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Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_11 | Pages 25 - 25
1 Sep 2021
Shah N Shafafy R Selvadurai S Benton A Herzog J Molloy S
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Introduction. Patients with metastatic spinal cord compression (MSCC) or unstable spinal lesions warrant early surgical consultation. In multiple myeloma, chemotherapy and radiotherapy have the potential to decompress the spinal canal effectively in the presence of epidural lesions. Mechanical stability conferred by bracing may potentiate intraosseous and extraosseous bone formation, thus increasing spinal stability. This study aims to review the role of non-operative management in myeloma patients with a high degree of spinal instability, in a specialist tertiary centre. Methods. Retrospective analysis of a prospectively collected database of 83 patients with unstable myelomatous lesions of the spine, defined by a Spinal Instability Neoplastic Score (SINS) of 13–18. Data collected include patient demographics, systemic treatment, neurological status, radiological presence of cord compression, most unstable vertebral level and presence of intraosseous and extraosseous bone formation. Post-treatment scores were calculated based on follow-up imaging which was carried out at 2 weeks for cord compression and 12 weeks for spinal instability. A paired t-test was used to identify any significant difference between pre- and post-treatment SINS and linear regression was used to assess the association between variables and the change in SINS. Results. A significant reduction in SINS was observed from a pre-treatment average score of 14 to a score of 9, following treatment for myeloma (p<0.001). A higher initial score and a younger age were associated with a larger overall reduction in SINS (p<0.001 and p=0.02 respectively). No single variable (bisphosphates, chemotherapy, radiotherapy and steroids) had a significant association with SINS reduction. 25 (30%) patients had spinal cord compression, all of which showed radiological resolution of cord compression at 2 weeks. No patients developed neurological deterioration during treatment and all patients had an improvement in their pain scores. 64 (77%) patients had evidence of intraosseous and/or extraosseous bone formation on their follow-up scan. Conclusion. Non-operative management in the form of bracing and systemic therapy is a safe and effective treatment for spinal instability and spinal cord compression in myeloma. Treatment of unstable myelomatous lesions of the spine with or without cord compression should not follow traditional guidelines for MSCC. The decision to adopt a non-operative approach in this cohort of patients should ideally be made in a tertiary centre with expertise in multiple myeloma and in a multidisciplinary setting


The Bone & Joint Journal
Vol. 103-B, Issue 5 | Pages 971 - 975
1 May 2021
Hurley P Azzopardi C Botchu R Grainger M Gardner A

Aims. The aim of this study was to assess the reliability of using MRI scans to calculate the Spinal Instability Neoplastic Score (SINS) in patients with metastatic spinal cord compression (MSCC). Methods. A total of 100 patients were retrospectively included in the study. The SINS score was calculated from each patient’s MRI and CT scans by two consultant musculoskeletal radiologists (reviewers 1 and 2) and one consultant spinal surgeon (reviewer 3). In order to avoid potential bias in the assessment, MRI scans were reviewed first. Bland-Altman analysis was used to identify the limits of agreement between the SINS scores from the MRI and CT scans for the three reviewers. Results. The limit of agreement between the SINS score from the MRI and CT scans for the reviewers was -0.11 for reviewer 1 (95% CI 0.82 to -1.04), -0.12 for reviewer 2 (95% CI 1.24 to -1.48), and -0.37 for reviewer 3 (95% CI 2.35 to -3.09). The use of MRI tended to increase the score when compared with that using the CT scan. No patient having their score calculated from MRI scans would have been classified as stable rather than intermediate or unstable when calculated from CT scans, potentially leading to suboptimal care. Conclusion. We found that MRI scans can be used to calculate the SINS score reliably, compared with the score from CT scans. The main difference between the scores derived from MRI and CT was in defining the type of bony lesion. This could be made easier by knowing the site of the primary tumour when calculating the score, or by using inverted T1-volumetric interpolated breath-hold examination MRI to assess the bone more reliably, similar to using CT. Cite this article: Bone Joint J 2021;103-B(5):971–975


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 6 | Pages 825 - 828
1 Jun 2012
Rajagopal TS Walia M Wilson HA Marshall RW Andrade AJ Iyer S

We report on two cases of infective spondylodiscitis caused by Gemella haemolysans in otherwise healthy patients. This organism has only rarely been identified as a cause of bone and joint infection, with only two previous reports of infective spondylodiscitis.

