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The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 8 | Pages 1027 - 1032
1 Aug 2011
Schilders E Dimitrakopoulou A Bismil Q Marchant P Cooke C

Labral tears are commonly associated with femoroacetabular impingement. We reviewed 151 patients (156 hips) with femoroacetabular impingement and labral tears who had been treated arthroscopically. These were subdivided into those who had undergone a labral repair (group 1) and those who had undergone resection of the labrum (group 2). In order to ensure the groups were suitably matched for comparison of treatment effects, patients with advanced degenerative changes (Tönnis grade > 2, lateral sourcil height < 2 mm and Outerbridge grade 4 changes in the weight-bearing area of the femoral head) were excluded, leaving 96 patients (101 hips) in the study. At a mean follow-up of 2.44 years (2 to 4), the mean modified Harris hip score in the labral repair group (group 1, 69 hips) improved from 60.2 (24 to 85) pre-operatively to 93.6 (55 to 100), and in the labral resection group (group 2, 32 hips) from 62.8 (29 to 96) pre-operatively to 88.8 (35 to 100). The mean modified Harris hip score in the labral repair group was 7.3 points greater than in the resection group (p = 0.036, 95% confidence interval 0.51 to 14.09). Labral detachments were found more frequently in the labral repair group and labral flap tears in the resection group. No patient in our study group required a subsequent hip replacement during the period of follow-up.

This study shows that patients without advanced degenerative changes in the hip can achieve significant improvement in their symptoms after arthroscopic treatment of femoroacetabular impingement. Where appropriate, labral repair provides a superior result to labral resection.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 10 | Pages 1352 - 1356
1 Oct 2008
Suh KT Park WW Kim S Cho HM Lee JS Lee JS

Between March 2000 and February 2006, we carried out a prospective study of 100 patients with a low-grade isthmic spondylolisthesis (Meyerding grade II or below), who were randomised to receive a single-level and instrumented posterior lumbar interbody fusion with either one or two cages. The minimum follow-up was for two years. At this stage 91 patients were available for review. A total of 47 patients received one cage (group 1) and 44 two cages (group 2). The clinical and radiological outcomes of the two groups were compared.

There were no significant differences between the two groups in terms of post-operative pain, Oswestry Disability Score, clinical results, complication rate, percentage of post-operative slip, anterior fusion rate or posterior fusion rate. On the other hand, the mean operating time was 144 minutes (100 to 240) for patients in group 1 and 167 minutes (110 to 270) for those in group 2 (p = 0.0002). The mean blood loss up to the end of the first post-operative day was 756 ml (510 to 1440) in group 1 and 817 ml (620 to 1730) in group 2 (p < 0.0001).

Our results suggest that an instrumented posterior lumbar interbody fusion performed with either one or two cages in addition to a bone graft around the cage has a low rate of complications and a high fusion rate. The clinical outcomes were good in most cases, regardless of whether one or two cages had been used.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 12 | Pages 1694 - 1699
1 Dec 2005
Floerkemeier T Hurschler C Witte F Wellmann M Thorey F Vogt U Windhagen H

The ability to predict load-bearing capacity during the consolidation phase in distraction osteogenesis by non-invasive means would represent a significant advance in the management of patients undergoing such treatment. Measurements of stiffness have been suggested as a promising tool for this purpose. Although the multidimensional characteristics of bone loading in compression, bending and torsion are apparent, most previous experiments have analysed only the relationship between maximum load-bearing capacity and a single type of stiffness. We have studied how compressive, bending and torsional stiffness are related to the torsional load-bearing capacity of healing callus using a common set of samples of bone regenerate from 26 sheep treated by tibial distraction osteogenesis.

Our findings showed that measurements of torsional, bending and compressive stiffness were all suitable as predictors of the load-bearing capacity of healing callus. Measurements of torsional stiffness performed slightly better than those of compressive and bending stiffness.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 9 | Pages 1234 - 1238
1 Sep 2008
Chung CY Lee SH Choi IH Cho T Yoo WJ Park MS

Our aim in this retrospective study of 52 children with spastic hemiplegia was to determine the factors which affected the amount of residual pelvic rotation after single-event multilevel surgery.

