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The Bone & Joint Journal
Vol. 106-B, Issue 9 | Pages 994 - 999
1 Sep 2024
El-Khaldi I Gude MH Gundtoft PH Viberg B

Aims

Pneumatic tourniquets are often used during the surgical treatment of unstable traumatic ankle fractures. The aim of this study was to assess the risk of reoperation after open reduction and internal fixation of ankle fractures with and without the use of pneumatic tourniquets.

Methods

This was a population-based cohort study using data from the Danish Fracture Database with a follow-up period of 24 months. Data were linked to the Danish National Patient Registry to ensure complete information regarding reoperations due to complications, which were divided into major and minor. The relative risk of reoperations for the tourniquet group compared with the non-tourniquet group was estimated using Cox proportional hazards modelling.


The Bone & Joint Journal
Vol. 106-B, Issue 9 | Pages 892 - 897
1 Sep 2024
Mancino F Fontalis A Kayani B Magan A Plastow R Haddad FS

Advanced 3D imaging and CT-based navigation have emerged as valuable tools to use in total knee arthroplasty (TKA), for both preoperative planning and the intraoperative execution of different philosophies of alignment. Preoperative planning using CT-based 3D imaging enables more accurate prediction of the size of components, enhancing surgical workflow and optimizing the precision of the positioning of components. Surgeons can assess alignment, osteophytes, and arthritic changes better. These scans provide improved insights into the patellofemoral joint and facilitate tibial sizing and the evaluation of implant-bone contact area in cementless TKA. Preoperative CT imaging is also required for the development of patient-specific instrumentation cutting guides, aiming to reduce intraoperative blood loss and improve the surgical technique in complex cases. Intraoperative CT-based navigation and haptic guidance facilitates precise execution of the preoperative plan, aiming for optimal positioning of the components and accurate alignment, as determined by the surgeon’s philosophy. It also helps reduce iatrogenic injury to the periarticular soft-tissue structures with subsequent reduction in the local and systemic inflammatory response, enhancing early outcomes. Despite the increased costs and radiation exposure associated with CT-based navigation, these many benefits have facilitated the adoption of imaged based robotic surgery into routine practice. Further research on ultra-low-dose CT scans and exploration of the possible translation of the use of 3D imaging into improved clinical outcomes are required to justify its broader implementation.

Cite this article: Bone Joint J 2024;106-B(9):892–897.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_16 | Pages 72 - 72
19 Aug 2024
Chen X
Full Access

Sequelae of Legg-Calve -Perthes disease (LCPD) and treatment of developmental dysplasia of the hip (DDH) can present a coxa breva or coxa magna deformity, sometimes associated with coxa vara. This unique deformity decreases the efficiency of the abductor mechanism, causing a Trendelenburg gait and hip pain, leg length discrepancy and leads to intra- and extra-articular impingement, and eventually osteoarthritis. Several surgical techniques have been advocated to treat this kind deformity, such as great trochanter transfer, relative femoral neck lengthening. We evaluated primary results of true femoral neck-lengthening osteotomy (TFNLO) in combination with periacetabular osteotomy (PAO) for treatment of Coxa Breva through surgical hip dislocation (SHD). Fourteen patients with Coxa Breva received true femoral neck lengthening osteotomy in combination of PAO through SHD between March 2020 and October 2023. Ten patients with minimum 1 year followed-up were retrospectively reviewed clinically and radiographically. Eight patients had Perthes disease, 2 had DDH received closed reduction and fixation during childhood. The mean age at surgery was 16 years (range, 12 to 31 years). Clinical findings, radiographic analyses including the change in horizontal femoral offset and the leg length discrepancy as well as complications were assessed. Horizontal femoral offset improved 19.5mm(6–28mm). Limb length increase 16.8mm(11–30mm). Mean HHS increased from 80.6(66–91) to 91.8(88–96). Complication: screw broken in 1(no need operation). Asymptomatic fibrous union of the great trochanter was found in 1. No infection and joint space narrow as well as nerve palsy happened. TFNLO combined with PAO can be effective for the treatment of patients with Coxa breva. But long term follow up is warranted


Bone & Joint Research
Vol. 13, Issue 7 | Pages 332 - 341
5 Jul 2024
Wang T Yang C Li G Wang Y Ji B Chen Y Zhou H Cao L

Aims

Although low-intensity pulsed ultrasound (LIPUS) combined with disinfectants has been shown to effectively eliminate portions of biofilm in vitro, its efficacy in vivo remains uncertain. Our objective was to assess the antibiofilm potential and safety of LIPUS combined with 0.35% povidone-iodine (PI) in a rat debridement, antibiotics, and implant retention (DAIR) model of periprosthetic joint infection (PJI).

