In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD. An in vitro model for oxidative stress-induced injury in NPCs was developed to elucidate the mechanisms underlying the upregulation of DDIT4 expression, activation of the reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NLRP3 signalling pathway, and nucleus pulposus pyroptosis. Furthermore, the mechanism of action of small interfering DDIT4 (siDDIT4) on NPCs in vitro was validated. A triplex hydrogel named siDDIT4@G5-P-HA was created by adsorbing siDDIT4 onto fifth-generation polyamidoamine (PAMAM) dendrimer using van der Waals interactions, and then coating it with hyaluronic acid (HA). In addition, we established a rat puncture IVDD model to decipher the hydrogel’s mechanism in IVDD.Aims
Methods
This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD). The gene expression profile of GSE23130 was downloaded from the Gene Expression Omnibus (GEO) database. Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases, and we used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the functions and pathways of EP-DEGs. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and identify hub EP-DEGs. NetworkAnalyst was used to analyze transcription factors (TFs) and microRNAs (miRNAs) that regulate hub EP-DEGs. A search of the Drug Signatures Database (DSigDB) for hub EP-DEGs revealed multiple drug molecules and drug-target interactions.Aims
Methods
Lumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to genetic variation. However, the correlation between genetic variation and pathological changes in LSS is insufficient, and it is difficult to provide a reference for the early diagnosis and treatment of the disease. We conducted a transcriptome-wide association study (TWAS) of spinal canal stenosis by integrating genome-wide association study summary statistics (including 661 cases and 178,065 controls) derived from Biobank Japan, and pre-computed gene expression weights of skeletal muscle and whole blood implemented in FUSION software. To verify the TWAS results, the candidate genes were furthered compared with messenger RNA (mRNA) expression profiles of LSS to screen for common genes. Finally, Metascape software was used to perform enrichment analysis of the candidate genes and common genes.Aims
Methods
CRP is an acute-phase protein that is used as a biomarker to follow severity and progression in infectious and inflammatory diseases. Its pathophysiological mechanisms of action are still poorly defined. CRP in its pentameric form exhibits weak anti-inflammatory activity. The monomeric isoform (mCRP) exerts potent proinflammatory properties in chondrocytes, endothelial cells, and leucocytes. No data exist regarding mCRP effects in human intervertebral disc (IVD) cells. This work aimed to verify the pathophysiological relevance of mCRP in the aetiology and/or progression of IVD degeneration. We investigated the effects of mCRP and the signalling pathways that are involved in cultured human primary annulus fibrosus (AF) cells and in the human nucleus pulposus (NP) immortalized cell line HNPSV-1. We determined messenger RNA (mRNA) and protein levels of relevant factors involved in inflammatory responses, by quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. We also studied the presence of mCRP in human AF and NP tissues by immunohistochemistry.Aims
Methods
This study was performed to explore the effect of melatonin on pyroptosis in nucleus pulposus cells (NPCs) and the underlying mechanism of that effect. This experiment included three patients diagnosed with lumbar disc herniation who failed conservative treatment. Nucleus pulposus tissue was isolated from these patients when they underwent surgical intervention, and primary NPCs were isolated and cultured. Western blotting, reverse transcription polymerase chain reaction, fluorescence staining, and other methods were used to detect changes in related signalling pathways and the ability of cells to resist pyroptosis.Aims
Methods
Non-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI. In the current study, the luciferase assay confirmed a binding site of bromodomain-containing protein 4 (BRD4) and Wnt family member 5A (WNT5A). Then we detected expression of miR-381, BRD4, and WNT5A in dorsal root ganglia (DRG) cells treated with MSC-isolated EVs and measured neuron apoptosis in culture by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. A rat model of SCI was established to detect the in vivo effect of miR-381 and MSC-EVs on SCI.Aims
Methods
The aim of this study was to determine the differences in spinal imaging characteristics between subjects with or without lumbar developmental spinal stenosis (DSS) in a population-based cohort. This was a radiological analysis of 2,387 participants who underwent L1-S1 MRI. Means and ranges were calculated for age, sex, BMI, and MRI measurements. Anteroposterior (AP) vertebral canal diameters were used to differentiate those with DSS from controls. Other imaging parameters included vertebral body dimensions, spinal canal dimensions, disc degeneration scores, and facet joint orientation. Mann-Whitney U and chi-squared tests were conducted to search for measurement differences between those with DSS and controls. In order to identify possible associations between DSS and MRI parameters, those who were statistically significant in the univariate binary logistic regression were included in a multivariate stepwise logistic regression after adjusting for demographics. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported where appropriate.Aims
Methods
Pulsed electromagnetic field (PEMF) stimulation was evaluated after anterior cervical discectomy and fusion (ACDF) procedures in a randomized, controlled clinical study performed for United States Food and Drug Administration (FDA) approval. PEMF significantly increased fusion rates at six months, but 12-month fusion outcomes for subjects at elevated risk for pseudoarthrosis were not thoroughly reported. The objective of the current study was to evaluate the effect of PEMF treatment on subjects at increased risk for pseudoarthrosis after ACDF procedures. Two evaluations were performed that compared fusion rates between PEMF stimulation and a historical control (160 subjects) from the FDA investigational device exemption (IDE) study: a Objectives
