Rheumatoid arthritis (RA) is an autoimmune disease characterized by symmetrical and chronic polyarthritis. Fibroblast-like synoviocytes are mainly involved in joint inflammation and cartilage and bone destruction by inflammatory cytokines and matrix-degrading enzymes in RA. Approaches that induce various cellular growth alterations of synoviocytes are considered as potential strategies for treating RA. However, since synoviocytes play a critical role in RA, the mechanism and hyperplastic modulation of synoviocytes and their motility need to be addressed. In this review, we focus on the alteration of synoviocyte signalling and cell fate provided by signalling proteins, various antioxidant molecules, enzymes, compounds, clinical candidates, to understand the pathology of the synoviocytes, and finally to achieve developed therapeutic strategies of RA. Cite this article:
Tranexamic acid (TXA) has been shown to reduce blood loss and transfusion requirements in patients undergoing orthopaedic surgery. There remains a lack of prospective evidence for the use of TXA in patients undergoing periacetabular osteotomy (PAO). The purpose of this study was to determine if intravenous (IV) TXA is effective in reducing calculated blood loss and transfusions after PAO. This was a single-centre prospective double-blind placebo-controlled randomized trial of 81 patients aged 12 to 45 years undergoing elective PAO by a single surgeon. The intervention group (n = 40) received two doses of IV TXA of a maximum 1 g in each dose; the control group (n = 41) received two doses of 50 ml 0.9% saline IV. The primary outcome was perioperative calculated blood loss. Secondary outcomes included allogenic transfusions and six-week postoperative complications.Aims
Methods
Chondrocyte hypertrophy represents a crucial turning point during endochondral bone development. This process is tightly regulated by various factors, constituting a regulatory network that maintains normal bone development. Histone deacetylase 4 (HDAC4) is the most well-characterized member of the HDAC class IIa family and participates in different signalling networks during development in various tissues by promoting chromatin condensation and transcriptional repression. Studies have reported that HDAC4-null mice display premature ossification of developing bones due to ectopic and early-onset chondrocyte hypertrophy. Overexpression of HDAC4 in proliferating chondrocytes inhibits hypertrophy and ossification of developing bones, which suggests that HDAC4, as a negative regulator, is involved in the network regulating chondrocyte hypertrophy. Overall, HDAC4 plays a key role during bone development and disease. Thus, understanding the role of HDAC4 during chondrocyte hypertrophy and endochondral bone formation and its features regarding the structure, function, and regulation of this process will not only provide new insight into the mechanisms by which HDAC4 is involved in chondrocyte hypertrophy and endochondral bone development, but will also create a platform for developing a therapeutic strategy for related diseases.
The early mortality in patients with hip fractures from bony metastases is unknown. The objectives of this study were to quantify 30- and 90-day mortality in patients with proximal femoral metastases, and to create a mortality prediction tool based on biomarkers associated with early death. This was a retrospective cohort study of consecutive patients referred to the orthopaedic department at a UK trauma centre with a proximal femoral metastasis (PFM) over a seven-year period (2010 to 2016). The study group were compared to a matched control group of non-metastatic hip fractures. Minimum follow-up was one year.Aims
Methods
The role of mechanical stress and transforming growth factor beta 1 (TGF-β1) is important in the initiation and progression of osteoarthritis (OA). However, the underlying molecular mechanisms are not clearly known. In this study, TGF-β1 from osteoclasts and knee joints were analyzed using a co-cultured cell model and an OA rat model, respectively. Five patients with a femoral neck fracture (four female and one male, mean 73.4 years (68 to 79)) were recruited between January 2015 and December 2015. Results showed that TGF-β1 was significantly upregulated in osteoclasts by cyclic loading in a time- and dose-dependent mode. The osteoclasts were subjected to cyclic loading before being co-cultured with chondrocytes for 24 hours.Objectives
Methods
Osteoporosis is a chronic disease. The aim of this study was to identify key genes in osteoporosis. Microarray data sets GSE56815 and GSE56814, comprising 67 osteoporosis blood samples and 62 control blood samples, were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified in osteoporosis using Limma package (3.2.1) and Meta-MA packages. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify biological functions. Furthermore, the transcriptional regulatory network was established between the top 20 DEGs and transcriptional factors using the UCSC ENCODE Genome Browser. Receiver operating characteristic (ROC) analysis was applied to investigate the diagnostic value of several DEGs.Objectives
Methods
Emerging evidence indicates that tendon disease is an active process with inflammation that is critical to disease onset and progression. However, the key cytokines responsible for driving and sustaining inflammation have not been identified. We performed a systematic review of the literature using MEDLINE (U.S. National Library of Medicine, Bethesda, Maryland) in March 2017. Studies reporting the expression of interleukins (ILs), tumour necrosis factor alpha (TNF-α) and interferon gamma in diseased human tendon tissues, and animal models of tendon injury or exercise in comparison with healthy control tissues were included.Objectives
Methods
This study looked to analyse the expression levels of microRNA-140-3p and microRNA-140-5p in synovial fluid, and their correlations to the severity of disease regarding knee osteoarthritis (OA). Knee joint synovial fluid samples were collected from 45 patients with OA of the knee (15 mild, 15 moderate and 15 severe), ten healthy volunteers, ten patients with gouty arthritis, and ten with rheumatoid arthritis. The Kellgren–Lawrence grading (KLG) was used to assess the radiological severity of knee OA, and the patients were stratified into mild (KLG < 2), moderate (KLG = 2), and severe (KLG > 2). The expression of miR-140-3p and miR-140-5p of individual samples was measured by SYBR Green quantitative polymerase chain reaction (PCR) analysis. The expression of miR-140-3p and miR-140-5p was normalised to U6 internal control using the 2-△△CT method. All data were processed using SPSS software.Objectives
Methods
The purpose of this study was to assess early physical function
after total hip or knee arthroplasty (THA/TKA), and the correlation
between patient-reported outcome measures, physical performance
and actual physical activity (measured by actigraphy). A total of 80 patients aged 55 to 80 years undergoing THA or
TKA for osteoarthritis were included in this prospective cohort
study. The main outcome measure was change in patient reported hip
or knee injury and osteoarthritis outcome score (HOOS/KOOS) from
pre-operatively until post-operative day 13 (THA) or 20 (TKA). Secondary measures
were correlations to objectively assessed change in physical performance
(paced-walk, chair-stand, stair-climb tests) at day 14 (THA) or
21 (TKA) and actual physical activity (actigraphy) measured at day
12 and 13 (THA) or 19 and 20 (TKA). Aims
Patients and Methods
Instability of the hip is the most common mode of failure after
reconstruction with a proximal femoral arthroplasty (PFA) using
an endoprosthesis after excision of a tumour. Small studies report
improved stability with capsular repair of the hip and other techniques,
but these have not been investigated in a large series of patients.