The patients were divided into two groups, those who had undergone femoral derotation osteotomy and those who had not. Pelvic rotation improved significantly after surgery in the femoral osteotomy group (p < 0.001) but not in the non-femoral osteotomy group. Multiple regressions identified the following three independent variables, which significantly affected residual pelvic rotation: the performance of femoral derotation osteotomy (p = 0.049), the pre-operative pelvic rotation (p = 0.003) and the post-operative internal rotation of the hip (p = 0.001).

We concluded that there is a decrease in the amount of pelvic rotation after single-event multilevel surgery with femoral derotation osteotomy. However, some residual rotation may persist when patients have severe rotation before surgery.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 5 | Pages 657 - 661
1 May 2008
Shen P Chern T Wu K Tai T Jou I

We evaluated the morphological changes to the ulnar nerve of both elbows in the cubital tunnel by sonography in a total of 237 children, of whom 117 were aged between six and seven years, 66 between eight and nine years, and 54 between ten and 11 years. We first scanned longitudinally in the extended elbow and then transversely at the medial epicondyle with the elbow extended to 0°. We repeated the scans with the elbow flexed at 45°, 90°, and 120°. There were no significant differences in the area of the ulnar nerve, but the diameter increased as the elbow moved from extension to flexion in all groups. More importantly, the ulnar nerve was subluxated anteriorly on to the medial epicondyle by 1.5% to 1.9% in extended elbows, by 5.9% to 7.9% in those flexed to 45°, by 40.0% to 44% in those flexed to 90°, and by 57.4% to 58.1% in those flexed to 120°, depending on the age group. Sonography clearly and accurately showed the ulnar nerve and was useful for localising the nerve before placing a medial pin. Because the ulnar nerve may translate anteriorly onto the medial epicondyle when the elbow is flexed to 90° or more, it should never be overlooked during percutaneous medial pinning.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 3 | Pages 333 - 340
1 Mar 2009
Sariali E Mouttet A Pasquier G Durante E Catone Y

Pre-operative computerised three-dimensional planning was carried out in 223 patients undergoing total hip replacement with a cementless acetabular component and a cementless modular-neck femoral stem. Components were chosen which best restored leg length and femoral offset. The post-operative restoration of the anatomy was assessed by CT and compared with the pre-operative plan.

The component implanted was the same as that planned in 86% of the hips for the acetabular implant, 94% for the stem, and 93% for the neck-shaft angle. The rotational centre of the hip was restored with a mean accuracy of 0.73 mm (sd 3.5) craniocaudally and 1.2 mm (sd 2) laterally. Limb length was restored with a mean accuracy of 0.3 mm (sd 3.3) and femoral offset with a mean accuracy of 0.8 mm (sd 3.1).

This method appears to offer high accuracy in hip reconstruction as the difficulties likely to be encountered when restoring the anatomy can be anticipated and solved pre-operatively by optimising the selection of implants. Modularity of the femoral neck helped to restore the femoral offset and limb length.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 9 | Pages 1265 - 1270
1 Sep 2011
Clement ND MacDonald D Howie CR Biant LC

Primary arthroplasty may be denied to very elderly patients based upon the perceived outcome and risks associated with surgery. This prospective study compared the outcome, complications, and mortality of total hip (TKR) and total knee replacement (TKR) in a prospectively selected group of patients aged ≥ 80 years with that of a control group aged between 65 and 74 years. There were 171 and 495 THRs and 185 and 492 TKRs performed in the older and control groups, respectively. No significant difference was observed in the mean improvement of Oxford hip and knee scores between the groups at 12 months (0.98, (95% confidence interval (CI) −0.66 to 2.95), p = 0.34 and 1.15 (95% CI −0.65 to 2.94), p = 0.16, respectively). The control group had a significantly (p = 0.02 and p = 0.04, respectively) greater improvement in the physical well being component of their SF-12 score, but the older group was more satisfied with their THR (p = 0.047). The older group had a longer hospital stay for both THR (5.9 versus 9.0 days, p < 0.0001) and TKR (6.2 versus 8.3 days, p < 0.0001). The rates of post-operative complications and mortality were increased in the older group.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 9 | Pages 1192 - 1196
1 Sep 2005
Argenson J Ryembault E Flecher X Brassart N Parratte S Aubaniac J

