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New surgical procedures can expose patients to harm and should be carefully evaluated before widespread use. The InSpace balloon (Stryker, USA) is an innovative surgical device used to treat people with rotator cuff tears that cannot be repaired. We aimed to determine the effectiveness of the InSpace balloon for people with irreparable rotator cuff tears.We conducted a double-blind, group-sequential, adaptive randomised controlled trial in 24 hospitals in the UK, comparing arthroscopic debridement of the subacromial space with biceps tenotomy (debridement only group) with the same procedure but including insertion of the InSpace balloon (debridement with device group). Participants had an irreparable rotator cuff tear, which had not resolved with conservative treatment, and they had symptoms warranting surgery. Eligibility was confirmed intraoperatively before randomly assigning (1:1) participants to a treatment group using a remote computer system. Participants and assessors were masked to group assignment. Masking was achieved by using identical incisions for both procedures, blinding the operation note, and a consistent rehabilitation programme was offered regardless of group allocation. The primary outcome was the Oxford Shoulder Score at 12 months. Pre-trial simulations using data from early and late timepoints informed stopping boundaries for two interim analyses. The primary analysis was on a modified intention-to-treat basis, adjusted for the planned interim analysis. The trial was registered with ISRCTN, ISRCTN17825590.Between June 1, 2018, and July 30, 2020, we assessed 385 people for eligibility, of which 317 were eligible. 249 (79%) people consented for inclusion in the study. 117 participants were randomly allocated to a treatment group, 61 participants to the debridement only group and 56 to the debridement with device group. A predefined stopping boundary was met at the first interim analysis and recruitment stopped with 117 participants randomised. 43% of participants were female, 57% were male. We obtained primary outcome data for 114 (97%) participants. The mean Oxford Shoulder Score at 12 months was 34·3 (SD 11·1) in the debridement only group and 30·3 (10·9) in the debridement with device group (mean difference adjusted for adaptive design -4·2 [95% CI -8·2 to -0·26];p=0·037) favouring control. There was no difference in adverse events between the two groups.In an efficient, adaptive trial design, our results favoured the debridement only group. We do not recommend the InSpace balloon for the treatment of irreparable rotator cuff tears.Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health and Care Research partnership.

Aims The diagnosis of joint infections is an inexact science using combinations of blood inflammatory markers and microscopy, culture, and sensitivity of synovial fluid (SF). There is potential for small molecule metabolites in infected SF to act as infection markers that could improve accuracy and speed of detection. The objective of this study was to use nuclear magnetic resonance (NMR) spectroscopy to identify small molecule differences between infected and noninfected human SF. Methods In all, 16 SF samples (eight infected native and prosthetic joints plus eight noninfected joints requiring arthroplasty for end-stage osteoarthritis) were collected from patients. NMR spectroscopy was used to analyze the metabolites present in each sample. Principal component analysis and univariate statistical analysis were undertaken to investigate metabolic differences between the two groups. Results A total of 16 metabolites were found in significantly different concentrations between the groups. Three were in higher relative concentrations (lipids, cholesterol, and N-acetylated molecules) and 13 in lower relative concentrations in the infected group (citrate, glycine, glycosaminoglycans, creatinine, histidine, lysine, formate, glucose, proline, valine, dimethylsulfone, mannose, and glutamine). Conclusion Metabolites found in significantly greater concentrations in the infected cohort are markers of inflammation and infection. They play a role in lipid metabolism and the inflammatory response. Those found in significantly reduced concentrations were involved in carbohydrate metabolism, nucleoside metabolism, the glutamate metabolic pathway, increased oxidative stress in the diseased state, and reduced articular cartilage breakdown. This is the first study to demonstrate differences in the metabolic profile of infected and noninfected human SF, using a noninfected matched cohort, and may represent putative biomarkers that form the basis of new diagnostic tests for infected SF. Cite this article: Bone Joint Res 2021;10(1):85–95.

