Objectives. Evidence -based medicine (EBM) is designed to inform clinical decision-making within all medical specialties, including orthopaedic surgery. We recently published a pilot survey of the Canadian Orthopaedic Association (COA) membership and demonstrated that the adoption of EBM principles is variable among Canadian orthopaedic surgeons. The objective of this study was to conduct a broader international survey of orthopaedic surgeons to identify characteristics of research studies perceived as being most influential in informing clinical decision-making. Materials and Methods. A 29-question electronic survey was distributed to the readership of an established orthopaedic journal with international readership. The survey aimed to analyse the influence of both extrinsic (journal quality, investigator profiles, etc.) and intrinsic characteristics (study design, sample size, etc.) of research studies in relation to their influence on practice patterns. Results. A total of 353 surgeons completed the survey. Surgeons achieved consensus on the ‘importance’ of three key designs on their practices: randomised controlled trials (94%), meta-analyses (75%) and systematic reviews (66%). The vast majority of respondents support the use of current evidence over historical clinical training; however subjective factors such as journal reputation (72%) and investigator profile (68%) continue to influence clinical decision-making strongly. Conclusion. Although intrinsic factors such as study design and sample size have some influence on clinical decision-making, surgeon respondents are equally influenced by extrinsic factors such as investigator reputation and perceived journal quality. Cite this article: Dr M. Ghert. An international survey to identify the intrinsic and extrinsic factors of research studies most likely to change orthopaedic practice. Bone Joint Res 2016;5:130–136. DOI: 10.1302/2046-3758.54.2000578

Cite this article: Bone Joint Res 2023;12(9):598–600.

The February 2023 Oncology Roundup. 360. looks at: Is the number of national database research studies in musculoskeletal sarcoma increasing, and are these studies reliable?; Re-excision after unplanned excision of soft-tissue sarcoma is associated with high morbidity; Adjuvant radiation in atypical lipomatous tumours; The oncological outcomes of isolated limb perfusion and neoadjuvant radiotherapy in soft-tissue sarcoma patients - a nationwide multicentre study; Can low-grade chondrosarcoma be treated with intralesional curettage and cryotherapy?; Efficacy and safety of carbon ion radiotherapy for bone sarcomas: a systematic review and meta-analysis; Doxorubicin-polymeric meshes prevent local recurrence after sarcoma resection while avoiding cardiotoxicity; How important are skip lesions in Ewing’s sarcoma?; Improving outcomes for amputees: the health-related quality of life and cost utility analysis of osseointegration prosthetics in transfemoral amputees

Aims. Patients with cauda equina syndrome (CES) require emergency imaging and surgical decompression. The severity and type of symptoms may influence the timing of imaging and surgery, and help predict the patient’s prognosis. Categories of CES attempt to group patients for management and prognostication purposes. We aimed in this study to assess the inter-rater reliability of dividing patients with CES into categories to assess whether they can be reliably applied in clinical practice and in research. Methods. A literature review was undertaken to identify published descriptions of categories of CES. A total of 100 real anonymized clinical vignettes of patients diagnosed with CES from the Understanding Cauda Equina Syndrome (UCES) study were reviewed by consultant spinal surgeons, neurosurgical registrars, and medical students. All were provided with published category definitions and asked to decide whether each patient had ‘suspected CES’; ‘early CES’; ‘incomplete CES’; or ‘CES with urinary retention’. Inter-rater agreement was assessed for all categories, for all raters, and for each group of raters using Fleiss’s kappa. Results. Each of the 100 participants were rated by four medical students, five neurosurgical registrars, and four consultant spinal surgeons. No groups achieved reasonable inter-rater agreement for any of the categories. CES with retention versus all other categories had the highest inter-rater agreement (kappa 0.34 (95% confidence interval 0.27 to 0.31); minimal agreement). There was no improvement in inter-rater agreement with clinical experience. Across all categories, registrars agreed with each other most often (kappa 0.41), followed by medical students (kappa 0.39). Consultant spinal surgeons had the lowest inter-rater agreement (kappa 0.17). Conclusion. Inter-rater agreement for categorizing CES is low among clinicians who regularly manage these patients. CES categories should be used with caution in clinical practice and research studies, as groups may be heterogenous and not comparable. Cite this article: Bone Joint J 2023;105-B(9):1007–1012

