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The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 12 | Pages 1655 - 1659
1 Dec 2012
Howells NR Eldridge JD

Hypermobility is an acknowledged risk factor for patellar instability. In this case control study the influence of hypermobility on clinical outcome following medial patellofemoral ligament (MPFL) reconstruction for patellar instability was studied.

A total of 25 patients with hypermobility as determined by the Beighton criteria were assessed and compared with a control group of 50 patients who were matched for age, gender, indication for surgery and degree of trochlear dysplasia. The patients with hypermobility had a Beighton Score of ≥ 6; the control patients had a score of < 4. All patients underwent MPFL reconstruction performed using semitendinosus autograft and a standardised arthroscopically controlled technique. The mean age of the patients was 25 years (17 to 49) and the mean follow-up was 15 months (6 to 30).

Patients with hypermobility had a significant improvement in function following surgery, with reasonable rates of satisfaction, perceived improvement, willingness to repeat and likelihood of recommendation. Functional improvements were significantly less than in control patients (p < 0.01).

Joint hypermobility is not a contraindication to MPFL reconstruction although caution is recommended in managing the expectations of patients with hypermobility before consideration of surgery.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 1 | Pages 36 - 40
1 Jan 2005
Mountney J Senavongse W Amis AA Thomas NP

The tensile strength of the medial patellofemoral ligament (MPFL), and of surgical procedures which reconstitute it, are unknown. Ten fresh cadaver knees were prepared by isolating the patella, leaving only the MPFL as its attachment to the medial femoral condyle. The MPFL was either repaired by using a Kessler suture or reconstructed using either bone anchors or one of two tendon grafting techniques. The tensile strength and the displacement to peak force of the MPFL were then measured using an Instron materials-testing machine. The MPFL was found to have a mean tensile strength of 208 N (SD 90) at 26 mm (SD 7) of displacement. The strengths of the other techniques were: sutures alone, 37 N (SD 27); bone anchors plus sutures, 142 N (SD 39); blind-tunnel tendon graft, 126 N (SD 21); and through-tunnel tendon graft, 195 N (SD 66). The last was not significantly weaker than the MPFL itself


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 9 | Pages 1202 - 1208
1 Sep 2012
Howells NR Barnett AJ Ahearn N Ansari A Eldridge JD

We report a prospective analysis of clinical outcome in patients treated with medial patellofemoral ligament (MPFL) reconstruction using an autologous semitendinosus graft. The technique includes superolateral portal arthroscopic assessment before and after graft placement to ensure correct graft tension and patellar tracking before fixation. Between October 2005 and October 2010, a total of 201 consecutive patients underwent 219 procedures. Follow-up is presented for 211 procedures in 193 patients with a mean age of 26 years (16 to 49), and mean follow-up of 16 months (6 to 42). Indications were atraumatic recurrent patellar dislocation in 141 patients, traumatic recurrent dislocation in 50, pain with subluxation in 14 and a single dislocation with persistent instability in six. There have been no recurrent dislocations/subluxations. There was a statistically significant improvement between available pre- and post-operative outcome scores for 193 patients (all p < 0.001). Female patients with a history of atraumatic recurrent dislocation and all patients with history of previous surgery had a significantly worse outcome (all p < 0.05). The indication for surgery, degree of dysplasia, associated patella alta, time from primary dislocation to surgery and evidence of associated cartilage damage at operation did not result in any significant difference in outcome.

This series adds considerably to existing evidence that MPFL reconstruction is an effective surgical procedure for selected patients with patellofemoral instability.


The Bone & Joint Journal
Vol. 105-B, Issue 12 | Pages 1265 - 1270
1 Dec 2023
Hurley ET Sherman SL Chahla J Gursoy S Alaia MJ Tanaka MJ Pace JL Jazrawi LM

Aims. The aim of this study was to establish consensus statements on medial patellofemoral ligament (MPFL) reconstruction, anteromedialization tibial tubercle osteotomy, trochleoplasty, and rehabilitation and return to sporting activity in patients with patellar instability, using the modified Delphi process. Methods. This was the second part of a study dealing with these aspects of management in these patients. As in part I, a total of 60 surgeons from 11 countries contributed to the development of consensus statements based on their expertise in this area. They were assigned to one of seven working groups defined by subtopics of interest. Consensus was defined as achieving between 80% and 89% agreement, strong consensus was defined as between 90% and 99% agreement, and 100% agreement was considered unanimous. Results. Of 41 questions and statements on patellar instability, none achieved unanimous consensus, 19 achieved strong consensus, 15 achieved consensus, and seven did not achieve consensus. Conclusion. Most statements reached some degree of consensus, without any achieving unanimous consensus. There was no consensus on the use of anchors in MPFL reconstruction, and the order of fixation of the graft (patella first versus femur first). There was also no consensus on the indications for trochleoplasty or its effect on the viability of the cartilage after elevation of the osteochondral flap. There was also no consensus on postoperative immobilization or weightbearing, or whether paediatric patients should avoid an early return to sport. Cite this article: Bone Joint J 2023;105-B(12):1265–1270


The Bone & Joint Journal
Vol. 101-B, Issue 3 | Pages 325 - 330
1 Mar 2019
Balcarek P Zimmermann F

Aims. The aim of this study was to evaluate cartilaginous patellotrochlear congruence and patellofemoral alignment parameters after deepening trochleoplasty in severe trochlear dysplasia. Patients and Methods. The study group comprised 20 patients (two male, 18 female; mean age 24 years (16 to 39)) who underwent deepening trochleoplasty and medial patellofemoral ligament (MPFL) reconstruction for the treatment of recurrent lateral patellar dislocation due to severe trochlear dysplasia (Dejour type B to D). Pre- and postoperative MRI investigations of the study group were compared with MRI data of 20 age- and gender-matched control patients (two male, 18 female; mean age 27 years (18 to 44)) regarding the patellotrochlear contact ratio, patellotrochlear contact area, posterior patellar edge-trochlear groove ratio, and patellar tilt. Results. Preoperatively, all parameters in the study group indicated significant patellar malalignment, including a reduced patellotrochlear contact ratio (mean 0.38 (0.13 to 0.59) vs mean 0.67 (0.48 to 0.88); p < 0.001), reduced contact area (mean 128 mm. 2. (87 to 190) vs mean 183 mm. 2. (155 to 227); p < 0.001), increased patellar lateralization (mean 0.82 (0.55 to 1.0) vs mean 0.99 (0.93 to 1.1); p < 0.001) and increased patellar tilt (mean 25.8° (8.1° to 43.0°) vs mean 9.1° (0.5° to 16.8°); p < 0.001). Postoperatively, all parameters in the study group improved significantly and reached normal values compared with the control group. The patellotrochlear contact ratio increased to a mean of 0.63 (0.38 to 0.85) (p < 0.001), the contact area increased to a mean of 187 mm. 2. (101 to 255) (p < 0.001), the posterior patellar edge-trochlear groove ratio improved to a mean of 0.96 (0.83 to 0.91) (p < 0.001), and the patellar tilt decreased to a mean of 13.9° (8.1° to 22.1°) (p < 0.001) postoperatively. Conclusion. Deepening trochleoplasty and MPFL reconstruction normalized the patellotrochlear congruence and patellofemoral alignment parameters. Modifying the dysplastic trochlea involves approximating the trochlear morphology to the shape of the patella rather than inducing a patella and trochlea mismatch. Cite this article: Bone Joint J 2019;101-B:325–330


The Bone & Joint Journal
Vol. 99-B, Issue 2 | Pages 159 - 170
1 Feb 2017
Clark D Metcalfe A Wogan C Mandalia V Eldridge J

Patellar instability most frequently presents during adolescence. Congenital and infantile dislocation of the patella is a distinct entity from adolescent instability and measurable abnormalities may be present at birth. In the normal patellofemoral joint an increase in quadriceps angle and patellar height are matched by an increase in trochlear depth as the joint matures. Adolescent instability may herald a lifelong condition leading to chronic disability and arthritis. Restoring normal anatomy by trochleoplasty, tibial tubercle transfer or medial patellofemoral ligament (MPFL) reconstruction in the young adult prevents further instability. Although these techniques are proven in the young adult, they may cause growth arrest and deformity where the physis is open. A vigorous non-operative strategy may permit delay of surgery until growth is complete. Where non-operative treatment has failed a modified MPFL reconstruction may be performed to maintain stability until physeal closure permits anatomical reconstruction. If significant growth remains an extraosseous reconstruction of the MPFL may impart the lowest risk to the physis. If minor growth remains image intensifier guided placement of femoral intraosseous fixation may impart a small, but acceptable, risk to the physis. This paper presents and discusses the literature relating to adolescent instability and provides a framework for management of these patients. Cite this article: Bone Joint J 2017;99-B:159–70


