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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_6 | Pages 24 - 24
2 May 2024
Lawrence J Woods S Roberts K Tuck E Balogh P Predeus A He P Polanski K Prigmore E Zhou D Webb S Jardine L
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The reliable production of _in vitro_ chondrocytes that faithfully recapitulate _in vivo_ development would be of great benefit for orthopaedic disease modelling and regenerative therapy(1,2). Current efforts are limited by off-target differentiation, resulting in a heterogeneous product, and by the lack of comparison to human tissue, which precludes detailed evaluation of _in vitro_ cells(3,4).

We performed single-cell RNA-sequencing of long bones dissected from first-trimester fetal limbs to form a detailed ‘atlas’ of endochondral ossification. Through 100-gene in-situ sequencing, we placed each sequenced cell type into its anatomical context to spatially resolve the process of endochondral ossification. We then used this atlas to perform deconvolution on a series of previously published bulk transcriptomes generated from _in vitro_ chondrogenesis protocols to evaluate their ability to accurately produce chondrocytes.

We then applied single-nuclear RNA-sequencing to cells from the best performing protocol collected at multiple time points to allow direct comparison between the differentiation of _in vitro_ and _in vivo_ cells.

We captured 275,000 single fetal cells, profiling the development of chondrocytes from multipotent mesenchymal progenitors to hypertrophic cells at full transcriptomic breadth. Using this atlas as the ground truth for evaluating _in vitro_ cells, we found substantial variability in cell states produced by each protocol, with many showing little similarity to _in vivo_ cells, and all exhibiting off-target differentiation.

Trajectory alignment between _in vivo_ and _in vitro_ single-cell data revealed key differences in gene expression dynamics between _in vitro_ and _in vivo cells,_ with several osteoblastic transcription factors erroneously unregulated _in vitro,_ including _FOXO1._

Using this information, we inhibited _FOXO1_ in culture to successfully increase chondrocyte yield _in vitro._

This study presents a new framework for evaluating tissue engineering protocols, using single-cell data to drive improvement and bring the prospect of true engineered cartilage closer to reality.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 8 - 8
1 Mar 2021
To K Bartlett J Lawrence J
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Various studies have demonstrated that the necessity for reversal of Warfarin through the use of Vitamin K (Vit K) in neck of femur fracture patients introduces increased duration of stay and poorer outcomes as measured by operative complications and mortality rate. One reason for this delay may be the time latency between admission and the clinicians decision to investigate the INR. In this study we aim to explore the different causes of latency which contribute to a delay to theatre and ascertain whether point of care testing may negate this.

We carried out an audit of a cohort of neck of femur fracture patients between 2012 and 2015. Between September 2011 and September 2013, paper notes of 25 patients who were on warfarin at the time of sustaining a Neck of femur fracture (NOF) was obtained within Addenbrookes hospital archives. An additional 80 patients records from the year 2015 were retrieved from EPIC digital records. Time intervals were recorded as follows (from time of A&E assessment by Medical doctor); Interval to orthopaedic specialist assessment, Interval to first INR order, Interval to first INR result seen by specialist, Interval to first Vit K prescribed, Interval to first Vit K given, Interval to Second INR ordered, Interval to second INR seen by specialist, Interval to operation time (as determined by time of team briefing). Analysis of the time intervals as a proportion of total time elapsed between A&E assessment and Time to theatre was performed. Point of care (POC) testing of INR on admission to A&E was introduced and a symmetrical time period was analysed for the same intervals.

The latency generated by time taken for a NOF to be assessed by an orthopaedic specialist occupied 8.60% of the total time, the interval between ordering and recording an INR value accounted for 7.96% of time to theatre, the interval between an INR being recorded and subsequently seen by a clinician accounted for 13.4% of time to theatre, the time between orthopaedic specialist assessment and prescription of Vit K took up 7.83% of the total time and the percentage time between Vit K prescription and administration was 12.3%. The time between the first dose of Vit K prescription and arriving at theatre accounted for 76.1% of latency and the time between viewing a second INR and time to theatre occupied 33% of the total time. Following introduction of POC INR testing, there was a statistically significant decrease in time taken for warfarin reversal and consequently a reduction between time of admission to time to theatres.