The aim of this study was to evaluate variables associated with
the patient and the operation that affect post-operative stability.
We hypothesised an association between capsular repair and stability. In a retrospective cohort study, we identified 527 adult patients
who were treated with a PFA for tumours. Our data included demographics,
the pathological diagnosis, the amount of resection of the abductor
muscles, the techniques of reconstruction and the characteristics
of the implant. We used regression analysis to compare patients
with and without post-operative instability.Aims
Patients and Methods
The long term biological effects of wear products
following total hip arthroplasty (THA) are unclear. However, the indications
for THA are expanding, with increasingly younger patients undergoing
the procedure. This prospective, randomised study compared two groups of patients
undergoing THA after being randomised to receive one of two different
bearing surfaces: metal-on-polyethylene (MoP) n = 22 and metal-on-metal
(MoM) n = 23. We investigated the relationship between three variables:
bearing surface (MoP Our results demonstrated significantly higher mean cobalt and
chromium (Co and Cr) blood levels in the MoM group at all follow-up
points following surgery (p <
0.01), but there were no significant
differences in the chromosomal aberration indices between MoM and
MoP at two or five years (two years: p = 0.56, p = 0.08, p = 0.91, p
= 0.51 and five years: p = 0.086, p = 0.73, p = 0.06, p = 0.34)
for translocations, breaks, loss and gain of chromosomes respectively.
Regression analysis showed a strong linear relationship between
Cr levels and the total chromosomal aberration indices in the MoM
group (R2 = 0.90016), but this was not as strong for
Co (R2 = 0.68991). In the MoP group, the analysis revealed
a poor relationship between Cr levels and the total chromosomal
aberration indices (R2 = 0.23908) but a slightly stronger
relationship for Co (R2 = 0.64292). Across both groups,
Spearman’s correlation detected no overall association between Co and Cr
levels and each of the studied chromosomal aberrations. There remains
no clear indication which THA bearing couple is the most biocompatible,
especially in young active patients. While THA continues to be very
successful at alleviating pain and restoring function, the long-term
biological implications of the procedure still require further scrutiny. Cite this article:
We hypothesised that the synovial white blood cell (WBC) count
in patients with a late periprosthetic joint infection (PJI) of
the hip would depend on the duration of a patient’s symptoms, and
that the optimal diagnostic threshold would also depend on this
period of time. The synovial WBC count and percentage of polymorphonuclear cells
(%PMN), and the serum CRP and ESR levels obtained >
six weeks after
primary THA were compared between 50 infected and 88 non-infected
THAs, and in patients with symptoms for more than or less than two
weeks. Diagnostic thresholds for the synovial WBC count were calculated
using area under the curve calculation.Aims
Patients and Methods
Patients undergoing femoral lengthening by external fixation
tolerate treatment less well when compared to tibial lengthening.
Lengthening of the femur with an intramedullary device may have
advantages. We reviewed all cases of simple femoral lengthening performed
at our unit from 2009 to 2014. Cases of nonunions, concurrent deformities,
congenital limb deficiencies and lengthening with an unstable hip
were excluded, leaving 33 cases (in 22 patients; 11 patients had
bilateral procedures) for review. Healing index, implant tolerance
and complications were compared.Aims
Patients and Methods
To explore the of age of onset distribution for Perthes’ disease
of the hip, with particular reference to gender, laterality and
conformity to the lognormal distribution. A total of 1082 patients were identified from the Liverpool Perthes’
Disease Register between 1976 and 2010, of which 992 had the date
of diagnosis recorded. In total, 682 patients came from the geographical
area exclusively served by Alder Hey Hospital, of which 673 had
a date of diagnosis. Age of onset curves were analysed, with respect to
the predefined subgroups.Aims
Patients and Methods
This article provides an overview of the role of genomics in sarcomas and describes how new methods of analysis and comparative screening have provided the potential to progress understanding and treatment of sarcoma. This article reviews genomic techniques, the evolution of the use of genomics in cancer, the current state of genomic analysis, and also provides an overview of the medical, social and economic implications of recent genomic advances.
Back pain is a common symptom in children and
adolescents. Here we review the important causes, of which defects
and stress reactions of the pars interarticularis are the most common
identifiable problems. More serious pathology, including malignancy
and infection, needs to be excluded when there is associated systemic
illness. Clinical evaluation and management may be difficult and
always requires a thorough history and physical examination. Diagnostic
imaging is obtained when symptoms are persistent or severe. Imaging
is used to reassure the patient, relatives and carers, and to guide
management. Cite this article:
