Objectives. Previously, we reported the improved transfection efficiency of a plasmid DNA-chitosan (pDNA-CS) complex using a phosphorylatable nuclear localization signal-linked nucleic kinase substrate short peptide (pNNS) conjugated to chitosan (pNNS-CS). This study investigated the effects of pNNS-CS-mediated miR-140 and interleukin-1 receptor antagonist protein (IL-1Ra) gene transfection both in rabbit chondrocytes and a cartilage defect model. Methods. The pBudCE4.1-miR-140, pBudCE4.1-IL-1Ra, and negative control pBudCE4.1 plasmids were constructed and combined with pNNS-CS to form pDNA/pNNS-CS complexes. These complexes were transfected into chondrocytes or injected into the knee joint cavity. Results. High IL-1Ra and miR-140 expression levels were detected both in vitro and in vivo. In vitro, compared with the pBudCE4.1 group, the transgenic group presented with significantly increased chondrocyte proliferation and glycosaminoglycan (GAG) synthesis, as well as increased collagen type II alpha 1 chain (COL2A1), aggrecan (ACAN), and TIMP metallopeptidase inhibitor 1 (TIMP-1) levels. Nitric oxide (NO) synthesis was reduced, as were a disintegrin and metalloproteinase with thrombospondin type 1 motif 5 (ADAMTS-5) and matrix metalloproteinase (MMP)-13 levels. In vivo, the exogenous genes reduced the synovial fluid GAG and NO concentrations and the ADAMTS-5 and MMP-13 levels in cartilage. In contrast, COL2A1, ACAN, and TIMP-1 levels were increased, and the cartilage Mankin score was decreased in the transgenic group compared with the pBudCE4.1 group. Double gene combination produced greater efficacies than each single gene, both in vitro and in vivo. Conclusion. This study suggests that pNNS-CS is a good candidate for treating cartilage defects via gene therapy, and that IL-1Ra in combination with miR-140 produces promising biological effects on cartilage defects. Cite this article: R. Zhao, S. Wang, L. Jia, Q. Li, J. Qiao, X. Peng. Interleukin-1 receptor antagonist protein (IL-1Ra) and miR-140 overexpression via pNNS-conjugated chitosan-mediated gene transfer enhances the repair of full-thickness cartilage defects in a rabbit model. Bone Joint Res 2019;8:165–178. DOI: 10.1302/2046-3758.83.BJR-2018-0222.R1

There have been marked changes in the management of Juvenile Idiopathic Arthritis (JIA) over recent decades, mainly with earlier use of methotrexate (MTX). Our aim was to describe orthopaedic interventions in a large group of adults with JIA followed up over several decades. This was a retrospective observational study of adult JIA patients attending a teaching hospital clinic, with information collated on JIA subtype, disease duration, orthopaedic interventions and exposure to MTX. The study included 144 patients with median disease duration of 19 years. Survival analysis showed that joint surgery was observed in the majority (75%) of patients with disease duration over 40 years with a trend for less joint surgery in patients with oligoarticular JIA. In total 41 patients (28.5%) had received joint surgery and 17/41(41%) have required multiple procedures. Of those who have required joint surgery, 20/41(48%) had started MTX in their adult years, with only 5/41 (12%), starting MTX prior to first joint replacement and none within five years of disease onset. Of the patients who have not had joint surgery to date, most (46/103, 45%) were receiving MTX or another immunosuppressive agent, in the majority of cases MTX was started within two years of disease onset. Many adults with JIA require joint replacement surgery and ongoing immunosuppressive treatments, emphasising that JIA is not a benign disease. Many patients who have had joint replacement surgery have had exposure to MTX albeit after many years after disease onset; it remains to be seen whether patients who have received MTX therapy early in their disease course will ultimately have less requirement for joint surgery

Juvenile idiopathic arthritis(JIA) is chronic inflammation commonly occurs in early childhood. Recently, biological therapies are used in JIA at the early stage as same as rheumatoid arthritis, due to retain joint cartilage. However, some of young patients have painful knee problems requiring knee replacement. We experienced 4 cases of JIA treated by knee arthroplasty. The average age at surgery was 33.5 years (range, 26–38 years) with a mean follow-up of 9.5 years (range, 5–18 years). We evaluated the knee range of motion and functional outcomes by the Knee Society Score (KSS), implant selection, postoperative complication, surgery of another joint. Mean range of motion improved from 76.3° (0°–120°) at pre-operation to 110.6° (80°–130°) at post-operation (P<0.05). Mean KSS increased from 47.3 ±20.1 preoperatively to 86.9 ±11.1 (P<0.01) at last follow-up and the mean KSS function from 27.5 ±25.9 to 62.5±20.2 at last follow-up (P<0.05). All of the TKAs were cemented, 5 were cruciate-retaining implant designs, whereas 2 TKAs had constrained posterior stabilized implant designs. Patellar resurfacing was undergone in all knees. Bone graft required in 1 knee within severe knee deformity. Complication were occurred in 5 knees. Medial instability in 2 knees. Skin necrosis, MCL avulsion, recurrence of the synovitis are one in each. All cases had polyarticular type. Previous THA had undergone in 5 hips, synovectomy in 3 knees, foot surgery in 2 feet. At latest follow-up, 1 of 8 TKAs (12.5%) had been revised, and had revision of its polyethylene exchange only. Patients with JIA often have valgus alignment with a flexion contracture and poor bone quality is also frequently compromised. Prescribed immunosuppressive medication or biological agents may cause to infection. In our series there were no infection, but some of these need much more soft tissue release because of severe deformity and flexion contracture. TKA survivorship for JIA is inferior to that typically seen in younger patients with osteoarthritis or rheumatoid arthritis. The knee of conservative therapy were often caused to severe functional limitations. Timimg of TKA may be indicated no matter how young the patient is. Extending timing of TKA may leads to worse outcome and postoperative function. But it may be caution that the surgical exposure can be difficult, because of stiffness, flexion contracture, bony deformity, osteopenia

The purpose of this study was to evaluate the mid- and long-term outcomes of total knee arthroplasty in adult patients who have advanced juvenile idiopathic arthritis (JIA). Between 1989 and 2001, twenty-two knees of JIA adult patients were treated with primary arthroplasty. Surgical challenges included fixed valgus and flexion deformity. All patients were evaluated (mean 8.0 years) using established and new scoring systems. Knee arthroplasty provided relief of pain and stiffness and moderate improvement in range of motion in this severely affected patients. Although outcomes were scored poorly on established instruments, patients rated their benefits of the operation highly. To evaluate the mid- and long-term outcomes of total knee arthroplasty in adult patients who have advanced juvenile idiopathic arthritis (JIA). Between 1989 and 2001, twenty-two knees in fourteen adult patients with severe JIA were treated with primary arthroplasty. Surgical challenges included relative condylar and patellar overgrowth within a contracted, inelastic soft tissue envelope, osteoporosis, small sized bones and fixed valgus and flexion deformity including ankylosis. All patients were evaluated (follow-up: mean 8.0 years) using established and new scoring systems (postoperatively at follow-up and preoperatively by recall). Patients’ postoperative pain and stiffness VAS were significantly less than preoperative scores, with mean changes of 8.8 and 7.2, respectively. A mean post-operative flexion arc of 77° (range 30°–130°) was observed. All lower limbs were post-operatively aligned between 0° and 5° of mechanical valgus. Incomplete radiolucent lines were present in 27% of knees, but were not associated with clinical symptoms. Final SF-36, EQ-5D and WOMAC scores were relatively low, but 82% of patients rated themselves satisfied with the functional outcome, 100% with pain relief, and 100% stated that the outcome met or exceeded their expectations. Issues deemed by JIA patients to be important were identified by the patient specific questionnaire (PASI-pg), but not by SF-36, EQ-5D or WOMAC. Knee arthroplasty provided relief of pain and stiffness and moderate improvement in range of motion in this severely affected adult JIA patients. Although outcomes were scored poorly on established instruments, patients rated their satisfaction with and benefits of the operation highly. Funding:. B. Jolles received a Ligue Vaudoise contre le Rhumatisme Award for her work on Rheumatoid Arthritis

Introduction The purpose of this study was to identify issues of importance to Juvenile Idiopathic Arthritis (JIA) patients before and after total hip arthroplasty (THA) and to determine if these issues are included in widely utilized, standardized outcome measures for THA (Western-Ontario and McMaster Universities Arthritis Index – WOMAC; Patient Specific Index – PASI). Methods JIA patients who underwent THA between 1986 and 1999 in our institution participated in the study (n=31). An independent observer was asked to gather data forms including patient demographics, a postoperative WOMAC questionnaire, postoperative patient-generated items from the PASI, a retrospectively completed preoperative PASI form, and changes in items from pre-operative to postoperative PASI. Descriptive analysis was completed on demographic information and clinical outcomes as well as for the WOMAC and PASI scores. Spearmans rank correlation coefficients were calculated to describe the association between WOMAC and PASI scores. Results Issues deemed important by JIA patients included four symptom areas (pain, joint motion, strength, discomfort) and five activity areas (light household, leisure, clothing, sports, sex); some indicated they had no symptoms or difficulties. Issues relevant to patients shifted from predominantly symptoms before surgery, to recreational and social activities at follow-up. Comparison of postoperative WOMAC questionnaires with preoperative and postoperative PASI questionnaires revealed fundamental differences between items found in the standardized WOMAC and items deemed important by the patient. The WOMAC included less than 10% of the unweighted content deemed important by these patients at follow-up.The shift in the PASI towards more physically demanding activities after surgery indicates that patients improved, which is not reflected in the WOMAC. Correlations between postoperative WOMAC and PASI scores for pain sub-scales were low to moderate (Spearman‘s coefficient rs=0.53) and 63% of JRA patients had higher PASI than WOMAC normalized scores. Conclusion The self-generated, self-reported portion of the PASI questionnaire provided a different perspective on the impact of THA in JIA patients. The WOMAC did not include content deemed to be important by JRA patients and did not correlate well with the patient specific instrument

The use of total hip arthroplasty in adolescents for end-stage degenerative hip disease is controversial with few reported outcomes in the literature. The purpose of the study was to report the outcomes of total hip arthroplasty in a cohort of adolescents managed by a multidisciplinary team of paediatric and adult orthopaedic surgeons from a single centre. A multidisciplinary clinic consisting of paediatric and adult hip surgeons was established in 2013 to identify, treat and prospectively follow adolescents who would potentially beneift from a total hip arthoplasty. To date 29 consecutive adolescent patients (20 female, 9 male, 32 hips) with end stage degenerative hip disease have undergone cementless primary total hip arthroplasty. Mean age at decision to treat was 15.7 years (age 11.4–18.5). Ten different underlying paediatric specific pathologies were documented including DDH, cerebral palsy, JIA, skeletal dysplasias, SCFE and idiopathic chondrolysis. Three patients had bilateral staged procedures. Clinical baseline and outcomes were measured using Oxford Hip Score (OHS), WOMAC score and ASKp scores. Radiographic follow-up was conducted at 6 weeks, 6 months and yearly thereafter. Post-operative complications were recorded. Twenty-five hips were eligible for minimum 2-year follow-up scoring at a mean 2.7 years (2.0–3.6 years). No intraoperative complications occurred. One case of recalcitrant postoperative psoas tendonitis occured. OHS improved from 25 (7–43) to 41 (23–48). WOMAC improved from 48 (12–8) to 12 (1–44), and ASKp improved from 78% (33–98%) to 93% (73–100%). Radiographic review revealed acceptable alignment of all components with no signs of loosening or wear. No revision of components was required. One patient died at 6 months post op from an unrelated condition. The early term results of total hip arthroplasty in adolescents from our multidisciplinary program are encouraging. Improvements in quality of life to normal values were seen as were hip scores consistent with satisfactory joint function. Depite the range of complex and varied causes of arthritis seen in this population the establishment of combined paediatric and adult orthopaedic surgical teams appears to be a successful model to manage end-stage degenerative hip disease in adolescents

Aims

Osteoporosis (OP) is a metabolic bone disease, characterized by a decrease in bone mineral density (BMD). However, the research of regulatory variants has been limited for BMD. In this study, we aimed to explore novel regulatory genetic variants associated with BMD.

Aims

Surgical approaches to cervical ossification of the posterior longitudinal ligament (OPLL) remain controversial. The purpose of the present study was to analyze and compare the long-term neurological recovery following anterior decompression with fusion (ADF) and posterior laminectomy and fusion with bone graft and internal fixation (PLF) based on > ten-year follow-up outcomes in a single centre.

Aims

This study was designed to characterize the recurrence incidence and risk factors of antibiotic-loaded cement spacer (ALCS) for definitive bone defect treatment in limb osteomyelitis.

