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Bone & Joint Open
Vol. 4, Issue 11 | Pages 873 - 880
17 Nov 2023
Swaby L Perry DC Walker K Hind D Mills A Jayasuriya R Totton N Desoysa L Chatters R Young B Sherratt F Latimer N Keetharuth A Kenison L Walters S Gardner A Ahuja S Campbell L Greenwood S Cole A

Aims

Scoliosis is a lateral curvature of the spine with associated rotation, often causing distress due to appearance. For some curves, there is good evidence to support the use of a spinal brace, worn for 20 to 24 hours a day to minimize the curve, making it as straight as possible during growth, preventing progression. Compliance can be poor due to appearance and comfort. A night-time brace, worn for eight to 12 hours, can achieve higher levels of curve correction while patients are supine, and could be preferable for patients, but evidence of efficacy is limited. This is the protocol for a randomized controlled trial of ‘full-time bracing’ versus ‘night-time bracing’ in adolescent idiopathic scoliosis (AIS).

Methods

UK paediatric spine clinics will recruit 780 participants aged ten to 15 years-old with AIS, Risser stage 0, 1, or 2, and curve size (Cobb angle) 20° to 40° with apex at or below T7. Patients are randomly allocated 1:1, to either full-time or night-time bracing. A qualitative sub-study will explore communication and experiences of families in terms of bracing and research. Patient and Public Involvement & Engagement informed study design and will assist with aspects of trial delivery and dissemination.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_9 | Pages 22 - 22
1 Oct 2022
Owen D Snuggs J Michael A Cole A Chiverton N Breakwell L Sammon C Le Maitre C
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Background

Current clinical treatment for spinal instability requires invasive spinal fusion with cages and screw instrumentation. We previously reported a novel injectable hydrogel (Bgel), which supports the delivery and differentiation of mesenchymal stem cells (MSCs) to bone forming cells and supports bone formation in vivo. Here, we investigated whether this system could be utilised to induce bone formation within intervertebral disc tissue as a potential injectable spinal fusion approach.

Methodology

Bovine and Human Nucleus pulpous tissue explants were injected with Bgel with and without MSCs. Tissue samples were cultured under hypoxia (5%) in standard culture media for 4 weeks. Cell viability, histological assessment of matrix deposition, calcium formation, and cell phenotype analysis using immunohistochemistry for NP matrix and bone markers.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_8 | Pages 5 - 5
1 Aug 2022
Wardell D Jayasuriya R Totton N Mills A Breakwell L Cole A
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Thermal sensors have been used in bracing research as self-reported diaries are inaccurate. Little is known about new low-profile sensors, optimal location within a brace, locational thermal micro-climate and effect of brace lining. Our objective is to Determine an optimal temperature threshold for sensor-measured and true wear time agreement. Identify optimal sensor location. Assess all factors to determine the best sensor option for the Bracing AdoleScent Idiopathic Scoliosis (BASIS) multicentre RCT.

Seven Orthotimer and five iButton (DS1925L) sensors were synchronised to record temperature at five-minute intervals. Three healthy participants donned a rigid spinal brace, embedded with both sensors across four anatomical locations (abdomen/axilla/lateral-gluteal/sacral). Universal-coordinated-time wear protocols were performed in/out-doors. Intraclass correlation coefficient (ICC) assessed sensor-measured and true wear time agreement at thresholds 15–36oC.

Optimal thresholds, determined by largest ICC estimate: Orthotimer: Abdomen=26oC, axilla=27oC, lateral-gluteal=24.5oC, sacral=22.5oC. iButton: Abdomen=26oC, axilla=27oC, lateral-gluteal=23.5oC, sacral=23.5oC. Warm-up time and error at optimal thresholds increased for moulded sensors covered with 6mm lining.

Location: anterior abdominal wall. Excellent reliability and higher optimal thresholds, less likely to be exceeded by ambient temperature; not a pressure area. Sensor: iButton, longer battery life and larger memory than Orthotimer; allows recording at 10 min intervals for life of brace. Orthotimer only able to record every 30 mins, increasing error between true and measured wear time; Orthotimer needs 6-monthly data download. Threshold: 26oC is optimal threshold to balance warm-up and cool-down times for accurately measuring wear time. Sensor should not be covered by lining foam as this significantly prolongs warm-up time.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_10 | Pages 4 - 4
1 Oct 2019
Partridge S Snuggs J Thorpe A Cole A Chiverton N Le Maitre C Sammon C
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Introduction

Injectable hydrogels via minimally invasive surgery offer benefits to the healthcare system, reduced risk of infection, scar formation and the cost of treatment. Development of new treatments with the use of novel biomaterials requires significant pre-clinical testing and must comply with regulations before they can reach the bedside. In the European economic area (EEA) one of the first hurdles of this process is attaining the CE marking which protects the health, safety and environmental aspects of a product. Implanted materials fall under the class III medical device EU745 regulation standards. To attain the CE marking for a product parties must provide evidence of the materials safety with an investigational medicinal product dossier (IMPD).

Methods and Results

We have been working to develop a new thermoresponsive injectable biomaterial hydrogel (NPgel) for the treatment of intervertebral disc (IVD) disease. A large part of the IMPD requires information on how the hydrogel physical properties change over time in bodily conditions. We have been studying 6 batches of NPgel over 18 months, tracking the materials wet/ dry weight, structure and composition. To date we have found that NPgel in liquids more similar to the body (with protein and salts) appear to be stable and safe, whilst those in distilled water swell and disintegrate over time. Subtle long-term changes to the material composition were found and we are currently investigating its ramifications.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_10 | Pages 45 - 45
1 Oct 2019
Partridge S Snugg J Michael A Cole A Chiverton N Sammon C Maitre C
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Introduction

Low back pain is the leading cause of musculoskeletal disease and the biggest cause of morbidity worldwide. Approximately 40% of these are cases are caused by disease of the intervertebral discs (IVDs): the shock absorbing, flexible material located between the bones (vertebrae) along the length of the spine. In severe cases, the spine becomes unstable and it becomes necessary to immobilise or fix the joint in position using a lumbar cage spacer between in the IVD and metal pins with supporting plates in the vertebrae. This is a complex, expensive, major surgery and it is associated with complications, such as spinal fusion failure and inappropriate implant position. These complications have a dramatic impact on the quality of life of the affected patients and the burden to society and the healthcare system is exacerbated.

Methods and Results

We present an in vitro study looking at the effect of our Bgel hydrogel on mesenchymal stem cells (MSCs) and their bone forming capacity within lumbar cages: devices used to space the bones apart in the fusion operation, as a mechanism to improve fixation and intra cage bone formation. MSCs were isolated from human hip joint, expanded, seeded within Bgel, cast into well inserts or lumbar cages and cultured for 4 weeks. Using 3D X-ray imaging micro computed tomography (μCT) scans we show that the MSC in the presence Bgel begin to mineralise within the lumbar cages. Histology is currently ongoing and will be presented at the meeting.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_10 | Pages 17 - 17
1 Oct 2019
Snuggs J Thorpe A Partridge S Chiverton N Cole A Michael A Sammon C Le Maitre C
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Purpose of study and background

We have previously reported the development of injectable hydrogels for potential disc regeneration (NPgel) or bone formation which could be utilized in spinal fusion (Bgel). As there are multiple sources of mesenchymal stem cells (MSCs), this study investigated the incorporation of patient matched hMSCs derived from adipose tissue (AD) and bone marrow (BM) to determine their ability to differentiate within both hydrogel systems under different culture conditions.

Methods and Results

Human fat pad and bone marrow derived MSCs were isolated from femoral heads of patients undergoing hip replacement surgery for osteoarthritis with informed consent. MSCs were encapsulated into either NPgel or Bgel and cultured for up to 6 weeks in 5% (NPgel) or 21% (Bgel) O2. Histology and immunohistochemistry was utilized to determine phenotype. Both fat and bone marrow derived MSCs, were able to differentiate into both cell lineages. NPgel culture conditions increased expression of matrix components such as collagen II and aggrecan and NP phenotypic markers FOXF1 and PAX1, whereas Bgel induced expression of collagen I and osteopontin, indicative of osteogenic differentiation.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_10 | Pages 22 - 22
1 Oct 2019
Snuggs J Thorpe A Hutson C Partridge S Chiverton N Cole A Sammon C Le Maitre C
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Purpose of study and background

IVD degeneration is a major cause of Low back pain. We have previously reported an injectable hydrogel (NPgel), which induces differentiation of human MSCs to disc cells and integrates with NP tissue following injection in vitro. However, the translation of this potential treatment strategy into clinic is dependent on survival and differentiation of MSCs into disc cells within the degenerate IVD. Here, we investigated the viability and differentiation of hMSCs incorporated into NPgel cultured under conditions mimicking the healthy and degenerate microenvironment of the disc.

