In this study of 41 patients, we used proteomic, Western blot and immunohistochemical analyses to show that several reactive oxygen species scavenging
Aims. Aseptic loosening is a leading cause of uncemented arthroplasty failure, often accompanied by fibrotic tissue at the bone-implant interface. A biological target, neutrophil extracellular traps (NETs), was investigated as a crucial connection between the innate immune system’s response to injury, fibrotic tissue development, and proper bone healing. Prevalence of NETs in peri-implant fibrotic tissue from aseptic loosening patients was assessed. A murine model of osseointegration failure was used to test the hypothesis that inhibition (through Pad4-/- mice that display defects in peptidyl arginine deiminase 4 (PAD4), an essential protein required for NETs) or resolution (via DNase 1 treatment, an
Better prediction of outcome after total hip arthroplasty (THA) is warranted. Systemic inflammation and central neuroinflammation are possibly involved in progression of osteoarthritis and pain. We explored whether inflammatory biomarkers in blood and cerebrospinal fluid (CSF) were associated with clinical outcome, and baseline pain or disability, 12 months after THA. A total of 50 patients from the Danish Pain Research Biobank (DANPAIN-Biobank) between January and June 2018 were included. Postoperative outcome was assessed as change in Oxford Hip Score (OHS) from baseline to 12 months after THA, pain was assessed on a numerical rating scale, and disability using the Pain Disability Index. Multiple regression models for each clinical outcome were included for biomarkers in blood and CSF, respectively, including age, sex, BMI, and Kellgren-Lawrence score.Aims
Methods
Interleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism. Porcine nucleus pulposus (NP) cells were treated with vehicle, 10 ng/ml IL-1β, 10 μM suramin, or 10 μM suramin plus IL-1β. The expression levels of catabolic and anabolic proteins, proinflammatory cytokines, mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB-related signalling molecules were assessed by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence analysis. Flow cytometry was applied to detect apoptotic cells. The ex vivo effects of suramin were examined using IDD organ culture and differentiation was analyzed by Safranin O-Fast green and Alcian blue staining.Aims
Methods
To evaluate the effect of ultrasound-targeted simvastatin-loaded microbubble destruction (UTMD In vitro, OA chondrocytes were treated with ultrasound (US), US-targeted microbubble destruction (UTMD), simvastatin (SV), and UTMDAims
Methods
This study aimed to determine if macrophages can attach and directly affect the oxide layers of 316L stainless steel, titanium alloy (Ti6Al4V), and cobalt-chromium-molybdenum alloy (CoCrMo) by releasing components of these alloys. Murine peritoneal macrophages were cultured and placed on stainless steel, CoCrMo, and Ti6Al4V discs into a 96-well plate. Cells were activated with interferon gamma and lipopolysaccharide. Macrophages on stainless steel discs produced significantly more nitric oxide (NO) compared to their control counterparts after eight to ten days and remained elevated for the duration of the experiment.Aims
Methods
Current treatments of prosthetic joint infection (PJI) are minimally effective against The ability of PlySs2 and vancomycin to kill biofilm and colony-forming units (CFUs) on orthopaedic implants were compared using in vitro models. An in vivo murine PJI model of DAIR was used to assess the efficacy of a combination of PlySs2 and vancomycin on periprosthetic bacterial load.Aims
Methods
This paper aims to review the evidence for patient-related factors associated with less favourable outcomes following hip arthroscopy. Literature reporting on preoperative patient-related risk factors and outcomes following hip arthroscopy were systematically identified from a computer-assisted literature search of Pubmed (Medline), Embase, and Cochrane Library using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and a scoping review.Aims
Methods
As adverse events related to metal on metal hip
arthroplasty have been better understood, there has been increased
interest in toxicity related to the high circulating levels of cobalt ions.
However, distinguishing true toxicity from benign elevations in
cobalt levels can be challenging. The purpose of this review is
to examine the use of cobalt alloys in total hip arthroplasty, to
review the methods of measuring circulating cobalt levels, to define
a level of cobalt which is considered pathological and to review
the pathophysiology, risk factors and treatment of cobalt toxicity.
To the best of our knowledge, there are 18 published cases where
cobalt metal ion toxicity has been attributed to the use of cobalt-chromium
alloys in hip arthroplasty. Of these cases, the great majority reported
systemic toxic reactions at serum cobalt levels more than 100 μg/L.
This review highlights some of the clinical features of cobalt toxicity,
with the goal that early awareness may decrease the risk factors
for the development of cobalt toxicity and/or reduce its severity. Take home message: Severe adverse events can arise from the release
of cobalt from metal-on-metal arthroplasties, and as such, orthopaedic
surgeons should not only be aware of the presenting problems, but
also have the knowledge to treat appropriately. Cite this article:
Abnormal wear of cobalt-containing metal-on-metal
joints is associated with inflammatory pseudotumours. Cobalt ions
activate human toll-like receptor 4 (TLR4), which normally responds
to bacterial lipopolysaccharide (LPS) in sepsis. Activation of TLR4
by LPS increases the expression of chemokines IL-8 and CXCL10, which
recruit leukocytes and activated T-cells, respectively. This study
was designed to determine whether cobalt induces a similar inflammatory
response to LPS by promoting the expression of IL-8 and CXCL10.
A human monocytic cell line, derived from acute monocytic leukaemia,
was treated with cobalt ions and expression of IL-8 and CXCL10 measured at
mRNA and protein levels. Cobalt-treated macrophages showed a 60-fold
increase in IL-8 mRNA, and an eightfold increase in production of
the mature chemokine (both p <
0.001); expression of the CXCL10
gene and protein was also significantly increased by cobalt (both
p <
0.001). Experiments were also performed in the presence of
CLI-095, a TLR4-specific antagonist which abrogated the cobalt-mediated
increase in IL-8 and CXCL10 expression. These findings suggest that cobalt ions induce inflammation similar
to that observed during sepsis by the simultaneous activation of
two TLR4-mediated signalling pathways. These pathways result in
increased production of IL-8 and CXCL10, and may be implicated in
pseudotumour formation following metal-on-metal replacement. Cite this article:
We measured the plasma 25-hydroxyvitamin D3 (25(OH)D3) levels in 62 consecutive Caucasian patients undergoing total hip replacement for osteoarthritis. The patients were divided into two groups based on whether they were vitamin D sufficient or deficient. The groups were matched for age, gender and the American Society of Anaesthesiologists (ASA) grade. The prevalence of vitamin D deficiency in our patients was comparable with recent population-based studies performed in the United Kingdom. Patients with vitamin D deficiency had lower pre-operative Harris hip scores (Mann-Whitney test, p = 0.018) and were significantly less likely to attain an excellent outcome from total hip replacement (chi-squared test, p = 0.038). Vitamin D levels were found to positively correlate with both pre- and post-operative Harris hip scores. These results warrant further study of vitamin D deficiency in patients undergoing joint replacement as it is a risk factor for a suboptimal outcome which is relatively simple and cheap to correct.
The systemic use of steroids and habitual alcohol
intake are two major causative factors in the development of idiopathic
osteonecrosis of the femoral head (ONFH). To examine any interaction
between oral corticosteroid use and alcohol intake on the risk of
ONFH, we conducted a hospital-based case-control study of 71 cases
with ONFH (mean age 45 years (20 to 79)) and 227 matched controls
(mean age 47 years (18 to 79)). Alcohol intake was positively associated
with ONFH among all subjects: the adjusted odds ratio (OR) of subjects
with ≥ 3032 drink-years was 3.93 (95% confidence interval (CI) 1.18
to 13.1) compared with never-drinkers. When stratified by steroid use,
the OR of such drinkers was 11.1 (95% CI 1.30 to 95.5) among those
who had never used steroids, but 1.10 (95% CI 0.21 to 4.79) among
those who had. When we assessed any interaction based on a two-by-two
table of alcohol and steroid use, the OR of those non-drinkers who
did use steroids was markedly elevated (OR 31.5) compared with users
of neither. However, no further increase in OR was noted for the
effect of using both (OR 31.6). We detected neither a multiplicative
nor an additive interaction (p for multiplicative interaction 0.19;
synergy index 0.95), suggesting that the added effect of alcohol
may be trivial compared with the overwhelming effect of steroids
in the development of ONFH. Cite this article:
We examined whether a selective cyclooxygenase-2 (COX-2) inhibitor (celecoxib) was as effective as a non-selective inhibitor (ibuprofen) for the prevention of heterotopic ossification following total hip replacement. A total of 250 patients were randomised to receive celecoxib (200 mg b/d) or ibuprofen (400 mg t.d.s) for ten days after surgery. Anteroposterior radiographs of the pelvis were examined for heterotopic ossification three months after surgery. Of the 250 patients, 240 were available for assessment. Heterotopic ossification was more common in the ibuprofen group (none 40.7% (50), Brooker class I 46.3% (57), classes II and III 13.0% (16)) than in the celecoxib group (none 59.0% (69), Brooker class I 35.9% (42), classes II and III 5.1% (6), p = 0.002). Celecoxib was more effective than ibuprofen in preventing heterotopic bone formation after total hip replacement.
