A A Cole

The cytokine and chemokine expression profile of nucleus pulposus cells: implications for degeneration and regeneration of the intervertebral disc.

IntroductionThe aims of these studies were to identify the cytokine and chemokine expression profile of nucleus pulposus (NP) cells and to determine the relationships between NP cell cytokine and chemokine production and the characteristic tissue changes seen during intervertebral disc (IVD) degeneration.MethodsReal-time q-PCR cDNA Low Density Array (LDA) was used to investigate the expression of 91 cytokine and chemokine associated genes in NP cells from degenerate human IVDs. Further real-time q-PCR was used to investigate 30 selected cytokine and chemokine associated genes in NP cells from non-degenerate and degenerate IVDs and those from IVDs with immune cell infiltrates (‘infiltrated’). Immunohistochemistry (IHC) was performed for four selected cytokines and chemokines to confirm and localize protein expression in human NP tissue samples.ResultsLDA identified the expression of numerous cytokine and chemokine associated genes including 15 novel cytokines and chemokines. Further q-PCR gene expression studies identified differential expression patterns in NP cells derived from non-degenerate, degenerate and infiltrated IVDs. IHC confirmed NP cells as a source of IL-16, CCL2, CCL7 and CXCL8 and that protein expression of CCL2, CCL7 and CXCL8 increases concordant with histological degenerative tissue changes.ConclusionsOur data indicates that NP cells are a source of cytokines and chemokines within the IVD and that these expression patterns are altered in IVD pathology. These findings may be important for the correct assessment of the ‘degenerate niche’ prior to autologous or allogeneic cell transplantation for biological therapy of the degenerate IVD.

Expression and regulation of neurotrophic and angiogenic factors during human intervertebral disc degeneration

IntroductionThe degenerate intervertebral disc (IVD) becomes innervated by sensory nerve fibres, and vascularised by blood vessels. This study aimed to identify neurotrophins, neuropeptides and angiogenic factors within native IVD tissue and to further investigate whether pro-inflammatory cytokines are involved in the regulation of expression levels within nucleus pulposus (NP) cells, nerve and endothelial cells.MethodsQuantitative real-time PCR (qRT-PCR) was performed on 53 human IVDs from 52 individuals to investigate native gene expression of neurotrophic factors and their receptors, neuropeptides and angiogenic factors. The regulation of these factors by cytokines was investigated in NP cells in alginate culture, and nerve and endothelial cells in monolayer using RT-PCR and substance P (SP) protein expression in interleukin-1 (IL-1β) stimulated NP cells.ResultsInitial investigation on uncultured NP cells identified expression of all neurotrophins by native NP cells, whilst the nerve growth factor (NGF) receptor was only identified in severely degenerate and infiltrated discs, and brain derived neurotrophic factor (BDNF) receptor expressed by more degenerate discs. BDNF expression was significantly increased in infiltrated and degenerate samples. SP and vascular endothelial growth factor (VEGF) were higher in infiltrated samples. In vitro stimulation by IL-1β induced NGF in NP cells. Neurotropin-3 was induced by tumour necrosis factor alpha in human dermal microvascular endothelial cells (HDMECs). SP gene and protein expression was increased in NP cells by IL-1β. Calcitonin gene related peptide was increased in SH-SY5Y cells upon cytokine stimulation. VEGF was induced by IL-1β and interleukin-6 in NP cells, whilst pleiotrophin was decreased by IL-1β. VEGF and pleiotrophin were expressed by SH-SY5Y cells, and VEGF by HDMECs, but were not modulated by cytokines.ConclusionsThe release of cytokines, in particular IL-1β during IVD degeneration, induced significant increases in NGF and VEGF which could promote neuronal and vascular ingrowth. SP which is released into the matrix could potentially up regulate the production of matrix degrading enzymes and also sensitise nerves, resulting in nociceptive transmission and chronic low back pain. This suggests that IL-1β is a key regulatory cytokine, involved in the up regulation of factors involved in innervation and vascularisation of tissues.