NOF patients who are on warfarin at time of injury introduces complexity to surgical management and planning for theatre. In our audit we demonstrate that causes of delay are distributed throughout the pathway of care and there are several stages. POC INR testing represents an effective method of reducing this latency and improves patient outcome.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_1 | Pages 19 - 19
1 Feb 2021
Wakelin E Plaskos C Shalhoub S Keggi J DeClaire J Lawrence J Koenig J Randall A Ponder C
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Introduction

Achieving a balanced joint with neutral alignment is not always possible in total knee arthroplasty (TKA). Intra-operative compromises such as accepting some joint imbalance, non-neutral alignment or soft-tissue release may result in worse patient outcomes, however, it is unclear which compromise will most impact outcome. In this study we investigate the impact of post-operative soft tissue balance and component alignment on postoperative pain.

Methods

135 patients were prospectively enrolled in robot assisted TKA with a digital joint tensioning tool (OMNIBotics with BalanceBot, Corin USA) (57% female; 67.0 ± 8.1 y/o; BMI: 31.9 ± 4.8 kg/m2). All surgeries were performed with a PCL sacrificing tibia or femur first techniques technique, using CR femoral components and a deep dish tibial insert (APEX, Corin USA). Gap measurements were acquired under load (average 80 N) throughout the range of motion during trialing with the tensioning tool inserted in place of the tibial trial. Component alignment parameters and post-operative joint gaps throughout flexion were recorded. Patients completed 1-year KOOS pain questionnaires. Spearman correlations and Mann-Whitney-U tests were used to investigate continuous and categorical data respectively. All analysis performed in R 3.5.3.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_2 | Pages 22 - 22
1 Feb 2020
Lawrence J Keggi J Randall A DeClaire J Ponder C Koenig J Shalhoub S Wakelin E Plaskos C
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Introduction

Soft-tissue balancing methods in TKA have evolved from surgeon feel to digital load-sensing tools. Such techniques allow surgeons to assess the soft-tissue envelope after bone cuts, however, these approaches are ‘after-the-fact’ and require soft-tissue release or bony re-cuts to achieve final balance. Recently, a robotic ligament tensioning device has been deployed which characterizes the soft tissue envelope through a continuous range-of-motion after just the initial tibial cut, allowing for virtual femoral resection planning to achieve a targeted gap profile throughout the range of flexion (figure-1). This study reports the first early clinical results and patient reported outcomes (PROMs) associated with this new technique and compares the outcomes with registry data.

Methods

Since November 2017, 314 patients were prospectively enrolled and underwent robotic-assisted TKA using this surgical technique (mean age: 66.2 ±8.1; females: 173; BMI: 31.4±5.3). KOOS/WOMAC, UCLA, and HSS-Patient Satisfaction scores were collected pre- and post-operatively. Three, six, and twelve-month assessments were completed by 202, 141, and 63 patients, respectively, and compared to registry data from the Shared Ortech Aggregated Repository (SOAR). SOAR is a TJA PROM repository run by Ortech, an independent clinical data collection entity, and it includes data from thousands of TKAs from a diverse cross-section of participating hospitals, teaching institutions and clinics across the United States and Canada who collect outcomes data. PROMs were compared using a two-tailed t-test for non-equal variance.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_2 | Pages 1 - 1
1 Feb 2020
Plaskos C Wakelin E Shalhoub S Lawrence J Keggi J Koenig J Ponder C Randall A DeClaire J
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Introduction

Soft tissue releases are often required to correct deformity and achieve gap balance in total knee arthroplasty (TKA). However, the process of releasing soft tissues can be subjective and highly variable and is often perceived as an ‘art’ in TKA surgery. Releasing soft tissues also increases the risk of iatrogenic injury and may be detrimental to the mechanically sensitive afferent nerve fibers which participate in the regulation of knee joint stability.

Measured resection TKA approaches typically rely on making bone cuts based off of generic alignment strategies and then releasing soft tissue afterwards to balance gaps. Conversely, gap-balancing techniques allow for pre-emptive adjustment of bone resections to achieve knee balance thereby potentially reducing the amount of ligament releases required. No study to our knowledge has compared the rates of soft tissue release in these two techniques, however. The objective of this study was, therefore, to compare the rates of soft tissue releases required to achieve a balanced knee in tibial-first gap-balancing versus femur-first measured-resection techniques in robotic assisted TKA, and to compare with release rates reported in the literature for conventional, measured resection TKA [1].