Methods and Results

MSCs were cultured in NP gel under 5% O2 in either: standard culture (DMEM, pH7.4); healthy disc (DMEM, pH7.1); degenerate disc (low glucose DMEM, pH6) or degenerate disc plus IL-1β. Following 4 weeks histological staining and immunohistochemical analysis investigated viability, ECM synthesis and matrix degrading enzyme expression.

Here we have shown that viability and NP cell differentiation of MSCs incorporated within NPgel was mostly unaffected by treatment with conditions such as low glucose, low pH and the presence of cytokines, all regarded as key contributors to disc degeneration. In addition, the NPgel was shown to prevent MSCs from displaying a catabolic phenotype with low expression of degradative enzymes, highlighting the potential of NPgel to differentiate hMSCs and protect them from the degenerate disc microenvironment.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_9 | Pages 7 - 7
1 Sep 2019
Snuggs J Chiverton N Cole A Michael R Bunning R Conner M Le Maitre C
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Introduction

The intervertebral disc (IVD) is a highly hydrated and hyperosmotic tissue, water and salt content fluctuate daily due to mechanical loading. Resident IVD cells must adapt to this ever-changing osmotic environment, to maintain normal behaviour. However, during IVD degeneration the disc becomes permanently dehydrated and cells can no longer perform their correct function. Here, we investigated how human nucleus pulposus (NP) cells respond to altered osmolality with regards to cell size and the rate of water permeability, along with the potential involvement of aquaporins (AQPs) and transient receptor potential vanilloid (TRPV) membrane channels.

Methods

Water permeability of NP cells exposed to altered osmolality (225–525mOsm/kg) in the presence or absence of AQP and TRPV channel inhibitors was investigated with the cell-permeable calcein-AM fluorescent dye, and cell size determined using microscopy and flow cytometry.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_9 | Pages 22 - 22
1 Sep 2019
Thorpe A Partridge S Snuggs J Vickers L Charlton F Cole A Chiverton N Sammon C Le Maitre C
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Background

Intervertebral disc (IVD) degeneration is a major cause of low back pain (LBP). We have developed an injectable hydrogel (NPgel), which following injection into bovine IVD explants, integrates with IVD tissue and promotes disc cell differentiation of delivered mesenchymal stem cells (MSCs) without growth factors. Here, we investigated the injection of NPgel+MSCs into IVD explants under degenerate culture conditions.

Methods and Results

The NPgel integrated with bovine and human degenerate Nucleus Pulposus (NP) tissue and hMSCs produced matrix components: aggrecan, collagen type II and chondroitin sulphate in standard and degenerate culture conditions. Significantly increased cellular immunopositivty for aggrecan was observed within native NP cells surrounding the site where NPgel+MSCs were injected (P≤0.05). In NP explants a significant decrease in catabolic factors were observed where NPgel+MSCs was injected in comparison to controls.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_9 | Pages 17 - 17
1 Sep 2019
Reddington M Walters S Cohen J Baxter S Cole A
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Purpose of the study

To investigate the feasibility of undertaking a definitive Randomised Controlled Trial (RCT) to determine the effectiveness of early physiotherapy for sciatica.

Methods

Patients over 18 presenting to their G.P with sciatica were eligible to participate in the study, those without a clear understanding of English or had co-morbidities preventing rehabilitation were ineligible. Process and patient reported outcomes including self-rated disability, pain and general health, were collected at baseline, 6,12 and 26 weeks post randomisation.

Participants were randomised into either early physiotherapy, receiving treatment within 2 weeks after randomisation or usual care with physiotherapy commencing 6 weeks post randomisation. Both groups received up to 6 treatment sessions of a patient-centred, goal orientated physiotherapy programme specific to their needs.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_9 | Pages 18 - 18
1 Sep 2019
Reddington M Walters S Cohen J Baxter S Cole A
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Purpose of the study

The aims of the study were to explore the experiences of sciatica sufferers, their perceptions of physiotherapy and healthcare service provision.

Methods

This was the qualitative element of a mixed methods study investigating the feasibility of early physiotherapy for sciatica. Participants in the pilot trial consented to take part in semi-structured interviews before and after they had undertaken an individualised physiotherapy programme. Data from the interviews was examined line by line using a thematic analysis approach with key themes and sub-themes emerging.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_16 | Pages 118 - 118
1 Nov 2018
Snuggs J Cole A Chiverton N Conner M Bunning R Risbud M Le Maitre C
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The IVD is a highly hydrated, hyperosmolar tissue that allows the correct biomechanical function of the spine. When degenerated, water and ions are lost from the disc, especially within the central nucleus pulposus (NP), producing a hypoosmotic environment in which the resident cells can no longer function correctly, exacerbating the degenerative cascade. One potential way that IVD cells may adapt to their environment is through the expression and regulation of aquaporin (AQP) channels that control the movement of water in and out of cells. During human IVD degeneration AQP1 and 5 expression is decreased, highlighting AQPs may be of importance for the correct function of NP cells. The regulation of AQPs in NP cells by healthy and degenerate conditions, and the potential underlying molecular mechanisms, were investigated in both human and rat IVD cells. The gene and protein expression of AQP1 and AQP5 was upregulated by hyperosmotic conditions (425mOsm/kg H2O) in rat and human NP cells. Lentiviral knockdown of tonicity enhancer binding protein (TonEBP), a transcription factor responsible for maintaining the function of NP cells, resulted in the loss of AQP1 and 5 gene expression under hyperosmotic conditions. The maintenance of the IVD environment and adaptation of cells is vital for the function of the IVD. The regulation of AQPs by physiological conditions and TonEBP suggests a role for these water channels related to the adaptation of disc cells to their environment, which is dysregulated during degeneration.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_2 | Pages 18 - 18
1 Feb 2018
Snuggs J Day R Chiverton N Cole A Bunning R Conner M Tryfonidou M Le Maitre C
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Introduction

During development the central disc contains large, vacuolated notochordal (NC) cells which in humans are replaced by mature nucleus pulposus (NP) cells during aging, but are maintained in certain breeds of dogs. During degeneration the disc becomes less hydrated which affects its normal function. Aquaporins (AQP) are a family of 13 transmembrane channel proteins that allow passage of water and are responsible for maintaining water homeostasis. AQP1, 2, 3 and 5 have been identified in the intervertebral disc (IVD). Here, expression of AQPs in human and canine IVDs to determine expression in NC v/s NP cells and whether expression changes during degeneration.

Methods

Gene expression of all 13 AQPs, were investigated in 102 human NP samples using RT-qPCR. AQPs which were expressed at gene level were further investigated by Immunohistochemistry in human and canine IVD samples.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_2 | Pages 17 - 17
1 Feb 2018
Thorpe A Vickers L Charlton F Cole A Chiverton N Sammon C Le Maitre C
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Background

Intervertebral disc (IVD) degeneration is a major cause of Low back pain (LBP). We have reported an injectable hydrogel (NPgel), which following injection into bovine NP explants, integrates with NP tissue and promotes NP cell differentiation of delivered mesenchymal stem cells (MSCs) without growth factors. Here we investigated the injection of NPgel+MSCs into bovine NP explants under degenerate culture conditions to mimic the in vivo environment of the degenerate IVD.

Methods

hMSCs were incorporated within liquid NPgel and injected into bovine NP explants alongside controls. Explants were cultured for 6 weeks under hypoxia (5%) with ± calcium 5.0mM CaCl2 or IL-1β individually or in combination to mimic the degenerate microenvironment. Cell viability was assessed by caspase 3 immunohistochemistry. Histological and immunohistochemical analysis was performed to investigate altered matrix synthesis and matrix degrading enzyme expression.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_10 | Pages 24 - 24
1 May 2017
Snuggs J Chiverton N Cole A Michael R Bunning R Conner M Le Maitre C
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Introduction

Within the intervertebral disc (IVD), nucleus pulposus (NP) cells reside within a unique microenvironment. Factors such as hypoxia, osmolality, pH and the presence of cytokines all dictate the function of NP cells and as such the cells must adapt to their environment to survive. Previously we have identified the expression of aquaporins (AQP) within human IVD tissue. AQPs allow the movement of water across the cell membrane and are important in cellular homeostasis. Here we investigated how AQP gene expression was regulated by the microenvironment of the IVD.

