Autologous chondrocyte implantation (ACI) is a promising treatment for articular cartilage degeneration and injury; however, it requires a large number of human hyaline chondrocytes, which often undergo dedifferentiation during in vitro expansion. This study aimed to investigate the effect of suramin on chondrocyte differentiation and its underlying mechanism. Porcine chondrocytes were treated with vehicle or various doses of suramin. The expression of collagen, type II, alpha 1 (COL2A1), aggrecan (ACAN); COL1A1; COL10A1; SRY-box transcription factor 9 (SOX9); nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX); interleukin (IL)-1β; tumour necrosis factor alpha (TNFα); IL-8; and matrix metallopeptidase 13 (MMP-13) in chondrocytes at both messenger RNA (mRNA) and protein levels was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot. In addition, the supplementation of suramin to redifferentiation medium for the culture of expanded chondrocytes in 3D pellets was evaluated. Glycosaminoglycan (GAG) and collagen production were evaluated by biochemical analyses and immunofluorescence, as well as by immunohistochemistry. The expression of reactive oxygen species (ROS) and NOX activity were assessed by luciferase reporter gene assay, immunofluorescence analysis, and flow cytometry. Mutagenesis analysis, Alcian blue staining, reverse transcriptase polymerase chain reaction (RT-PCR), and western blot assay were used to determine whether p67phox was involved in suramin-enhanced chondrocyte phenotype maintenance.Aims
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The aim of this study was to determine whether early surgical treatment results in better neurological recovery 12 months after injury than late surgical treatment in patients with acute traumatic spinal cord injury (tSCI). Patients with tSCI requiring surgical spinal decompression presenting to 17 centres in Europe were recruited. Depending on the timing of decompression, patients were divided into early (≤ 12 hours after injury) and late (> 12 hours and < 14 days after injury) groups. The American Spinal Injury Association neurological (ASIA) examination was performed at baseline (after injury but before decompression) and at 12 months. The primary endpoint was the change in Lower Extremity Motor Score (LEMS) from baseline to 12 months.Aims
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Aims. Patients with a deformity of the hindfoot present a particular challenge when performing total knee arthroplasty (TKA). The literature contains little information about the relationship between TKA and hindfoot alignment. This systematic review aimed to determine from both clinical and radiological studies whether TKA would alter a preoperative hindfoot deformity and whether the outcome of TKA is affected by the presence of a postoperative hindfoot deformity. Methods. A systematic literature search was performed in the databases PubMed, EMBASE, Cochrane Library, and Web of Science. Search terms consisted of “total knee arthroplasty/replacement” combined with “hindfoot/ankle alignment”. Inclusion criteria were all English language studies analyzing the association between TKA and the alignment of the hindfoot, including the clinical or radiological outcomes. Exclusion criteria consisted of TKA performed with a concomitant extra-articular osteotomy and case reports or expert opinions. An assessment of quality was conducted using the modified Methodological Index for Non-Randomized Studies (MINORS). The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and registered in the PROSPERO database (CRD42019106980). Results. A total of 17 studies were found to be eligible for review. They included six prospective and ten retrospective studies, and one case-control study. The effects of TKA showed a clinical improvement in the hindfoot deformity in three studies, but did not if there was osteoarthritis (OA) of the ankle (one study) or a persistent deformity of the knee (one study). The radiological alignment of the hindfoot corrected in 11 studies, but did not in the presence of a rigid hindfoot varus deformity (in two studies). The effects of a hindfoot deformity on TKA included a clinical association with instability of the knee in one study, and a shift in the radiological weightbearing axis in two studies. The mean MINORS score was 9.4 out of 16 (7 to 12). Conclusion. TKA improves both the
The primary aim was to estimate the cost-effectiveness of routine operative fixation for all patients with humeral shaft fractures. The secondary aim was to estimate the health economic implications of using a Radiographic Union Score for HUmeral fractures (RUSHU) of < 8 to facilitate selective fixation for patients at risk of nonunion. From 2008 to 2017, 215 patients (mean age 57 yrs (17 to 18), 61% female (n = 130/215)) with a nonoperatively managed humeral diaphyseal fracture were retrospectively identified. Union was achieved in 77% (n = 165/215) after initial nonoperative management, with 23% (n = 50/215) uniting after surgery for nonunion. The EuroQol five-dimension three-level health index (EQ-5D-3L) was obtained via postal survey. Multiple regression was used to determine the independent influence of patient, injury, and management factors upon the EQ-5D-3L. An incremental cost-effectiveness ratio (ICER) of < £20,000 per quality-adjusted life-year (QALY) gained was considered cost-effective.Aims
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Periprosthetic joint infections (PJIs) with prior multiple failed surgery for reinfection represent a huge challenge for surgeons because of poor vascular supply and biofilm formation. This study aims to determine the results of single-stage revision using intra-articular antibiotic infusion in treating this condition. A retrospective analysis included 78 PJI patients (29 hips; 49 knees) who had undergone multiple prior surgical interventions. Our cohort was treated with single-stage revision using a supplementary intra-articular antibiotic infusion. Of these 78 patients, 59 had undergone more than two prior failed debridement and implant retentions, 12 patients had a failed arthroplasty resection, three hips had previously undergone failed two-stage revision, and four had a failed one-stage revision before their single-stage revision. Previous failure was defined as infection recurrence requiring surgical intervention. Besides intravenous pathogen-sensitive agents, an intra-articular infusion of vancomycin, imipenem, or voriconazole was performed postoperatively. The antibiotic solution was soaked into the joint for 24 hours for a mean of 16 days (12 to 21), then extracted before next injection. Recurrence of infection and clinical outcomes were evaluated.Aims
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Aims. The purpose of our study was to determine whether mesenchymal stem cells (MSCs) are an effective and safe therapeutic agent for the treatment of knee osteoarthritis (OA), owing to their cartilage regeneration potential. Methods. We searched PubMed, Embase, and the Cochrane Library, with keywords including “knee osteoarthritis” and “mesenchymal stem cells”, up to June 2019. We selected randomized controlled trials (RCTs) that explored the use of MSCs to treat knee OA. The visual analogue scale (VAS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), adverse events, and the whole-organ MRI score (WORMS) were used as the primary evaluation tools in the studies. Our meta-analysis included a subgroup analysis of cell dose and cell source. Results. Seven trials evaluating 256 patients were included in the meta-analysis. MSC treatment significantly improved the VAS (mean difference (MD), –13.24; 95% confidence intervals (CIs) –23.28 to –3.20, p = 0.010) and WOMAC (MD, –7.22; 95% CI –12.97 to –1.47, p = 0.010). The low-dose group with less than 30 million cells showed lower p-values for both the VAS and WOMAC. Adipose and umbilical cord–derived stem cells also had lower p-values for pain scores than those derived from bone marrow. Conclusion. Overall, MSC-based cell therapy is a relatively safe treatment that holds great potential for OA, evidenced by a positive effect on pain and knee
Aims. This study aimed to examine the effects of tumour necrosis factor-alpha (TNF-α) on osteoblasts in metal wear-induced bone loss. Methods. TNF-α immunoexpression was examined in periprosthetic tissues of patients with failed metal-on-metal hip arthroplasties and also in myeloid MM6 cells after treatment with cobalt ions. Viability and
Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models. Literature research was performed on PubMed and Embase databases. Keywords used for search criteria were “bone AND biofilm”. Information on the species of the animal model, bacterial strain, evaluation of biofilm and bone infection, complications, key findings on observations, prevention, and treatment of biofilm were extracted.Aims
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Diabetic foot care is a significant burden on the NHS in England. We have conducted a nationwide survey to determine the current participation of orthopaedic surgeons in diabetic foot care in England. A questionnaire was sent to all 136 NHS trusts audited in the 2018 National Diabetic Foot Audit (NDFA). The questionnaire asked about the structure of diabetic foot care services.Aims
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Developmental dysplasia of the hip (DDH) describes a pathological relationship between the femoral head and acetabulum. Periacetabular osteotomy (PAO) may be used to treat this condition. The aim of this study was to evaluate the results of PAO in adolescents and adults with persistent DDH. Patients were divided into four groups: A, adolescents who had not undergone surgery for DDH in childhood (25 hips); B, adolescents who had undergone surgery for DDH in childhood (20 hips); C, adults with DDH who had not undergone previous surgery (80 hips); and D, a control group of patients with healthy hips (70 hips). The radiological evaluation of digital anteroposterior views of hips included the Wiberg angle (centre-edge angle (CEA)), femoral head cover (FHC), medialization, distalization, and the ilioischial angle. Clinical assessment involved the Harris Hip Score (HHS) and gluteal muscle performance assessment.Aims
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Adolescent idiopathic scoliosis (AIS), defined by an age at presentation of 11 to 18 years, has a prevalence of 0.47% and accounts for approximately 90% of all cases of idiopathic scoliosis. Despite decades of research, the exact aetiology of AIS remains unknown. It is becoming evident that it is the result of a complex interplay of genetic, internal, and environmental factors. It has been hypothesized that genetic variants act as the initial trigger that allow epigenetic factors to propagate AIS, which could also explain the wide phenotypic variation in the presentation of the disorder. A better understanding of the underlying aetiological mechanisms could help to establish the diagnosis earlier and allow a more accurate prediction of deformity progression. This, in turn, would prompt imaging and therapeutic intervention at the appropriate time, thereby achieving the best clinical outcome for this group of patients. Cite this article:
Aims. Despite advances in the treatment of paediatric hip disease, adolescent and young adult patients can develop early onset end-stage osteoarthritis. The aims of this study were to address the indications and medium-term outcomes for total hip arthroplasty (THA) with ceramic bearings for teenage patients. Methods. Surgery was performed by a single surgeon working in the paediatric orthopaedic unit of a tertiary referral hospital. Databases were interrogated from 2003 to 2017 for all teenage patients undergoing THA with a minimum 2.3 year follow-up. Data capture included patient demographics, the underlying hip pathology, number of previous surgeries, and THA prostheses used. Institutional ethical approval was granted to contact patients for prospective clinical outcomes and obtain up-to-date radiographs. In total, 60 primary hips were implanted in 51 patients (35 female, 16 male) with nine bilateral cases. The mean age was 16.7 years (12 to 19) and mean follow-up was 9.3 years (2.3 to 16.8). Results. The most common indication for teenage hip arthroplasty was avascular necrosis secondary to slipped upper femoral epiphysis (31%; n = 16). Overall, 64% of patients (n = 33) had undergone multiple previous operations. The survival at follow-up was 97%; two patients required revision for aseptic loosening (one femoral stem, one acetabular component). Both patients had fused hips noted at the time of arthroplasty. A further two patients had radiolucent lines but were asymptomatic. At latest follow-up the mean Oxford Hip Score was 44 (31 to 48) and a Visual Analogue Scale measurement of 1.5, indicating satisfactory
We assessed the value of the Clinical Frailty Scale (CFS) in the prediction of adverse outcome after hip fracture. Of 1,577 consecutive patients aged > 65 years with a fragility hip fracture admitted to one institution, for whom there were complete data, 1,255 (72%) were studied. Clinicians assigned CFS scores on admission. Audit personnel routinely prospectively completed the Standardised Audit of Hip Fracture in Europe form, including the following outcomes: 30-day survival; in-hospital complications; length of acute hospital stay; and new institutionalization. The relationship between the CFS scores and outcomes was examined graphically and the visual interpretations were tested statistically. The predictive values of the CFS and Nottingham Hip Fracture Score (NHFS) to predict 30-day mortality were compared using receiver operating characteristic area under the curve (AUC) analysis.Aims
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Aims. To analyze the potential role of synovial fluid peptidase activity as a measure of disease burden and predictive biomarker of progression in knee osteoarthritis (KOA). Methods. A cross-sectional study of 39 patients (women 71.8%, men 28.2%; mean age of 72.03 years (SD 1.15) with advanced KOA (Ahlbäck grade ≥ 3 and clinical indications for arthrocentesis) recruited through the (Orthopaedic Department at the Complejo Asistencial Universitario de León, Spain (CAULE)), measuring synovial fluid levels of puromycin-sensitive aminopeptidase (PSA), neutral aminopeptidase (NAP), aminopeptidase B (APB), prolyl endopeptidase (PEP), aspartate aminopeptidase (ASP), glutamyl aminopeptidase (GLU) and pyroglutamyl aminopeptidase (PGAP). Results. Synovial fluid peptidase activity varied significantly as a
There is an increasing concern of osteoporotic fractures in the ageing population. Low-magnitude high-frequency vibration (LMHFV) was shown to significantly enhance osteoporotic fracture healing through alteration of osteocyte lacuno-canalicular network (LCN). Dentin matrix protein 1 (DMP1) in osteocytes is known to be responsible for maintaining the LCN and mineralization. This study aimed to investigate the role of osteocyte-specific DMP1 during osteoporotic fracture healing augmented by LMHFV. A metaphyseal fracture was created in the distal femur of ovariectomy-induced osteoporotic Sprague Dawley rats. Rats were randomized to five different groups: 1) DMP1 knockdown (KD), 2) DMP1 KD + vibration (VT), 3) Scramble + VT, 4) VT, and 5) control (CT), where KD was performed by injection of short hairpin RNA (shRNA) into marrow cavity; vibration treatment was conducted at 35 Hz, 0.3 g; 20 minutes/day, five days/week). Assessments included radiography, micro-CT, dynamic histomorphometry and immunohistochemistry on DMP1, sclerostin, E11, and fibroblast growth factor 23 (FGF23). In vitro, murine long bone osteocyte-Y4 (MLO-Y4) osteocyte-like cells were randomized as in vivo groupings. DMP1 KD was performed by transfecting cells with shRNA plasmid. Assessments included immunocytochemistry on osteocyte-specific markers as above, and mineralized nodule staining.Aims
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The aim of this study was to describe the demographic details of patients who sustain a femoral periprosthetic fracture (PPF), the epidemiology of PPFs, PPF characteristics, and the predictors of PPF types in the UK population. This is a multicentre retrospective cohort study including adult patients presenting to hospital with a new PPF between 1 January 2018 and 31 December 2018. Data collected included: patient characteristics, comorbidities, anticoagulant use, social circumstances, level of mobility, fracture characteristics, Unified Classification System (UCS) type, and details of the original implant. Descriptive analysis by fracture location was performed, and predictors of PPF type were assessed using mixed-effects logistic regression models.Aims
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This study aimed to identify risk factors (patient, healthcare system, and socioeconomic) for mortality after hip fractures and estimate their relative importance. Further, we aimed to elucidate mortality and survival patterns following fractures and the duration of excess mortality. Data on 37,394 hip fractures in the Norwegian Hip Fracture Register from January 2014 to December 2018 were linked to data from the Norwegian Patient Registry, Statistics Norway, and characteristics of acute care hospitals. Cox regression analysis was performed to estimate risk factors associated with mortality. The Wald statistic was used to estimate and illustrate relative importance of risk factors, which were categorized in modifiable (healthcare-related) and non-modifiable (patient-related and socioeconomic). We calculated standardized mortality ratios (SMRs) comparing deaths among hip fracture patients to expected deaths in a standardized reference population.Aims
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