracture (n=1), and instability (n=2). The Kaplan-Meier revision estimate was 3.4% (95% C.I. 1.7% to 6.7%) at five years compared to AOANJRR rate of 6.9%. There was no differential risk by sex. The revision rate of the second-generation guided motion knee system is lower in younger patients compared to registry controls.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 51 - 51
1 Mar 2021
Harris A O'Grady C Sensiba P Vandenneucker H Huang B Cates H Christen B Hur J Marra D Malcorps J Kopjar B
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Outcomes for guided motion primary total knee arthroplasty (TKA) in obese patients are unknown. 1,684 consecutive patients underwent 2,059 primary TKAs with a second-generation guided motion implant between 2011–2017 at three European and seven US sites. Of 2,003 (97.3%) TKAs in 1,644 patients with BMI data: average age 64.5 years; 58.4% females; average BMI 32.5 kg/m2; 13.4% had BMI ≥ 40 kg/m2. Subjects with BMI ≥ 40 kg/m2 had longest length of hospital stay (LOS) at European sites; LOS similar at US sites. Subjects with BMI ≥ 40 kg/m2 (P=0.0349) had longest surgery duration. BMI ≥ 40 kg/m2 had more re-hospitalizations or post-TKA reoperations than BMI < 40 kg/m2 (12.7% and 9.2% at five-year post-TKA, P<0.0495). Surgery duration and long-term complication rates are higher in patients with BMI ≥ 40 kg/m2, but device revision risk is not elevated.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_1 | Pages 96 - 96
1 Feb 2020
Harris A Christen B Malcorps J O'Grady C Sensiba P Vandenneucker H Huang B Cates H Hur J Marra D Kopjar B
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Introduction

Patients ≤ 55 years have a high primary TKA revision rate compared to patients >55 years. Guided motion knee devices are commonly used in younger patients yet outcomes remain unknown.

Materials and Methods

In this sub-group analysis of a large multicenter study, 254 TKAs with a second-generation guided motion knee implant (Journey II Bi-Cruciate Stabilized Knee System, Smith & Nephew, Inc., Memphis) were performed between 2011–2017 in 202 patients ≤ 55 years at seven US and three European sites. Revision rates were compared with Australian Joint Registry (AOANJRR) 2017 data.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_1 | Pages 95 - 95
1 Feb 2020
Harris A Christen B Malcorps J O'Grady C Sensiba P Vandenneucker H Huang B Cates H Hur J Marra D Kopjar B
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Introduction/Aim

Outcomes for guided motion primary total knee arthroplasty (TKA) in obese patients are unknown.

Materials and Methods

1,684 consecutive patients underwent 2,059 primary TKAs with a second-generation guided motion implant (Journey II Bi-Cruciate Stabilized Knee System, Smith & Nephew, Inc., Memphis) between 2011–2017 at three European and seven US sites.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 197 - 197
1 Mar 2010
McEwen P Harris A Bell C
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A technical goal in total knee arthroplasty is the production of a neutral coronal plane mechanical axis. Errors may produce large mechanical axis deviations precipitating early implant failure. This study sought to test if measured distal femoral resection produced more accurate and consistent coronal alignment than arbitrarily set distal femoral resection.

Data from a cohort of 255 consecutive unselected primary total knee arthroplasties undertaken by the senior author (PM) was collected prospectively and independently assessed. In the first 167 cases distal femoral resection was arbitrarily set to 5 degrees of valgus. In the remaining 88 cases the distal femoral resection angle was determined on a preoperative long leg standing AP radiograph. Postoperative coronal alignment was measured on long leg standing AP radiograph in all cases.

The measured distal femoral valgus angle was between 4 and 7 degrees. An equal number measured either 5 or 6 degrees and accounted for 85% of the total number. Statistically insignificant improvements in mean axis and standard deviation were observed in the measured group: mean axis deviation −0.31 vs −0.51: p=0.17 (independent samples t test) and standard deviation 0.91 vs 1.09: p=0.055 (Levene test).

Acceptable coronal alignment in total knee arthroplasty can reliably be obtained with conventional instrumentation. Improvement in standard deviation with measured distal femoral valgus angle approaches statistical significance.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 292 - 292
1 May 2009
Kotwal R Harris A Wright A Hodgson P Hughes C Roberts S Richardson J Caterson B Dent C
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Introduction: Monoclonal antibodies (mAbs) recognizing linear sulphation motifs in keratan sulphate (KS) were first developed in the early 1980’s. Over the years, ELISAs using 5-D-4 or other related anti-KS mAbs have been used in many studies monitoring increased cartilage aggrecan degradation with the onset of degenerative joint diseases. However, whilst these studies have in general been useful for monitoring some aspects of disease progression (usually in parallel with other biomarker assays), many longitudinal studies have shown efficacy in only the transient (early, mid or late) stages of the degenerative joint disease process. During the onset of degenerative joint disease, the pathological tissue attempts to repair/regenerate the cartilage, the chondrocytes thus synthesizing cartilage aggrecan with KS substitution [and chondroitin sulphate (CS) isomer composition] that is more like that found in developing or immature cartilage. This immature cartilage aggrecan contains much less KS substitution with shorter chain size and less linear sulphation motifs. Thus, during the different stages of degenerative joint disease progression one would expect to find variable changes in different linear sulphation epitopes present in the serum or synovial fluids. The aim of this study was to investigate the use of several monoclonal antibodies that recognise different sulphation epitopes [high sulphation (5-D-4), low sulphation (1-B-4) and KS-stubs (BKS-1)] to see if patterns of their expression could be used to distinguish different stages of degenerative joint disease. We have also developed ELISAs using mAbs recognising the KS-proteoglycans, keratocan (Ker 1) and lumican (Lum 1) for their quantification as potential biomarkers of osteoarthritis.