Methods

Human NP cells were cultured in alginate beads prior to cytokine, osmolality, pH and hypoxia treatments and subsequent RT-qPCR to assess regulation of AQP gene expression.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_10 | Pages 23 - 23
1 May 2017
Snuggs J Day R Chiverton N Cole A Bunning R Conner M Le Maitre C
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Introduction

The intervertebral disc (IVD) is a highly hydrated tissue which is reduced during degeneration leading to loss of function. Aquaporins (AQP) are a family of 13 (AQP0-12) transmembrane channel proteins that selectively allow the passage of water and other small molecules in and out of cells and are responsible for maintaining water homeostasis. AQP1, 2, 3 and 5 have been identified in the IVD. Here gene and protein expression of all 13 AQPs was investigated in a large cohort of human IVDs to investigate expression during IVD degeneration.

Methods

Gene expression of all 13 AQPs was investigated in non-degenerate and degenerate tissue from 102 human NP samples using RT-qPCR. AQPs which were expressed at gene level were further investigated in 30 IVD samples by Immunohistochemistry.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_2 | Pages 4 - 4
1 Feb 2015
Park A Bettany-Saltikov J Cole A Ling J
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Aim

The primary aim of this pilot study was to assess and evaluate the SpineCor Pain Relief Brace as a method of reducing the pain experienced by patients diagnosed with degenerative scoliosis

Method

Participants (n=24) with an average age of 67 (+/− 8) old that fulfilled the study inclusion criteria were randomly allocated into either a treatment or control group. Both sets of participants received questionnaires (ODI, SF 36v2 and EQ5D-5L) at 1,3,6,9 and 18 months. In addition to the questionnaires the treatment group also received the SpineCor Pain Relief Brace and took part in a semi structured interview.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_15 | Pages 18 - 18
1 Oct 2014
Humphries T Baker M Lee LB Cole A Hughes-Lawson C Naylor B Michael A
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This study aimed to verify the accuracy of the DIERS Formetric Scan when assessing vertebral rotation of the apical vertebrae in Adolescent Idiopathic Scoliosis (A.I.S) patients, to determine whether the DIERS Formetric Scans can be used instead of or alongside radiographs when assessing A.I.S patients.

Both the radiographs and the DIERS Formetric Scans of 60 Preoperative A.I.S patients. All patients included in our study had predominant thoracic curves using the Lenke classification method, Cobb angle range 33° – 85°. Each radiograph was categorised into groups according to the severity of Nash-Moe rotation score of the apical vertebrae. Three groups were formed Nash-Moe +1 (20 patients), Nash-Moe +2 (27 patients), Nash-Moe +3 (13 patients). Each result was then compared to the maximal rotation analysed by the DIERS Formetric Scan, which took place on the same day as the radiographs. The results were then assessed using a Pearson Correlation Coefficient and a One-Way ANOVA with Post-Hoc Tukey HSD Analysis.

The Nash-Moe +1 Group scored a mean maximal rotation of 14.65° ±6.56 (11.82 – 17.48) (95% Confidence Interval), Nash-Moe +2 mean maximal rotation was 19.6° ±7.1 (16.92 – 22.28) and Nash-Moe +3 scored 21.53° ±8.9 (16.99 – 26.37). The Pearson Correlation Coefficient of this assessment was +0.342 (p value 0.07) demonstrating a weak positive correlation. The One-Way ANOVA analysis with Post-Hoc Tukey HSD analysis. The results of this analysis was an F value score of +4.115 (p Value 0.021) for the overall One-Way ANOVA test. The Post-Hoc Tukey HSD tests demonstrate that there is a statistical difference between Group 1 and Group 3 (p value 0.030) but there is no statistical difference between Group 1 and Group 2 (p value 0.068) as well as no statistical difference between Group 2 and Group 3 (p value 0.716).

DIERS Formetric Scan assessment of vertebral rotation shows a positive correlation with the Nash-Moe method. This allows us to rely on the Formetric scans and thus a possible reduction in radiographs when assessing A.I.S, this reduces the exposure to ionising radiation in A.I.S patients.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 15 - 15
1 Jul 2014
Binch A Phillips K Chiverton N Cole A Breakwell L Michael A Cross A Le Maitre C
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Summary

Cytokines produced within the degenerate disc induce expression of neurotrophic factors and pain related peptides which could be important in nerve ingrowth and pain sensitisation leading to low back pain.

The intervertebral disc (IVD) is considered the largest aneural and avascular structure within the human body, yet during degeneration vascularisation of the IVD is seen to be accompanied by nociceptive nerves. Low back pain is a highly debilitating condition affecting around 80% of the population, 40% of which are attributed to IVD degeneration. Discogenic pain was largely thought to be a result of irritation and compression of the nerve root, yet recent data suggests that pain may be attributed to the sensitisation of sensory nerves by the synthesis of pain related peptides, calcitonin gene related peptide (CGRP) and substance P. It is known that cytokines and chemokines produced by nucleus pulposus cells elicit various effects including the production of matrix degrading enzymes, and decreased matrix molecules. Here, we investigate the hypothesis that cytokines regulate both neurotrophic factor and pain related peptide synthesis within nucleus pulposus and nerve cells which may elicit algesic effects.

Real-Time PCR was performed to investigate gene expression of the neurotrophic factors NGF, BDNF, NT3 and their receptors Trk A, B and C along with Substance P and CGRP on directly extracted RNA from human NP cells and NP cells cultured in alginate for 2 weeks prior to treatment for 48hours with IL-1, IL-6 or TNFα at 0–100ng/mL. Similarly SH-SY5Y neuroblastoma cells were differentiated in retinoic acid for 7 days prior to stimulation with IL-1, IL-6 or TNFα at 0ng/mL and 10ng/mL for 48hours. Immunohistochemistry was used to localise neurotrophic factor receptors Trk A, B and C in both degenerate discs and neuronal cells.

NGF expression was present in normal and degenerate disc samples, however only degenerate discs expressed the high affinity receptor TrkA. Similarly Trk B was present in 22% of normal samples increasing to 100% expression within degenerate disc samples. All cytokines increased expression of NGF in NP cells (P≤0.05). TNFα also increased BDNF significantly, whereas no significant affects were seen in NT3 expression in NP cells. Trk B expression was significantly increased by IL-1 and TNFα treatment of NP cells. Conversely Trk C was down regulated by IL-6. Substance P was significantly increased by IL-1 and TNFα treatments whilst IL-6 and TNFα increased CGRP expression in NP cells. In SH-SY5Y cells, IL-1 significantly increased BDNF whilst IL-6 and TNFα failed to induce significant differences in neurotrophic factors. All cytokines increased Trk expression in the nerve cell line; however this failed to reach significance. Immunohistochemistry confirmed the presence of Trk receptors within the neuronal cell line.

Here we have demonstrated that a number of cytokines known to be up regulated during disc degeneration and disc prolapse, induce expression of various neurotrophic factors, their receptors and pain related peptides within human NP cells, as well as SH-SY5Y cells. This data suggests that the presence and production of cytokines within the degenerate disc may be responsible for nerve ingrowth and sensitisation of nerves which may result in discogenic pain.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 299 - 299
1 Jul 2014
Daniels J Phillips K Binch A Chiverton N Breakwell L Micheal A Cole A Dunn S Le Maitre C
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Summary

Anabolic and catabolic signalling processes within IVDs display overlapping pathways, however some pathways were identified as selective to catabolic signalling and inhibition of one of these pathways inhibited some of the catabolic factors induced by IL-1 although NFkB inhibition also affected anabolic expression.

Degeneration of intervertebral discs (IVDs) is implicated in 40% of low back pain cases. In the normal disc the balance between anabolic and catabolic processes are carefully balanced. During degeneration this balance is lost in favour of catabolic processes which lead to degradation of the IVD, infiltration of blood vessels and nerves and release of cytokines which sensitise nerves to pain. Interleukin 1 (IL-1) is known to be important in the pathogenesis of IVD degeneration, here we investigated the intracellular signalling pathways activated by IL-1 and those activated by an anabolic factor (CDMP-1) to investigate differential pathways.

Human nucleus pulposus cells (NP) removed during discetomy for nerve root pain were stimulated with IL-1 or CDMP-1 for 30 minutes. Site-specific phosphorylation of 46 signalling molecules were identified using R&D proteome array. The activation of ERK1/2, p38, c-jun, and IkB were confirmed using cell based ELISAs, in addition pNFκB localisation in stimulated cells was determined using immunohistochemisty. Pre-treatment with inhibitors to p38, and NFkB for 30 minutes, followed by stimulation with IL-1 (10ng/mL) or CDMP-1 (10ng/mL) for 24 hours was investigated to determine effects on anabolic and catabolic factors. In addition localisation of phosphorylated c-jun, p38 and NFkB were investigated within paraffin embedded sections of human IVD to investigate the presence of active pathways in vivo.