Aims. Open lower limb fracture is life-changing, resulting in substantial morbidity and resource demand, while inconsistent outcome-reporting hampers systematic review and meta-analysis. A core outcome set establishes consensus among key stakeholders for the recommendation of a minimum set of outcomes. This study aims to define a core outcome set for adult open lower limb fracture. Methods. Candidate outcomes were identified from a previously published systematic review and a secondary thematic analysis of 25 patient interviews exploring the lived experience of recovery from open lower limb fracture. Outcomes were categorized and sequentially refined using healthcare professional and patient structured discussion groups. Consensus methods included a multi-stakeholder two-round online Delphi survey and a consensus meeting attended by a purposive sample of stakeholders, facilitated discussion, and voting using a nominal group technique. Results. Thematic analysis and systematic review identified 121 unique outcomes, reduced to 68 outcomes following structured discussion groups. Outcomes were presented to 136 participants who completed a two-round online Delphi survey. The Delphi survey resulted in 11 outcomes identified as consensus ‘in’ only. All outcomes were discussed at a consensus meeting attended by 15 patients, 14 healthcare professionals, 11 researchers, and one patient-carer. Consensus was achieved for a four-core outcome set: ‘Walking, gait and mobility’, ‘Being able to return to life roles’, ‘Pain or discomfort’, and ‘Quality of life’. Conclusion. This study used robust consensus methods to establish a core outcome set that should be measured in all future research studies and audits of clinical practice without precluding the measurement of additional outcomes. Cite this article: Bone Joint Res 2023;12(4):294–305

Aims. This scoping review aims to identify patient-related factors associated with a poorer outcome following total ankle arthroplasty (TAA). Methods. A scoping review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A computer-based literature search was performed in PubMed, Embase, Cochrane trials, and Web of Science. Two reviewers independently performed title/abstract and full-text screening according to predetermined selection criteria. English-language original research studies reporting patient-related factors associated with a poorer outcome following TAA were included. Outcomes were defined as patient-reported outcome measures (PROMs), perioperative complications, and failure. Results. A total of 94 studies reporting 101,552 cases of TAA in 101,177 patients were included. The most common patient-related risk factor associated with poorer outcomes were younger age (21 studies), rheumatoid arthritis (17 studies), and diabetes (16 studies). Of the studies using multivariable regression specifically, the most frequently described risk factors were younger age (12 studies), rheumatoid arthritis (eight studies), diabetes (eight studies), and high BMI (eight studies). Conclusion. When controlling for confounding factors, the most commonly reported risk factors for poor outcome are younger age, rheumatoid arthritis, and comorbidities such as diabetes and increased BMI. These patient-related risk factors reported may be used to facilitate the refinement of patient selection criteria for TAA and inform patient expectations. Cite this article: Bone Joint J 2023;105-B(9):985–992

Purpose and background. Work-related musculoskeletal disorders, particularly back pain, are a significant issue for healthcare workers, with patient handling being the most frequently reported risk factor. Patient handling is often performed without assistive devices or equipment, which can cause healthcare staff to maintain awkward postures or experience high loads. This review aimed to comprehensively map the literature surrounding manual patient handling (without assistive devices) by healthcare practitioners to identify the current evidence-base on moving and handling of patients and explore what primary research had been conducted. Methods and results. JBI methodology for scoping reviews and an a priori registered protocol (DOI 10.17605/OSF.IO/8PR7A) was followed and AMED, CINAHL, MEDLINE, SPORTDiscus and EMBASE databases were searched. Literature published in English between 2002 and 2021 was included. Forty-nine records were included: 36 primary research studies, 1 systematic review and 12 ‘other’ including narrative and government reports. Primary research predominantly used observational cross-sectional designs (n = 21 studies). Most studies took place in hospitals (n = 13) and laboratories (n = 12). Nurses formed the largest population group (n = 13), with very little research on physiotherapists and other allied health professionals. Conclusion. This scoping review comprehensively reviewed the available literature in the area. Most of the included primary research was observational. Nurses were often investigated in hospitals and laboratories. Qualitative research investigating moving and handling and further biomechanical investigation into therapeutic handling by healthcare staff were identified as areas for further research. Conflicts of interest. None. Sources of funding. None. This work has been published in Physiotherapy: Johnson, K., Swinton, P., Pavlova, A. and Cooper, K., 2023. Manual patient handling in the healthcare setting: a scoping review. Physiotherapy. (120) 60–77 . https://doi.org/10.1016/j.physio.2023.06.003

