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
Degenerative cervical spondylosis (DCS) is a common musculoskeletal disease that encompasses a wide range of progressive degenerative changes and affects all components of the cervical spine. DCS imposes very large social and economic burdens. However, its genetic basis remains elusive. Predicted whole-blood and skeletal muscle gene expression and genome-wide association study (GWAS) data from a DCS database were integrated, and functional summary-based imputation (FUSION) software was used on the integrated data. A transcriptome-wide association study (TWAS) was conducted using FUSION software to assess the association between predicted gene expression and DCS risk. The TWAS-identified genes were verified via comparison with differentially expressed genes (DEGs) in DCS RNA expression profiles in the Gene Expression Omnibus (GEO) (Accession Number: GSE153761). The Functional Mapping and Annotation (FUMA) tool for genome-wide association studies and Meta tools were used for gene functional enrichment and annotation analysis.Aims
Methods
We evaluated the efficacy of Escherichia
coli-derived recombinant human bone morphogenetic protein-2
(E-BMP-2) in a mini-pig model of spinal anterior interbody fusion.
A total of 14 male mini-pigs underwent three-level anterior lumbar
interbody fusion using polyether etherketone (PEEK) cages containing
porous hydroxyapatite (HA). Four groups of cages were prepared:
1) control (n = 10 segments); 2) 50 μg E-BMP-2 (n = 9); 3) 200 μg
E-BMP-2 (n = 10); and 4) 800 μg E-BMP-2 (n = 9). At eight weeks
after surgery the mini-pigs were killed and the specimens were evaluated
by gross inspection and manual palpation, radiological evaluation
including plain radiographs and micro-CT scans, and histological
analysis. Rates of fusion within PEEK cages and overall union rates
were calculated, and bone formation outside vertebrae was evaluated.
One animal died post-operatively and was excluded, and one section
was lost and also excluded, leaving 38 sites for assessment. This
rate of fusion within cages was 30.0% (three of ten) in the control
group, 44.4% (four of nine) in the 50 μg E-BMP-2 group, 60.0% (six
of ten) in the 200 μg E-BMP-2 group, and 77.8% (seven of nine) in
the 800 μg E-BMP-2 group. Fusion rate was significantly increased
by the addition of E-BMP-2 and with increasing E-BMP-2 dose (p =
0.046). In a mini-pig spinal anterior interbody fusion model using
porous HA as a
Two collagen type IX gene polymorphisms that introduce a tryptophan residue into the protein’s triple-helical domain have been linked to an increased risk of lumbar disc disease. To determine whether a particular subset of symptomatic lumbar disease is specifically associated with these polymorphisms, we performed a prospective case-control study of 107 patients who underwent surgery of the lumbar spine. Patients were assigned to one of five clinical categories (fracture, disc degeneration, disc herniation, spinal stenosis without spondylolisthesis and spinal stenosis with spondylolisthesis) based on history, imaging results, and findings during surgery. Of the 11 tryptophan-positive patients, eight had spinal stenosis with spondylolisthesis and three had disc herniation. The presence of the tryptophan allele was significantly associated with African-American or Asian designation for race (odds ratio 4.61, 95% CI 0.63 to 25.35) and with the diagnosis of spinal stenosis with spondylolisthesis (odds ratio 6.81, 95% CI 1.47 to 41.95). Our findings indicate that tryptophan polymorphisms predispose
This study assessed the frequency of acute injury to the spinal cord in Irish Rugby over a period of ten years, between 1995 and 2004. There were 12 such injuries; 11 were cervical and one was thoracic. Ten occurred in adults and two in schoolboys. All were males playing Rugby Union and the mean age at injury was 21.6 years (16 to 36). The most common mechanism of injury was hyperflexion of the cervical spine and the players injured most frequently were playing at full back, hooker or on the wing. Most injuries were sustained during the tackle phase of play. Six players felt their injury was preventable. Eight are permanently disabled as a result of their injury.
Increasing numbers of posterior lumbar fusions
are being performed. The purpose of this study was to identify trends
in demographics, mortality and major complications in patients undergoing
primary posterior lumbar fusion. We accessed data collected for
the Nationwide Inpatient Sample for each year between 1998 and 2008
and analysed trends in the number of lumbar fusions, mean patient
age, comorbidity burden, length of hospital stay, discharge status,
major peri-operative complications and mortality. An estimated 1 288 496
primary posterior lumbar fusion operations were performed between
1998 and 2008 in the United States. The total number of procedures,
mean patient age and comorbidity burden increased over time. Hospital
length of stay decreased, although the in-hospital mortality (adjusted
and unadjusted for changes in length of hospital stay) remained
stable. However, a significant increase was observed in peri-operative
septic, pulmonary and cardiac complications. Although in-hospital mortality
rates did not change over time in the setting of increases in mean
patient age and comorbidity burden, some major peri-operative complications
increased. These trends highlight the need for appropriate peri-operative services
to optimise outcomes in an increasingly morbid and older population
of patients undergoing lumbar fusion.