Changes in surface and radiographic deformity after universal spine system for right thoracic adolescent idiopathic scoliosis: is rib-hump reassertion a mechanical problem of the thoracic cage rather than an effect of relative anterior spinal overgrowth

Study Design. Analysis of preoperative, 8-week, 1-year, and 2-year data from patients with right thoracic adolescent idiopathic scoliosis treated by posterior Universal Spine System (Stratec Medical, Oberdorf, Switzerland). Objective. Report 2-year results and the association between back surface and radiographic assessments. Summary of Background Data. Few longitudinal studies have related surface and radiographic data in the follow-up of surgical patients. Methods. Of 34 patients with right thoracic adolescent idiopathic scoliosis having posterior Universal Spine System instrumentation, 27 had complete prospective back surface and radiographic appraisal. Results. Cobb angle corrected from 58° to 34° (41%), apical vertebral rotation from 26° to 20° (23%), apical vertebral translation from 4.5 to 2.4 cm (47%), and maximum angle of trunk inclination from 17° to 13° (22%) (preoperative to 2 years). Rib-hump reassertion occurred between 8 weeks and 1 year, regardless of age, and correlated with changes in vertebral translation (for 10 vertebral levels corresponding to 10 back surface levels between C7 and S1, P = 0.001 MANOVA). Preoperative frontal tilt of L1 with concave fifth rib-spinal angle predicted the percentage correction of maximum angle of trunk inclination, and the concave ninth rib-spinal angle predicted reassertion of maximum angle of trunk inclination. Conclusions. Almost half of initial back surface correction is lost by 2 years. Segmental vertebral translation measurements most strongly correlate with segmental angle of trunk inclination measurements during follow-up. Rib-hump reassertion is best explained by unwinding of the thoracic cage tensioned by surgery rather than through relative anterior spinal overgrowth. Spine and thoracic cage factors determine rib-hump correction, so surgical disruption of the latter by costoplasty may prevent rib-hump reassertion. Results of scoliosis sur-gery should include surface data.

Nerves are more abundant than blood vessels in the degenerate human intervertebral disc.

BackgroundChronic low back pain (LBP) is the most common cause of disability worldwide. New ideas surrounding LBP are emerging that are based on interactions between mechanical, biological and chemical influences on the human IVD. The degenerate IVD is proposed to be innervated by sensory nerve fibres and vascularised by blood vessels, and it is speculated to contribute to pain sensation. However, the incidence of nerve and blood vessel ingrowth, as well as whether these features are always associated, is unknown. We investigated the presence of nerves and blood vessels in the nucleus pulposus (NP) of the IVD in a large population of human discs.MethodsImmunohistochemistry was performed with 61 human IVD samples, to identify and localise nerves (neurofilament 200 [NF200]/protein gene product 9.5) and blood vessels (CD31) within different regions of the IVD.ResultsImmunopositivity for NF200 was identified within all regions of the IVD within post-mortem tissues. Nerves were seen to protrude across lamellar ridges and through matrix towards NP cells. Nerves were identified deep within the NP and were in many cases, but not always, seen in close proximity to fissures or in areas where decreased matrix was seen. Fifteen percent of samples were degenerate and negative for nerves and blood vessels, whilst 16 % of all samples were degenerate with nerves and blood vessels. We identified 52 % of samples that were degenerate with nerves but no blood vessels. Interestingly, only 4 % ofall samples were degenerate with no nerves but positive for blood vessels. Of the 85 samples investigated, only 6 % of samples were non-degenerate without nerves and blood vessels and 7 % had nerves but no blood vessels.ConclusionsThis study addresses the controversial topic of nerve and blood vessel ingrowth into the IVD in a large number of human samples. Our findings demonstrate that nerves are present within a large proportion of NP samples from degenerate IVDs. This study shows a possible link between nerve ingrowth and degeneration of the IVD and suggests that nerves can migrate in the absence of blood vessels.

The management of weakness caused by lumbar and lumbosacral nerve root compression

Spinal stenosis and disc herniation are the two most frequent causes of lumbosacral nerve root compression. This can result in muscle weakness and present with or without pain. The difficulty when managing patients with these conditions is knowing when surgery is better than non-operative treatment: the evidence is controversial. Younger patients with a lesser degree of weakness for a shorter period of time have been shown to respond better to surgical treatment than older patients with greater weakness for longer. However, they also constitute a group that fares better without surgery. The main indication for surgical treatment in the management of patients with lumbosacral nerve root compression should be pain rather than weakness.