Using radiography and computer tomography (CT) we studied the morphology of 83 hips in 69 Caucasian adults with osteoarthritis secondary to developmental dysplasia of the hip (DDH). A previously published series of 310 hips with primary osteoarthritis was used as a control group. According to the Crowe classification, 33 of the dysplastic hips were graded as class I, 27 as class II and 23 as class III or class IV.

The intramedullary femoral canal had reduced mediolateral and anteroposterior dimensions in all groups compared with the control group. Only in Crowe class II hips was the femoral neck-shaft angle increased. The proximal femur had more anteversion in all the developmental dysplasia of the hip groups, ranging from 2° to 80°. Templated measurement of acetabular dimensions for plain radiography closely matched measurements taken by CT.

The results of our study confirm the observations previously confined to the Japanese population.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 4 | Pages 451 - 454
1 Apr 2008
Amin A Watson A Mangwani J Nawabi DH Ahluwalia R Loeffler M

We undertook a prospective randomised controlled trial to investigate the efficacy of autologous retransfusion drains in reducing the need for allogenic blood requirement after unilateral total knee replacement. We also monitored the incidence of post-operative complications. There were 86 patients in the control group, receiving standard care with a vacuum drain, and 92 who received an autologous drain and were retransfused postoperatively. Following serial haemoglobin measurements at 24, 48 and 72 hours, we found no difference in the need for allogenic blood between the two groups (control group 15.1%, retransfusion group 13% (p = 0.439)). The incidence of post-operative complications, such as wound infection, deep-vein thrombosis and chest infection, was also comparable between the groups. There were no adverse reactions associated with the retransfusion of autologous blood.

Based on this study, the cost-effectiveness and continued use of autologous drains in total knee replacement should be questioned.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 11 | Pages 1568 - 1574
1 Nov 2005
Day RE Megson S Wood D

Allograft bone is widely used in orthopaedic surgery, but peri-operative infection of the graft remains a common and disastrous complication. The efficacy of systemic prophylactic antibiotics is unproven, and since the graft is avascular it is likely that levels of antibiotic in the graft are low.

Using an electrical potential to accelerate diffusion of antibiotics into allograft bone, high levels were achieved in specimens of both sheep and human allograft. In human bone these ranged from 187.1 mg/kg in endosteal (sd 15.7) to 124.6 (sd 46.2) in periosteal bone for gentamicin and 31.9 (sd 8.9) in endosteal and 2.9 (sd 1.1) in periosteal bone for flucloxacillin. The antibiotics remained active against bacteria in vitro after iontophoresis and continued to elute from the allograft for up to two weeks.

Structural allograft can be supplemented directly with antibiotics using iontophoresis. The technique is simple and inexpensive and offers a potential means of reducing the rate of peri-operative infection in allograft surgery. Iontophoresis into allograft bone may also be applicable to other therapeutic compounds.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 7 | Pages 942 - 948
1 Jul 2011
Chaudhury S Holland C Vollrath F Carr AJ

This study reports the application of a novel method for quantitatively determining differences in the mechanical properties of healthy and torn rotator cuff tissues. In order to overcome problems of stress risers at the grip-tendon interface that can obscure mechanical measurements of small tendons, we conducted our investigation using dynamic shear analysis.

Rotator cuff tendon specimens were obtained from 100 patients during shoulder surgery. They included 82 differently sized tears and 18 matched controls. We subjected biopsy samples of 3 mm in diameter to oscillatory deformation under compression using dynamic shear analysis. The storage modulus (G’) was calculated as an indicator of mechanical integrity.

Normal tendons had a significantly higher storage modulus than torn tendons, indicating that torn tendons are mechanically weaker than normal tendons (p = 0.003). Normal tendons had a significantly higher mean shear modulus than tendons with massive tears (p < 0.01).

Dynamic shear analysis allows the determination of shear mechanical properties of small tissue specimens obtained intra-operatively that could not be studied by conventional methods of tensile testing. These methods could be employed to investigate other musculoskeletal tissues. This pilot study provides some insight into mechanisms that might contribute to the failure of repair surgery, and with future application could help direct the most appropriate treatment for specific rotator cuff tears.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 5 | Pages 644 - 649
1 May 2011
Yonekura Y Miyamoto H Shimazaki T Ando Y Noda I Mawatari M Hotokebuchi T

A silver-containing hydroxyapatite (Ag-HA) coating has been developed using thermal spraying technology. We evaluated the osteoconductivity of this coating on titanium (Ti) implants in rat tibiae in relation to bacterial infection in joint replacement.

At 12 weeks, the mean affinity indices of bone formation of a Ti, an HA, a 3%Ag-HA and a 50%Ag-HA coating were 97.3%, 84.9%, 81.0% and 40.5%, respectively. The mean affinity indices of bone contact of these four coatings were 18.8%, 83.7%, 77.2% and 40.5%, respectively. The indices of bone formation and bone contact around the implant of the 3%Ag-HA coating were similar to those of the HA coating, and no significant differences were found between them (bone formation, p = 0.99; bone contact, p = 0.957). However, inhibition of bone formation was observed with the 50%Ag-HA coating.

These results indicate that the 3%Ag-HA coating has low toxicity and good osteoconductivity, and that the effect of silver toxicity on osteoconductivity depends on the dose.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 9 | Pages 1186 - 1192
1 Sep 2008
Lyu S

The outcome of arthroscopic medial release of 255 knees in 173 patients for varying grades of osteoarthritis involving the medial compartment is reported. All operations were performed by a single surgeon between January 2001 and May 2003. The Knee Society score for pain and the patient’s subjective satisfaction were used for the outcome evaluation. Overall, satisfactory outcome was reported for 197 knees (77.3%) and the mean Knee Society score for pain improved from 17.6 (95% confidence interval, 16.7 to 18.5), pre-operatively to 39.4 (95% confidence interval, 37.9 to 41.1) (p < 0.001). There were minor manageable complications of persistent effusion in 16 knees and prolonged wound discomfort in 11. In total, 15 of the 21 knees with poor results were converted to total knee replacements and two other patients (three knees) were offered this option after a mean period of 16 months.

Based on these observations arthroscopic medial release is an effective treatment for osteoarthritis of the medial compartment of the knee joint and can be expected to reduce the pain in the majority of patients for at least four years post-operatively.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 12 | Pages 1655 - 1659
1 Dec 2007
Anwar HA Aldam CH Visuvanathan S Hart AJ

The biological significance of cobalt-chromium wear particles from metal-on-metal hip replacements may be different to the effects of the constituent metal ions in solution. Bacteria may be able to discriminate between particulate and ionic forms of these metals because of a transmembrane nickel/cobalt-permease. It is not known whether wear particles are bacteriocidal.

We compared the doubling time of coagulase negative staphylococcus, Staphylococcus aureus and methicillin resistant S. aureus when cultured in either wear particles from a metal-on-metal hip simulator, wear particles from a metal-on-polyethylene hip simulator, metal ions in solution or a control.

Doubling time halved in metal-on-metal (p = 0.003) and metal-on-polyethylene (p = 0.131) particulate debris compared with the control.