We describe the clinical features, investigations and treatment options.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_15 | Pages 33 - 33
7 Aug 2024
Williams R Evans S Maitre CL Jones A
Full Access

Background. It has become increasingly important to conduct studies assessing clinical outcomes, reoperation rates, and revision rates to better define the indications and efficacy of lumbar spinal procedures and its association with symptomatic adjacent segment degeneration (sASD). Adjacent segment degeneration (ASD) is defined as the radiographic change in the intervertebral discs adjacent to the surgically treated spinal level. SASD represents adjacent segment degeneration which causes pain or numbness due to post-operative spinal instability or nerve compression at the same level. The most common reason for early reoperation and late operation is sASD, therefore is in our best interest to understand the causes of ASD and make steps to limit the occurrence. Method. A comprehensive literature search was performed selecting Randomized controlled trials (RCTs) and retrospective or prospective studies published up to December 2023. Meta-analysis was performed on 38 studies that met the inclusion criteria and included data of clinical outcomes of patients who had degenerative disc disease, disc herniation, radiculopathy, and spondylolisthesis and underwent lumbar fusion or motion-preservation device surgery; and reported on the prevalence of ASD, sASD, reoperation rate, visual analogue score (VAS), and Oswestry disability index (ODI) improvement. Results. When compared to fusion surgery, a significant reduction of ASD, sASD and reoperation was observed in the cohort of patients that underwent motion-preserving surgery. Conclusion. Dynamic fusion constructs are treatment options that may help to prevent sASD. Conflicts of interest. This research was funded by Paradigm Spine. Sources of funding. Paradigm Spine


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. Results. Following injection of B-gel into tissue explants following culture for 4 weeks, cells were visualized within the regions of the B-gel. Demonstrating that native cells were able to migrate into regions of B-gel. Increased collagen deposition was seen in tissue explants injected with Bgel, with increased collagen type I and X but decreased collagen type II staining in explants injected with Bgel. Tissue explants, in the absence of Bgel, showed limited calcium deposition, which was increased in B-gel injected explants. Furthermore, disc cells increased expression of bone markers (alkaline phosphatase & osteocalcin), but decreased NP matrix (Aggrecan and Collagen type II) following Bgel injection. Conclusion. This system could have potential to support spinal fusion via direct injection into the disc. Conflict of interest: C Le Maitre & C Sammon are inventors on the hydrogel discussed. Funding: This work was funded by GrowMed Tech Proof of Concept funding


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_11 | Pages 8 - 8
1 Sep 2021
Abdalla M Nyanzu M Fenner C Fragkakis E Ajayi B Lupu C Bishop T Bernard J Willis F Reyal Y Pereira E Papadopoulos M Crocker M Lui D
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Introduction. Spine is a common site for haematological malignancies. Multiple myeloma affects the spine in 70% of cases. New guidelines were published in 2015 to help manage spinal haematological malignancies. Despite neural compression or spinal instability, instrumentation of the spine should be avoided. Surgery carries significant risks of wound complications and more importantly delaying the definitive chemotherapy and radiotherapy. Cement augmentation and bracing for pain and prevention of deformity is key to the new strategies. We aimed to evaluate the different treatment modalities adopted in the spine unit at St George's hospital for spinal haematological malignancies. We compared our practice to the current guidelines published in 2015. Methods. Retrospective review of all spinal haematological malignancy patients who were discussed in the spinal MDT and managed through the spine unit at St George's hospital in the period between April 2019 and February 2021. We analysed the demographics of the patients treated in this period and compared the management modalities adopted in the unit to the current British haematological guidelines. Results. 139 patients were included in this study, 61.9% of them were male. 70 cases came through the MSCC pathway. 15 patients had their spinal involvement in the lumbar spine only below the conus. The Bilsky Grades of the other 124 cases were B0: 35.97 % 1a: 4.31%%, 1b: 7.19%, 1c: 3.59%, 2: 5.75% 3: 32.37%. 43 patients (30.9 %) had neurological deficits on presentation. 70 cases were treated conservatively (50.35%), 21 were treated with brace only (15.1%), 25 had BKP (17.98%) and 23 were treated with instrumentation (16.54%). The number of instrumented cases was small and trending down and cement augmentation and bracing were more frequently chosen for these patients. This comes in accordance to the British haematological guidelines. Conclusion. Utilising BJH 2015 guidelines we have reduced our instrumented operative case load. There is a higher percentage of BKP and Bracing in accordance to the algorithm