Methods

The number and type of soft tissue releases were documented and reviewed in 615 robotic-assisted gap-balancing and 76 robotic-assisted measured-resection TKAs as part of a multicenter study. In the robotic-assisted gap balancing group, a robotic tensioner was inserted into the knee after the tibial resection and the soft tissue envelope was characterized throughout flexion under computer-controlled tension (fig-1). Femoral bone resections were then planned using predictive ligament balance gap profiles throughout the range of motion (fig-2), and executed with a miniature robotic cutting-guide. Soft tissue releases were stratified as a function of the coronal deformity relative to the mechanical axis (varus knees: >1° varus; valgus knees: >1°). Rates of releases were compared between the two groups and to the literature data using the Fischer's exact test.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_2 | Pages 21 - 21
1 Feb 2020
DeClaire J Lawrence J Keggi J Randall A Ponder C Koenig J Shalhoub S Wakelin E Plaskos C
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Background

Achieving good ligament balance in total knee arthroplasty (TKA) is essential to prevent early failure and revision surgery. Poor balance and instability are well-defined, however, an ideal ligament balance target across all patients is not well-understood. In this study we investigate the achieved ligament balance using an imageless, intra-operative dynamic balancing tool and its relation to patient reported outcomes.

Methods

A prospective, multi-surgeon, multi-center study investigated the use of a dynamic ligament-balancing tool in combination with a robotic-assisted navigation platform using the APEX knee (OMNI-Corin, Raynham MA). After all resections, the femoral trial and a computer-controlled tensioning device in place of the tibial tray was inserted into the knee joint. The difference in medial and lateral (ML) gaps when balancing the knee under constant load at extension (10°), mid-flexion (30°) and flexion (90°) was captured. Patients completed the KOOS questionnaire at 3 months ± 2 weeks post-surgery and considered the past 7 days as a timeframe for responses. Pearson's correlation was used to determine linear correlations between factors and ANOVA tests were used to determine differences in categorical data.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_2 | Pages 7 - 7
1 Feb 2020
Wakelin E Shalhoub S Lawrence J DeClaire J Koenig J Ponder C Randall A Keggi J Plaskos C
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Introduction

Achieving a well-balanced midflexion and flexion soft tissue envelope is a major goal in Total Knee Arthroplasty (TKA). The definition of soft tissue balance that results in optimal outcomes, however, is not well understood. Studies have investigated the native soft tissue envelope in cadaveric specimen and have shown loosening of the knee in flexion, particularly on the lateral side. These methods however do not reflect the post TKA environment, are invasive, and not appropriate for intra-operative use. This study utilizes a digital gap measuring tool to investigate the impact of soft tissue balance in midflexion and flexion on post-operative pain.

Methods

A prospective multicenter multi-surgeon study was performed in which patients underwent TKA with a dynamic ligament-balancing tool in combination with a robotic-assisted navigation platform. All surgeries were performed with APEX implants (Corin Ltd., USA) using a variety of tibia and femur first techniques. Gap measurements were acquired under load (average 80 N) throughout the range of motion during trialing with the balancing tool inserted in place of the tibial trial. Patients completed KOOS pain questionnaires at 3months±2weeks post-op. Linear correlations were investigated between KOOS pain and coronal gap measurements in midflexion (30°–60°) and flexion (>70°). T-tests were used to compare outcomes between categorical data.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_9 | Pages 6 - 6
1 May 2018
Bartlett J Lawrence J Yan M Guevel B Stewart M Khanduja V
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Introduction

Decreases in trainees' working hours, coupled with evidence of worse outcomes when hip arthroscopies are performed by inexperienced surgeons, mandate the development of additional means of arthroscopic training. Though virtual reality simulation training has been adopted by other surgical specialities, its slow uptake in arthroscopic training is due to a lack of evidence as to its benefits. These benefits can be demonstrated through learning curves associated with simulator training – with practice reflecting measurable increases in validated performance metrics.

Materials & Methods

Twenty-five medical students completed seven simulated arthroscopies of a healthy virtual hip joint in the supine position on a simulator previously shown to have construct validity. Twelve targets had to be visualised within the central compartment; six via the anterior portal, three via the anterolateral portal and three via the posterolateral portal. Eight students proceeded to complete seven probe examinations of a healthy virtual hip joint. Eight targets were probed via the anterolateral portal. Task duration, number of collisions with soft tissue and bone, and distance travelled by arthroscope were measured by the simulator for every session.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_12 | Pages 46 - 46
1 Jun 2017
Lawrence J Khanduja V Audenaert E
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Hip arthroscopy is a rapidly expanding technique that has a steep learning curve. Simulation may have a role in helping trainees overcome this. However there is as yet no validated hip arthroscopy simulator. This study aimed to test the construct validity of a virtual reality hip arthroscopy simulator.