Bacterial nickel/cobalt-transporters allow metal ions but not wear particles to cross bacterial membranes. This may be useful for testing the biological characteristics of different wear debris. This experiment also shows that metal-on-metal hip wear debris is not bacteriocidal.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 4 | Pages 510 - 516
1 Apr 2011
Sugata Y Sotome S Yuasa M Hirano M Shinomiya K Okawa A

Several bisphosphonates are now available for the treatment of osteoporosis. Porous hydroxyapatite/collagen (HA/Col) composite is an osteoconductive bone substitute which is resorbed by osteoclasts. The effects of the bisphosphonate alendronate on the formation of bone in porous HA/Col and its resorption by osteoclasts were evaluated using a rabbit model. Porous HA/Col cylinders measuring 6 mm in diameter and 8 mm in length, with a pore size of 100 μm to 500 μm and 95% porosity, were inserted into a defect produced in the lateral femoral condyles of 72 rabbits. The rabbits were divided into four groups based on the protocol of alendronate administration: the control group did not receive any alendronate, the pre group had alendronate treatment for three weeks prior to the implantation of the HA/Col, the post group had alendronate treatment following implantation until euthanasia, and the pre+post group had continuous alendronate treatment from three weeks prior to surgery until euthanasia. All rabbits were injected intravenously with either saline or alendronate (7.5 μg/kg) once a week. Each group had 18 rabbits, six in each group being killed at three, six and 12 weeks post-operatively. Alendronate administration suppressed the resorption of the implants. Additionally, the mineral densities of newly formed bone in the alendronate-treated groups were lower than those in the control group at 12 weeks post-operatively. Interestingly, the number of osteoclasts attached to the implant correlated with the extent of bone formation at three weeks.

In conclusion, the systemic administration of alendronate in our rabbit model at a dose-for-weight equivalent to the clinical dose used in the treatment of osteoporosis in Japan affected the mineral density and remodelling of bone tissue in implanted porous HA/Col composites.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 3 | Pages 319 - 323
1 Mar 2008
Moonot P Singh PJ Cronin MD Kalairajah YE Kavanagh TG Field RE

Hip resurfacing is a bone-conserving procedure with respect to proximal femoral resection, but there is debate in the literature as to whether the same holds true for the acetabulum. We have investigated whether the Birmingham hip resurfacing conserves acetabular bone.

Between 1998 and 2005, 500 Birmingham hip resurfacings were performed by two surgeons. Between 1996 and 2005 they undertook 700 primary hip replacements, with an uncemented acetabular component. These patients formed the clinical material to compare acetabular component sizing. The Birmingham hip resurfacing group comprised 350 hips in men and 150 hips in women. The uncemented total hip replacement group comprised 236 hips in men and 464 hips in women. Age- and gender-matched analysis of a cohort of patients for the sizes of the acetabular components required for the two types of replacement was also undertaken. Additionally, an analysis of the sizes of the components used by each surgeon was performed.

For age-matched women, the mean outside diameter of the Birmingham hip resurfacing acetabular components was 2.03 mm less than that of the acetabular components in the uncemented total hip replacements (p < 0.0001). In similarly matched men there was no significant difference (p = 0.77). A significant difference was also found between the size of acetabular components used by the two surgeons for Birmingham hip resurfacing for both men (p = 0.0015) and women (p = 0.001). In contrast, no significant difference was found between the size of acetabular components used by the two surgeons for uncemented total hip replacement in either men or women (p = 0.06 and p = 0.14, respectively). This suggests that variations in acetabular preparation also influence acetabular component size in hip resurfacing.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 7 | Pages 907 - 913
1 Jul 2011
Ward TR Burns AW Gillespie MJ Scarvell JM Smith PN

Bicruciate-stabilised total knee replacement (TKR) aims to restore normal kinematics by replicating the function of both cruciate ligaments. We performed a prospective, randomised controlled trial in which bicruciate- and posterior-stabilised TKRs were implanted in 13 and 15 osteo-arthritic knees, respectively. The mean age of the bicruciate-stabilised group was 63.9 years (sd 10.00) and that of the posterior-stabilised group 63.2 years (sd 6.7). A control group comprised 14 normal subjects with a mean age of 67.9 years (sd 7.9). The patellar tendon angle (PTA) was measured one week pre-operatively and at seven weeks post-operatively during knee extension, flexion and step-up exercises.