The hip joints are commonly affected in Juvenile Idiopathic Arthritis (JIA) in childhood. Common features are pain, subluxation, femoral anteversion, coxa valga, significant fixed flexion deformity and a true arthritis, with loss of articular cartilage principally from the femoral head but also the acetabulum. In children with JIA, it is accepted that a medial soft tissue release of the hips, dividing adductor longus, adductor brevis and the ilio-psoas, is a useful tool in the management of significant hip joint involvement. The principal indication for surgery is the relief of pain, but other benefits are correction of fixed flexion deformity, restoration of articular cartilage, increased abduction of the hips and, in those children who are unable to walk, frequently a transition to the potential to walk. The procedure is nearly always performed bilaterally. Our study aimed to document the restoration of articular cartilage at the hips following soft tissue release. It has been noted in the literature that there is regrowth of articular cartilage in the hip but there has been no true documentation of this and x-ray studies are unreliable as the elimination of fixed flexion deformity can prejudice accurate analysis of femoral head geometry on 2 –dimensional views. We therefore carried out MRI scanning of the hips, immediately prior to the soft tissue release and 12–18 months post-operatively. In 10 consecutive patients analysed, scans demonstrated true articular cartilage regrowth in 8 cases. We thus conclude that soft tissue release of the hips in JIA is a useful management tool, and may to some extent reverse the severe articular cartilage loss seen in these children. The next stage of our study is to analyse the articular cartilage at the time of subsequent hip arthroplasty to determine whether true hyaline cartilage is reformed or whether the reconstitute represents fibrocartilage

Aims

There are concerns regarding complications and longevity of total elbow arthroplasty (TEA) in young patients, and the few previous publications are mainly limited to reports on linked elbow devices. We investigated the clinical outcome of unlinked TEA for patients aged less than 50 years with rheumatoid arthritis (RA).

Aims

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.

Aims

This study aimed to evaluate the effectiveness of the induced membrane technique for treating infected bone defects, and to explore the factors that might affect patient outcomes.

Aims

Despite the interest in the association of gut microbiota with bone health, limited population-based studies of gut microbiota and bone mineral density (BMD) have been made. Our aim is to explore the possible association between gut microbiota and BMD.

Abstract

The purpose of this study is to assess the improvement in pain and function of the ankle when arthrodiastasis is used for end stage juvenile idiopathic arthritis [JIA] in the paediatric population. All patients treated with ankle arthrodiastasis, 2009–2013 were studied. Clinical, radiological and survivorship data were examined. The Oxford Ankle Foot Questionnaire for Children (OxAFQ-C) and Parents (OxAFQ-P), along with the American Orthopaedic Foot and Ankle Society (AOFAS) Clinical rating system for Ankle-Hindfoot were recorded pre-operatively and at 6 months. Eight patients (9 ankles) with severe tibiotalar JIA, refractory to medical management were treated. Average age at surgery was 14.5 years (range 8–19). Average length of arthrodiastasis was 3.5 months. Length of follow-up averaged 13 months (range 5–28 months). All scores showed an improvement at 6 months. OxAFQ-C scores (out of 60) improved on average from 23 to 43. OxAFQ-P scores also improved from19 to 39. The largest improvement was found for the physical subsection. AOFAS Ankle-Hindfoot score (out of 100) averaged 34 pre-op and 74 at 6 months. Pain scored out of 10 decreased from an average of 7.4 to 4.3 at 6 months. All patients and parents were satisfied with the surgery and would have the procedure performed again. Radiological studies demonstrated cartilage regeneration, joint restoration and deformity correction with arthrodiastasis. Survivorship was good (75%) at 36 months, but 2 patients (3 ankles) had subsequent surgery in the adult sector for progression of disease despite initial improvement following arthrodiastasis. This case series demonstrates the efficacy of ankle arthrodiastasis as a surgical option in severe end-stage ankle inflammatory arthritis in paediatric patients in the short to midterm. It improved functional scores and pain scores which should delay the need for more radical joint fusion or replacement procedures in this challenging surgical condition

Juvenile idiopathic arthritis (JIA) affecting the hip can cause debilitating pain and walking disability in children. Total hip replacement offers the potential of a pain free joint and a significant improvement in function. There remains the concern regarding the high rates of aseptic loosening of cemented total hip replacements in this group of patients, and there is evidence that younger patients have higher failure rates. The aim of this study was to look at the results of uncemented total hip replacement in children with Juvenile Idiopathic Arthritis and in particular to assess any problems associated with performing this surgery in the presence of open growth plates in the acetabular and trochanteric regions. Between 1995 and 2005, 56 uncemented total hip replacements were carried out in 37 children with JIA with a mean follow up of 7.5 years (range 3 to 12.5). 25 of the hips had ceramic on ceramic bearings. The mean age at surgery was 13.9 years (range 11–16). 19 patients underwent bilateral procedures. All patients showed a significant improvement in their HSS Hip scores (p< 0.01). Two CAD CAM femoral stems were revised for gross subsidence and three acetabular components were revised for loosening. Four polyethylene liners were exchanged due to wear. 51 of 53 (96%) femoral stems and 50 (94%) acetabular components remain well fixed at latest follow up with no signs of loosening. There were no dislocations or infections. Uncemented fixation appears to work well in this challenging group of patients even in the presence of open growth plates. Implant choice is important to avoid problems of subsidence and loosening. Ceramic bearings available for small implant sizes give promise of improved performance compared to polyethylene over the long term

In 2004, our centre has changed from the “STAR” to the “Mobility” Total Ankle Replacement device and a study was undertaken in order to ascertain if there was a learning curve to useage of this new device and perform a comparison in terms of survival, function, additional procedures and complications. The indications were 55% osteoarthritis, 30% Rheumatoid and 8% JIA with the remainder being haemophiliac, haemochromatosis and ankylosing spondylitis. One third of TARs in this unit are combined with additional procedures such as subtalar fusion. Only isolated TARs were considered in this study and the tourniquet time, wound problems, length of stay and known complications for the last 20 STAR TARs was compared to the first 20 Mobility TARs. 68 Mobility TARs have been implanted since Oct 2004 and survival data was collected for this entire cohort and compared to a similar number of STARs. Results: There was no significant difference in operative time (63 vs 65 mins) between the prostheses, no difference in intra-operative complications (0), no difference in deep infections (0% ) and a minimal difference in hospital stay (4.3 vs 5.1 days) due to non-surgeon factors. The survival curve of the mobility and STAR shows no loss of the Mobility due to revision at up to 3 years. Clinical outcome scores will be presented. Summary: There is no learning curve for an experienced Foot and Ankle Surgeon in changing prosthesis and no apparent effect on morbidity for the patient. All 40 TARs are in situ and functioning acceptably at up to 3 years. The early results for this new prosthesis show no cause for concern and surveillance is ongoing

Aims

To investigate the efficacy of ethylenediaminetetraacetic acid-normal saline (EDTA-NS) in dispersing biofilms and reducing bacterial infections.

Tarsal coalition has been well recognized as the commonest cause of peroneal spastic flat feet in children and adolescents (Mosier and Asher 1984). Other rare causes are tuberculosis and rheumatoid arthritis. If no etiology can be found the term idiopathic peroneal spastic flat foot has been coined by Schoenecker (2000). We prospectively assessed all children and adolescents with peroneal spastic flat feet seen at our clinic in the period 2002 to 2004. Twelve patients (17 feet) were assessed. The average age was 11,9 years (range10 to15years). Seventy five percent of the patients were above the 95th percentile weight for age. Screening for tuberculosis (ESR, Mantoux and chest radiograph) was negative in all patients. Rheumatoid factor was positive in one patient with juvenile idiopathic arthritis (JIA). Radiology was standardized. Plain radiographs were standing lateral and 45 degree oblique views. CT and MRI:. axial: parallel to plantar surface;. coronal oblique: gantry perpendicular to the plane of the subtalar joint. This latter view best illustrates a talocalcaneal coalition (Newman 2000). Two patients (four feet) had a calcaneonavicular coalition on the 45 degree oblique plane radiographs. This was also shown on the axial CT and MRI views. No talocalcaneal coalition was visualized on the coronal oblique CT and MRI views. In order to find a diagnosis and to confirm the accuracy of the MRI and CT, the middle facet of the talocalcaneal joint was explored in eight feet and a synovial biopsy done. No talocalcaneal coalition was found. JIA was histologically confirmed in one patient. The authors concluded that the idiopathic type is by far the commonest peroneal spastic flat foot seen in our clinic. The 45 degree oblique plain radiograph is as accurate as axial CT and MRI to diagnose calcaneonavicular coalition. The coronal oblique CT and MRI views are equally accurate to exclude a talocalcaneal coalition