The Bone & Joint Journal
Vol. 95-B, Issue 7 | Pages 900 - 905
1 Jul 2013
Singhal R Rogers S Charalambous CP

Medial patellofemoral ligament (MPFL) reconstruction is used to treat patellar instability and recurrent patellar dislocation. Anatomical studies have found the MPFL to be a double-bundle structure. We carried out a meta-analysis of studies reporting outcomes of patellofemoral reconstruction using hamstring tendon autograft in a double-bundle configuration and patellar fixation via mediolateral patellar tunnels. A literature search was undertaken with no language restriction in various databases from their year of inception to July 2012. The primary outcome examined was the post-operative Kujala score. We identified 320 MPFL reconstructions in nine relevant articles. The combined mean post-operative Kujala score was 92.02 (standard error (. se. ) 1.4, p = 0.001) using a fixed effects model and 89.45 (. se. 37.9, p = 0.02) using random effect modelling. The reported rate of complications with MPFL reconstruction was 12.5% (40 of 320) with stiffness of the knee being the most common. High-quality evidence in assessing double-bundle MPFL reconstruction is lacking. The current literature consists of a mixture of prospective and retrospective case series. High-quality randomised trials evaluating this procedure are still awaited. Cite this article: Bone Joint J 2013;95-B:900–5


The Bone & Joint Journal
Vol. 105-B, Issue 12 | Pages 1259 - 1264
1 Dec 2023
Hurley ET Hughes AJ Savage-Elliott I Dejour D Campbell KA Mulcahey MK Wittstein JR Jazrawi LM

Aims

The aim of this study was to establish consensus statements on the diagnosis, nonoperative management, and indications, if any, for medial patellofemoral complex (MPFC) repair in patients with patellar instability, using the modified Delphi approach.

Methods

A total of 60 surgeons from 11 countries were invited to develop consensus statements based on their expertise in this area. They were assigned to one of seven working groups defined by subtopics of interest within patellar instability. Consensus was defined as achieving between 80% and 89% agreement, strong consensus was defined as between 90% and 99% agreement, and 100% agreement was considered to be unanimous.


Bone & Joint Open
Vol. 3, Issue 11 | Pages 894 - 897
15 Nov 2022
Makaram NS Murray IR Geeslin AG Chahla J LaPrade RF

Aims

Multiligament knee injuries (MLKI) are devastating injuries that can result in significant morbidity and time away from sport. There remains considerable variation in strategies employed for investigation, indications for operative intervention, outcome reporting, and rehabilitation following these injuries. At present no study has yet provided a comprehensive overview evaluating the extent, range, and overall summary of the published literature pertaining to MLKI. Our aim is to perform a methodologically rigorous scoping review, mapping the literature evaluating the diagnosis and management of MLKI.

Methods

This scoping review will address three aims: firstly, to map the current extent and nature of evidence for diagnosis and management of MLKI; secondly, to summarize and disseminate existing research findings to practitioners; and thirdly, to highlight gaps in current literature. A three-step search strategy as described by accepted methodology will be employed to identify peer-reviewed literature including reviews, technical notes, opinion pieces, and original research. An initial limited search will be performed to determine suitable search terms, followed by an expanded search of four electronic databases (MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Web of Science). Two reviewers will independently screen identified studies for final inclusion.


The Bone & Joint Journal
Vol. 105-B, Issue 10 | Pages 1078 - 1085
1 Oct 2023
Cance N Batailler C Shatrov J Canetti R Servien E Lustig S

Aims

Tibial tubercle osteotomy (TTO) facilitates surgical exposure and protects the extensor mechanism during revision total knee arthroplasty (rTKA). The purpose of this study was to determine the rates of bony union, complications, and reoperations following TTO during rTKA, to assess the functional outcomes of rTKA with TTO at two years’ minimum follow-up, and to identify the risk factors of failure.

Methods

Between January 2010 and September 2020, 695 rTKAs were performed and data were entered into a prospective database. Inclusion criteria were rTKAs with concomitant TTO, without extensor mechanism allograft, and a minimum of two years’ follow-up. A total of 135 rTKAs were included, with a mean age of 65 years (SD 9.0) and a mean BMI of 29.8 kg/m2 (SD 5.7). The most frequent indications for revision were infection (50%; 68/135), aseptic loosening (25%; 34/135), and stiffness (13%; 18/135). Patients had standardized follow-up at six weeks, three months, six months, and annually thereafter. Complications and revisions were evaluated at the last follow-up. Functional outcomes were assessed using the Knee Society Score (KSS) and range of motion.


The Bone & Joint Journal
Vol. 103-B, Issue 10 | Pages 1586 - 1594
1 Oct 2021
Sharma N Rehmatullah N Kuiper JH Gallacher P Barnett AJ

Aims

The Oswestry-Bristol Classification (OBC) is an MRI-specific assessment tool to grade trochlear dysplasia. The aim of this study is to validate clinically the OBC by demonstrating its use in selecting treatments that are safe and effective.

Methods

The OBC and the patellotrochlear index were used as part of the Oswestry Patellotrochlear Algorithm (OPTA) to guide the surgical treatment of patients with patellar instability. Patients were assigned to one of four treatment groups: medial patellofemoral ligament reconstruction (MPFLr); MPFLr + tibial tubercle distalization (TTD); trochleoplasty; or trochleoplasty + TTD. A prospective analysis of a longitudinal patellofemoral database was performed. Between 2012 and 2018, 202 patients (233 knees) with a mean age of 24.2 years (SD 8.1), with recurrent patellar instability were treated by two fellowship-trained consultant sports/knee surgeons at The Robert Jones and Agnes Hunt Orthopaedic Hospital. Clinical efficacy of each treatment group was assessed by Kujala, International Knee Documentation Committee (IKDC), and EuroQol five-dimension questionnaire (EQ-5D) scores at baseline, and up to 60 months postoperatively. Their safety was assessed by complication rate and requirement for further surgery. The pattern of clinical outcome over time was analyzed using mixed regression modelling.


Bone & Joint Open
Vol. 2, Issue 8 | Pages 638 - 645
1 Aug 2021
Garner AJ Edwards TC Liddle AD Jones GG Cobb JP

Aims

Joint registries classify all further arthroplasty procedures to a knee with an existing partial arthroplasty as revision surgery, regardless of the actual procedure performed. Relatively minor procedures, including bearing exchanges, are classified in the same way as major operations requiring augments and stems. A new classification system is proposed to acknowledge and describe the detail of these procedures, which has implications for risk, recovery, and health economics.

Methods

Classification categories were proposed by a surgical consensus group, then ranked by patients, according to perceived invasiveness and implications for recovery. In round one, 26 revision cases were classified by the consensus group. Results were tested for inter-rater reliability. In round two, four additional cases were added for clarity. Round three repeated the survey one month later, subject to inter- and intrarater reliability testing. In round four, five additional expert partial knee arthroplasty surgeons were asked to classify the 30 cases according to the proposed revision partial knee classification (RPKC) system.


The Bone & Joint Journal
Vol. 102-B, Issue 1 | Pages 102 - 107
1 Jan 2020
Sharma N Brown A Bouras T Kuiper JH Eldridge J Barnett A

Aims

Trochlear dysplasia is a significant risk factor for patellofemoral instability. The Dejour classification is currently considered the standard for classifying trochlear dysplasia, but numerous studies have reported poor reliability on both plain radiography and MRI. The severity of trochlear dysplasia is important to establish in order to guide surgical management. We have developed an MRI-specific classification system to assess the severity of trochlear dysplasia, the Oswestry-Bristol Classification (OBC). This is a four-part classification system comprising normal, mild, moderate, and severe to represent a normal, shallow, flat, and convex trochlear, respectively. The purpose of this study was to assess the inter- and intraobserver reliability of the OBC and compare it with that of the Dejour classification.