Nineteen orthopaedic surgeons performed a simulated arthroscopic examination of a healthy hip joint in the supine position. Surgeons were categorized as either expert (those who had performed 250 hip arthroscopies or more) or novice (those who had performed fewer than this). Twenty-one targets were visualized within joint; nine via the anterior portal, nine via the anterolateral and three via the posterolateral. This was followed by a task testing basic probe examination of the joint in which a series of eight targets were probed via the anterolateral portal. Each surgeon's performance was evaluated by the simulator using a set of pre-defined metrics including task duration, number of soft tissue & bone collisions, and distance travelled by instruments. No repeat attempts at the tasks were permitted. Construct validity was then evaluated by comparing novice and expert group performance metrics over the two tasks using the Mann–Whitney test, with a p value of less than 0.05 considered significant.

On the visualization task, the expert group outperformed the novice group on time taken (P=0.0003), number of collisions with soft tissue (P=0.001), number of collisions with bone (P=0.002) and distance travelled by the arthroscope (P=0.02). On the probe examination, the two groups differed only in the time taken to complete the task (P=0.025).

Increased experience in hip arthroscopy was reflected by significantly better performance on the VR simulator across two tasks, supporting its construct validity.

This study validates a virtual reality hip arthroscopy simulator and supports its potential for developing basic arthroscopic skills.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_12 | Pages 49 - 49
1 Jun 2017
Bartlett J Lawrence J Khanduja V
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To quantify the risk posed to the Lateral Femoral Cutaneous Nerve (LFCN) during Total Hip Arthroplasty using the Minimally Invasive Anterior Approach (MIAA), and during placement of the Anterior Portal (AP) in Supine Hip Arthroscopy (SHA).

Forty-five hemipelves from thirty-nine cadavers were dissected. The LFCN was identified proximal to the inguinal ligament (IL), and its path in the thigh identified. The positions of the nerve and its branches in relation to the MIAA incision and the site for AP placement were measured using Vernier Callipers.

44% of nerves crossed the incision line used in the MIAA, at an average distance of 47 ± 28mm from the proximal end of the incision. Of those that did not cross the incision line, the average minimum distance between the nerve and incision was 14.4 ± 7.4mm, occurring on average 74.0 ± 37.3mm from the proximal end of the incision. In addition, the AP was placed in the path of the nerve on 38% of occasions. The nerve took an oblique path, and when found not to intersect with the AP portal, was located 5.7 ± 4.5mm from the portal's edge. We found a reduction in risk if the portal is moved medially or laterally by 15mm from its current location.

The LFCN is at high risk of injury during both THA using the MIAA and SHA using the AP. Our study emphasises the need for meticulous dissection during these procedures, and thorough explanation of these risk whilst consenting patients. We suggest that relocation of the AP 15mm more laterally or medially will reduce the risk posed to the LFCN.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_8 | Pages 52 - 52
1 Apr 2017
Cundall-Curry D Lawrence J
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Background

Since it's establishment in 2007, the National Hip Fracture Database [NHFD] has been the key driving force in improving care for hip fracture patients across the UK. It has facilitated the setting of standards to which all musculoskeletal units are held, and guides service development to optimise outcomes in this group of patients. As with any audit, the ability to draw conclusions and make recommendations for changes in practise relies on the accuracy of data collection. This project aimed to scrutinise the data submitted to the NHFD from a Major Trauma Centre [MTC], focusing on procedure coding, and discuss the implications of any inaccuracies.

Method

The authors performed a retrospective analysis of all procedure coding data entered into the NHFD from July 2009 to July 2014 at Cambridge University Hospitals NHS Foundation Trust. We examined 1978 cases for discrepancies, comparing procedure codes entered into the NHFD with post-procedure imaging and operative notes.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_19 | Pages 9 - 9
1 Nov 2016
Lawrence J Nasr P Fountain D Berman L Robinson A
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Aims

This prospective cohort study aimed to determine if the size of the tendon gap following acute tendo Achillis rupture influences the functional outcome following non-operative treatment.

Patients and methods

All patients presenting with acute unilateral tendo Achillis rupture were considered for the study. Dynamic ultrasound examination was performed to confirm the diagnosis and measure the gap between ruptured tendon ends. Outcome was assessed using dynamometric testing of plantarflexion and the Achilles tendon rupture score (ATRS) six months after the completion of a rehabilitation programme.