At near full extension during step-up, the bicruciate-stabilised TKR produced a higher mean PTA than the posterior-stabilised TKR, indicating that the bicruciate design at least partially restored the kinematic role of the anterior cruciate ligament. The bicruciate-stabilised TKR largely restored the pre-operative kinematics, whereas the posterior-stabilised TKR resulted in a consistently lower PTA at all activities. The PTA in the pre-operative knees was higher than in the control group during the step-up and at near full knee extension. Overall, both groups generated a more normal PTA than that seen in previous studies in high knee flexion. This suggested that both designs of TKR were more effective at replicating the kinematic role of the posterior cruciate ligament than those used in previous studies.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 8 | Pages 1143 - 1149
1 Aug 2005
Akmal M Singh A Anand A Kesani A Aslam N Goodship A Bentley G

The purpose of this study was to examine the effects of hyaluronic acid supplementation on chondrocyte metabolism in vitro. The clinical benefits of intra-articular hyaluronic acid injections are thought to occur through improved joint lubrication. Recent findings have shown that exogenous hyaluronic acid is incorporated into articular cartilage where it may have a direct biological effect on chondrocytes through CD44 receptors.

Bovine articular chondrocytes were isolated and seeded into alginate constructs. These were cultured in medium containing hyaluronic acid at varying concentrations. Samples were assayed for biochemical and histological changes.

There was a dose-dependent response to the exposure of hyaluronic acid to bovine articular chondrocytes in vitro. Low concentrations of hyaluronic acid (0.1 mg/mL and 1 mg/mL) significantly increase DNA, sulphated glycosaminoglycan and hydroxyproline synthesis. Immunohistology confirmed the maintenance of cell phenotype with increased matrix deposition of chondroitin-6-sulphate and collagen type II. These findings confirm a stimulatory effect of hyaluronic acid on chondrocyte metabolism.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 8 | Pages 1033 - 1044
1 Aug 2011
Periasamy K Watson WS Mohammed A Murray H Walker B Patil S Meek RMD

The ideal acetabular component is characterised by reliable, long-term fixation with physiological loading of bone and a low rate of wear. Trabecular metal is a porous construct of tantalum which promotes bony ingrowth, has a modulus of elasticity similar to that of cancellous bone, and should be an excellent material for fixation.

Between 2004 and 2006, 55 patients were randomised to receive either a cemented polyethylene or a monobloc trabecular metal acetabular component with a polyethylene articular surface. We measured the peri-prosthetic bone density around the acetabular components for up to two years using dual-energy x-ray absorptiometry.

We found evidence that the cemented acetabular component loaded the acetabular bone centromedially whereas the trabecular metal monobloc loaded the lateral rim and behaved like a hemispherical rigid metal component with regard to loading of the acetabular bone. We suspect that this was due to the peripheral titanium rim used for the mechanism of insertion.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 7 | Pages 899 - 905
1 Jul 2008
Dias JJ Dhukaram V Abhinav A Bhowal B Wildin CJ

We report the outcome at a mean of 93 months (73 to 110) of 71 patients with an acute fracture of the scaphoid who were randomised to Herbert screw fixation (35) or below-elbow plaster cast immobilisation (36). These 71 patients represent the majority of a randomised series of 88 patients whose short-term outcome has previously been reported. Those patients available for later review were similar in age, gender and hand dominance.

There was no statistical difference in symptoms and disability as assessed by the mean Patient Evaluation Measure (p = 0.4), or mean Patient-Rated Wrist Evaluation (p = 0.9), the mean range of movement of the wrist (p = 0.4), mean grip strength (p = 0.8), or mean pinch strength (p = 0.4).

Radiographs were available from the final review for 59 patients. Osteoarthritic changes were seen in the scaphotrapezial and radioscaphoid joints in eight (13.5%) and six patients (10.2%), respectively. Three patients had asymptomatic lucency surrounding the screw. One non-operatively treated patient developed nonunion with avascular necrosis. In five patients who were treated non-operatively (16%) there was an abnormal scapholunate angle ( > 60°), but in four of these patients this finding was asymptomatic.

No medium-term difference in function or radiological outcome was identified between the two treatment groups.