Osteoarthritis (OA) is a multifactorial disease contributing to significant disability and economic burden in Western populations. The aetiology of OA remains poorly understood, but is thought to involve genetic, mechanical and environmental factors. Currently, the diagnosis of OA relies predominantly on clinical assessment and plain radiographic changes long after the disease has been initiated. Recent advances suggest that there are changes in joint fluid metabolites that are associated with OA development. If this is the case, biochemical and metabolic biomarkers of OA could help determine prognosis, monitor disease progression and identify potential therapeutic targets. Moreover, for focussed management and personalised medicine, novel biomarkers could sub-stratify patients into OA phenotypes, differentiating metabolic OA from post-traumatic, age-related and genetic OA. To date, OA biomarkers have concentrated on cytokine action and protein signalling with some progress. However, these remain to be adopted into routine clinical practice. In this review, we outline the emerging metabolic links to OA pathogenesis and how an elucidation of the metabolic changes in this condition may provide future, more descriptive biomarkers to differentiate OA subtypes.

Aims Metabolic profiling is a top-down method of analysis looking at metabolites, which are the intermediate or end products of various cellular pathways. Our primary objective was to perform a systematic review of the published literature to identify metabolites in human synovial fluid (HSF), which have been categorized by metabolic profiling techniques. A secondary objective was to identify any metabolites that may represent potential biomarkers of orthopaedic disease processes. Methods A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines using the MEDLINE, Embase, PubMed, and Cochrane databases. Studies included were case series, case control series, and cohort studies looking specifically at HSF. Results The primary analysis, which pooled the results from 17 published studies and four meeting abstracts, identified over 200 metabolites. Seven of these studies (six published studies, one meeting abstract) had asymptomatic control groups and collectively suggested 26 putative biomarkers in osteoarthritis, inflammatory arthropathies, and trauma. These can broadly be categorized into amino acids plus related metabolites, fatty acids, ketones, and sugars. Conclusion The role of metabolic profiling in orthopaedics is fast evolving with many metabolites already identified in a variety of pathologies. However, these results need to be interpreted with caution due to the presence of multiple confounding factors in many of the studies. Future research should include largescale epidemiological metabolic profiling studies incorporating various confounding factors with appropriate statistical analysis to account for multiple testing of the data. Cite this article: Bone Joint Res. 2020;9(3):108–119.

Background:Implant wear in joint replacements is influenced by the chemical and physical properties of human synovial fluid (HSF). In vitro testing for implant wear uses 25% weight bovine calf serum (25BCS) to substitute for HSF, due to similar rheology and total protein content. However, previous studies have shown differences in the macromolecular composition. We aimed to evaluate the differences in small molecule composition between fluids and correlate these differences with their effects on implant material wear.Methods:HSF was harvested from osteoarthritis patients undergoing primary knee replacement (n=14). Nuclear magnetic resonance (NMR) spectroscopy with linear regression modelling analysed the metabolites present in HSF and commercially sourced 25BCS and investigated the differences. Wear properties of the fluids were evaluated using a validated quantitative laboratory bench-test utilising a cobalt/chromium/molybdenum (CoCrMo) ball oscillating against a CoCrMo disc and analysing the resulting wear scar. The variation in metabolite levels in both HSF and 25BCS was correlated to the wear properties of the fluids.Results:Differences in the levels of metabolites, lipids, and glycosaminoglycans (GAG) were observed between HSF and 25BCS: significance was confirmed by O-PLS-DA (pConclusions:The small molecule concentration differences between the fluids questions the validity of 25BCS as a model for wear analysis. The demonstration of variable metabolites present in HSF which correlate with material wear has implications for implant failure and targeted therapeutic manipulation of these metabolites. Trial Registration:Ethical approval was granted by the NRES Committee London, Chelsea, UK on the 12th May 2015. The study was performed in accordance with the ethical standards in the 1964 Declaration of Helsinki.

