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 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.Background
Methodology
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. We present an Introduction
Methods and Results
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. 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.Purpose of study and background
Methods and Results
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.
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.Summary
To Determine The Effect Of Posterior Instrumented Fusion On Lung Function In Patients With Idiopathic Scoliosis Aged 8–11. 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.Aim:
Method:
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 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.Purpose of study and background
Methods
To investigate the views and experiences of patients with sciatica who have undergone a bespoke physiotherapy programme whilst awaiting primary lumbar microdiscectomy. 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.Objectives
Methods
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. 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.Introduction
Materials & methods
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. 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.Introduction
Materials and Methods
To question the reliability of Thoracic Spine pain as a red flag and symptoms of a possible cause of Serious Spinal Pathology (SSP). 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.Purpose
Methods
To evaluate the competencies of spinal extended scope physiotherapists (ESP) following the introduction of requesting rights for magnetic resonance imaging (MRI) one year later. 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.Purpose
Methods
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. 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.Introduction
Materials and Methods
Serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and synovial fluid white blood cell (WBC) count and differential are effective in diagnosing periprosthetic joint infection (PPJI); however their utility in patients with inflammatory arthritis is unknown. The purpose of this study is to determine the utility of these tests in patients with inflammatory arthritis. 934 Consecutive revision hip and knee arthroplasties were prospectively evaluated for PPJI. 202 Cases were excluded due to acute post-operative or hematogenous infection. 690 Patients had non-inflammatory and 42 had inflammatory arthritis. Receiver operating characteristic (ROC) curves were used to establish optimal ESR, CRP, WBC, and % neutrophil values for diagnosis of PPJI, and the area under the curve (AUC) was calculated to determine the overall accuracy.Introduction
Methods
To evaluate and describe the plain radiographic changes observed with time in fusions using SiS-CaP. We describe, for the first time, 4 stages of bone substitute fusion mass (BSFM) radiographic appearance in relation to time post-op. Retrospective, radiological evaluation. Over 200 plain radiographs were evaluated. 70 consecutive fusions for degenerative spinal stenosis were included, in all cases performed by the same surgeon using the same operative technique. Follow-up was from 3 months to 2 years post-op. Radiographs were evaluated for the presence or absence of SiS-CaP granules, bone formation and for evidence of pseudarthrosis. Trends were seen within the BSFM with respect to time. At 6-12 weeks post-op a ‘homogenous granular stage’ indicates the presence of the unchanged SiS-CaP. At 12 weeks, small pockets appear within the BSFM in the ‘vacuolation stage’, indicating bioresorption of the graft. Vacuoles become increasingly radio-opaque indicating bone proliferation during the ‘homogenous lamellar stage’. At variable time between 6 months and 2 years, the BSFM becomes encapsulated in the ‘cortication stage’ visible as a sclerotic rim around the BSFM. We have seen a clear trend in the behaviour of the fusion mass in this case series. The radiological stages we have described above can be closely correlated with previously reported in-vitro and in-vivo studies looking at the micro-function of SiS-CaP. We hope that this description will help to judge the progress of graft incorporation and fusion. Further study of inter and intra-observer correlation will be required.
To report on the management of a patient with grade 1 holocord pilocytic astrocytoma and scoliosis. Case report of a rare spinal cord tumour and a management of the scoliosis. An 11 year boy complained of gradually worsening neck, back pain and pain in all limbs. This was accompanied by unsteadiness, weakness of lower limbs and bed wetting of recent onset. There was a family history of spinal cord tumour. Examination revealed signs of spinal cord compression and a left thoracic scoliosis. Magnetic resonance imaging showed an intra-medullary tumour extending through the spinal cord and syrinx formation. He underwent T1-3 approach for drainage of syrinx, biopsy of tumour and laminoplasty with plates. He was started on chemotherapy for 14 months. During this period a syringo-peritoneal shunt was inserted. There was further growth of the tumour and neurological deterioration. He subsequently underwent T8-L1 laminoplasty, debulking of tumour and insertion of dual diameter growing rods. There has been no significant neurological deterioration. There was good correction of the scoliosis with Cobb angle reducing from 50 to 15 degrees. Lengthening of growing rods has been done 4 times with good length achieved. Excision of tumour and growing rod insertion (not previously reported) is a good way of controlling neurological symptoms and the scoliosis in this rare spinal cord tumour.
To determine factors such as age, sex and curve severity in patients with idiopathic scoliosis presenting for the first time to a spine deformity clinic. A prospective study at a regional spine clinic. Patients with idiopathic scoliosis presenting for the first time to the scoliosis clinic were entered into a database recording information such as age, symptoms, severity of scoliosis as measured by the Cobb angle (CA), spine rotation measured by Scoliometer, geographical region, person detecting the curve, neurological findings etc. The study period was from June 2008 to September 2009 inclusive. Fifty consecutive patients with all required information in the database were included in the analysis. All eligible patients were not entered due to logistical reasons. 13 males and 37 females, average age 13.96 (range 1 to 23). 68% were unhappy with the shape of their back, 48% presented with significant pain and 32% had both. The mother first saw the scoliosis in 52%, the rest were seen by either the patient, friends or doctors. 36 were single curves with a mean CA of 34 degrees ranging from 10 to 80 degrees. 52% of patients presented with a curve of 40 degrees or more. 14 had double curves. None of the patients were found to have any abnormal neurological findings. There are few epidemiological studies in the recent literature. This data was not previously available in our region and initial presentation with a severe curve is a worrying trend which triggered this study.