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 7 | Pages 954 - 962
1 Sep 2001
Rajasekaran S

The progression of post-tubercular kyphosis in 61 children who received ambulatory chemotherapy was studied prospectively. The angles of deformity and kyphosis were measured for each patient at diagnosis, 3, 6, 9, 12 and 18 months later and every year thereafter for 15 years. During the course of the disease signs of instability appeared on the radiographs of some of the children. These were dislocation of the facets, posterior retropulsion of the diseased fragments, lateral translation of the vertebrae in the anteroposterior view and toppling of the superior vertebra. Each sign was allocated one point to create a spinal instability score. The influence on the progression of the deformity of the level of the lesion, the vertebral body loss, the number of segments involved, the angle of deformity before treatment and the spinal instability score was analysed. The mean angle of deformity at the start of treatment was 35°. This increased to 41° at 15 years. Progression occurred during the active phase of the disease and again after cure when variations in progression were observed. Type-I progression showed an increase in deformity until growth had ceased. This could occur either continuously (type Ia) or after a lag period of three to five years (type Ib). Type-II progression showed decrease in deformity with growth. This could occur immediately after the active phase (type IIa) or after a lag period of three to five years (type IIb). Type-III progression showed minimal change during either the active or healed phases and was seen only in those with limited disease. Multiple regression analysis showed that a spinal instability score of more than 2 was a reliable predictor of patients with an increase of more than 30° in deformity and a final deformity of over 60°. Since signs of radiological instability appear early in the disease, they can be reliably used to identify children whose spine is at risk for late progressive collapse. Surgery is advised in these cases


Bone & Joint Open
Vol. 5, Issue 5 | Pages 435 - 443
23 May 2024
Tadross D McGrory C Greig J Townsend R Chiverton N Highland A Breakwell L Cole AA

Aims

Gram-negative infections are associated with comorbid patients, but outcomes are less well understood. This study reviewed diagnosis, management, and treatment for a cohort treated in a tertiary spinal centre.

Methods

A retrospective review was performed of all gram-negative spinal infections (n = 32; median age 71 years; interquartile range 60 to 78), excluding surgical site infections, at a single centre between 2015 to 2020 with two- to six-year follow-up. Information regarding organism identification, antibiotic regime, and treatment outcomes (including clinical, radiological, and biochemical) were collected from clinical notes.


The Bone & Joint Journal
Vol. 105-B, Issue 6 | Pages 679 - 687
1 Jun 2023
Lou Y Zhao C Cao H Yan B Chen D Jia Q Li L Xiao J

Aims

The aim of this study was to report the long-term prognosis of patients with multiple Langerhans cell histiocytosis (LCH) involving the spine, and to analyze the risk factors for progression-free survival (PFS).

Methods

We included 28 patients with multiple LCH involving the spine treated between January 2009 and August 2021. Kaplan-Meier methods were applied to estimate overall survival (OS) and PFS. Univariate Cox regression analysis was used to identify variables associated with PFS.


Bone & Joint Open
Vol. 4, Issue 11 | Pages 832 - 838
3 Nov 2023
Pichler L Li Z Khakzad T Perka C Pumberger M Schömig F

Aims

Implant-related postoperative spondylodiscitis (IPOS) is a severe complication in spine surgery and is associated with high morbidity and mortality. With growing knowledge in the field of periprosthetic joint infection (PJI), equivalent investigations towards the management of implant-related infections of the spine are indispensable. To our knowledge, this study provides the largest description of cases of IPOS to date.