Fusion for lumbar spinal stenosis

Decompression is all that most patients with one and two level stenosis require

Spontaneous methicillin-sensitive Staphylococcus aureus spondylodiscitis—-Short course antibiotic therapy may be adequate: Evidence from a single centre cohort

Spontaneous methicillin-sensitive Staphylococcus aureus spondylodiscitis is increasing in prevalence and there appears to be little consensus on the optimum management of this condition. This paper analyses antimicrobial therapy and associated outcomes over a seven-year period at a large UK hospital trust. A retrospective search strategy identified 55 patients; notes were available for 39. Patients were treated with a median 12 weeks of antibiotics (IQR 7), with 6 weeks intravenous (IQR 3) and 9 weeks oral therapy (IQR 6). 23 different treatment regimens were utilised. 33/36 (92%) patients for whom outcomes were available were cured or improved at latest follow-up. This study reports a wide variation in antibiotic prescribing at a single centre. Outcomes were generally positive regardless of total duration of therapy and proportion of intravenous therapy. These findings highlight the need for multi-centre prospective randomised controlled trials to determine the most clinically effective and low-risk treatment strategy.

Osteochondroma arising from a lumbar facet joint in a 16-year-old.

Osteochondromas are benign tumours of bony or cartilaginous origin, which may be solitary or multiple. They are rare in the axial skeleton and have previously been reported to arise from facet joints only in four cases in the English literature. We report the case of a 16-year-old girl who presented with a palpable bony lump and a short history of back pain. Imaging showed a bony lesion arising from a left-sided facet joint in the lumbar spine. Following excision biopsy, there was complete resolution of symptoms. The literature on the origin and management of spinal osteochondromas is discussed.

Editorial: Spinal education, training and research in the UK.

The British Association of Spine Surgeons (BASS) with over 350 members is the largest spinal society in the UK, following the amalgamation with the British Cervical Spine Society in 2009. Many of the members are also members of the British Scoliosis Society (BSS) and The Society for Back Pain Research (SBPR). The Society has grown not only in numbers but also in stature, and actively promotes the study of spinal disorders with particular attention to the surgical treatment of spinal disease and disorders. The web site (http://www.spinesurgeons.ac.uk/) is now well developed and for patients offers advice on back pain and a number of the common spinal complaints; and for members promotes educational activities, has recommended reading on topical issues and has a forum for discussion. Our annual meetings are increasingly well attended with an accompanying increase in the number of submitted abstracts, and hence an overall increase in the quality of submissions. High quality research is dependent on the production of good data. One of our focuses in recent years is the development of a National Registry to be made available on line for our members to enable the collection of patient data. It will enable the prospective evaluation of existing and new treatments, devices and materials at single or multiple sites and the easier organisation and co-ordination of multicentre randomised trials. The data produced could enable surgeons and industry to work together for mutual benefit, as well as providing invaluable information for the National Health Service, the National Institute for Clinical Excellence and most importantly for the benefit of patients. Hopefully it will raise the standing of the surgical treatments for back pain to a level of evidence base that will satisfy everyone involved in back pain management. The UK must have the most frequently “reformed” and re-organised health care system in the world resulting in many new and poorly defined government bodies with which we have to engage. In addition, we have three spinal societies and to bring them together as one voice, we have set up a body the United Kingdom Spine Societies Board (UKSSB), for the three societies not only to organise the combined bi-annual Britspine meetings but also to act as the conduit to EuroSpine, Government, industry and other bodies. By publishing the abstracts of Britspine 2012 in the European Spine Journal, we hope this will represent an important step in forging closer links between the UK Spine Societies and the Spine Society of Europe. The papers in this special edition of the journal show the spectrum of good quality research currently being produced. We hope that as we progress with our development, that in time this will not only be maintained but also significantly improved upon. Generations of spine surgeons come and go. The current generation of UK Spine Surgeons face significant challenges with growing political opposition to procedures with limited scientific evidence and reduced NHS budgets. This makes it even more important that the current generation be remembered for both significant achievements in good quality research and political reform. This can only be achieved by Spinal Consultants who are prepared to commit their own time and work as a team to achieve these important goals to the long-term benefit of patients with spine problems.

The National Health Service (NHS) in England: Trying to Achieve Value-Based Healthcare

The National Health System (NHS) in England allows system-wide control of quality determined at a national level. This chapter brings together the three processes which have been influencing quality and value in spinal care in England over the last 8 years: (1) a national system for commissioning specialised spinal surgery, (2) a national programme called ‘Getting It Right First Time’ comparing spinal services with feedback to influence changes and (3) utilizing the British Spine Registry to allow collection of surgical procedures, complications and patient-reported outcome and experience measures.