Twenty intracellular signalling pathways were activated following CDMP-1 treatment and 8 signalling pathways activated by IL-1. Of note key classical IL-1 signalling pathways p38 MAPK, ERK 1/2 and JNK were activated by IL-1, however of these ERK 1/2 particularly was also activated by CDMP-1, whilst p38 and c-jun were only activated by IL-1. IL-1 induced activation of NFkB signalling to a greater extent than CDMP-1, these results were confirmed by the ‘in cell ELISAs’. IVD tissue samples displayed immunopositive staining for phosphorylated c-jun, NFkB and p38. Inhibition of p38 signalling inhibited IL-1 induced MMP 13 expression, but had little effect on the induction of IL-8. However inhibitors of NFkB signalling pathway failed to inhibit the induction of MMP 13 but abrogated the induced IL-6 and IL-8 expression. IL-1 induced a complete aberration of aggrecan expression by NP cells in alginate culture, this effect was partly inhibited by p38 MAPK inhibitor but was completely restored by inhibiting NFkB signalling. However the aggrecan expressed in CDMP-1 treated cells was decreased by inhibiting NFkB but not p38.

Here, we have shown that anabolic and catabolic signalling processes within IVDs show a number of overlapping pathways, however a number of differential pathways were identified and inhibition of p38 MAPK and NFkB pathways inhibited a number of catabolic processes investigated which were induced by IL-1. Thus inhibition of signalling pathways could be a novel mechanism of inhibiting catabolic processes which could hold promise to inhibit degeneration at early stages of disease but also create the correct tissue niche to promote regeneration of the disc.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_6 | Pages 3 - 3
1 Apr 2014
Burwell G Aujla R Grevitt M Randell T Dangerfield P Cole A Pratt R Kirby A Polak F Web J Moulton A
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Aim:

Right-Handed Girls With Rt-Ais Measured Using Holtain Equipment Have Upper Arm Length Asymmetry (Right-Minus-Left) Which Is: 1) Relatively Longer On Scoliosis Curve Convexity; 2) Significantly Associated With Scoliosis Curve Severity (Cobb Angle And Apical Vertebral Rotation); And 3) Transient, Decreasing With Age And Years After Menarche [1,2]. The Aim Is To Test Whether The Right Upper Arm Length Relative Overgrowth And Spinal Deformity Severity Were Associated With Right Or Left Upper Arm Length Size-For-Age.

Method:

94 Right-Handed Girls With Rt-Ais, Age 11–18 Years, (Mean Cobb Angle 46 Degrees, Range 10–102 Degrees), Were Evaluated Using A Harpenden Anthropometer For Upper Arm Length Asymmetry, Plotted Against Right And Left Upper Arm Length Standard Deviation Scores (Sds), Calculated From 378 Normal Girls, Age 11–18 Years.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_6 | Pages 7 - 7
1 Apr 2014
Stedman T Smith L Cole A Breakwell L Michael A Naylor B
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Aim:

To Determine The Effect Of Posterior Instrumented Fusion On Lung Function In Patients With Idiopathic Scoliosis Aged 8–11.

Method:

Lung Function (Fvc And Fev1) Was Measured Before Surgery In 13 Patients (Aged 8 To 11) With Idiopathic Scoliosis. All Patients Had Curves Greater Than 50 And Had Undergone Posterior Instrumented Scoliosis Correction And Fusion With (3 Patients) Or Without (10 Patients) Same Day Anterior Convex Growth Arrest. Lung Function Tests Were Repeated 1–8 Years (Mean 5.3 Years) After Surgery. The Data Was Normalised To Take Into Account Standing Height And Loss Of Stature Due To Lateral Curvature, Allowing A Direct Comparison Of Percent Predicted Fev1 And Fvc Before And After Surgery.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_4 | Pages 28 - 28
1 Feb 2014
Newsome R Reddington M Breakwell L Chiverton N Cole A Michael A Boote J Dimairo M
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Purpose of study and background

The primary aim of the study was to test the feasibility of conducting a full RCT with economic analysis and help to inform the provision of physiotherapy in a specific sub-group of patients with sciatica

Methods

60 patients waiting for primary, unilateral, single level, lumbar micro-discectomy surgery were recruited and randomised into two groups. The intervention group received a new spinal physiotherapy regimen. Primary outcome measure was the number of patients who did not require surgery at the time of consent clinic. Secondary measures were the Visual Analogue Scale (VAS) Oswestry Disability Index (ODI) and EQ5DL, taken at recruitment, 1 week before surgery and 2 weeks and 3 months after surgery.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_4 | Pages 6 - 6
1 Feb 2014
Newsome R Reddington M Boote J Breakwell L Chiverton N Michael A Cole A Dimairo M
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Objectives

To investigate the views and experiences of patients with sciatica who have undergone a bespoke physiotherapy programme whilst awaiting primary lumbar microdiscectomy.

Methods

This is a qualitative study, nested within a preliminary RCT. All patients were listed for primary, single-level microdiscectomy surgery. In the experimental arm of the study 29 patients had up to 6 sessions of physiotherapy over an 8 week period while on the waiting list for lumbar microdiscectomy. After surgery, they were invited to participate in an in-depth semi-structured interview. At this time patients had either decided not to have the surgery, or had undergone surgery. Interviews were audio-recorded, transcribed, and thematically analysed. Two researchers were involved in the analysis of the data to ensure the interpretation of the findings was robust, credible and trustworhy.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_1 | Pages 187 - 187
1 Jan 2013
Sharma H Breakwell L Chiverton N Michael A Cole A
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Introduction

Spinal infections constitute a spectrum of disease comprising pyogenic, tuberculous, nonpyogenic-nontuberculous and postoperative spinal infections. The aim of this study was to review the epidemiology, diagnostic yield of first and second biopsy procedures and microbiology trends from Sheffield Spinal Infection Database along with analysing prognostic predictors in spinal infections.

Materials & methods

Sheffield Spinal Infection Database collects data prospectively from regularly held Spinal infection MDTs. We accrued 125 spinal infections between September 2008 and October 2010. The medical records, blood results, radiology and bacteriology results of all patients identified were reviewed. In patients with negative first biopsy, second biopsy is contemplated and parenteral broad spectrum antibiotic treatment initiated.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXVI | Pages 55 - 55
1 Jun 2012
Sharma H Breakwell L Chiverton N Michael A Townsend R Highland A Chapman A Cole A
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Introduction

Spinal infections constitute a spectrum of disease comprising pyogenic, tuberculous, nonpyogenic-nontuberculous and postoperative spinal infections. The aim of this study was to review the epidemiology, diagnostic yield of first and second biopsy procedures and microbiology trends from Sheffield Spinal Infection Database along with analysing prognostic predictors in spinal infections.

Materials and Methods

Sheffield Spinal Infection Database collects data prospectively from regularly held Spinal infection MDTs. We accrued 125 spinal infections between September 2008 and October 2010. The medical records, blood results, radiology and bacteriology results of all patients identified were reviewed. In patients with negative first biopsy, second biopsy is contemplated and parenteral broad spectrum antibiotic treatment initiated.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXVI | Pages 60 - 60
1 Jun 2012
Newsome R Reddington M Breakwell L Chiverton N Cole A Michael A
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Purpose

To question the reliability of Thoracic Spine pain as a red flag and symptoms of a possible cause of Serious Spinal Pathology (SSP).

Methods

The clinical notes and Magnetic Resonance Imaging (MRI) results of patients presenting to the Sheffield Spinal Service with Thoracic spine symptoms but no signs were retrospectively reviewed over the period of 2 year (September 2008-August 2010).

The clinical reason for request of Thoracic MRIs were noted and the patient notes were reviewed to determine their presentation, length of time of symptoms, age and also it was noted whether any other recognized red flag symptoms were present. Exclusion criteria consisted of patients referred with known SSP or myelopathic symptoms.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXVI | Pages 84 - 84
1 Jun 2012
Newsome R Reddington M Breakwell L Chiverton N Cole A Michael A
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Purpose

To evaluate the competencies of spinal extended scope physiotherapists (ESP) following the introduction of requesting rights for magnetic resonance imaging (MRI) one year later.