Methods
The aim of this study was to determine whether the sequential
application of povidone iodine-alcohol (PVI) followed by chlorhexidine
gluconate-alcohol (CHG) would reduce surgical wound contamination
to a greater extent than PVI applied twice in patients undergoing
spinal surgery. A single-centre, interventional, two arm, parallel group randomised
controlled trial was undertaken, involving 407 patients who underwent
elective spinal surgery. For 203 patients, the skin was disinfected before surgery using
PVI (10% [w/w (1% w/w available iodine)] in 95% industrial denatured
alcohol, povidone iodine; Videne Alcoholic Tincture) twice, and
for 204 patients using PVI once followed by CHG (2% [w/v] chlorhexidine
gluconate in 70% [v/v] isopropyl alcohol; Chloraprep with tint).
The primary outcome measure was contamination of the wound determined
by aerobic and anaerobic bacterial growth from samples taken after
disinfection.Aims
Patients and Methods
Aims. To evaluate the incidence of primary venous thromboembolism (VTE),
epidural haematoma, surgical site infection (SSI), and 90-day mortality
after elective spinal surgery, and the effect of two protocols for
prophylaxis. Patients and Methods. A total of 2181 adults underwent 2366 elective spinal procedures
between January 2007 and January 2012. All patients wore anti-embolic
stockings, mobilised early and were kept adequately hydrated. In
addition, 29% (689) of these were given low
The aim of this study was to evaluate the time course of changes
in parameters of diffusion tensor imaging (DTI) such as fractional
anisotropy (FA) and apparent diffusion coefficient (ADC) in patients
with symptomatic lumbar disc herniation. We also investigated the
correlation between the severity of neurological symptoms and these parameters. A total of 13 patients with unilateral radiculopathy due to herniation
of a lumbar disc were investigated with DTI on a 1.5T MR scanner
and underwent micro discectomy. There were nine men and four women,
with a median age of 55.5 years (19 to 79). The changes in the mean
FA and ADC values and the correlation between these changes and the
severity of the neurological symptoms were investigated before and
at six months after surgery. Aims
Patients and Methods
The lack of an accurate, rapid diagnostic test
for mycobacterium tuberculosis (TB) is a major handicap in the management
of spinal TB. GeneXpert, a new, rapid
We determined the frequency, rate and extent
of development of scoliosis (coronal plane deformity) in wheelchair-dependent
patients with Duchenne muscular dystrophy (DMD) who were not receiving
steroid treatment. We also assessed kyphosis and lordosis (sagittal
plane deformity). The extent of scoliosis was assessed on sitting anteroposterior
(AP) spinal radiographs in 88 consecutive non-ambulatory patients
with DMD. Radiographs were studied from the time the patients became
wheelchair-dependent until the time of spinal fusion, or the latest assessment
if surgery was not undertaken. Progression was estimated using a
longitudinal mixed-model regression analysis to handle repeated
measurements. Scoliosis ≥ 10° occurred in 85 of 88 patients (97%), ≥ 20° in
78 of 88 (89%) and ≥ 30° in 66 of 88 patients (75%). The fitted
longitudinal model revealed that time in a wheelchair was a highly
significant predictor of the magnitude of the curve, independent
of the age of the patient (p <
0.001). Scoliosis developed in
virtually all DMD patients not receiving steroids once they became
wheelchair-dependent, and the degree of deformity deteriorated over
time. In general, scoliosis increased at a constant rate, beginning
at the time of wheelchair-dependency (p <
0.001). In some there
was no scoliosis for as long as three years after dependency, but
scoliosis then developed and increased at a constant rate. Some
patients showed a rapid increase in the rate of progression of the
curve after a few years – the clinical phenomenon of a rapidly collapsing
curve over a few months. A sagittal plane kyphotic deformity was seen in 37 of 60 patients
(62%) with appropriate radiographs, with 23 (38%) showing lumbar
lordosis (16 (27%) abnormal and seven (11%) normal). This study provides a baseline to assess the effects of steroids
and other forms of treatment on the natural history of scoliosis
in patients with DMD, and an approach to assessing spinal deformity
in the coronal and sagittal planes in wheelchair-dependent patients
with other neuromuscular disorders. Cite this article:
Mesenchymal stem-cell based therapies have been
proposed as novel treatments for intervertebral disc degeneration,
a prevalent and disabling condition associated with back pain. The
development of these treatment strategies, however, has been hindered
by the incomplete understanding of the human nucleus pulposus phenotype
and by an inaccurate interpretation and translation of animal to
human research. This review summarises recent work characterising
the nucleus pulposus phenotype in different animal models and in
humans and integrates their findings with the anatomical and physiological
differences between these species. Understanding this phenotype
is paramount to guarantee that implanted cells restore the native
functions of the intervertebral disc. Cite this article:
We evaluated the efficacy of Cite this article:
In order to elucidate the influence of sympathetic nerves on
lumbar radiculopathy, we investigated whether sympathectomy attenuated
pain behaviour and altered the electrical properties of the dorsal
root ganglion (DRG) neurons in a rat model of lumbar root constriction. Sprague-Dawley rats were divided into three experimental groups.
In the root constriction group, the left L5 spinal nerve root was
ligated proximal to the DRG as a lumbar radiculopathy model. In
the root constriction + sympathectomy group, sympathectomy was performed
after the root constriction procedure. In the control group, no
procedures were performed. In order to evaluate the pain relief
effect of sympathectomy, behavioural analysis using mechanical and
thermal stimulation was performed. In order to evaluate the excitability
of the DRG neurons, we recorded action potentials of the isolated
single DRG neuron by the whole-cell patch-clamp method.Objectives
Methods
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.
The post-operative changes in the serum levels of CRP and serum amyloid A (SAA) were investigated prospectively in 106 patients after posterior lumbar interbody fusion. In 96 patients who did not have complications related to infection within the first year after operation, the median levels of CRP before operation and on days 3, 7 and 13 after were 0.02 (0.01 to 0.03), 9.12 (2.36 to 19.82), 1.64 (0.19 to 6.10) and 0.53 (0.05 to 2.94) mg/dl, respectively and for SAA, 2.6 (2.0 to 3.8), 1312.1 (58.0 to 3579.8), 77.3 (1.8 to 478.4), 14.1 (0.5 to 71.9) μg/ml, respectively. The levels on day 3 were the highest for both CRP and SAA and significantly decreased (p <
0.01) by day 7 and day 13. In regard to CRP, no patient had less than the reference level (0.1 mg/dl) on day 7. In only three had the level decreased to the reference level, while in 93 it was above this on day 13. However, for SAA, the levels became normal on day 7 in 10 cases and on day 13 in 34 cases. The ratios relative to the levels on day 3 were significantly lower for SAA compared with CRP on day 7 and day 13. Of the ten patients with infection in the early stages, the level of CRP decreased slightly but an increase in SAA was observed in six. We concluded that SAA is better than CRP as a post-operative inflammatory marker.
Between January 1990 and December 2000 we carried out 226 SB Charité III disc replacements for lumbar disc degeneration in 160 patients. They were reviewed at a mean follow-up of 79 months (31 to 161) to determine the clinical and radiological outcome. The clinical results were collected by an independent observer, who was not involved in patient selection, treatment or follow-up, using a combination of outcome measures, including the Oswestry Disability Index. Pain was recorded using a visual analogue score, and the most recent radiographs were reviewed. Survival of the device was analysed by the Kaplan-Meier method and showed a cumulative survival of 35% at 156 months when radiological failure was taken as the endpoint. The mean improvement in the Oswestry disability index scores after disc replacement was 14% (6% to 21%) and the mean improvement in the pain score was 1.6 (0.46 to 2.73), both falling below the clinically significant threshold. Removal of the implant was required in 12 patients, four because of implant failure. These poor results indicate that further use of this implant is not justified.
Non-tuberculous mycobacterial infections pose a significant diagnostic and therapeutic challenge. We report two cases of such infection of the spine in HIV-negative patients who presented with deformity and neurological deficit. The histopathological features in both specimens were diagnostic of tuberculosis. The isolates were identified as Mycobacterium intracellulare and M. fortuitum by genotyping (MicroSeq 16S rDNA Full Gene assay) and as M. tuberculosis and a mycobacterium other than tuberculosis, respectively, by culture. There is a growing need for