Early evidence has emerged suggesting that ceramic-on-ceramic
articulations induce a different tissue reaction to ceramic-on-polyethylene
and metal-on-metal bearings. Therefore, the aim of this study was
to investigate the tissue reaction and cellular response to ceramic
total hip arthroplasty (THA) materials We investigated tissue collected at revision surgery from nine
ceramic-on-ceramic articulations. we compared our findings with
tissue obtained from five metal-on-metal THA revisions, four ceramic-on-polyethylene
THAs, and four primary osteoarthritis synovial membranes. The latter
were analyzed to assess the amount of tissue fibrosis that might
have been present at the time of implantation to enable evaluation,
in relation to implantation time, of any subsequent response in
the tissues.Aims
Patients and Methods
Sustained intra-articular delivery of pharmacological agents is an attractive modality but requires use of a safe carrier that would not induce cartilage damage or fibrosis. Collagen scaffolds are widely available and could be used intra-articularly, but no investigation has looked at the safety of collagen scaffolds within synovial joints. The aim of this study was to determine the safety of collagen scaffold implantation in a validated A total of 96 rabbits were randomly and equally assigned to four different groups: arthrotomy alone; arthrotomy and collagen scaffold placement; contracture surgery; and contracture surgery and collagen scaffold placement. Animals were killed in equal numbers at 72 hours, two weeks, eight weeks, and 24 weeks. Joint contracture was measured, and cartilage and synovial samples underwent histological analysis.Objectives
Materials and Methods
Osteophytes are products of active endochondral and intramembranous ossification, and therefore could theoretically provide significant efficacy as bone grafts. In this study, we compared the bone mineralisation effectiveness of osteophytes and cancellous bone, including their effects on secretion of growth factors and anabolic effects on osteoblasts. Osteophytes and cancellous bone obtained from human patients were transplanted onto the calvaria of severe combined immunodeficient mice, with Calcein administered intra-peritoneally for fluorescent labelling of bone mineralisation. Conditioned media were prepared using osteophytes and cancellous bone, and growth factor concentration and effects of each graft on proliferation, differentiation and migration of osteoblastic cells were assessed using enzyme-linked immunosorbent assays, MTS ((3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium)) assays, quantitative real-time polymerase chain reaction, and migration assays.Objectives
Methods
The molecular mechanism of rheumatoid arthritis (RA) remains elusive. We conducted a protein-protein interaction network-based integrative analysis of genome-wide association studies (GWAS) and gene expression profiles of RA. We first performed a dense search of RA-associated gene modules by integrating a large GWAS meta-analysis dataset (containing 5539 RA patients and 20 169 healthy controls), protein interaction network and gene expression profiles of RA synovium and peripheral blood mononuclear cells (PBMCs). Gene ontology (GO) enrichment analysis was conducted by DAVID. The protein association networks of gene modules were generated by STRING.Objectives
Methods
Pathological assessment of periprosthetic tissues is important, not only for diagnosis, but also for understanding the pathobiology of implant failure. The host response to wear particle deposition in periprosthetic tissues is characterised by cell and tissue injury, and a reparative and inflammatory response in which there is an innate and adaptive immune response to the material components of implant wear. Physical and chemical characteristics of implant wear influence the nature of the response in periprosthetic tissues and account for the development of particular complications that lead to implant failure, such as osteolysis which leads to aseptic loosening, and soft-tissue necrosis/inflammation, which can result in pseudotumour formation. The innate response involves phagocytosis of implant-derived wear particles by macrophages; this is determined by pattern recognition receptors and results in expression of cytokines, chemokines and growth factors promoting inflammation and osteoclastogenesis; phagocytosed particles can also be cytotoxic and cause cell and tissue necrosis. The adaptive immune response to wear debris is characterised by the presence of lymphoid cells and most likely occurs as a result of a cell-mediated hypersensitivity reaction to cell and tissue components altered by interaction with the material components of particulate wear, particularly metal ions released from cobalt-chrome wear particles. Cite this article: Professor N. A. Athanasou. The pathobiology and pathology of aseptic implant failure.
