Aims. Extracellular vesicles (EVs) are nanoparticles secreted by all cells, enriched in proteins, lipids, and nucleic acids related to cell-to-cell communication and vital components of cell-based therapies. Mesenchymal stromal cell (MSC)-derived EVs have been studied as an alternative for osteoarthritis (OA) treatment. However, their clinical translation is hindered by industrial and regulatory challenges. In contrast, platelet-derived EVs might reach clinics faster since platelet concentrates, such as platelet lysates (PL), are already used in therapeutics. Hence, we aimed to test the therapeutic potential of PL-derived extracellular vesicles (pEVs) as a new treatment for OA, which is a degenerative joint disease of articular cartilage and does not have any curative or regenerative treatment, by comparing its effects to those of human umbilical cord MSC-derived EVs (cEVs) on an ex vivo OA-induced model using human cartilage explants. Methods. pEVs and cEVs were isolated by size exclusion chromatography (SEC) and physically characterized by nanoparticle tracking analysis (NTA), protein content, and purity. OA conditions were induced in human cartilage explants (10 ng/ml oncostatin M and 2 ng/ml tumour necrosis factor alpha (TNFα)) and treated with 1 × 10. 9. particles of pEVs or cEVs for 14 days. Then, DNA, glycosaminoglycans (GAG), and collagen content were quantified, and a histological study was performed. EV uptake was monitored using PKH26 labelled EVs. Results. Significantly higher content of DNA and collagen was observed for the pEV-treated group compared to control and cEV groups. No differences were found in GAG quantification nor in EVs uptake within any treated group. Conclusion. In conclusion, pEVs showed better performance than cEVs in our in vitro OA model. Although further studies are needed, pEVs are shown as a potential alternative to cEVs for cell-free regenerative medicine. Cite this article: Bone Joint Res 2023;12(10):667–676

Segmental vessel ligation during anterior spinal surgery has been associated with paraplegia. However, the incidence and risk factors for this devastating complication are debated. We reviewed 346 consecutive paediatric and adolescent patients ranging in age from three to 18 years who underwent surgery for anterior spinal deformity through a thoracic or thoracoabdominal approach, during which 2651 segmental vessels were ligated. There were 173 patients with idiopathic scoliosis, 80 with congenital scoliosis or kyphosis, 43 with neuromuscular and 31 with syndromic scoliosis, 12 with a scoliosis associated with intraspinal abnormalities, and seven with a kyphosis. There was only one neurological complication, which occurred in a patient with a 127° congenital thoracic scoliosis due to a unilateral unsegmented bar with contralateral hemivertebrae at the same level associated with a thoracic diastematomyelia and tethered cord. This patient was operated upon early in the series, when intra-operative spinal cord monitoring was not available. Intra-operative spinal cord monitoring with the use of somatosensory evoked potentials alone or with motor evoked potentials was performed in 331 patients. This showed no evidence of signal change after ligation of the segmental vessels. In our experience, unilateral segmental vessel ligation carries no risk of neurological damage to the spinal cord unless performed in patients with complex congenital spinal deformities occurring primarily in the thoracic spine and associated with intraspinal anomalies at the same level, where the vascular supply to the cord may be abnormal

Metal-on-metal bearings are being increasingly used in young patients. The potential adverse effects of systemic metal ion elevation are the subject of ongoing investigation. The purpose of this study was to investigate whether cobalt and chromium ions cross the placenta of pregnant women with a metal-on-metal hip resurfacing and reach the developing fetus. Whole blood levels were estimated using high-resolution inductively-coupled plasma mass spectrometry. Our findings showed that cobalt and chromium are able to cross the placenta in the study patients with metal-on-metal hip resurfacings and in control subjects without any metal implants. In the study group the mean concentrations of cobalt and chromium in the maternal blood were 1.39 μg/l (0.55 to 2.55) and 1.28 μg/l (0.52 to 2.39), respectively. The mean umbilical cord blood concentrations of cobalt and chromium were comparatively lower, at 0.839 μg/l (0.42 to 1.75) and 0.378 μg/l (0.14 to 1.03), respectively, and this difference was significant with respect to chromium (p < 0.05). In the control group, the mean concentrations of cobalt and chromium in the maternal blood were 0.341 μg/l (0.18 to 0.54) and 0.199 μg/l (0.12 to 0.33), and in the umbilical cord blood they were 0.336 μg/l (0.17 to 0.5) and 0.194 μg/l (0.11 to 0.56), respectively. The differences between the maternal and umbilical cord blood levels in the controls were marginal, and not statistically significant (p > 0.05). The mean cord blood level of cobalt in the study patients was significantly greater than that in the control group (p < 0.01). Although the mean umbilical cord blood chromium level was nearly twice as high in the study patients (0.378 μg/l) as in the controls (0.1934 μg/l), this difference was not statistically significant. (p > 0.05). The transplacental transfer rate was in excess of 95% in the controls for both metals, but only 29% for chromium and 60% for cobalt in study patients, suggesting that the placenta exerts a modulatory effect on the rate of metal ion transfer