Aims. This systematic review aimed to summarize the full range of complications reported following ankle arthroscopy and the frequency at which they occur. Methods. A computer-based search was performed in PubMed, Embase, Emcare, and ISI Web of Science. Two-stage title/abstract and full-text screening was performed independently by two reviewers. English-language original research studies reporting perioperative complications in a cohort of at least ten patients undergoing ankle arthroscopy were included. Complications were pooled across included studies in order to derive an overall complication rate. Quality assessment was performed using the Oxford Centre for Evidence-Based Medicine levels of evidence classification. Results. A total of 150 studies describing 7,942 cases of ankle arthroscopy in 7,777 patients were included. The overall pooled complication rate was 325/7,942 (4.09%). The most common complication was neurological injury, accounting for 180/325 (55.4%) of all complications. Of these, 59 (32.7%) affected the superficial peroneal nerve. Overall, 36/180 (20%) of all nerve injuries were permanent. The overall complication rate following anterior ankle arthroscopy was 205/4,709 (4.35%) compared to a rate of 35/528 (6.6%) following posterior arthroscopy. Neurological injury occurred in 52/1,998 (2.6%) of anterior cases using distraction, compared to 59/2,711 (2.2%) in cases with no distraction. The overall rate of major complications was 16/7,942 (0.2%), with the most common major complication – deep vein thrombosis – occurring in five cases. Conclusion. This comprehensive systematic review demonstrates that ankle arthroscopy is a safe procedure with a low overall complication rate. The majority of complications are minor, with potentially life-threatening complications reported in only 0.2% of patients. Cite this article: Bone Joint J 2023;105-B(3):239–246

A key cause of low back pain is the degeneration of the intervertebral disc (IVD). Causality between infection of the IVD and its degenerative process gained great interest over the last decade. Granville Smith et al. (2021) identified 36 articles from 34 research studies investigating bacteria in human IVDs. Bacteria was identified in 27 studies, whereas 9 attributed bacterial presence to contamination. Cutibacterium acnes was the most abundant, followed by coagulase-negative staphylococcus. However, whether bacteria identified were present in vivo or represent perioperative contamination remains unclear. This study investigated whether bacteria are present in IVDs and what potential effects they may have on native disc cells. Immunohistochemical staining for Gram positive bacteria was performed on human IVD tissue to identify presence and characterise bacterial species. Nucleus pulposus (NP) cells in monolayer and 3D alginate were stimulated with LPS and Peptidoglycan (0.1-50 µg/ml) for 48hrs. Following stimulation qPCR for factors associated with disc degeneration including matrix genes, matrix degrading enzymes, cytokines, neurotrophic factors and angiogenic factors and conditioned media collected for ELISA and luminex analysis. Gram positive bacteria was detected within human IVD tissue. Internalisation of bacteria by NP cells influenced the cell and nuclei morphology. Preliminary results of exposure of NP cells to bacterial components indicate that LPS as well as Peptidoglycan increase IL-8 and ADAMTS-4 gene expression following 48 hours of stimulation with a dose response seen for IL-8 induction by peptidoglycan compared to the control group. Underlining these results, IL-8 protein release was increased for treated groups compared to non-treated control. Further analysis is underway investigating other output measures and additional biological repeats. This study has demonstrated bacteria are present within IVD cells within IVD tissue removed from degenerate IVD and is determining the potential influence of these on disc degeneration

Introduction. Research studies have established mathematical correlations between the lengths of bone segments and the possible biomechanical implications of these correlations. The Lucas sequence comprises a series of integers that adhere to the same recurrence relation as the Fibonacci sequence; it differs in that it can start with any two initial integers. The purpose of this study is to determine whether segmental lengths of the foot height, tibia, femur, and upper body follow a Lucas sequence pattern. Method. This was a retrospective radiographic review of patients who underwent full-body EOS scans. The AP scan was used to measure standing foot height (Ft), tibial length (T), femoral length (Fe), upper body length (UB), and full body length. A linear regression test was performed to determine whether a Lucas sequence-based relationship exists between Ft + T and Fe, and between T + Fe and UB. Result. The regression for the relationship between Ft + T and Fe for the entire cohort (R= 0.82, R2= 0.70), the female subset (R= 0.94, R2= 0.88) and the male subset (R= 0.75, R2= 0.57), all demonstrated a strong positive correlation between Ft + T and Fe and showed that Ft + T is a likely predictor of Fe. The regression test for the entire cohort demonstrated a moderately positive correlation between T + Fe and UB (R= 0.41, R2= 0.17, F(1, 145) = 29.42, p= 2.4E-07). A stronger correlation was found for the relationship between T + Fe and UB (R= 0.57, R2= 0.32, F(1, 35) = 16.64, p= 2.5E-05) for the female subset relative to the male subset (R= 0.20, R2= 0.038, F(1, 35) = 4.37, p= 0.04). Conclusion. This study demonstrates that total height is made up of sequential segments whose lengths approximate a Lucas series. The Fibonacci sequence is therefore once again implicated in human body proportions