The LockDown device (previously called Surgilig)
is a braided polyester mesh which is mostly used to reconstruct the
dislocated acromioclavicular joint. More than 11 000 have been implanted
worldwide. Little is known about the tissue reaction to the device
nor to its wear products when implanted in an extra-articular site
in humans. This is of importance as an adverse immunological reaction
could result in osteolysis or damage to the local tissues, thereby affecting
the longevity of the implant. We analysed the histology of five LockDown implants retrieved
from five patients over the last seven years by one of the senior
authors. Routine analysis was carried out in all five cases and
immunohistochemistry in one. The LockDown device acts as a scaffold for connective tissue
which forms an investing fibrous pseudoligament. The immunological
response at the histological level seems favourable with a limited
histiocytic and giant cell response to micron-sized wear particles.
The connective tissue envelope around the implant is less organised
than a native ligament. Cite this article:
Previous studies support the important role of
vascular endothelial growth factor (VEGF) and syndecan-4 in the pathogenesis
of osteoarthritis (OA). Both VEGF and syndecan-4 are expressed by
chondrocytes and both are involved in the regulation of matrix metalloproteinase-3,
resulting in the activation of aggrecanase II (ADAMTS-5), which
is essential in the pathogenesis of OA. However, the relationship
between VEGF and syndecan-4 has not been established. As a pilot
study, we assayed the expression of VEGF and syndecan-4 in cartilage
samples and cultured chondrocytes from osteoarthritic knee joints
and analysed the relationship between these two factors. Specimens were collected from 21 female patients (29 knees) who
underwent total knee replacement due to severe medial OA of the
knee (Kellgren–Lawrence grade 4). Articular cartilage samples, obtained
from bone and cartilage excised during surgery, were analysed and
used for chondrocyte culture. We found that the levels of expression
of VEGF and syndecan-4 mRNA did not differ significantly between
medial femoral cartilage with severe degenerative changes and lateral
femoral cartilage that appeared grossly normal (p = 0.443 and 0.622,
respectively). Likewise, the levels of expression of VEGF and syndecan-4
mRNA were similar in cultured chondrocytes from medial and lateral
femoral cartilage. The levels of expression of VEGF and syndecan-4
mRNAs were significantly and positively correlated in cartilage
explant (r = 0.601, p = 0.003) but not in cultured chondrocytes.
These results suggest that there is a close relationship between
VEGF and syndecan-4 in the cartilage of patients with OA. Further
studies are needed to determine the exact pathway by which these
two factors interact in the pathogenesis of OA. Cite this article:
The June 2014 Knee Roundup360 looks at: acute repair preferable in hamstring ruptures; osteoarthritis a given in ACL injury, even with reconstruction?; chicken and egg: patellofemoral dysfunction and hip weakness; meniscal root tears as bad as we thought; outcomes in the meniscus; topical NSAIDs have a measurable effect on synovitis; nailing for tibial peri-prosthetic fracture.
Osteoarthritis (OA) is an important cause of
pain, disability and economic loss in humans, and is similarly important in
the horse. Recent knowledge on post-traumatic OA has suggested opportunities
for early intervention, but it is difficult to identify the appropriate
time of these interventions. The horse provides two useful mechanisms
to answer these questions: 1) extensive experience with clinical
OA in horses; and 2) use of a consistently predictable model of
OA that can help study early pathobiological events, define targets
for therapeutic intervention and then test these putative therapies.
This paper summarises the syndromes of clinical OA in horses including
pathogenesis, diagnosis and treatment, and details controlled studies
of various treatment options using an equine model of clinical OA.
We conducted a retrospective study to assess
the prevalence of adverse reactions to metal debris (ARMD) in patients
operated on at our institution with metal-on-metal (MoM) total hip
replacements with 36 mm heads using a Pinnacle acetabular shell.
A total of 326 patients (150 males, 175 hips; 176 females, 203 hips)
with a mean age of 62.7 years (28 to 85) and mean follow-up of 7.5
years (0.1 to 10.8) participating in our in-depth modern MoM follow-up
programme were included in the study, which involved recording whole
blood cobalt and chromium ion measurements, Oxford hip scores (OHS)
and plain radiographs of the hip and targeted cross-sectional imaging. Elevated
blood metal ion levels (>
5 parts per billion) were seen in 32 (16.1%)
of the 199 patients who underwent unilateral replacement. At 23
months after the start of our modern MoM follow-up programme, 29
new cases of ARMD had been revealed. Hence, the nine-year survival
of this cohort declined from 96% (95% CI 95 to 98) with the old
surveillance routine to 86% (95% CI 82 to 90) following the new
protocol. Although ARMD may not be as common in 36 mm MoM THRs as
in those with larger heads, these results support the Medicines
and Healthcare Products Regulatory Agency guidelines on regular
reviews and further investigations, and emphasise the need for specific
a follow-up programme for patients with MoM THRs. Cite this article:
Our objective in this article is to test the hypothesis that
type 2 diabetes mellitus (T2DM) is a factor in the onset and progression
of osteoarthritis, and to characterise the quality of the articular
cartilage in an appropriate rat model. T2DM rats were obtained from the UC Davis group and compared
with control Lewis rats. The diabetic rats were sacrificed at ages
from six to 12 months, while control rats were sacrificed at six
months only. Osteoarthritis severity was determined via histology
in four knee quadrants using the OARSI scoring guide. Immunohistochemical
staining was also performed as a secondary form of osteoarthritic
analysis.Objectives
Methods
We have previously shown that joint distraction and movement with a hinged external fixation device for 12 weeks was useful for repairing a large articular cartilage defect in a rabbit model. We have now investigated the results after six months and one year. The device was applied to 16 rabbits who underwent resection of the articular cartilage and subchondral bone from the entire tibial plateau. In group A (nine rabbits) the device was applied for six months. In group B (seven rabbits) it was in place for six months, after which it was removed and the animals were allowed to move freely for an additional six months. The cartilage remained sound in all rabbits. The areas of type II collagen-positive staining and repaired soft tissue were larger in group B than in group A. These findings provide evidence of long-term persistence of repaired cartilage with this technique and that weight-bearing has a positive effect on the quality of the cartilage.
We produced large full-thickness articular cartilage defects in 33 rabbits in order to evaluate the effect of joint distraction and autologous culture-expanded bone-marrow-derived mesenchymal cell transplantation (ACBMT) at 12 weeks. After fixing the knee on a hinged external fixator, we resected the entire surface of the tibial plateau. We studied three groups: 1) with and without joint distraction; 2) with joint distraction and collagen gel, and 3) with joint distraction and ACBMT and collagen gel. The histological scores were significantly higher in the groups with ACBMT collagen gel (p <
0.05). The area of regenerated soft tissue was smaller in the group allowed to bear weight (p <
0.05). These findings suggest that the repair of large defects of cartilage can be enhanced by joint distraction, collagen gel and ACBMT.
To review the current best surgical practice and detail a multi-disciplinary
approach that could further reduce joint replacement infection. Review of relevant literature indexed in PubMed.Objectives
Methods
The outcome of arthroscopic medial release of 255 knees in 173 patients for varying grades of osteoarthritis involving the medial compartment is reported. All operations were performed by a single surgeon between January 2001 and May 2003. The Knee Society score for pain and the patient’s subjective satisfaction were used for the outcome evaluation. Overall, satisfactory outcome was reported for 197 knees (77.3%) and the mean Knee Society score for pain improved from 17.6 (95% confidence interval, 16.7 to 18.5), pre-operatively to 39.4 (95% confidence interval, 37.9 to 41.1) (p <
0.001). There were minor manageable complications of persistent effusion in 16 knees and prolonged wound discomfort in 11. In total, 15 of the 21 knees with poor results were converted to total knee replacements and two other patients (three knees) were offered this option after a mean period of 16 months. Based on these observations arthroscopic medial release is an effective treatment for osteoarthritis of the medial compartment of the knee joint and can be expected to reduce the pain in the majority of patients for at least four years post-operatively.
Animal studies have shown that implanted anterior cruciate ligament (ACL) grafts initially undergo a process of revascularisation prior to remodelling, ultimately increasing mechanical strength. We investigated whether minimal debridement of the intercondylar notch and the residual stump of the ruptured ACL leads to earlier revascularisation in ACL reconstruction in humans. We undertook a randomised controlled clinical trial in which 49 patients underwent ACL reconstruction using autologous four-strand hamstring tendon grafts. Randomised by the use of sealed envelopes, 25 patients had a conventional clearance of the intercondylar notch and 24 had a minimal debridement method. Three patients were excluded from the study. All patients underwent MR scanning postoperatively at 2, 6 and 12 months, together with clinical assessment using a KT-1000 arthrometer and International Knee Documentation Committee (IKDC) evaluation. All observations were made by investigators blinded to the surgical technique. Signal intensity was measured in 4 mm diameter regions of interest along the ACL graft and the mid-substance of the posterior cruciate ligament. Our results indicate that minimal debridement leads to earlier revascularisation within the mid-substance of the ACL graft at two months (paired
Matrix-induced autologous chondrocyte implantation
(MACI) is an established technique used to treat osteochondral lesions
in the knee. For larger osteochondral lesions (>
5 cm2)
deeper than approximately 8 mm we have combined the use of two MACI
membranes with impaction grafting of the subchondral bone. We report
our results of 14 patients who underwent the ‘bilayer collagen membrane’
technique (BCMT) with a mean follow-up of 5.2 years (2 to 8). There
were 12 men and two women with a mean age of 23.6 years (16 to 40).