Summary Objective To perform a systematic review of the small molecule metabolism studies of osteoarthritis utilising nuclear magnetic resonance (NMR) or mass spectroscopy (MS) analysis (viz., metabolomics or metabonomics), thereby providing coherent conclusions and reference material for future study. Method We applied PRISMA guidelines (PROSPERO 95068) with the following MESH terms: 1. “osteoarthritis” AND (“metabolic” OR “metabonomic” OR “metabolomic” OR “metabolism”) 2. (“synovial fluid” OR “cartilage” OR “synovium” OR “serum” OR “plasma” OR “urine”) AND (“NMR” or “Mass Spectroscopy”). Databases searched were “Medline” and “Embase”. Studies were searched in English and excluded review articles not containing original research. Study outcomes were significant or notable metabolites, species (human or animal) and the Newcastle–Ottawa Score. Results In the 27 studies meeting the inclusion criteria, there was a shift towards anaerobic and fatty acid metabolism in OA disease, although whether this represents the inflammatory state remains unclear. Lipid structure and composition was altered within disease subclasses including phosphatidyl choline (PC) and the sphingomyelins. Macromolecular proteoglycan destruction was described, but the correlation to disease factors was not demonstrated. Collated results suggested arachidonate signalling pathways and androgen sex hormones as future metabolic pathways for investigation. Conclusion Our meta-analysis demonstrates significant small molecule differences between sample types, between species (such as human and bovine), with potential OA biomarkers and targets for local or systemic therapies. Studies were limited by numbers and a lack of disease correlation. Future studies should use NMR and MS analysis to further investigate large population subgroups including inflammatory arthropathy, OA subclasses, age and joint differences.

The impact of metabolism upon the altered pathology of joint disease is rapidly becoming recognized as an important area of study. Synovial joint fluid is an attractive and representative biofluid of joint disease. A systemic review revealed little evidence of the metabolic stability of synovial joint fluid collection, handling or storage, despite recent reports characterizing the metabolic phenotype in joint disease. We aim to report the changes in small molecule detection within human synovial fluid (HSF) using nuclear magnetic resonance (NMR) spectroscopy at varying storage temperatures, durations and conditions. HSF was harvested by arthrocentesis from patients with isolated monoarthropathy or undergoing joint replacement (n = 30). Short-term storage (0-12 h, 4°C18°C) and the effect of repeated freeze-thaw cycles (-80°C to 18°C) was assessed. Long-term storage was evaluated by early (-80°C,21days) and late analysis (-80°C, 10-12 months). 1D NMR spectroscopy experiments, NOESYGPPR1D and CPMG identified metabolites and semi-quantification was performed. Samples demonstrated broad stability to freeze-thaw cycling and refrigeration of4 h. Short-term room temperature or refrigerated storage showed significant variation in 2-ketoisovalerate, valine, dimethylamine, succinate, 2-hydroxybutyrate, and acetaminophen glucuronide. Lipid and macromolecule detection was variable. Long-term storage demonstrated significant changes in: acetate, acetoacetate, creatine, N,N-dimethylglycine, dimethylsulfone, 3-hydroxybutyrate and succinate. Changeable metabolites during short-term storage appeared to be energy-synthesis intermediates. Most metabolites were stable for the first four hours at room temperature or refrigeration, with notable exceptions. We therefore recommend that HSF samples should be kept refrigerated for no more than 4 hours prior to freezing at -80°C. Furthermore, storage of HSF samples for 10-12 months before analysis can affect the detection of selected metabolites.

A new test was developed to measure friction and wear of hip implant materials under reciprocating sliding conditions. The method requires a very small amount of lubricant (

CoCrMo ball-on-flat wear tests were carried out with 25 wt% bovine calf serum (25BCS) and human synovial fluid (HSF) to investigate artificial joint lubricating mechanisms. Post-test the wear scar on the disc was measured and surface deposits in and around the rubbed region were analysed by Micro InfraRed Reflection Absorption Spectroscopy (Micro-IRRAS). In most tests the HSF samples gave higher wear than the 25BCS solution; in some cases, up to 77%. After rinsing a similar pattern of surface deposits was observed in and around the wear scar for both the model and HSF. Micro-IRRAS showed the deposits were primarily denatured proteins with an increased β-sheet content. In some cases, trans-alkyl chain/carbonyl components were also present and these were assigned to lipids. Thioflavin T fluorescent imaging also indicated aggregated non-native β-sheet fibrils were present in the deposits and their presence was associated with lower wear. The formation of insoluble, denatured protein films is thought to be the primary lubrication mechanism contributing to surface protection during rubbing. From this and earlier work we suggest inlet shear induces denaturing of proteins resulting in the formation of non-native β-sheet aggregates. This material is entrained into the contact region where it forms the lubricating film. Patient synovial fluid chemistry appears to influence wear, at least in the bench test, and thus could contributes to increased risk of failure, or success, with metal-metal hips. Finally using 25BCS as a reference screening fluid gives an overly optimistic view of wear in these systems.