Methods

From September 2009 to August 2010 each MRI scan requested by the 2 spinal ESPs within the orthopaedic clinic was recorded along with their clinical diagnosis to ascertain why the scan was requested. This was indicated on a four point scale of likelihood of pathology which had been introduced to give evidence for MRI requesting rights. This was then audited to determine the total number of scans requested along with the accuracy or justification of the request.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXVII | Pages 30 - 30
1 Jun 2012
Burwell R Aujla R Grevitt M Randell T Dangerfield P Cole A Kirby A Polak F Pratt R Webb J Moulton A
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Introduction

In patients with adolescent idiopathic scoliosis (AIS), anomalous extra-spinal left-right skeletal length asymmetries in upper limbs, periapical ribs, and ilia beg the question as to whether these bilateral asymmetries are connected in some way with pathogenesis. The upper arm and iliac length asymmetries correlate significantly with adjacent spinal curve severity respectively in thoracic and lower (thoracolumbar and lumbar) spine. In lower limbs, skeletal length asymmetries and proximo-distal disproportion are unrelated to spinal curve severity. Overall, these observations raise questions about mechanisms that determine skeletal bilateral symmetry of vertebrates in health and disorder, and whether such mechanisms are involved in the cause of this disease. We investigated upper arm length (UAL) asymmetries in two groups of right-handed girls aged 11–18 years, with right thoracic adolescent idiopathic scoliosis (RT-AIS, n=98) from preoperative and screening referrals (mean Cobb angle 45°) and healthy controls (n=240).

Methods

Right and left UAL were measured with a Harpenden anthropometer of the Holtain equipment, by one of four observers (RGB, AAC, RKP, FJP). UAL asymmetry was calculated as UAL difference, right minus left, in mm. Repeatability of the measurements was assessed by technical error of the measurement (TEM) and coefficient of reliability (R).


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXVI | Pages 81 - 81
1 Jun 2012
Sharma H Spearman C Walter D Breakwell L Chiverton N Michael A Cole A
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Introduction

Medical Exposure Directive of the European Commission, 97/43/Euratom recommended setting-up local national diagnostic reference levels (DRLs) for the most common radiological examinations in order to comply with the law and to maintain safe clinical practice. There are no guidelines for spinal diagnostic and therapeutic procedures. The aims of this study were to evaluate local radiation doses & screening times for diagnostic spinal blocks, to look at PACS image intensifier films for diagnostic representation and to assess the accuracy of data in IR(ME) document.

Materials and Methods

Between 1/01/2009 and 15/07/2010, all spinal blocks done under care of three spinal surgeons (LB/NC/AAC) were reviewed. Images revisited on PACS for confirmation. We reviewed 229 patients (included single & two levels nerve root blocks, facet joint and lysis blocks). Data were collected with regard to radiation dose, screening times, third-quartile values used to establish DRLs, IR(ME) documentation and PACS fluoroscopic image documentation.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_IV | Pages 5 - 5
1 Mar 2012
Cole A Newsome R Chiverton N Breakwell L
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Objective

To investigate, through a randomised, single blind, Quasi-experimental trial, whether immediate physiotherapy after lumbar micro-discectomy enables patients to become independently mobile more rapidly with no increase in risk of complications.

Background data

Although studies have demonstrated the efficacy of rehabilitation after lumbar discectomy, nos have looked at physiotherapy commencing immediately post-operatively.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_IV | Pages 567 - 567
1 Oct 2010
Sharma S Breakwell L Cole A Douglas D Hughes C Naylor B Qaimkhani S
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Background: Surgery in adolescent idiopathic scoliosis is done mainly for cosmesis and outcomes are reported in terms of radiological measurements (Cobb angle), outcome questionnaires (SRS-22) and back surface measurements (Scoliometer & Quantec). Previous studies have shown correlations between SRS-22 and objective radiological and back surface measures at a point in time (Asher et al 2003 & 2004).

Aim: of the study was to evaluate the association between subjective and objective outcomes in posterior instrumented scoliosis correction.

Patients and Methods: 43 patients with late-onset thoracic idiopathic scoliosis were included in the study with 39 girls and 4 boys with a mean age 13.2 years. Mean pre-operative Cobb angle was 71o. The objective assessment of back surface was done using a scoliometer and the POTSI & Suzuki Hump Sum scores. The subjective assessment was done using the Scoliosis Research Society (SRS)-22 score. The assessments were done pre-operatively and then post-operatively at 8-weeks and one year.

Results: The average percentage improvement in various outcomes after surgery was as follows: Cobb angle (71%), Maximum Angle of Trunk Inclination (Max. ATI) (52 % at 8 weeks and 39 % at 1 year), POTSI (57%), Hump Sum (24%), SRS-Total (14%), SRS-self image (14%). Pre-operatively, there were good inter-correlations (r= 0.4–0.7) between the objective measures (Max. ATI, POTSI and Hump Sum). Significant correlation was found between SRS-22 total versus Cobb angle (p-0.001, r=0.41). No significant correlation was found between the SRS-22 (total & domains) versus the Max. ATI, POTSI or the Hump Sum scores. Post-operatively, good correlation (r=0.6) was again found between the objective measures (Max. ATI, POTSI and Hump Sum) of back surface measurements (absolute and percentage). No significant correlation was found between SRS-22 (domains & total) versus Cobb angle correction, Max. ATI, POTSI, or Hump Sum.

Conclusion: In this study SRS-22 was found to be responsive to change with surgery, especially the self-image/appearance domain. However the SRS-22 score after surgery and the change in this score did not correlate with the change in objective measures of back surface deformity after surgery.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_IV | Pages 499 - 499
1 Oct 2010
Tryfonidis M Anjarwalla N Cole A
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A number of studies have looked at the incidence of cervical rib in various ethnic groups, but have a number of limitations. This is the first large scale study looking at the incidence in White British with direct comparison to the Asian population. A total of 1545 consecutive cervical spine radiographs performed for any reason were collected and reviewed. 5.9% of White British and 24.9% of Asian patients had evidence of cervical rib. This was statistically significant (p< 0.0001, χ2 test). Asians are 5 times more likely compared to White British to have cervical rib (OR=5.303, 95% CI=3.825–7.354). An analysis of male Vs female difference as well as incidence of the various subtypes of cervical rib will be presented. We reccomend that the results of this study should

be considered in the assessment of patients with symptoms of thoracic outlet syndrome,

taken into account during review of cervical spine radiographs and

included in anatomy textbooks in the future.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 429 - 429
1 Jul 2010
Cooke G Breakwell L Douglas D Cole A
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Purpose: To assess quality of life in quadriplegic cerebral palsy (CP) after scoliosis surgery.

Methods: This is a study of 43 consecutive patients undergoing instrumented scoliosis correction for quadriplegic CP (2003–2008). The parents completed (telephone) the original DuPont questionnaire (Tsirikos et al 2004, JPO) and 4 additional questions. Each of the 17 items scores from 1 (best) to 5 (worst) with 3 being no change. Retrospective case note and radiograph review was performed.

Two patients had died by the time of follow-up (1 perioperative, 1 unrelated) leaving 41 patients (23 female, 18 male) for analysis. Mean age was 14.0 at surgery, mean follow-up of 2.6 years (0.25–5.3). GMFCS types 2–4 (8), 5 (31). Mean preoperative Cobb angle 78° and pelvic obliquity 18°. There were 34 posterior and 7 anterior and posterior instrumentations.

Results: Mean DuPont score for the original 13 questions was 2.00 compared with 1.75 in the DuPont study. The scores for individual questions ranged from 1.35 to 2.76. The mean score of the 4 additional questions was 2.43, related to transfer ability, reflux and communication. 95% of parents would recommend the surgery again. 75.6% reported an improvement in their child’s ability to sit. Cobb angle correction was 53%, pelvic obliquity correction was 47%. The mean DuPont score is not significantly correlated with Cobb angle or pelvic obliquity correction.

Conclusions: This is the first UK study evaluating the parental view of outcome for scoliosis surgery in quadriplegic CP. Outcome does not seem to be related to radiographic correction. 39 of 41 parents would recommend the surgery.

Ethics approval: none – Clinical Effectiveness Department & PALS

Interest Statement: None


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 378 - 378
1 Jul 2010
Newsome R Reddington M Breakwell L Chiverton N Cole A
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Purpose: To investigate whether patients who present with Lumbar radicular signs and symptoms and who have MRI scans reported as showing no nerve root compression, improve following Nerve Root Injection (NRI).