Methods

Four observers (two senior and two junior orthopaedic surgeons) independently assessed 32 CT and axial MRI scans for trochlear dysplasia and classified each according to the OBC and the Dejour classification systems. Assessments were repeated following a four-week interval. The inter- and intraobserver agreement was determined by using Fleiss’ generalization of Cohen’s kappa statistic and S-statistic nominal and linear weights.


Bone & Joint Research
Vol. 8, Issue 11 | Pages 509 - 517
1 Nov 2019
Kang K Koh Y Park K Choi C Jung M Shin J Kim S

Objectives

The aim of this study was to investigate the biomechanical effect of the anterolateral ligament (ALL), anterior cruciate ligament (ACL), or both ALL and ACL on kinematics under dynamic loading conditions using dynamic simulation subject-specific knee models.

Methods

Five subject-specific musculoskeletal models were validated with computationally predicted muscle activation, electromyography data, and previous experimental data to analyze effects of the ALL and ACL on knee kinematics under gait and squat loading conditions.


Bone & Joint Research
Vol. 6, Issue 1 | Pages 31 - 42
1 Jan 2017
Kang K Koh Y Jung M Nam J Son J Lee Y Kim S Kim S

Objectives

The aim of the current study was to analyse the effects of posterior cruciate ligament (PCL) deficiency on forces of the posterolateral corner structure and on tibiofemoral (TF) and patellofemoral (PF) contact force under dynamic-loading conditions.

Methods

A subject-specific knee model was validated using a passive flexion experiment, electromyography data, muscle activation, and previous experimental studies. The simulation was performed on the musculoskeletal models with and without PCL deficiency using a novel force-dependent kinematics method under gait- and squat-loading conditions, followed by probabilistic analysis for material uncertain to be considered.


The Bone & Joint Journal
Vol. 99-B, Issue 3 | Pages 344 - 350
1 Mar 2017
Metcalfe AJ Clark DA Kemp MA Eldridge JD

Aims

The Bereiter trochleoplasty has been used in our unit for 12 years to manage recurrent patellar instability in patients with severe trochlea dysplasia. The aim of this study was to document the outcome of a large consecutive cohort of patients who have undergone this operation.

Patients and Methods

Between June 2002 and August 2013, 214 consecutive trochleoplasties were carried out in 185 patients. There were 133 women and 52 men with a mean age of 21.3 years (14 to 38). All patients were offered yearly clinical and radiological follow-up. They completed the following patient reported outcome scores (PROMs): International Knee Documentation Committee subjective scale, the Kujala score, the Western Ontario and McMaster Universities Arthritis Index score and the short-form (SF)-12.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 2 | Pages 180 - 185
1 Feb 2007
Koëter S Diks MJF Anderson PG Wymenga AB

An abnormal lateral position of the tibial tuberosity causes distal malalignment of the extensor mechanism of the knee and can lead to lateral tracking of the patella causing anterior knee pain or objective patellar instability, characterised by recurrent dislocation. Computer tomography is used for a precise pre-operative assessment of the tibial tubercle-trochlear groove distance. A distance of more than 15 mm is considered to be pathological and an indication for surgery in symptomatic patients.

In a prospective study we performed a subtle transfer of the tibial tuberosity according to the information gained from the pre-operative CT scan. This method was applied to two groups of patients, those with painful lateral tracking of the patella, and those with objective patellar instability. We evaluated the clinical results in 30 patients in each group. The outcome was documented at 3, 12 and 24 months using the Lysholm scale, the Kujala score, and a visual analogue pain score.

Post-operatively, all but one patient in the instability group who had a patellar dislocation requiring further surgery reported good improvement with no further subluxation or dislocation. All patients in both groups had a marked improvement in pain and functional score. Two patients sustained a tibial fracture six and seven weeks after surgery. One patient suffered a per-operative fracture of the tibial tubercle which later required further fixation.

If carefully performed, this type of transfer of the tibial tubercle appears to be a satisfactory technique for the treatment of patients with an increased tibial tubercle-trochlear groove distance and who present with symptoms related to lateral maltracking of the patella.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 10 | Pages 1376 - 1380
1 Oct 2010
Tecklenburg K Feller JA Whitehead TS Webster KE Elzarka A

We evaluated the outcome in a series of patients with recurrent patellar dislocation who had either medial transfer of the tibial tuberosity and lateral release or an isolated lateral release as the primary treatment. The decision to use one or other procedure was based on a pre-operative distance between the tibial tuberosity to the trochlear groove (TTTG) of less than 10 mm to include the tibial tuberosity transfer in addition to the lateral release.

Between April 2002 and December 2006, 49 patients (63 knees) underwent one of these procedures. A total of 35 patients (46 knees) was evaluated at a mean of 38 months (13 to 71) post-operatively. Medial transfer of the tibial tuberosity was performed in 33 knees and isolated lateral release in the remaining 13. Evaluation included the International Knee Documentation Committee (IKDC), the Kujala and the Short-form 36 scores. From the tibial tuberosity group 23 knees also underwent radiological examination at follow-up.

There were further episodes of patellar dislocation in six of the 46 knees available for review. Further dislocation was noted in five of 33 knees (15.2%) in the tibial tuberosity transfer group and in one of 13 knees (7.7%) in the lateral release group. The mean subjective IKDC score was 80.4 (sd 11.6), the mean Kujala score 88 (sd 8.2) and the mean objective IKDC score was 79% normal and 21% nearly normal. The mean post-operative TTTG distance in the tibial tuberosity transfer group was 8.9 mm (3.2 to 15.7) compared with the mean pre-operative value of 16.8 mm (12.2 to 24.4).


The Bone & Joint Journal
Vol. 97-B, Issue 3 | Pages 329 - 336
1 Mar 2015
Tigchelaar S van Essen P Bénard M Koëter S Wymenga A

An increased tibial tubercle–trochlear groove (TT-TG) distance is related to patellar maltracking and instability. Tibial tubercle transfer is a common treatment option for these patients with good short-term results, although the results can deteriorate over time owing to the progression of osteoarthritis. We present a ten-year follow-up study of a self-centring tibial tubercle osteotomy in 60 knees, 30 with maltracking and 30 with patellar instability. Inclusion criteria were a TT-TG ≥ 15 mm and symptoms for > one year. One patient (one knee) was lost to follow-up and one required total knee arthroplasty because of progressive osteoarthritis. Further patellar dislocations occurred in three knees, all in the instability group, one of which required further surgery. The mean visual analogue scores for pain, and Lysholm and Kujala scores improved significantly and were maintained at the final follow-up (repeated measures, p = 0.000, intergroup differences p = 0.449). Signs of maltracking were found in only a minority of patients, with no difference between groups (p > 0.05). An increase in patellofemoral osteoarthritis was seen in 16 knees (31%) with a maximum of grade 2 on the Kellgren–Lawrence scale. The mean increase in grades was 0.31 (0 to 2) and 0.41 (0 to 2) in the maltracking and instability groups respectively (p = 0.2285)

This self-centring tibial tubercle osteotomy provides good results at ten years’ follow-up without inducing progressive osteoarthritis.

Cite this article: Bone Joint J 2015;97-B:329–36.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 2 | Pages 180 - 185
1 Feb 2008
Utting MR Mulford JS Eldridge JDJ

Trochlear dysplasia is a developmental condition characterised by an abnormally flat or dome-shaped trochlea and is an important contributory factor to patellofemoral instability and recurrent dislocation. We studied prospectively a series of 54 consecutive patients (59 knees) with patellofemoral instability secondary to trochlear dysplasia, who were treated by a trochleoplasty by a single surgeon between June 2002 and June 2007.

Pre- and post-operative scores were assessed by the patients and a satisfaction questionnaire was completed.

Of the 54 patients (59 knees) in the series, 39 (44 knees) were female and 15 (15 knees) were male. Their mean age at surgery was 21 years and 6 months (14 years 4 months to 33 years 11 months). In 40 patients (42 knees) the mean follow-up was for 24 months (12 to 58). One patient was unable to attend for follow-up. An analysis of the results of those patients followed up for at least 12 months showed a statistically significant improvement in outcome (p < 0.001 for all scores). Overall, 50 patients (92.6%) were satisfied with the outcome of their procedure.

The early results of trochleoplasty are encouraging in this challenging group of patients.