Summary Objective The hip and knee joints differ biomechanically in terms of contact stresses, fluid lubrication and wear patterns. These differences may be reflected in the synovial fluid (SF) composition of the two joints, but the nature of these differences remains unknown. The objective was to identify differences in osteoarthritic hip and knee SF metabolites using metabolic profiling with Nuclear Magnetic Resonance (NMR) spectroscopy. Design Twenty-four SF samples (12 hip, 12 knee) were collected from patients with end-stage osteoarthritis (ESOA) undergoing hip/knee arthroplasty. Samples were matched for age, gender, ethnicity and had similar medical comorbidities. NMR spectroscopy was used to analyse the metabolites present in each sample. Principal Component Analysis and Orthogonal Partial Least Squares Discriminant Analysis were undertaken to investigate metabolic differences between the groups. Metabolites were identified using 2D NMR spectra, statistical spectroscopy and by comparison to entries in published databases. Results There were significant differences in the metabolic profile between the groups. Four metabolites were found in significantly greater quantities in the knee group compared to the hip group (N-acetylated molecules, glycosaminoglycans, citrate and glutamine). Conclusions This is the first study to indicate differences in the metabolic profile of hip and knee SF in ESOA. The identified metabolites can broadly be grouped into those involved in collagen degradation, the tricarboxylic acid cycle and oxidative metabolism in diseased joints. These findings may represent a combination of intra and extra-articular factors.

Background: Scapula fractures are uncommon in sports and are poorly understood in this patient group. Purpose: To report on scapula fractures in contact and collision athletes and assess the injury patterns of different mechanisms of injury. Study Design: Case series; Level of evidence, 4. Methods: A retrospective case series was performed of all sports-related scapula fractures treated at a single institution between 2007 and 2015. The mechanisms of injury were divided into direct lateral impact, fall onto an outstretched arm, or abduction/external rotation. Results: A total of 11 patients were identified: 9 professional rugby players, 1 professional soccer player, and 1 amateur soccer player. The mean age was 28 years (range, 18-35 years). The mean return to play was 127 days in those treated nonoperatively and 163 days in those treated operatively. A direct impact mechanism occurred in 7 patients, all of whom sustained glenoid neck and body fractures and were treated nonoperatively. Two rugby players had a concomitant suprascapular nerve injury. An outstretched arm mechanism occurred in 2 cases, leading to posterior and inferior glenoid fractures. Both patients were treated operatively. An abduction/external rotation mechanism occurred in 2 cases, resulting in an anteroinferior and an anterior glenoid rim fracture. One case was treated operatively and the other was treated nonoperatively. Of those with glenoid fractures, 75% were not visible on plain radiographs and required further imaging. Conclusion: Scapula fractures acquired in sports are a serious injury with a prolonged recovery period. The mechanism of injury can help predict the injury pattern and highlight the need for further imaging. There is a high association with suprascapular nerve injuries.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder. The estimated incidence is one in 4 million births. Orthopaedic manifestations include abnormality of the hips occurring early in the disease process. Severe coxa valga can be apparent by the age of 2 years. We report two cases of HGPS, one in a 7-year-old girl with avascular necrosis of the left hip and the second in a 13-year-old girl with recurrent traumatic hip dislocations. We demonstrate the pathoanatomical changes in the hip with HGPS using a combination of imaging modalities including radiographic, computed tomographic and MRI scans. These include coxa magna, coxa valga and acetabular dysplasia. We also comment on how these would affect the surgical management of this high-risk group of patients.