Methods

Patients treated for IPOS from January 2006 to December 2020 were included. Patient demographics, parameters upon admission and discharge, radiological imaging, and microbiological results were retrieved from medical records. CT and MRI were analyzed for epidural, paravertebral, and intervertebral abscess formation, vertebral destruction, and endplate involvement. Pathogens were identified by CT-guided or intraoperative biopsy, intraoperative tissue sampling, or implant sonication.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_X | Pages 135 - 135
1 Apr 2012
Timothy J Phillips H Michaels R Pal D
Full Access

The aim of this study was to prospectively assess the outcome of patients with metastatic spinal disease who underwent minimally invasive fixation of the spine for intractable pain or spinal instability. This is a prospective audit of patients with metastatic spinal cord disease who have undergone minimally invasive fixation of the spine from August 2009 until the present date. This was assessed by pre and post-operative Oswestry Disability Index (ODI), EQ5D and Tokuhashi scores. Intra- and post-operative complications, time to theatre, length of inpatient stay, analgesia requirements, mobility, chest drain requirement and post-operative HDU and ITU stays were also recorded. So far, 10 patients have met the criteria. There were no intra-operative complications. Post-operatively, there were no complications, chest drains, increase in analgesia or stay on the HDU or ITU. All patients showed an improvement in mobility. The mean post-operative day of mobilisation was 2 days, post-operative days until discharge 5.3 days and length of inpatient stay was shorter than traditional surgery. Blood loss was minimum except one patient with metastatic renal cell carcinoma who needed transfusion intraoperatively. ODI, VAS and EQ-5D scores were calculated and were significantly improved compared to preoperatively. This novel approach to management of metastatic spinal disease has resulted in improved mobility, short inpatient stays without the need for chest drains, HDU or ITU and an improved the quality of life in pallliative patients. This is a completely new strategy to treat the pain in these patients without the usual associated risks of surgery and has major advantages over traditional surgical techniques which may preclude this group of patients having any surgical stabilisation procedure at all


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_X | Pages 10 - 10
1 Apr 2012
El-Abed K Barakat M Ainscow D
Full Access

We carried out a prospective study looking at the functional outcome and post-procedure segmental instability after lumbar decompression using a flip osteotomy technique that involved unilateral subperiosteal muscle dissection with hinging of the spinous processes thereby preserving the integrity of the posterior elements for unilateral or bilateral lumbar spine decompression. Between February 2007 and February 2008, 51 patients (29 male and 22 female) diagnosed with degenerative and congenital lumbar stenosis with an average age of 60, underwent central and lateral canal decompression using the flip osteotomy technique. An average of two segments (range 1-3 segments) was decompressed. Patients with a history of previous spinal surgery, spinal fusion, existing degenerative spondylolisthesis or cauda equina syndrome were excluded. All patients were followed up for a mean of 1.5 years. Five outcome measures were used – visual analogue scale for pain, Likert scale for functional status, symptom specific well-being score, general well-being score, number of days incapacitated in last 4 weeks. The outcomes measures were recorded pre-operatively, 6 weeks and one year post-operatively. Successful surgical outcome was defined as an improvement in at least four out of five outcome measures. 90% (46 patients) of patients had a successful surgical outcome. There was a statistically significant improvement in all outcome criteria (p<0.005) at the 6-week post-operative mark as compared to pre-operatively, with marginal improvement at one year post-surgery. There was no evidence of progressive lumbar segmental instability at one year post-operatively using our flip osteotomy technique. Decompression of the lumbar spine for lumbar stenosis using the flip osteotomy technique is a safe approach for one or multi-level stenosis with good outcomes and no evidence of significant iatrogenic segmental spinal instability. We declare no conflict of interest and ethical approval was obtained


The Journal of Bone & Joint Surgery British Volume
Vol. 79-B, Issue 6 | Pages 948 - 951
1 Nov 1997
Lundy DW Murray HH