Methods

A total of 56 male Sprague-Dawley rats were established in acute PJI models by intra-articular injection of bacteria. The rats were divided into four groups: a Control group, a 0.35% PI group, a LIPUS and saline group, and a LIPUS and 0.35% PI group. All rats underwent DAIR, except for Control, which underwent a sham procedure. General status, serum biochemical markers, weightbearing analysis, radiographs, micro-CT analysis, scanning electron microscopy of the prostheses, microbiological analysis, macroscope, and histopathology evaluation were performed 14 days after DAIR.


The Bone & Joint Journal
Vol. 106-B, Issue 7 | Pages 662 - 668
1 Jul 2024
Ahmed I Metcalfe A

Aims

This study aims to identify the top unanswered research priorities in the field of knee surgery using consensus-based methodology.

Methods

Initial research questions were generated using an online survey sent to all 680 members of the British Association for Surgery of the Knee (BASK). Duplicates were removed and a longlist was generated from this scoping exercise by a panel of 13 experts from across the UK who provided oversight of the process. A modified Delphi process was used to refine the questions and determine a final list. To rank the final list of questions, each question was scored between one (low importance) and ten (high importance) in order to produce the final list.


The Bone & Joint Journal
Vol. 106-B, Issue 6 | Pages 516 - 521
1 Jun 2024
Al-Hourani K Haddad FS


Bone & Joint Open
Vol. 5, Issue 5 | Pages 411 - 418
20 May 2024
Schneider P Bajammal S Leighton R Witges K Rondeau K Duffy P

Aims

Isolated fractures of the ulnar diaphysis are uncommon, occurring at a rate of 0.02 to 0.04 per 1,000 cases. Despite their infrequency, these fractures commonly give rise to complications, such as nonunion, limited forearm pronation and supination, restricted elbow range of motion, radioulnar synostosis, and prolonged pain. Treatment options for this injury remain a topic of debate, with limited research available and no consensus on the optimal approach. Therefore, this trial aims to compare clinical, radiological, and functional outcomes of two treatment methods: open reduction and internal fixation (ORIF) versus nonoperative treatment in patients with isolated ulnar diaphyseal fractures.

Methods

This will be a multicentre, open-label, parallel randomized clinical trial (under National Clinical Trial number NCT01123447), accompanied by a parallel prospective cohort group for patients who meet the inclusion criteria, but decline randomization. Eligible patients will be randomized to one of the two treatment groups: 1) nonoperative treatment with closed reduction and below-elbow casting; or 2) surgical treatment with ORIF utilizing a limited contact dynamic compression plate and screw construct. The primary outcome measured will be the Disabilities of the Arm, Shoulder and Hand questionnaire score at 12 months post-injury. Additionally, functional outcomes will be assessed using the 36-Item Short Form Health Survey and pain visual analogue scale, allowing for a comparison of outcomes between groups. Secondary outcome measures will encompass clinical outcomes such as range of motion and grip strength, radiological parameters including time to union, as well as economic outcomes assessed from enrolment to 12 months post-injury.


Aims

The aim of this study was to investigate the distribution of phenotypes in Asian patients with end-stage osteoarthritis (OA) and assess whether the phenotype affected the clinical outcome and survival of mechanically aligned total knee arthroplasty (TKA). We also compared the survival of the group in which the phenotype unintentionally remained unchanged with those in which it was corrected to neutral.

Methods

The study involved 945 TKAs, which were performed in 641 patients with primary OA, between January 2000 and January 2009. These were classified into 12 phenotypes based on the combined assessment of four categories of the arithmetic hip-knee-ankle angle and three categories of actual joint line obliquity. The rates of survival were analyzed using Kaplan-Meier methods and the log-rank test. The Hospital for Special Surgery score and survival of each phenotype were compared with those of the reference phenotype with neutral alignment and a parallel joint line. We also compared long-term survival between the unchanged phenotype group and the corrected to neutral alignment-parallel joint line group in patients with Type IV-b (mild to moderate varus alignment-parallel joint line) phenotype.