Approximately 10% of patients with osteoarthritis (OA) of the knee have unicompartmental disease confined to the patellofemoral joint (PFJ). These patients are typically younger and predominantly female.1) Although the pathophysiology is multifactorial, the final common pathway is believed to be the result of abnormal load across the PFJ.2) Patients often complain of anterior knee pain particularly when going up or down stairs, standing from a seated position and on kneeling. In many cases there is no obvious cause, although in younger patients there may be specific risk factors such as recurrent patellar dislocation, trauma or trochlear dysplasia.3) Initial treatment of patellofemoral OA (PFOA) may be conservative, but in more severe cases a number of operative strategies have been tried. These include arthroscopic procedures, such as chondroplasty, microfracture and lateral release; attempts at restoring the articular surface by autologous cartilage reimplantation; and tibial tubercle transfer/advancement. However, none of these has produced consistent results.4) The remaining options are total knee replacement (TKR) and PFJ replacement (PFJR). Many surgeons feel that TKR is excessive as it involves resurfacing a normal tibiofemoral joint. PFJR has a number of advantages over TKR, including preservation of the unaffected parts of the knee and maintenance of normal knee biomechanics, potentially allowing faster recovery and better range of motion and function.5) The majority of literature pertaining to second generation PFJR relates to the Avon PFR (Stryker, Howmedica Osteonics, Allendale, NJ, USA). The patellar component is manufactured from ultra-high-molecular-weight polyethylene with a 3 mm medially offset dome to facilitate tracking and optimise patella stability. The femoral component has a broad, symmetrical trochlear flange that narrows distally, ensuring patellar engagement during flexion whilst allowing it to be relatively unconstrained in extension There have been a number of published series, both from the Bristol Knee Group (originating centre) and from other authors. Ackroyd et al.6) described 95.8% survivorship at 5 years and significant improvements in pain and function with low complication rates in 83 consecutive PFRs. Odumenya et al.7) reported 50 knees with 100% survivorship at 5 years, and similarly favourable clinical outcomes. We present our independent experience of the Avon implant in 61 consecutive PFRs followed up to a maximum of 10 years.

Lateral humeral condyle fractures account for 17 % of the distal humeral condyle fractures. Displaced and/or rotated fractures require appropriate reduction and stabilisation. There are, however, a number of controversies in the surgical management of these patients. The aim of the present study was to review the results of patients with a displaced lateral humeral condyle fracture treated with open reduction and internal fixation (ORIF). We retrospectively reviewed children treated with ORIF of lateral humeral condyle fractures at a single institution over a period of 13 years. All cases were identified through the trauma register. Case notes and radiographs were retrieved. Fracture classification, mode of fixation, time to union, and final outcomes at the latest follow-up were reviewed. One hundred and five lateral condyle fractures were identified in 76 male and 29 female patients. Average age was 6.2 years. Ninety-two were Milch type II and 13 Milch type I. According to the Jacob’s classification, 38 were type II and 67 type III. All fractures were treated with open reduction and fixation with K-wires. Average time to radiological union was 33 days. Follow-up ranged between 2 and 8 years (average 3.2 years). Radiological hypertrophy of the lateral condyle was present in 45 cases (42 %). Three patients developed a pseudo-cubitus varus deformity. Further four patients developed a true cubitus varus. There was one case of superficial infection of the K-wires and one case of delayed union. At the latest follow-up, 96 % of the patients achieved an excellent final result and 4 % a good final result. Our results demonstrate that fracture union and excellent final outcomes can be expected in all patients using our protocol, whereby all patients with a displaced fracture are managed by ORIF with K-wire fixation, with the wires only being removed after there is evidence of radiological union. Compared to recent reports of closed reduction internal fixation, this series demonstrates good results with no complications directly relating to the open reduction technique. Level of evidence Case series, Level IV.

Introduction Chylous ascites may result from diverse pathologies. Ascites results either due to blockage of the lymphatics or leak secondary to inadvertent trauma during surgery. Case presentation We report the first case of chylous ascites following radical nephrectomy for a renal cell carcinoma involving the right half of a crossed fused renal ectopia. The patient was managed conservatively. Conclusion Post-operative chylous ascites is a rare complication of retroperitoneal and mediastinal surgery. Most cases resolve with conservative treatment which aims at decreasing lymph production and optimizing nutritional requirements along with palliative measures. Refractory cases need either open or laparoscopic ligation of the leaking lymphatic channels. A review of the current literature on the management of post-operative chylous ascites is presented.