Posterior cervical wiring is commonly performed for patients with spinal instability, but has inherent risks. We report eight patients who had neurological deterioration after sublaminar or spinous process wiring of the cervical spine; four had complete injuries of the spinal cord, one had residual leg spasticity and three recovered after transient injuries. We found no relation between the degree of spinal canal encroachment and the severity of the spinal-cord injury, but in all cases neurological worsening appeared to have been caused by either sublaminar wiring or spinous process wiring which had been placed too far anteriorly. Sublaminar wiring has substantial risks and should be used only at atlantoaxial level, and then only after adequate reduction. Fluoroscopic guidance should be used when placing spinous process wires especially when the posterior spinal anatomy is abnormal


The Bone & Joint Journal
Vol. 104-B, Issue 1 | Pages 120 - 126
1 Jan 2022
Kafle G Garg B Mehta N Sharma R Singh U Kandasamy D Das P Chowdhury B

Aims

The aims of this study were to determine the diagnostic yield of image-guided biopsy in providing a final diagnosis in patients with suspected infectious spondylodiscitis, to report the diagnostic accuracy of various microbiological tests and histological examinations in these patients, and to report the epidemiology of infectious spondylodiscitis from a country where tuberculosis (TB) is endemic, including the incidence of drug-resistant TB.

Methods

A total of 284 patients with clinically and radiologically suspected infectious spondylodiscitis were prospectively recruited into the study. Image-guided biopsy of the vertebral lesion was performed and specimens were sent for various microbiological tests and histological examinations. The final diagnosis was determined using a composite reference standard based on clinical, radiological, serological, microbiological, and histological findings. The overall diagnostic yield of the biopsy, and that for each test, was calculated in light of the final diagnosis.


The Bone & Joint Journal
Vol. 102-B, Issue 12 | Pages 1709 - 1716
1 Dec 2020
Kanda Y Kakutani K Sakai Y Yurube T Miyazaki S Takada T Hoshino Y Kuroda R

Aims

With recent progress in cancer treatment, the number of advanced-age patients with spinal metastases has been increasing. It is important to clarify the influence of advanced age on outcomes following surgery for spinal metastases, especially with a focus on subjective health state values.

Methods

We prospectively analyzed 101 patients with spinal metastases who underwent palliative surgery from 2013 to 2016. These patients were divided into two groups based on age (< 70 years and ≥ 70 years). The Eastern Cooperative Oncology Group (ECOG) performance status (PS), Barthel index (BI), and EuroQol-5 dimension (EQ-5D) score were assessed at study enrolment and at one, three, and six months after surgery. The survival times and complications were also collected.


The Bone & Joint Journal
Vol. 102-B, Issue 8 | Pages 1062 - 1071
1 Aug 2020
Cheung JPY Fong HK Cheung PWH

Aims

To determine the effectiveness of prone traction radiographs in predicting postoperative slip distance, slip angle, changes in disc height, and lordosis after surgery for degenerative spondylolisthesis of the lumbar spine.

Methods

A total of 63 consecutive patients with a degenerative spondylolisthesis and preoperative prone traction radiographs obtained since 2010 were studied. Slip distance, slip angle, disc height, segmental lordosis, and global lordosis (L1 to S1) were measured on preoperative lateral standing radiographs, flexion-extension lateral radiographs, prone traction lateral radiographs, and postoperative lateral standing radiographs. Patients were divided into two groups: posterolateral fusion or posterolateral fusion with interbody fusion.


The Bone & Joint Journal
Vol. 100-B, Issue 4 | Pages 499 - 506
1 Apr 2018
Minamide A Yoshida M Simpson AK Nakagawa Y Iwasaki H Tsutsui S Takami M Hashizume H Yukawa Y Yamada H

Aims

The aim of this study was to investigate the clinical and radiographic outcomes of microendoscopic laminotomy in patients with lumbar stenosis and concurrent degenerative spondylolisthesis (DS), and to determine the effect of this procedure on spinal stability.