Methods: The clinic notes and MRI results of 127 patients who underwent NRI under the care of two spinal surgeons were reviewed retrospectively. Those patients with radicular pain and MRI scans reported as showing no nerve root compression were evaluated further. All patients had a selective NRI using a standard image intensifier guided oblique approach with 40 mg Kenalog and 1 ml 0.25% bupivacaine injected around the nerve root. The patients’ symptoms and signs were noted at the follow up appointment six weeks later.

Results: 43 of the 127 patients who underwent selective NRI had MRI scan reports suggesting no nerve root compression. Of the 47 patients 30 (69%) reported a significant improvement (p=0.0009) in their leg pain following the NRI, the remaining 13 patients reported no relief.

Conclusions: Clinicians treating patients presenting with lumbar radicular signs and symptoms should not rely on MRI report alone in the diagnosis and management of the patient. The results show that patients who exhibit lumbar radicular signs and symptoms who have non-concordant MRI results may still benefit from treatment (NRI).

Ethics approval: None required

Statement of interest: None


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 425 - 425
1 Jul 2010
Short J Breakwell L Cole A
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Purpose: To ascertain whether the methods of prone positioning we use have any influence on the incidence of perioperative critical incidents and development of postoperative liver dysfunction in our scoliosis patients.

Methods: A retrospective review of 72 patients undergoing posterior correction and fusion for scoliosis from August 2006 to November 2007. Details were recorded from anaesthetic charts, operation notes, blood results and cell salvage data.

Results: Patients ranged in age from 2 to 24 years. The methods of prone positioning were Transverse Bolsters (23), Allen Frame 4-point support (25), Lateral Bolsters (11) and the Knight Table (13). Perioperative haemodynamic instability was noted in 8% of patients on the Allen Frame, 43% on transverse bolsters, 15% on the Knight Table and 55% on lateral bolsters. Two cardiac arrests, one fatal and one with good recovery, both occurred on transverse bolsters. Of 22 other complications attributable to mechanical effects of prone positioning, 16 occurred on transverse bolsters, 4 on the Allen Frame, 1 on lateral bolsters and 1 on the Knight Table. 34% of patients had liver dysfunction postoperatively. None had been positioned on the Knight Table or lateral bolsters. There was no significant difference between the incidence of liver dysfunction associated with the Allen Frame or transverse bolsters.

Conclusion: Transverse bolsters are associated with a high number of critical incidents and should be avoided if possible.

Ethics approval – not required

Interest Statement - none


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 429 - 429
1 Jul 2010
Gummerson N Bishop N Cole A
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Purpose: to analyse the outcomes of scoliosis surgery in osteogenisis imperfecta (OI) in this single–surgeon series.

Methods: Case notes of OI patients having scoliosis surgery from September 2003 were analysed.

Results: 15 patients (three male) were identified. Mean age was 15.6 years (range 10–23). There were 11 cases of OI III and 4 cases of OI IV. The mean duration of bisphosphonate treatment was 6.1 years (range 2–10). The mean BMD was 0.840 g/cm2.

There was a double-curve in 10 cases, single-curve in 5. The mean Cobb-angle was 72°.

The standard construct was a double rod with pedicle/pelvic screws at the base, double claw at the proximal end and sublaminar wires at intervening levels. The most proximal level was T1–T4 in 13 cases. Instrumentation was carried to the pelvis in 7 cases. Intra-operative fractures occurred in 5 cases.

The mean blood loss was 999 mls (range 295–5500).

Spinal cord monitoring was abnormal in 3 cases. 1 case resulted in postoperative lower limb paralysis, which recovered.

The mean hospital stay was 7.5 days. Serious postoperative complications included one case of bilateral anterior compartment syndrome and one tibial fracture.

The mean curve correction was 31%. Two cases required revision surgery: extension of fusion to the pelvis.

The mean follow-up was 22.7 months (range 4–40). There was no measurable change in position over time.

Conclusion: Scoliosis surgery in OI is effective, but may have serious complications. Fusion to the pelvis should be considered, especially in OI III.

Ethics approval: None – Audit

Interest statement: None


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 377 - 377
1 Jul 2010
Konyves A Chiverton N Douglas D Breakwell L Cole A
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Purpose of study: There is a controversy in the surgical treatment of unstable thoracolumbar burst fractures scoring high on the Load Sharing Classification (LSC). We have been treating unstable thoracolumbar fractures with postero-lateral fusion using short segment instrumentation and in this study we investigated our complication rate.

Methods and results: We retrospectively reviewed notes and radiographs of patients presenting with thoracolumbar burst fractures and stabilised with a short-segment instrumented postero-lateral fusion between 1998 and 2007. We identified 31 patients who had adequate documentation and radiographs. Twenty patients had a high (> =7) LSC score and none of these fixations failed. Overall early and late complication rate was low (one wound infection, one dehiscence and four unrelated infections), the one metalwork failure related to infection. Fifty-five percent of patients returned to full-time work. Approximately 50% of correction of kyphosis was lost but the average kyphosis at final follow-up was 11 degrees that we thought was acceptable.

Conclusion: We concluded that treating unstable burst fractures with posterior instrumented fusion alone using a pedicle screw construct does not result in late instrumentation failure, high complication rate or unacceptable final deformity.

Ethics approval: None

Interest Statement: None


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_III | Pages 489 - 489
1 Sep 2009
Newsome R Reddington M Breakwell L Chiverton N Cole A
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Objective: To determine whether extended scope physiotherapists (ESP’s) in spinal clinics are able to accurately assess and diagnose patient pathology as verified by MRI findings.

Methods: This is a prospective study of 318 new spinal outpatients assessed and examined by one of two spinal ESP’s. 76 patients (24%) were referred for an MRI scan. At the time of request for MRI scan the likelihood of specific spinal pathology correlating with the MRI scan was noted on a four point scale dividing the patients into 4 groups:

Group 4 = Very high suspicion of pathology (n=41)

Group 3 = Moderate suspicion of pathology (n=21)

Group 2 = Some suspicion of pathology (n=10)

Group 1 = Pathology unlikely but scan indicated eg thoracic pain (n=4).

Results: Of the 76 patients referred for an MRI scan, 54 (71%) had an MRI scan result that would correlate with the clinical picture. Looking at the percentage of scans correlating with the clinical picture for each of the 4 groups:

Group 4: 88%

Group 3: 67%

Group 2: 40%

Group 1: 0%

Conclusion: Dividing the patients into groups by clinical suspicion is essential for evaluating a clinician’s ability in spinal assessment. Further evaluation of Consultants, Fellows and Specialist Registrars is on going. This type of study could form a basis for competency measures for staff development and training if they are undertaking extended roles.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_III | Pages 486 - 486
1 Sep 2009
Bridgens J Gleave M Douglas D Breakwell L Davies G Cole A
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Introduction: Blood conservation is important in surgery for adolescent idiopathic scoliosis due to the potential for significant blood loss and need to avoid allogeneic transfusion in young, commonly female, patients. Previous studies have shown that a combination of blood conservation methods may be effective in reducing the need for allogeneic blood transfusion. We have carried out a study to investigate if the sole use of intraoperative red cell salvage in surgery for adolescent idiopathic scoliosis is effective and can lead to a reduced rate of allogeneic transfusion.

Patients and Methods: 56 patients aged between 10 and 17 underwent posterior spinal surgery for correction of idiopathic scoliosis. In 34 patients intraoperative cell salvage was used and salvaged blood re-infused perioperatively. This group was compared with a control group of 22 patients in whom only allogeneic blood transfusion was used. All patients underwent hypotensive anaesthesia. Other forms of blood conservation, such as predonation, were not used. Data was gathered on patient demographics, operative details, quantity of blood reinfused, pre and post operative haemoglobin levels and total allogeneic transfusion requirement. Operative data was gathered prospectively and blood transfusion data provided by the transfusion centre.

Results: In the cell salvage group an average of 309mls of blood was reinfused and these patients were transfused an average of 1.8 units less allogeneic blood in the peri-and post-operative period (p< 0.001). 74% of these patients required no allogeneic blood compared with 27% in the control group. There were no complications related to the use of intraoperative red cell salvage.

Conclusion: Intraoperative red cell salvage is effective in reducing the need for allogeneic transfusion in children undergoing posterior surgery for scoliosis correction.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_III | Pages 482 - 482
1 Sep 2009
Tambe A Sharma S White G Chiverton N Cole A
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Introduction: Metastatic spinal disease continues to be a challenge in the management of patients with advanced malignancy. Anterior en bloc spondylectomy and stabilisation, a more extensive procedure, is favoured as it is thought to provide a curative resection and improve the overall outcome (Tomita et al,2002; Wiegel, 1999).

Aim: The aim of this study was to see if there is still a role for extensive posterior decompression (Wide laminectomy and transpedicular decompression) with stabilisation in the treatment of these patients which is the mode of treatment used in our institution and favoured by some others (Bauer, 1997)

Patients and Methods: We retrospectively reviewed a cohort of patients treated in our institute by extensive posterior decompression and stabilisation between 2000 to 2006. We excluded patients having haematological primaries and anterior surgery and those with inadequate data.

Outcome measures used were post operative mortality, Post operative improvement in Frankel score, level of pain perception, level of mobility and ability to perform activities of daily living.

Results: 52 patients had posterior surgery with Colarado instrumentation being used in a majority. There was a slight male preponderance with an average age of 67 years. The mean length of follow up was 12 months.57% patients were dead at last review. 52 % patients showed an improvement in Frankel scores. There was a significant decrease in analgesic requirement post operatively with an improvement in pain scores. Similarly there was an improvement in the ability to perform activities of daily living and the level of mobility. No major surgical complications were noted bar a few superficial wound infections. Revision surgery was done in 6 cases. In 2 it was for a tumour recurrence, for broken rods in 2 and converted to anterior in 2. There were 4 immediate peri operative deaths.

Conclusion: Our results are comparable to Bauer et al, 1997 and other series. Posterior spinal surgery is very much a viable treatment option to treat selected cases with metastatic spinal disease. It avoids all the complications and morbidity of anterior surgery while producing an overall improvement in pain, the quality of life, level of mobility and neurological status.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_III | Pages 434 - 434
1 Aug 2008
Burwell R Freeman B Dangerfield P Aujla R Cole A Kirby A Polak F Pratt R Webb J Moulton A
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The possibility that AIS aetiology involves undetected neuromuscular dysfunction is considered likely by several workers [1,2]. Yet in the extensive neuroscience research of idiopathic scoliosis certain neurodevelopmental concepts have been neglected. These include [3]:

a CNS body schema (“body in the brain”) for posture and movement control generated during development and growth by establishing a long-lasting memory, and

pruning of cortical synapses at puberty.

During normal development the CNS has to adapt to the rapidly growing skeleton of adolescence, and in AIS to developing spinal asymmetry from whatever cause. Examination of publications relating to the CNS body schema, parietal lobe and temporo-parietal junction [4,5] led us to a new concept: namely, that a delay in maturation of the CNS body schema during adolescence with an early AIS deformity at a time of rapid spinal growth results in the CNS attempting to balance the deformity in a trunk that is larger than the information on personal space (self) already established in the brain by that time of development. It is postulated that this CNS maturational delay allows scoliosis curve progression to occur – unless the delay is temporary when curve progression would cease. The maturational delay may be primary in the brain or secondary to impaired sensory input from end-organs [6], nerve fibre tracts [2,7,8] or central processing [9,10]. The motor component of the concept could be evaluated using transcranial magnetic stimulation [11].

Conclusion: Any maturational delay of the CNS body schema could impair postural mechanisms in girls and boys with or without early AIS deformity. The “body in the brain” concept adds a particular CNS mechanism (maturational delay) to the neuro-osseous timing of maturation (NOTOM) hypothesis for the pathogenesis of AIS [12,13]. The NOTOM hypothesis states that there are more girls than boys with progressive AIS because of different developmental timing of skeletal maturation and postural maturation between the sexes in adolescence [12,13].


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_III | Pages 445 - 445
1 Aug 2008
Burwell R Aujla R Dangerfield P Cole A Freeman B Kirby A Pratt R Webb J Moulton A
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In subjects with lumbar, thoracolumbar or pelvic tilt scoliosis no pattern of structural leg length inequality has been reported [1]. Forty-seven girls of 108 consecutive adolescent patients referred from routine scoliosis school screening during 1996–1999 had lower spinal scoliosis – lumbar (LS) 17, or thoracolumbar (TLS) 30 (mean Cobb angle 16 degrees, range 4–38 degrees, mean age 14.8 years, left curves 25). The controls were 280 normal girls (11–18 years, mean age 13.4 years). Anthropometric measurements were made of total leg lengths (LL), tibiae (TL) and feet (FL) by one observer (RGB) and asymmetries calculated for LL, TL and FL, as absolutes and percentage asymmetries of right/left lengths. There are no detectable changes of absolute asymmetries with age for LL, TL or FL in scoliotic or normal girls. Asymmetries are found in scoliotic girls compared with normals with relative lengthening on the right for each of LL (0.95%) and TL (0.99%) (each p< 0.001), but not FL (0.38%).

Conclusion: The relative lengthenings in the right leg are unrelated statistically to the severity or side of the lower spinal scoliosis; the cause is unknown and may be related to posture – free standing on the right leg [2] – to neuromuscular mechanisms, or to primary skeletal changes in growth plates of femur(s) and tibia(e).


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_III | Pages 445 - 445
1 Aug 2008
Burwell R Aujla R Freeman B Cole A Kirby A Pratt R Webb J Moulton A
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Patterns of extra-spinal skeletal length asymmetry have been reported for upper limbs [1] and ribcage [2] of patients with upper spine adolescent idiopathic scoliosis. This paper reports a third pattern in the ilia. Seventy of 108 consecutive adolescent patients referred from routine scoliosis school screening during 1996–1999 had lower spine scoliosis – lumbar (LS), thoracolumbar (TLS), or pelvic tilt scoliosis (PTS). Radiologic bi-iliac and hip tilt angles were both measurable in 60 subjects: LS 18, TLS 31, and PTS 11 (girls 44, boys 16, mean age 14.6 years). Cobb angle (CA), apical vertebral rotation (AVR) and apical vertebral translation from the T1-S1 line (AVT) were measured on standing full spine radiographs (mean Cobb angle 14 degrees, range 4–38 degrees, 33 left, 27 right curves). Bi-iliac tilt angle (BITA) and hip tilt angle (HTA) were measured trigonometrically and iliac height asymmetry calculated as BITA minus HTA (corrected BITA=CBITA) and directly as iliac height asymmetry. Iliac height is relatively taller on the concavity of these curves (p< 0.001). CBITA is associated with Cobb angle, AVR and AVT (each p< 0.001).

Conclusion: The relatively taller concave ilium may be 1) real from primary skeletal changes or asymmetric muscle traction on iliac apophyses [3], or 2) apparent from rotation/torsion at the sacro-iliac joint(s).


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_III | Pages 445 - 445
1 Aug 2008
Burwell R Aujla R Freeman B Cole A Kirby A Pratt R Webb J Moulton A
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In schoolchildren screened for scoliosis about 40% have minor, non-progressive, lumbar scolioses secondary to pelvic tilt with leg-length and/or sacral inequality [1] not reported with preoperative thoracic curves [2]. Forty-nine of 108 consecutive adolescent patients referred from routine scoliosis school screening during 1996–1999 had lower spinal scoliosis with measurable radiological sacral alar and hip tilt angles – lumbar scoliosis 18, thoracolumbar scoliosis 31 (girls 41, boys 8, mean Cobb angle 16 degrees, range 4–38 degrees). In standing full spine antero-posterior radiographs measurements were made of Cobb angle and pelvic asymmetries as sacral alar and iliac heights (left minus right). From anthropometric measurements derivatives were calculated as ilio-femoral length (total leg length minus tibial length) and several length asymmetries, namely: ilio-femoral length asymmetry, total leg length inequality and tibial length asymmetry (all left minus right). Ilio-femoral length asymmetry correlates significantly with sacral alar height asymmetry (girls negatively r= − 0.456, p=0.002, boys positively r=0.726 p=0.041) but not iliac height asymmetry (girls p=0.201) from which three types are identified. Total leg length inequality but not tibial length asymmetry in the girls is associated with sacral alar height asymmetry (r= − 0.367 p=0.017 & r=0.039 p=0.807 respectively). Interpretation is complicated by total leg lengths each including some ilium in which there is asymmetry [3]. But lack of association between ilio-femoral length asymmetry and iliac height asymmetry suggests that the femoral component is more important than iliac component in determining the associations between sacral alar height asymmetry and each of ilio-femoral length asymmetry and total leg length inequality.

Conclusions:

Sacral alar height asymmetry and leg length asymmetries. The evidence suggests that sacral alar height asymmetry is not secondary to the leg length inequalities at least in most girls (negative correlations) and is more likely to result from primary skeletal changes in femur(s) and sacrum.

