Prevalence and Significance of Vitamin D Deficiency in Patients Undergoing Corrective Surgery for Adolescent Idiopathic Scoliosis.

BACKGROUND: The exact etiology of adolescent idiopathic scoliosis (AIS) is unknown, but recently, vitamin D has been suggested to be of importance in the pathophysiology of AIS. This article sought to (1) highlight the prevalence of vitamin D deficiency in patients undergoing corrective surgery for AIS within the United Kingdom and (2) evaluate the correlation and clinical relevance of preoperative back pain with vitamin D deficiency. METHODS: Data were collected on 201 consecutive patients undergoing corrective surgery for AIS. Baseline data included patient demographics, medical diagnoses, and standing preoperative Cobb angles. All patients had a preoperative 25-hydroxyvitamin D level recorded. One hundred ninety-six patients completed preoperative Scoliosis Research Society-22 outcome scores to quantify preoperative back pain. RESULTS: A total of 177 (89%) patients were young women, and the mean age at time of surgery was 14.9 years (13-18 years). All patients were diagnosed with AIS. The mean Cobb angles at time of surgery was 64°. Only 11 (5.5%) patients had "normal" vitamin D levels (>75 nmol/L), with 147 (74%) patients having deficient levels requiring treatment with supplementation. There was no correlation between vitamin D levels and preoperative Cobb angles (r s = -0.12), and there was a moderate correlation identified between the severity of preoperative vitamin D levels and preoperative back pain scores (r s =0.42). CONCLUSION: Vitamin D deficiency is common in patients with AIS; however, it is comparable to the national prevalence of vitamin D deficiency in healthy adolescent children. There was a strong correlation between preoperative back pain scores and the severity of vitamin D deficiency. These findings suggest that all patients with AIS should be screened for vitamin D deficiency and that supplementation where appropriate may lead to improved pain scores. CLINICAL RELEVANCE: If vitamin D is prevelant and if vitamin D deficiency is found to cause back pain, then there is an easy/cheap/safe treatement with supplementation.

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

BACKGROUND: Chronic 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. METHODS: Immunohistochemistry 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. RESULTS: Immunopositivity 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% of all 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. CONCLUSIONS: This 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.

Class 3 semaphorins expression and association with innervation and angiogenesis within the degenerate human intervertebral disc.

Nerve and blood vessel ingrowth during intervertebral disc degeneration, is thought to be a major cause of low back pain, however the regulation of this process is poorly understood. Here, we investigated the expression and regulation of a subclass of axonal guidance molecules known as the class 3 semaphorins, and their receptors; plexins and neuropilins within human NP tissue and their regulation by pro-inflammatory cytokines. Importantly this determined whether semaphorin expression was associated with the presence of nerves and blood vessels in tissues from human intervertebral discs. The study demonstrated that semaphorin3A, 3C, 3D, 3E and 3F and their receptors were expressed by native NP cells and further demonstrated their expression was regulated by IL-1ß but to a lesser extent by IL-6 and TNFα. This is the first study to identify sema3C, sema3D and their receptors within the nucleus pulposus of intervertebral discs. Immunopositivity shows significant increases in semaphorin3C, 3D and their receptor neuropilin-2 in degenerate samples which were shown to contain nerves and blood vessels, compared to non-degenerate samples without nerves and blood vessels. Therefore data presented here suggests that semaphorin3C may have a role in promoting innervation and vascularisation during degeneration, which may go on to cause low back pain.

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.

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

INTRODUCTION: The 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. METHODS: Quantitative 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-1ß) stimulated NP cells. RESULTS: Initial 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-1ß 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-1ß. Calcitonin gene related peptide was increased in SH-SY5Y cells upon cytokine stimulation. VEGF was induced by IL-1ß and interleukin-6 in NP cells, whilst pleiotrophin was decreased by IL-1ß. VEGF and pleiotrophin were expressed by SH-SY5Y cells, and VEGF by HDMECs, but were not modulated by cytokines. CONCLUSIONS: The release of cytokines, in particular IL-1ß 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-1ß is a key regulatory cytokine, involved in the up regulation of factors involved in innervation and vascularisation of tissues.

Complications in spinal deformity surgery in the United Kingdom: 5-year results of the annual British Scoliosis Society National Audit of Morbidity and Mortality.

PURPOSE: To provide a 5-year national overview of corrective spinal deformity surgery in the United Kingdom. METHODS: Since 2008, the British Scoliosis Society has collected predefined data on spinal deformity surgeries carried out by its members. Participating units collect and submit annual anonymised data pertaining to the number of deformity surgeries performed, age groups, aetiology (idiopathic versus non-idiopathic), mortality, deep infections and neurological deficit (complete, incomplete without resolution and incomplete with resolution). Overall aetiology proportions and complication rates were calculated, as well as funnel plots with control limits of individual complication rates by cases performed. RESULTS: Between 2008 and 2012, 9,295 corrective spinal deformity procedures were performed. 4,445 (48%) were recorded as idiopathic and 2,917 (31%) as non-idiopathic. There were a total of 339 complications (3.6%). Deep infections occurred in 222 (2.82%), incomplete neurological deficit with resolution in 59 (0.65%), incomplete neurological deficit without resolution in 29 (0.32%), complete neurological deficit in 12 (0.13%) and mortality in 17 (0.19%). CONCLUSION: The complication rates reported in this study compare well with previously published studies. These reported results will hopefully serve to provide a benchmark for units in the UK providing corrective spinal deformity surgery to allow individual units to compare their complication rates against national averages and to provide national complication figures to aid in the consenting process of patients. Use of a spinal deformity registry, such as the British Spine Registry, is required to ensure ongoing service development and optimal healthcare provision.

Complications in pediatric scoliosis surgery.

BACKGROUND: Scoliosis surgery in childhood is associated with a range of postoperative complications that may require admission to the pediatric intensive care unit (PICU) or high-dependency unit (HDU). AIM: The aim of this study was to identify preoperative factors associated with PICU and HDU admissions after corrective surgery and devise a scoring system that could be used by clinicians to predict the level of dependency required postoperatively. METHODS: A retrospective case note review was carried out in 90 patients who underwent corrective scoliosis surgery at Sheffield Children's Hospital (SCH) between January 2008 and October 2010. Predictors of PICU and HDU requirement postoperatively were identified and a simple scoring system created using multiple logistic regression and receiver operator characteristic (ROC). RESULTS: There was a statistically significant difference in the preoperative parameters (pulmonary function, Cobb angle, and number of vertebrae fused) of those patients who required PICU or HDU care compared with those who did not. The area under the receiver operator characteristic curve for the final scoring system was 0.95 for PICU admission and 0.87 for HDU admission at the optimal cut-off point, demonstrating good diagnostic accuracy. CONCLUSIONS: The authors have identified a significant relationship between preoperative variables and the levels of dependency required postoperatively and have proposed a scoring system which can be used to aid decision-making involving bed planning for patients after corrective scoliosis surgery. However, this work is based on the clinical course of a single set of patients who had surgery in a single tertiary center and has not been tested on patients from other centers.

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

INTRODUCTION: The 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. METHODS: Real-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. RESULTS: LDA 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. CONCLUSIONS: Our 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.

Dual growing rod technique followed for three to eleven years until final fusion: the effect of frequency of lengthening.

STUDY DESIGN: Retrospective case review of children completing dual growing rod treatment at our institutions. Patients had a minimum of 2 years follow-up. OBJECTIVE: To identify the factors influencing dual growing rod treatment outcome followed to final fusion. SUMMARY OF BACKGROUND DATA: Published reports on dual growing rod technique results for early onset scoliosis demonstrate it to be safe and effective in curve correction and maintenance as well as in allowing spinal growth. METHODS: Between 1990 and 2003, 13 patients with no previous surgery and noncongenital curves underwent final fusion. All had preoperative curve progression over 10 degrees after unsuccessful nonoperative treatment. There were 10 females and 3 males. Average age was 6.6 +/- 2.9 years at initial surgery. There were 3 idiopathic, 1 nonspine congenital anomaly, and 9 syndromic patients. Analysis included age at initial surgery and final fusion, number and frequency of lengthenings, and complications. Radiographic evaluation included changes in Cobb angle, T1-S1 length, and instrumentation length over the treatment period. RESULTS: Cobb angle improved from 81.0 +/- 23 degrees to 35.8 +/- 15 degrees postinitial and 27.7 +/- 17 degrees after final fusion. Average number of lengthenings was 5.2 +/- 3 at an interval of 9.4 +/- 5 months. T1-S1 length increased from 24.4 +/- 3.4 to 29.3 +/- 3.6 cm postinitial and 35.0 +/- 3.7 cm postfinal fusion. Average growth was 1.46 +/- 0.66 cm/year. Those lengthened at