Patients and Methods

A total of 304 consecutive patients with single-level lumbar DS with concomitant stenosis underwent microendoscopic laminotomy without fusion between January 2004 and December 2010. Patients were divided into two groups, those with and without advanced DS based on the degree of spondylolisthesis and dynamic instability. A total of 242 patients met the inclusion criteria. There were 101 men and 141 women. Their mean age was 68.1 years (46 to 85). Outcome was assessed using the Japanese Orthopaedic Association and Roland Morris Disability Questionnaire scores, a visual analogue score for pain and the Short Form Health-36 score. The radiographic outcome was assessed by measuring the slip and the disc height. The clinical and radiographic parameters were evaluated at a mean follow-up of 4.6 years (3 to 7.5).


The Bone & Joint Journal
Vol. 98-B, Issue 6 | Pages 834 - 839
1 Jun 2016
Wang S Ma H Lin C Chou P Liu C Yu W Chang M

Aim

Many aspects of the surgical treatment of patients with tuberculosis (TB) of the spine, including the use of instrumentation and the types of graft, remain controversial. Our aim was to report the outcome of a single-stage posterior procedure, with or without posterior decompression, in this group of patients.

Patients and Methods

Between 2001 and 2010, 51 patients with a mean age of 62.5 years (39 to 86) underwent long posterior instrumentation and short posterior or posterolateral fusion for TB of the thoracic and lumbar spines, followed by anti-TB chemotherapy for 12 months. No anterior debridement of the necrotic tissue was undertaken. Posterior decompression with laminectomy was carried out for the 30 patients with a neurological deficit.


The Bone & Joint Journal
Vol. 97-B, Issue 2 | Pages 235 - 239
1 Feb 2015
Prime M Al-Obaidi B Safarfashandi Z Lok Y Mobasheri R Akmal M

This study examined spinal fractures in patients admitted to a Major Trauma Centre via two independent pathways, a major trauma (MT) pathway and a standard unscheduled non-major trauma (NMT) pathway. A total of 134 patients were admitted with a spinal fracture over a period of two years; 50% of patients were MT and the remainder NMT. MT patients were predominantly male, had a mean age of 48.8 years (13 to 95), commonly underwent surgery (62.7%), characteristically had fractures in the cervico-thoracic and thoracic regions and 50% had fractures of more than one vertebrae, which were radiologically unstable in 70%. By contrast, NMT patients showed an equal gender distribution, were older (mean 58.1 years; 12 to 94), required fewer operations (56.7%), characteristically had fractures in the lumbar region and had fewer multiple and unstable fractures. This level of complexity was reflected in the length of stay in hospital; MT patients receiving surgery were in hospital for a mean of three to four days longer than NMT patients. These results show that MT patients differ from their NMT counterparts and have an increasing complexity of spinal injury.

Cite this article: Bone Joint J 2015;97-B:235–9.


The Bone & Joint Journal
Vol. 95-B, Issue 7 | Pages 960 - 965
1 Jul 2013
Försth P Michaëlsson K Sandén B

Whether to combine spinal decompression with fusion in patients with symptomatic lumbar spinal stenosis remains controversial. We performed a cohort study to determine the effect of the addition of fusion in terms of patient satisfaction after decompressive spinal surgery in patients with and without a degenerative spondylolisthesis.

The National Swedish Register for Spine Surgery (Swespine) was used for the study. Data were obtained for all patients in the register who underwent surgery for stenosis on one or two adjacent lumbar levels. A total of 5390 patients fulfilled the inclusion criteria and completed a two-year follow-up. Using multivariable models the results of 4259 patients who underwent decompression alone were compared with those of 1131 who underwent decompression and fusion. The consequence of having an associated spondylolisthesis in the operated segments pre-operatively was also considered.

At two years there was no significant difference in patient satisfaction between the two treatment groups for any of the outcome measures, regardless of the presence of a pre-operative spondylolisthesis. Moreover, the proportion of patients who required subsequent further lumbar surgery was also similar in the two groups.

In this large cohort the addition of fusion to decompression was not associated with an improved outcome.

Cite this article: Bone Joint J 2013;95-B:960–5.