To assess radiological fusion rates in posterolateral fusions using SiS-CaP. Retrospective, radiological follow-up study. Single surgeon series of 76 consecutive patients were evaluated, in a regional spinal unit. All patients had clinical and radiological (MRI) spinal canal stenosis secondary to degenerative spondylosis or spondylolisthesis. Surgery consisted of instrumentation, decompression and meticulous preparation of the posterolateral graft bed by removal of all soft tissues posterior to the inter-transverse membrane and decortication of transverse processes (TPs). SiS-CaP putty was injected into this gutter and moulded around the instrumentation. Good quality, well prepared bone chips from the posterior decompression were seeded into the putty. Patient radiographs were reviewed at 3-6 months, 1 year and 2 years. Radiographs were assessed using a protocol to examine granularity, bone formation and evidence of pseudarthrosis, based upon previously reported literature 1 and our personal experience. Of the 76 patients, 26 were excluded. M:F was 21:29. Mean age was 58yrs. Average number of motion segments fused per case was 2.2. There was one pseudarthrosis with metalwork fracture, and thus a total fusion rate of 98%. In addition, one patient had scanty bridging of TPs, and one patient had lucency around the S1 screws. SiS-CaP, as a bone graft substitute in posterolateral instrumented fusions, gives comparable results to published fusion rates using autologous iliac crest grafting and/or Bone Morphogenic Protein 2. Moreover, it avoids the associated morbidity of iliac bone harvest.
To determine the current practice of scoliosis surgery in the UK. A 10 point questionnaire was constructed to identify the philosophy of surgeons on various aspects of scoliosis surgery such as choice of implant, bone graft, autologous blood transfusion (ABT), cord monitoring and computer assisted surgery. Results are compared with the current best evidence. Consultants and Fellows attending the 2009 British Scoliosis Society meeting. 50 questionnaires were completed: 45 Consultants and 5 Fellows. All pedicle screw construct favored by 25/50, hybrid 24/50 (one undecided). Posterior construct of less than 10 levels, 20/50 would not cross-link, 11/50 used one and 19/20 used two or more. More than ten levels 17/50 considered cross-links unnecessary, 4/50 used one and 29/50 used two or more. 88% preferred titanium alloy implants, while a mixture of stainless steel and cobalt chrome was used by others. For bone graft, substitutes (24), iliac crest (14), allograft (12) and demineralised bone matrix (9) in addition to local bone. 10/50 would use recombinant bone morphogenetic protein (3 for revision cases only). 39/50 routinely used intra-operative cell salvage or ABT drains and 4/50 never used autologous blood. All used cord monitoring, Sensory (19/50), Motor (2/50) and combined (29/50). None used computer-aided surgery. 26 operated alone 12 operated in pairs and 12 varied depending on type of case. This survey has brought to light interesting variations in scoliosis surgery in UK. It may reflect the conflicting evidence in the literature.
We aim to describe mortality in orthopaedic patients with Clostridium difficile associated diarrhoea (CDAD), to identify prognostic factors for 30 day mortality, and to modify a CDAD risk score to fit to orthopaedic patients. This was a two centre, retrospective, observational study including consecutive patients with a first episode of CDAD between 2005–2007. 79 patients were identified, comprising 11 elective patients (14%) and 68 emergency patients (86%). 73 patients (92%) underwent surgery and all but two patients received broad spectrum antibiotics prior to CDAD. The overall 30 day mortality was 29% (n=26). The predominant diagnosis was a fractured femoral neck (66%, n=52). The most significant multivariable model in predicting 30 day mortality comprised increasing white cell count (WCC, OR 1.20 [for 10% variable increase]; 95% CI 1.06–1.36 p=0.003) and decreasing albumin (OR 0.86 [for single unit decrease]; 0.86–0.95, p=0.003), with adjustment for age ł80 years (OR 6.39, 1.15–35.52, p=0.04). CRP was found to be not significant. Based on this, modification of the previously described Clostridium difficile prognostic index leads to a point awarded for WCC ł20, albumin Ł20, age ł80, urea ł15 or clinically severe disease (peritonitis, sepsis, ł10 episodes of diarrhoea per day). This produces low (0–1 points), medium (2–3 points) and high (4–5 points) risk of death groups, with mortalities of 15%, 47% and 75% respectively for all orthopaedic patients, and 14%, 41% and 67% respectively in only the validation cohort. CDAD in orthopaedic patients mainly affects emergency patients, in particular those with fractured femoral neck. Inpatient mortality is high, and a high white count and low albumin are significant predictors of mortality. Modification of an easily remembered scoring system based on this can help identify orthopaedic patients likely to die from an episode of CDAD, allowing early aggressive therapy and early objective referral to gastrointestinal teams.