Sacral alar height asymmetry and Cobb angle. Scoliosis progression and iliac height asymmetry [3] appear to need factors additional to those that determine ilio-femoral length asymmetry – for in the girls Cobb angle is associated with both sacral alar height asymmetry and iliac height asymmetry (each p< 0.001) but not with either ilio-femoral length asymmetry (p=0.249) or total leg length inequality (p=0.650). The additional factors may be biomechanical [4], and/or biological in the trunk [5] and central nervous system [6].


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_III | Pages 524 - 524
1 Aug 2008
Newsome R Chiverton N Cole A
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Study Design. Randomized, single blind, Quasi-experimental trial.

Objective. To investigate whether immediate physiotherapy post lumbar micro-discectomy enables patients to become independently mobile more rapidly with no increase in risk of complications

Summary of Background Data. Although studies have demonstrated the efficacy of rehabilitation post lumbar discectomy, none have looked at physiotherapy commencing immediately post operatively.

Methods. A total of thirty patients were randomized to an immediate group commencing physiotherapy within two hours post-operatively or a control group receiving physiotherapy first day post-operatively. Outcome measures included the time taken for the patient to become independently mobile post-surgery, Oswestry Disability Index and pain scores (VAS and short form McGill) collected pre-operatively, post-operatively at four weeks, and three months.

Results. The results indicated significantly reduced time to independent mobility (p=0.009) and return to work (p=0.002) in the immediate group. There was no significant difference in disability and pain scores at four weeks and three months between the groups. Early mobilisation did not result in increased complications.

Conclusions. Immediate physiotherapy following first time single level lumbar micro-discectomy enables patients to become independently mobile more rapidly and return to work sooner. Immediate physiotherapy may enable patients to experience earlier discharge with associated cost benefits to healthcare.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_III | Pages 445 - 445
1 Aug 2008
Burwell R Dangerfield P Freeman B Aujla R Cole A Kirby A Pratt R Webb J Moulton A
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In idiopathic scoliosis the detection of extra-spinal left-right skeletal length asymmetries in the upper limbs, ribs, ilia and lower limbs [1–7] begs the question: are these asymmetries unconnected with the pathogenesis, or are they an indicator of what may also be happening in immature vertebrae of the spine? The vertebrate body plan has mirror-image bilateral symmetries (mirror symmetrical, homologous morphologies) that are highly conserved culminating in the adult form [8]. The normal human body can be viewed as containing paired skeletal structures in the axial and appendicular skeleton as a) separate left and right paired forms (e.g. long limb bones, ribs, ilia), and b) united in paired forms (e.g. vertebrae, skull, mandible). Each of these separate and united pairs are mirror-image forms – enantiomorphs. In idiopathic scoliosis, genetic and epigenetic (environmental) mechanisms [9–11] may disturb the symmetry control of enantiomorphic immature bones [12–13] and, by creating left-right endochondral growth asymmetries, cause the extra-spinal bone length asymmetries, and within one or more vertebrae create growth conflict with distortion as deformities (= unsynchronised bone growth concept) [14].

Conclusion: This enantiomorphic disorder concept applied to the axial skeleton during infancy, juvenility and adolescence – through reductionism into the molecular mechanisms of growth plate responses to different hormones at successive phases of development – provides a new theoretical insight to explain the whole body deformity of AIS. The concept suggests preventive surgery on spine and ribs.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_III | Pages 459 - 459
1 Aug 2008
GORVA AD Bishop NJ Cole A
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Introduction: Lumbar spine morphology is well described in healthy children but has not been described in children with Osteogenesis Imperfecta (OI).

Aims: To look at lumbar bony morphometry in OI children and to consider the importance of these factors in spinal surgery in these children.

Methods: 21 lumbar vertebrae (from L3–5) of 7 OI (6 OI type 3 and 1 OI type 4) children with scoliosis were analysed using Reformatted Computer Tomographic scans. The following measurements obtained: Spinal canal diameters, Transverse pedicle width, Total pedicle length, Pedicle root length, Transverse pedicle angle and Sagittal pedicle angle. Results are compared with previously published data of normal age-matched lumbar spine measurements.

Results: The mean age was 12 years (range 7–18 years). 6 females and 1 male. All had spondylolisthesis at L5-S1. Results were analysed by Wilcoxon Signed Rank test (nonparametric test). The transverse pedicle width was significantly narrower at all 3 levels (p< 0.01). Transverse pedicle angle was significantly less angled at all 3 levels (L3 p=0.04, L4 & L5 p< 0.01) whilst the sagittal pedicle angle was significantly more angled at all 3 levels (p< 0.01). Spinal canal diameter (AP) was significantly increased at all 3 levels (L3 & L5 p< 0.01, L4 p=0.02). And no significant differences in spinal canal transverse diameter and total pedicle length. Pedicle root length Significantly longer at all 3 levels (L3 & L4 p< 0.05, L5 p< 0.01). All children had grade-I spondylolisthesis at L5/S1.

Conclusions: A longer pedicle root with a narrower transverse diameter (and thinner cortices) and a reduced transverse angle is essential knowledge when passing pedicle screws in the lumbar spine in children with OI. This is a difficult technique and its safety requires further evaluation.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 383 - 383
1 Jul 2008
Gorva A Bishop N Cole A
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Introduction: Lumbar spine morphology is well described in healthy children but has not been described in children with Osteogenesis Imperfecta (OI).

Aims: To look at lumbar bony morphometry in OI children and to consider the importance of these factors in spinal surgery in these children

Methods: 21 lumbar vertebrae (from L3-5) of 7 OI (6 OI type 3 and 1 OI type 4) children with scoliosis were analysed using Reformatted Computer Tomographic scans. The following measurements obtained: Spinal canal diameters, Transverse pedicle width, Total pedicle length, Pedicle root length, Transverse pedicle angle and Sagittal pedicle angle. Results are compared with previously published data of normal age-matched lumbar spine measurements

Results: The mean age was 12 years (range 7-18 years). 6 females and 1 male. All had spondylolisthesis at L5-S1. Results were analysed by Wilcoxon Signed Rank test (nonparametric test). The transverse pedicle width was significantly narrower at all 3 levels (p< 0.01). Transverse pedicle angle was significantly less angled at all 3 levels (L3 p=0.04, L4 & L5 p< 0.01) whilst the sagittal pedicle angle was significantly more angled at all 3 levels (p< 0.01). Spinal canal diameter (AP) was significantly increased at all 3 levels (L3 & L5 p< 0.01, L4 p=0.02). And no significant differences in spinal canal transverse diameter and total pedicle length. Pedicle root length Significantly longer at all 3 levels (L3 & L4 p< 0.05, L5 p< 0.01). All children had grade-I spondylolisthesis at L5/S1.

Conclusions: A longer pedicle root with a narrower transverse diameter (and thinner cortices) and a reduced transverse angle is essential knowledge when passing pedicle screws in the lumbar spine in children with OI. This is a difficult technique and its safety requires further evaluation.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_II | Pages 230 - 230
1 May 2006
Cole A Burwell R Webb J
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Background: The study evaluates the inter-relationships between Cobb angle (CA), apical vertebral rotation (AVR), apical vertebral translation (AVT) and maximal angle of trunk inclination (max ATI). The effects of sex, curve laterality, curve type and apical levels will be studied

Methods: This is a study of consecutive pre-operative AIS patients. There are 122 pre-operative AIS patients (106 thoracic, 16 thoracolumbar), with a mean age of 15.6 years. From the pre-operative AP radiograph, CA, AVR (Perdriolle) and AVT are measured. The max ATI is measured using the Scoliometer with the patient in a standing forward bending position. Ratios between the measurements are calculated to allow comparison between different curve types and curves at different apical levels.

Results: For a given Cobb angle, each of AVR, AVT and max ATI are largest in King type IV curves, less in King type III curves and smallest in King type II curves (p=0.001 to 0.015). For curves without a significant compensatory curve, for a given AVR, the max ATI reduces significantly as the curve apex passes caudally (p=0.002 to 0.019). Sex and curve laterality are not significant factors.

Conclusion: It is suggested that as a curve develops, the interaction between the measurements in different planes may be responsible for determining the curve type (presence or absence of a compensatory curve). The smaller surface hump as the curve apex passes caudally is probably due to the transition from fixed ribs to floating ribs to no ribs. These finding also have implications for surgery. In King type IV and III curves, the emphasis should be on correcting translation and derotation perhaps with a primary costoplasty whilst in King type II curves, the emphasis should be on the correct selection of fusion levels and achieving a balanced spine.