We assessed the frequency and causes of neurological deterioration in 59 patients with spinal cord injury on whom reports were prepared for clinical negligence litigation. In those who deteriorated neurologically we assessed the causes of the change in neurology and whether that neurological deterioration was potentially preventable. In all 27 patients (46%) changed neurologically, 20 patients (74% of those who deteriorated) had no primary neurological deficit. Of those who deteriorated, 13 (48%) became Frankel A. Neurological deterioration occurred in 23 of 38 patients (61%) with unstable fractures and/or dislocations; all 23 patients probably deteriorated either because of failures to immobilise the spine or because of inappropriate removal of spinal immobilisation. Of the 27 patients who altered neurologically, neurological deterioration was, probably, avoidable in 25 (excess movement in 23 patients with unstable injuries, failure to evacuate an epidural haematoma in one patient and over-distraction following manipulation of the cervical spine in one patient). If existing guidelines and standards for the management of actual or potential spinal cord injury had been followed, neurological deterioration would have been prevented in 25 of the 27 patients (93%) who experienced a deterioration in their neurological status. Cite this article: Bone Joint J 2015;97-B:527–31

Aims. Platelet concentrates, like platelet-rich plasma (PRP) and platelet lysate (PL), are widely used in regenerative medicine, especially in bone regeneration. However, the lack of standard procedures and controls leads to high variability in the obtained results, limiting their regular clinical use. Here, we propose the use of platelet-derived extracellular vesicles (EVs) as an off-the-shelf alternative for PRP and PL for bone regeneration. In this article, we evaluate the effect of PL-derived EVs on the biocompatibility and differentiation of mesenchymal stromal cells (MSCs). Methods. EVs were obtained first by ultracentrifugation (UC) and then by size exclusion chromatography (SEC) from non-activated PL. EVs were characterized by transmission electron microscopy, nanoparticle tracking analysis, and the expression of CD9 and CD63 markers by western blot. The effect of the obtained EVs on osteoinduction was evaluated in vitro on human umbilical cord MSCs by messenger RNA (mRNA) expression analysis of bone markers, alkaline phosphatase activity (ALP), and calcium (Ca. 2+. ) content. Results. Osteogenic differentiation of MSCs was confirmed when treated with UC-isolated EVs. In order to disprove that the effect was due to co-isolated proteins, EVs were isolated by SEC. Purer EVs were obtained and proved to maintain the differentiation effect on MSCs and showed a dose-dependent response. Conclusion. PL-derived EVs present an osteogenic capability comparable to PL treatments, emerging as an alternative able to overcome PL and PRP limitations. Cite this article: Bone Joint Res 2020;9(10):667–674

Aims. The aim of this study was to explore the prognostic factors for postoperative neurological recovery and survival in patients with complete paralysis due to neoplastic epidural spinal cord compression. Patients and Methods. The medical records of 135 patients with complete paralysis due to neoplastic cord compression were retrospectively reviewed. Potential factors including the timing of surgery, muscular tone, and tumour characteristics were analyzed in relation to neurological recovery using logistical regression analysis. The association between neurological recovery and survival was analyzed using a Cox model. A nomogram was formulated to predict recovery. Results. A total of 52 patients (38.5%) achieved American Spinal Injury Association Impairment Scale (AIS) D or E recovery postoperatively. The timing of surgery (p = 0.003) was found to be significant in univariate analysis. In multivariate analysis, surgery within one week was associated with better neurological recovery than surgery within three weeks (p = 0.002), with a trend towards being associated with a better neurological recovery than surgery within one to two weeks (p = 0.597) and two to three weeks (p = 0.055). Age (p = 0.039) and muscle tone (p = 0.018) were also significant predictors. In Cox regression analysis, good neurological recovery (p = 0.004), benign tumours (p = 0.039), and primary tumours (p = 0.005) were associated with longer survival. Calibration graphs showed that the nomogram did well with an ideal model. The bootstrap-corrected C-index for neurological recovery was 0.72. Conclusion. In patients with complete paralysis due to neoplastic spinal cord compression, whose treatment is delayed for more than 48 hours from the onset of symptoms, surgery within one week is still beneficial. Surgery undertaken at this time may still offer neurological recovery and longer survival. The identification of the association between these factors and neurological recovery may help guide treatment for these patients. Cite this article: Bone Joint J 2019;101-B:872–879

The identification of the extent of neural damage in patients with acute or chronic spinal cord injury is imperative for the accurate prediction of neurological recovery. The changes in signal intensity shown on routine MRI sequences are of limited value for predicting functional outcome. Diffusion tensor imaging (DTI) is a novel radiological imaging technique which has the potential to identify intact nerve fibre tracts, and has been used to image the brain for a variety of conditions. DTI imaging of the spinal cord is currently only a research tool, but preliminary studies have shown that it holds considerable promise in predicting the severity of spinal cord injury. . This paper briefly reviews our current knowledge of this technique

Injury to the spinal cord and kyphosis are the two most feared complications of tuberculosis of the spine. Since tuberculosis affects principally the vertebral bodies, anterior decompression is usually recommended. Concomitant posterior instrumentation is indicated to neutralise gross instability from panvertebral disease, to protect the anterior bone graft, to prevent graft-related complications after anterior decompression in long-segment disease and to correct a kyphosis. Two-stage surgery is usually performed in these cases. We present 38 consecutive patients with tuberculosis of the spine for whom anterior decompression, posterior instrumentation, with or without correction of the kyphus, and anterior and posterior fusion was performed in a single stage through an anterolateral extrapleural approach. Their mean age was 20.4 years (2.0 to 57.0). The indications for surgery were panvertebral disease, neurological deficit and severe kyphosis. The patients were operated on in the left lateral position using a ‘T’-shaped incision sited at the apex of kyphosis or lesion. Three ribs were removed in 34 patients and two in four and anterior decompression of the spinal cord was carried out. The posterior vertebral column was shortened to correct the kyphus, if necessary, and was stabilised by a Hartshill rectangle and sublaminar wires. Anterior and posterior bone grafting was performed. The mean number of vertebral bodies affected was 3.24 (2.0 to 9.0). The mean pre-operative kyphosis in patients operated on for correction of the kyphus was 49.08° (30° to 72°) and there was a mean correction of 25° (6° to 42°). All except one patient with a neural deficit recovered complete motor and sensory function. The mean intra-operative blood loss was 1175 ml (800 to 2600), and the mean duration of surgery 3.5 hours (2.7 to 5.0). Wound healing was uneventful in 33 of 38 patients. The mean follow-up was 33 months (11 to 74). None of the patients required intensive care. The extrapleural anterolateral approach provides simultaneous exposure of the anterior and posterior aspects of the spine, thereby allowing decompression of the spinal cord, posterior stabilisation and anterior and posterior bone grafting. This approach has much less morbidity than the two-stage approaches which have been previously described

This study evaluates factors related to myelopathic symptoms in patients with ossification of the posterior longitudinal ligament (OPLL). A total of 87 patients with OPLL were included. Of these, 53 (Group I) had no symptoms or presented with neck pain and radiculopathy and 34 (Group II) had myelopathic symptoms. Gender, age, and history of trauma were evaluated in the two groups. The range of movement of the cervical spine was measured using plain radiographs. The number of involved segments, type of OPLL, and maximal compression ratio were analysed using CT and signal change in the spinal cord was evaluated using MRI. The patients’ age was found to be significant (p = 0.001). No difference was found between gender and the range of movement in the two groups. The maximum compression of the spinal canal showed a difference (p = 0.03). The signal change of the spinal cord was different between the two groups. In patients with OPLL of the cervical spine, myelopathic symptoms are not related to the range of movement or the number of involved segments.

We have reviewed 1858 patients who had undergone a cervical laminoplasty and identified 43 (2.3%) who had developed a C5 palsy with a MMT (MRC) grade of 0 to 2 in the deltoid, with or without involvement of the biceps, but with no loss of muscular strength in any other muscles. The clinical features and radiological findings of patients with (group P; 43 patients) and without (group C; 100 patients) C5 palsy were compared. CT scanning of group P revealed a significant narrowing of the intervertebral foramen of C5 (p < 0.005) and a larger superior articular process (p < 0.05). On MRI, the posterior shift of the spinal cord at C4–5 was significantly greater in group P, than in group C (p < 0.01). This study is the first to correlate impairment of the C5 nerve root with a C5 palsy. It may be that early foraminotomy in susceptible individuals and the avoidance of tethering of the cord by excessive laminoplasty may prevent a post-operative palsy of the C5 nerve root

Aims

The optimal procedure for the treatment of ossification of the posterior longitudinal ligament (OPLL) remains controversial. The aim of this study was to compare the outcome of anterior cervical ossified posterior longitudinal ligament en bloc resection (ACOE) with posterior laminectomy and fusion with bone graft and internal fixation (PTLF) for the surgical management of patients with this condition.

Aims

Surgical approaches to cervical ossification of the posterior longitudinal ligament (OPLL) remain controversial. The purpose of the present study was to analyze and compare the long-term neurological recovery following anterior decompression with fusion (ADF) and posterior laminectomy and fusion with bone graft and internal fixation (PLF) based on > ten-year follow-up outcomes in a single centre.

Aims

The involvement of cyclin D1 in the proliferation of microglia, and the generation and maintenance of bone cancer pain (BCP), have not yet been clarified. We investigated the expression of microglia and cyclin D1, and the influences of cyclin D1 on pain threshold.

1. Five cases of scoliosis with paraplegia are reported, and thirty-six comparable cases from the literature are reviewed. These forty-one cases have been studied with the object of determining the etiology of scoliosis, the reason why cord compression sometimes develops, and the results of conservative and operative treatment of such compression of the cord. 2. The cause of paraplegia is nearly always compression of the spinal cord by the dura, which, in severe scoliosis, is under longitudinal tension because of its firm attachment to the foramen magnum above and the sacrum below. Such tension, resisting displacement of the spinal cord from the straight line, may be shown to cause incomplete spinal block even when there is no paralysis. 3. When paralysis occurs it usually develops during the years of most rapid growth, the tight dura being unable to accommodate itself to the rate of growth of the spinal column; cord compression is probably increased by narrowing of the dural sac by rotational displacement. 4. The most striking results have been secured by laminectomy with section of the dura and sometimes division of dentate ligaments and tight nerve roots. After such division there is evidence of release of compression: the cord herniates through the dural slit; and spinal pulsation returns. 5. It is important to control bleeding in order to avoid post-operative compression by blood clot; and to prevent leakage of cerebro-spinal fluid through the arachnoid. 6. It is unwise to perform spinal fusion at the same time as decompression because it increases the danger of haematoma formation. Moreover the improvement gained by decompression is maintained even if no fusion of the spine is performed. 7. Conservative treatment of scoliosis with paraplegia should not be continued for long periods unless there is evidence of early and progressive improvement because prolonged compression causes irreversible changes in the cord. 8. In three cases, paraplegia was not due to dural compression: one turned out later to be a case of syringomyelia; one, reported by Heyman, was due to the pressure of a bone spur; and one, reported in this series, was due to a congenital tight band of developmental origin which might have caused the scoliosis as well as the paralysis, and in which, after resection of the band, recovery from the paralysis was complete

Aims. To address the natural history of severe post-tuberculous (TB) kyphosis, with focus upon the long-term neurological outcome, occurrence of restrictive lung disease, and the effect on life expectancy. . Patients and Methods. This is a retrospective clinical review of prospectively collected imaging data based at a single institute. A total of 24 patients of Southern Chinese origin who presented with spinal TB with a mean of 113° of kyphosis (65° to 159°) who fulfilled inclusion criteria were reviewed. Plain radiographs were used to assess the degree of spinal deformity. Myelography, CT and MRI were used when available to assess the integrity of the spinal cord and canal. Patient demographics, age of onset of spinal TB and interventions, types of surgical procedure, intra- and post-operative complications, and neurological status were assessed. . Results. All except one of the 24 patients were treated with anti-TB chemotherapy when they were first diagnosed with spinal TB. They subsequently received surgery either for neurological deterioration, or deformity correction in later life. The mean follow-up was 34 years (11 to 59) since these surgical interventions. Some 16 patients (66.7%) suffered from late neurological deterioration at a mean of 26 years (8 to 49) after the initial drug treatment. The causes of neurological deterioration were healed disease in nine patients (56.2%), re-activation in six patients (37.5%) and adjacent level spinal stenosis in one patient (6.3%). The result of surgery was worse in healed disease. Eight patients without neurological deterioration received surgery to correct the kyphosis. The mean correction ranged from 97° to 72°. Three patients who were clinically quiescent with no neurological deterioration were found to have active TB of the spine. Solid fusion was achieved in all cases and no patient suffered from neurological deterioration after 42 years of follow-up. On final follow-up, six patients were noted to have deceased (age range: 47 years to 75 years). Conclusion. Our study presents one of the longest assessments of spinal TB with severe kyphosis. Severe post-TB kyphosis may lead to significant health problems many years following the initial drug treatment. Early surgical correction of the kyphosis, solid fusion and regular surveillance may avoid late complications. Paraplegia, restrictive lung disease and early onset kyphosis might relate to early death. Clinically quiescent disease does not mean cure. . Cite this article: Bone Joint J 2017;99-B:1381–8