Methods: Competitive ELISAs were developed using monoclonal antibodies (mAbs) 5-D-4, 1B4, BKS-1, Ker-1 and Lum-1. Bovine corneal KS-proteoglycans pre-treated with keratanase were used as both the coating antigen and “standard” antigen on the same ELISA plate. Blood, synovial fluid and cartilage samples (surgical waste) obtained from patients undergoing arthroplasty with different Kellgren & Lawrence grades were analysed.

Results and Discussion: 5-D-4 and BKS-1 showed similar inhibition curves and relative 50% inhibition points. However, the curve obtained with 1B4 indicated lower relative expression of 1B4 epitope. Analysis of serum and synovial fluid sample with 5-D-4 mAb showed the presence of the epitope in both samples, but there was significantly less KS in serum than in the synovial fluid. Our results show that competitive ELISA for quantification of several different KS sulphation or “stub” epitopes and two KS-proteoglycans can all be quantified and compared using the same experimental conditions. These studies are ongoing as part of an Arthritis Research Campaign (UK) funded study. In addition the data indicates that keratocan and lumican are also increased in their expression with the progression of disease. Future studies will be performed in an attempt to quantify increased keratocan and lumican expression as potential biomarkers of degenerative joint disease.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 219 - 220
1 Jul 2008
Deogaonkar K Kerr B Harris A Hughes C Roberts S Eisenstein S Evans R Dent C Caterson B
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Introduction: Several small leucine-rich proteoglycans (SLRPs) are involved in the regulation of collagen fibril size(s) in a variety of different soft and hard musculosk-eletal tissues. In the intervertebral disc (IvD) the major SLRPs involved in regulation of types I & II collagen fibril size are believed to be decorin, fibromodulin and lumican. Research into IvD degeneration and backpain is hampered by a lack of specific biomarkers to detect and monitor the disease process. We have discovered that two keratan sulphate (KS) substituted members of the SLRP family, Keratocan and Lumican (that are major KS-pro-teoglycans found in cornea) were unusually expressed in extracts from degenerative disc tissues.

Methods: Non-degenerate disc tissue (n=10) was obtained from 2 scoliosis patients and degenerate disc tissue from 11 patients undergoing surgery. The degenerate discs were graded using criteria described by Pfir-rman et al (Spine26: 1873; 2001). Tissue samples were extracted with 4M guanidine HCl and after dialysis subjected to SDS-PAGE and Western blot analyses using monoclonal antibodies that recognise epitopes on kera-tocan and lumican.

Results & Discussion: Keratocan was not found in the non-degenerate disc tissue but was present in all degenerate IvD tissues tested. Lumican showed and increased expression in extracts of degenative IvD tissues. Our working hypothesis is that the increased expression of these two SLRPs in degenerative disc tissue results from a reparative depostion of a type I collagen fibrillar ‘scar’. This unusual expression suggests their potential as biomarkers for detecting the onset of degenrative disc disease.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 407 - 407
1 Oct 2006
Kerr B Harris A Deogaonkar K Hughes CE Evans R Caterson B Dent CM
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Introduction: Several small leucine-rich proteoglycans (SLRPs) are involved in the regulation of collagen fibril size(s) in a variety of different musculoskeletal tissues. In hyaline articular cartilage the major SLRPs involved in regulation of type II collagen fibrils are believed to be decorin and fibromodulin. These two SLRPs along with another family member, lumican, have also been identified in intervertebral disc tissues. In recent studies, we serendipitously discovered that, keratocan and lumican [two keratan sulphate (KS) substituted members of the SLRP family] were unusually expressed in extracts from degenerative joint and degenerative disc tissues. The object of this study has been to further investigate this finding with a view to examining the increased expression of keratocan and lumican using qualitative Western blot analysis and quantitative ELISA methods. Our working hypothesis is that the increased expression of these two SLRPs in degenerative joint and disc tissue results from a reparative deposition of a type I collagen fibrillar ¡®scar¡-.

Methods: Monoclonal antibodies were produced to core protein epitopes in lumican and keratocan. Degenerate cartilage was obtained from patients undergoing routine joint replacement for either hip or knee joints, whilst normal articular cartilage tissue was obtained from surgical knee procedures. In addition, disc samples were obtained from patients undergoing a variety of spinal procedures and were Graded I-IV using a modified Thompson score. The tissue was diced and extracted in a 4M guanidine HCl buffer, pH6.8 containing an inhibitor cocktail for 48 h at 4¢ªC. Samples were then dialysed exhaustively against Milli Q water and assayed for glycosaminoglycan (GAG) content using the DMMB assay. Cartilage extracts containing equal amounts of GAG were then separated by SDS-PAGE and transferred to nitrocellulose for Western blotting using mMAbs to either keratocan or lumican. In addition, a competitive ELISA has been developed for quantifying keratocan and lumican.

Results: Western blot analysis of normal and degenerative articular cartilage revealed the presence of both keratocan and lumican. However, the presence of these SLRPs was substantially increased in the degenerate articular cartilge extracts. In addition, these proteins were also present in extracts of intervertabral disc with an increase being apparent in those disc samples with increased pathology. Preliminary data for the development of a quantitative ELISA for these two SLRPs shows promise.

Discussion: The unexpected increase in the detection of keratocan and lumican in degenerative articular cartilage and disc suggests their potential as biomarkers for the onset of degenerative joint and disc disease. However, this will involve the development of a quantitative assay and the investigation of the presence of these molecules in synovial fluid and serum.