The Bone & Joint Journal
Vol. 106-B, Issue 5 Supple B | Pages 82 - 88
1 May 2024
Villa JM Rajschmir K Hosseinzadeh S Manrique-Succar J Grieco P Higuera-Rueda CA Riesgo AM

Aims

Large bone defects resulting from osteolysis, fractures, osteomyelitis, or metastases pose significant challenges in acetabular reconstruction for total hip arthroplasty. This study aimed to evaluate the survival and radiological outcomes of an acetabular reconstruction technique in patients at high risk of reconstruction failure (i.e. periprosthetic joint infection (PJI), poor bone stock, immunosuppressed patients), referred to as Hip Reconstruction In Situ with Screws and Cement (HiRISC). This involves a polyethylene liner embedded in cement-filled bone defects reinforced with screws and/or plates for enhanced fixation.

Methods

A retrospective chart review of 59 consecutive acetabular reconstructions was performed by four surgeons in a single institution from 18 October 2018 to 5 January 2023. Cases were classified based on the Paprosky classification, excluding type 1 cases (n = 26) and including types 2 or 3 for analysis (n = 33). Radiological loosening was evaluated by an orthopaedic surgeon who was not the operating surgeon, by comparing the immediate postoperative radiographs with the ones at latest follow-up. Mean follow-up was 557 days (SD 441; 31 to 1,707).


The Bone & Joint Journal
Vol. 106-B, Issue 5 | Pages 430 - 434
1 May 2024
Eardley WGP


The Bone & Joint Journal
Vol. 106-B, Issue 5 Supple B | Pages 40 - 46
1 May 2024
Massè A Giachino M Audisio A Donis A Giai Via R Secco DC Limone B Turchetto L Aprato A

Aims

Ganz’s studies made it possible to address joint deformities on both the femoral and acetabular side brought about by Perthes’ disease. Femoral head reduction osteotomy (FHRO) was developed to improve joint congruency, along with periacetabular osteotomy (PAO), which may enhance coverage and containment. The purpose of this study is to show the clinical and morphological outcomes of the technique and the use of an implemented planning approach.

Methods

From September 2015 to December 2021, 13 FHROs were performed on 11 patients for Perthes’ disease in two centres. Of these, 11 hips had an associated PAO. A specific CT- and MRI-based protocol for virtual simulation of the corrections was developed. Outcomes were assessed with radiological parameters (sphericity index, extrusion index, integrity of the Shenton’s line, lateral centre-edge angle (LCEA), Tönnis angle), and clinical parameters (range of motion, visual analogue scale (VAS) for pain, Merle d'Aubigné-Postel score, modified Harris Hip Score (mHHS), and EuroQol five-dimension five-level health questionnaire (EQ-5D-5L)). Early and late complications were reported.


The Bone & Joint Journal
Vol. 106-B, Issue 4 | Pages 352 - 358
1 Apr 2024
Wilson JM Trousdale RT Bedard NA Lewallen DG Berry DJ Abdel MP

Aims

Dislocation remains a leading cause of failure following revision total hip arthroplasty (THA). While dual-mobility (DM) bearings have been shown to mitigate this risk, options are limited when retaining or implanting an uncemented shell without modular DM options. In these circumstances, a monoblock DM cup, designed for cementing, can be cemented into an uncemented acetabular shell. The goal of this study was to describe the implant survival, complications, and radiological outcomes of this construct.

Methods

We identified 64 patients (65 hips) who had a single-design cemented DM cup cemented into an uncemented acetabular shell during revision THA between 2018 and 2020 at our institution. Cups were cemented into either uncemented cups designed for liner cementing (n = 48; 74%) or retained (n = 17; 26%) acetabular components. Median outer head diameter was 42 mm. Mean age was 69 years (SD 11), mean BMI was 32 kg/m2 (SD 8), and 52% (n = 34) were female. Survival was assessed using Kaplan-Meier methods. Mean follow-up was two years (SD 0.97).


The Bone & Joint Journal
Vol. 106-B, Issue 3 | Pages 277 - 285
1 Mar 2024
Pinto D Hussain S Leo DG Bridgens A Eastwood D Gelfer Y

Aims

Children with spinal dysraphism can develop various musculoskeletal deformities, necessitating a range of orthopaedic interventions, causing significant morbidity, and making considerable demands on resources. This systematic review aimed to identify what outcome measures have been reported in the literature for children with spinal dysraphism who undergo orthopaedic interventions involving the lower limbs.

Methods

A PROSPERO-registered systematic literature review was performed following PRISMA guidelines. All relevant studies published until January 2023 were identified. Individual outcomes and outcome measurement tools were extracted verbatim. The measurement tools were assessed for reliability and validity, and all outcomes were grouped according to the Outcome Measures Recommended for use in Randomized Clinical Trials (OMERACT) filters.


The Bone & Joint Journal
Vol. 106-B, Issue 3 | Pages 293 - 302
1 Mar 2024
Vogt B Lueckingsmeier M Gosheger G Laufer A Toporowski G Antfang C Roedl R Frommer A

Aims

As an alternative to external fixators, intramedullary lengthening nails (ILNs) can be employed for distraction osteogenesis. While previous studies have demonstrated that typical complications of external devices, such as soft-tissue tethering, and pin site infection can be avoided with ILNs, there is a lack of studies that exclusively investigated tibial distraction osteogenesis with motorized ILNs inserted via an antegrade approach.

Methods

A total of 58 patients (median age 17 years (interquartile range (IQR) 15 to 21)) treated by unilateral tibial distraction osteogenesis for a median leg length discrepancy of 41 mm (IQR 34 to 53), and nine patients with disproportionate short stature treated by bilateral simultaneous tibial distraction osteogenesis, with magnetically controlled motorized ILNs inserted via an antegrade approach, were retrospectively analyzed. The median follow-up was 37 months (IQR 30 to 51). Outcome measurements were accuracy, precision, reliability, bone healing, complications, and patient-reported outcome assessed by the Limb Deformity-Scoliosis Research Society Score (LD-SRS-30).


Bone & Joint Open
Vol. 5, Issue 2 | Pages 101 - 108
6 Feb 2024
Jang SJ Kunze KN Casey JC Steele JR Mayman DJ Jerabek SA Sculco PK Vigdorchik JM

Aims

Distal femoral resection in conventional total knee arthroplasty (TKA) utilizes an intramedullary guide to determine coronal alignment, commonly planned for 5° of valgus. However, a standard 5° resection angle may contribute to malalignment in patients with variability in the femoral anatomical and mechanical axis angle. The purpose of the study was to leverage deep learning (DL) to measure the femoral mechanical-anatomical axis angle (FMAA) in a heterogeneous cohort.

Methods

Patients with full-limb radiographs from the Osteoarthritis Initiative were included. A DL workflow was created to measure the FMAA and validated against human measurements. To reflect potential intramedullary guide placement during manual TKA, two different FMAAs were calculated either using a line approximating the entire diaphyseal shaft, and a line connecting the apex of the femoral intercondylar sulcus to the centre of the diaphysis. The proportion of FMAAs outside a range of 5.0° (SD 2.0°) was calculated for both definitions, and FMAA was compared using univariate analyses across sex, BMI, knee alignment, and femur length.


Bone & Joint Open
Vol. 5, Issue 2 | Pages 94 - 100
5 Feb 2024
Mancino F Kayani B Gabr A Fontalis A Plastow R Haddad FS

Anterior cruciate ligament (ACL) injuries are among the most common and debilitating knee injuries in professional athletes with an incidence in females up to eight-times higher than their male counterparts. ACL injuries can be career-threatening and are associated with increased risk of developing knee osteoarthritis in future life. The increased risk of ACL injury in females has been attributed to various anatomical, developmental, neuromuscular, and hormonal factors. Anatomical and hormonal factors have been identified and investigated as significant contributors including osseous anatomy, ligament laxity, and hamstring muscular recruitment. Postural stability and impact absorption are associated with the stabilizing effort and stress on the ACL during sport activity, increasing the risk of noncontact pivot injury. Female patients have smaller diameter hamstring autografts than males, which may predispose to increased risk of re-rupture following ACL reconstruction and to an increased risk of chondral and meniscal injuries. The addition of an extra-articular tenodesis can reduce the risk of failure; therefore, it should routinely be considered in young elite athletes. Prevention programs target key aspects of training including plyometrics, strengthening, balance, endurance and stability, and neuromuscular training, reducing the risk of ACL injuries in female athletes by up to 90%. Sex disparities in access to training facilities may also play an important role in the risk of ACL injuries between males and females. Similarly, football boots, pitches quality, and football size and weight should be considered and tailored around females’ characteristics. Finally, high levels of personal and sport-related stress have been shown to increase the risk of ACL injury which may be related to alterations in attention and coordination, together with increased muscular tension, and compromise the return to sport after ACL injury. Further investigations are still necessary to better understand and address the risk factors involved in ACL injuries in female athletes. Cite this article: Bone Jt Open 2024;5(2):94–100


Bone & Joint Open
Vol. 4, Issue 12 | Pages 932 - 941
6 Dec 2023
Oe K Iida H Otsuki Y Kobayashi F Sogawa S Nakamura T Saito T

Aims

Although there are various pelvic osteotomies for acetabular dysplasia of the hip, shelf operations offer effective and minimally invasive osteotomy. Our study aimed to assess outcomes following modified Spitzy shelf acetabuloplasty.

Methods

Between November 2000 and December 2016, we retrospectively evaluated 144 consecutive hip procedures in 122 patients a minimum of five years after undergoing modified Spitzy shelf acetabuloplasty for acetabular dysplasia including osteoarthritis (OA). Our follow-up rate was 92%. The mean age at time of surgery was 37 years (13 to 58), with a mean follow-up of 11 years (5 to 21). Advanced OA (Tönnis grade ≥ 2) was present preoperatively in 16 hips (11%). The preoperative lateral centre-edge angle ranged from -28° to 25°. Survival was determined by Kaplan-Meier analysis, using conversions to total hip arthroplasty as the endpoint. Risk factors for joint space narrowing less than 2 mm were analyzed using a Cox proportional hazards model.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_18 | Pages 9 - 9
1 Dec 2023
Garneti A Clark M Stoddard J Hancock G Hampton M
Full Access

Introduction. Anterior cruciate ligament reconstruction (ACLr) is the most widely published operation in the orthopaedic literature. Over recent years there has been increased interest in the surgical technique and role of concomitant procedures performed during ACLr. The National Ligament Registry (NLR) collects robust data on ACLr performed in the UK. In this registry analysis we explore trends in ACLr surgery and how they relate to published literature and the growing industry portfolio available to surgeons. Methods. Using data from the NLR, 14,352 ACLr performed between 2013–2021 were analysed. High impact papers on ACLr were then cross referenced against this data to see if surgical practice was influenced by literature or whether surgical practice dictated publication. Common trends were also compared to key surgical industry portfolios (Arthrex, Smith and Nephew) to see how new technology influenced surgical practice. Results. The number of ACLr performed in isolation is decreasing. The number of ACL reconstructions involving meniscal surgery shows an increasing trend since 2013, with 57% of ACLr in 2021 now involving meniscus surgery. The number of ACLr with lateral extra-articular tenodesis (LET) has increased sharply since 2018, preceding the stability trial publication in 2020. Graft preference and size has remained static despite the introduction of new graft harvest and fixation devices. Additional procedures such as other ligament reconstruction and additional cartilage surgery have also remained static over time. Conclusion. In this analysis we looked at surgical trends in ACLr and their relation to literature and industry. Meniscal intervention is increasing, in keeping with the growing level of literature in this area. In the setting of LET, a high impact level 1 study appears to have significantly changed the practice of UK surgeons with a sharp increase in the number of LET procedures being performed. Industry appears to have little influence on the change in surgical trends, suggesting high quality evidence is what drives innovation in ACLr while industry supports rather than influences innovation. It will be interesting to see the impact of the stability 2 study, recent work on the medial structures of the knee and the commissioning of cartilage centres on future trends


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_18 | Pages 2 - 2
1 Dec 2023
Basheer S Kwaees T Tang C Ali F Haslam P Nicolaou N
Full Access

Objectives. Congenital cruciate ligament deficiency is a rare condition that may occur in isolation or in association with longitudinal limb deficiencies such as fibular hemimelia or proximal femoral focal deficiency. Often anomalies of the menisci and their attachments can be very abnormal and impact on surgical management by standard techniques. Arthroscopic surgical knee reconstruction is undertaken to improve symptomatic instability and/or to stabilise and protect the knee for future planned limb lengthening surgery. The aim of this study is to evaluate the arthroscopic findings of patients undergoing surgery for congenital cruciate ligament deficiency, and specifically to determine the frequency and types of meniscal anatomical variations seen in these cases. Methods. Patients undergoing surgery for congenital cruciate ligament deficiency were identified from a prospectively collated database. Diagnosis was confirmed through review of the clinical notes and imaging. Operative notes and 4K saved arthroscopic images and video recordings for these cases were reviewed. Results. Over a six-year period (July 2017 – September 2023), 42 patients underwent surgery for congenital ligament deficiency and tibiofemoral instability (45 surgical episodes). Median age of patients at time of surgery was 10 years (range 4 – 17 years). The most frequent diagnosis was congenital longitudinal limb deficiency syndromes in 27 cases, with the most frequent being fibular hemimelia. Isolated congenital ligament deficiency without any other associated extra-articular manifestations occurred in 11 cases. Absence of meniscal root attachments or hypertrophy of meniscofemoral ligaments acting as ‘pseudo-cruciates’ were seen in over 25% of patients. In isolated ACL deficiency these were injured causing onset of instability symptoms and pain following trauma. Often these abnormal structures required addressing to allow surgical reconstruction. Conclusions. Our findings demonstrate that there are often meniscal variations seen in association with congenital absence or hypoplasia of the cruciate ligaments. In these patients hypertrophied meniscofemoral ligaments may act as cruciate-like structures and play a role in providing a degree of sagittal plane stability to the knee. However, when the knee becomes unstable to the point that cruciate ligament reconstruction is indicated, these meniscal variants may often require stabilisation using complex meniscal root repair techniques or variations to standard cruciate ligament reconstruction techniques to accommodate the variant anatomy


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_18 | Pages 7 - 7
1 Dec 2023
Jones M Pinheiro V Church S Ball S Williams A
Full Access

Introduction. To determine if elite athletes can return to professional sport after MCL or posterolateral (PLC) reconstruction using LARS ligaments. The secondary aims are to demonstrate the safety and efficacy of LARS by reporting sport longevity, subsequent surgeries, and complications. Methods. A retrospective review of all extra-articular knee ligament reconstructions, utilising a LARS synthetic ligament, by 3 sports knee surgeons between 2013 and 2020 was undertaken. All elite athletes aged over 16 years and a minimum of 2 years post reconstruction were included. No LARS were used for ACL reconstructions, and they were excluded if a LARS ligament was used for a PCL reconstruction. Return to play (RTP) was defined as competing at professional level or national/ international level in amateur sport. Results. Sixty-four (84.2%) MCL reconstructions and 12 (15.8%) PLC reconstructions were included. 52 (68.4%) underwent concomitant autograft cruciate(s) reconstruction including 6 (7.8%) bicruciate reconstructions. The mean age was 25.1 years (SD +/− 4.50). 35 (46.1%) were footballers and 35 (46.1%) were rugby players. Sixty-seven athletes (88.2%) returned to elite sport, 7 (9.2%) did not RTP and RTP status was unknown for 2 (2.6%) (Figure 1). 65 out of 67 (97.0%) RTP at the same/higher Tegner level. 56 (83.6%) and 20 (57.1%) were still playing at 2- and 5-years post-surgery Six (7.9%) players required further surgery due to irritation from the metal fixation implants. One had an inflammation adjacent to the synthetic material at the femoral end and the other cases involved the tibial staples. All six cases were able to RTP. One athlete, following bicruciate /MCL surgery had the LARS removed due to laxity. There was one MCL re-rupture, sustained while jumping, 4 years after returning to football. Conclusions. Utilising LARS in extra-articular knee ligament reconstructions allows 88.2% of athletes with a variety of knee ligament injuries to return to elite sport. The results compare well regarding RTP, complication, and revision rates with the published evidence for other types of MCL and PLC grafts. This, coupled with 57% of athletes still playing 5 years post-surgery suggests the LARS is safe and effective in these cases. For any figures or tables, please contact authors directly