The mean size of the defect was 7.2 cm2 (5.2 to 12 cm2)
and were located on the medial (ten) or lateral (four) femoral condyles.
The mean modified Cincinnati knee score improved from 45.1 (22 to
70) pre-operatively to 82.8 (34 to 98) at the most recent review
(p <
0.05). The visual analogue pain score improved from 7.3
(4 to 10) to 1.7 (0 to 6) (p <
0.05). Twelve patients were considered
to have a good or excellent clinical outcome. One graft failed at
six years. The BCMT resulted in excellent functional results and durable
repair of large and deep osteochondral lesions without a high incidence
of graft-related complications.
We investigated the clinical response to arthroscopic
synovectomy in patients with undifferentiated chronic monoarthritis
(UCMA) of the wrist. Arthroscopic synovectomy was performed on 20
wrists in 20 patients with UCMA of the wrist who had not responded
to non-steroidal anti-inflammatory drugs. The mean duration of symptoms
at the time of surgery was 4.3 months (3 to 7) and the mean follow-up
was 51.8 months (24 to 94). Inflamed synovium was completely removed
from the radiocarpal, midcarpal and distal radioulnar joints using
more portals than normal. After surgery, nine patients had early
remission of synovitis and 11 with uncontrolled synovitis received
antirheumatic medication. Overall, there was significant improvement
in terms of pain relief, range of movement and Mayo score. Radiological
deterioration was seen in five patients who were diagnosed as having rheumatoid
arthritis during the follow-up period. Lymphoid follicles and severe
lymphocyte infiltration were seen more often in synovial biopsies
from patients with uncontrolled synovitis. These results suggest that arthroscopic synovectomy provides
pain relief and functional improvement, and allows rapid resolution
of synovitis in about half of patients with UCMA of the wrist.
It has been proposed that intervertebral disc degeneration might be caused by low-grade infection. The purpose of the present study was to assess the incidence of herpes viruses in intervertebral disc specimens from patients with lumbar disc herniation. A polymerase chain reaction based assay was applied to screen for the DNA of eight different herpes viruses in 16 patients and two controls. DNA of at least one herpes virus was detected in 13 specimens (81.25%). Herpes Simplex Virus type-1 (HSV-1) was the most frequently detected virus (56.25%), followed by Cytomegalovirus (CMV) (37.5%). In two patients, co-infection by both HSV-1 and CMV was detected. All samples, including the control specimens, were negative for Herpes Simplex Virus type-2, Varicella Zoster Virus, Epstein Barr Virus, Human Herpes Viruses 6, 7 and 8. The absence of an acute infection was confirmed both at the serological and mRNA level. To our knowledge this is the first unequivocal evidence of the presence of herpes virus DNA in intervertebral disc specimens of patients with lumbar disc herniation suggesting the potential role of herpes viruses as a contributing factor to the pathogenesis of degenerative disc disease.
We compared inflammation in the knee after total knee replacement (TKR) for primary osteoarthritis between two groups of patients undergoing joint replacement with and without synovectomy. A total of 67 patients who underwent unilateral TKR were randomly divided into group I, TKR without synovectomy, and group II, TKR with synovectomy. Clinical outcomes, serial serum inflammatory markers (including interleukin-6 (IL-6), CRP and ESR) and the difference in temperature of the skin of the knee, compared with the contralateral side, were sequentially evaluated until 26 weeks after surgery. Pre-operatively, there were no statistically different clinical parameters between groups I and II. At the 26-week follow-up, both groups had a similarly significantly improved American Knee Society clinical score (p <
0.001) and functional score (p <
0.001) with no differences between the groups. Similar changes in serial inflammatory markers were found in both groups, including mean peak levels of IL-6 (189 pg/ml ( We concluded that synovectomy at the time of TKR does not provide any benefit to the clinical outcome or shorten the duration of the inflammatory response after surgery.