Deriving autologous mesenchymal stem cells (MSCs) from adipose tissues without using enzymes requires sophisticated biomedical instruments. Applied pressure on tissues and cells are adjusted manually although centrifugation and filtration systems are frequently used. The number of derived MSCs therefore could differ between instruments. We compared the number of MSCs obtained from four commercially available devices and our newly designed and produced instrument (A2, B3, L3, M2 and T3). Three-hundred mL of adipose tissue was obtained from a female patient undergoing liposuction using the transillumination solution. Obtained tissue was equally distributed to each device and handled according to the producers' guides. After handling, 3 mL stromal vascular fraction (SVF) was obtained from each device. Freshly isolated SVF was characterized using multi-color flow cytometry (Navios Flow Cytometer, Beckman Coulter, USA). Cell surface antigens were chosen according to IFATS and ISCT. CD31-FITC, CD34-PC5,5, CD73-PE, CD90-PB and CD45-A750 (Backman Coulter, USA) fluorochrome-labeled monoclonal antibodies were assessed. Markers were combined with ViaKrome (Beckman Coulter, USA) to determine cell viability. At least 10. 5. cells were acquired from each sample. A software (Navios EX, Beckman Coulter, USA) was used to create dot plots and to calculate the cell composition percentages. The data was analyzed in the Kaluza 2.1 software package (Beckman Coulter, USA). Graphs were prepared in GraphPad Prism. CD105 PC7/CD31 FITC cell percentages were 23,9%, 13,5%, 24,6%, 11,4% and 28,8% for the A2, B3, L3, M2 and T3 devices, respectively. We conclude that the isolated MSC percentage ranged from 11,4% to 28,8% between devices. The number of MSCs in SVF are key determinants of success in orthobiological treatments. Developing a device should focus on increasing the number of MSCs in the SVF while preserving its metabolic activity. Acknowledgments: Scientific and Technological Research Council of Türkiye (TÜBİTAK)- Technology and Innovation Funding Program Directorate (TEYDEB) funded this project (#321893). Servet Kürümoğlu and Bariscan Önder of Disposet Ltd., Ankara, Türkiye (. www.disposet.com. ) contributed to the industrial design and research studies. Ali Tuncel and Feza Korkusuz are members of the Turkish Academy of Sciences (TÜBA). Nilsu Baysal was funded by the STAR Program of TÜBITAK Grant # 3210893

Background. Low back pain can lead to neuroplastic changes in the central nervous system, known as nociplastic pain. As nociplastic pain may be provoked by premorbid sensory profiles, such profiles may be prognostic in the development of nociplastic pain over time. Objectives. To investigate whether four sensory profiles are prognostic in the development of symptoms of nociplastic pain in people with acute low back pain. Methods. A longitudinal type 2 prognostic factor research study was performed in accordance with the PROGRESS framework, using a baseline and a follow-up after 12 weeks, between the Adolescent/Adult Sensory Profile and the Central Sensitisation Inventory. Study participants were consecutively included from primary care physiotherapy practices randomly spread throughout the Netherlands. A multivariable regression analysis was performed to adjust sensory profiles by the level of pain, disability, age, and duration of low back pain. Results. After adjustment Low Registration B=0.41, 95%CI (0.37, 0.99), Sensory Seeking B=0.37, 95%CI (0.24, 0.73), Sensory Sensitive B=0.51, 95%CI (0.50, 1.06), Sensation Avoiding B=0.46, 95%CI (0.43, 0.99) were significantly associated with the development of nociplastic pain symptoms. Conclusion. Sensory profiles in people with acute low back pain predict symptoms of nociplastic pain after 12 weeks. Conflict of interest: No conflict of interest. Sources of funding: No funding obtained

Objectives. This study aims to investigate whether bacteria are present in intervertebral discs (IVDs) and their influence. Causality between chronic infection of the IVD and its degenerative process gained great interest recently. Granville Smith et al. (2021) identified 36 articles from 34 research studies investigating bacteria in IVDs, from these 27 studies found, Cutibacterium acnes being the most abundant. However, whether bacteria identified were present in vivo or if they represent contamination remains unclear. Methods. Human IVD tissue was fixed in paraffin and Immunohistochemical stained for Gram-positive bacteria. NP cells in monolayer have been stimulated with LPS (0.1–50 µg/ml) and Peptidoglycan (0.1–50 µg/ml) for 24, 48 and 72 hrs to investigate their influence. The concentration of proinflammatory and catabolic cytokines in the media is being measured using ELISA. RNA extracted and RT-qPCR utilised for factors associated with disc degeneration matrix genes, matrix degrading enzymes, cytokines, neurotrophic factors and angiogenic factors. Results. Bacteria were detected within IVD tissue. Bacteria was internalized by the NP cells and influenced the nuclei morphology. Preliminary results of the exposure of NP cells to bacterial components demonstrate that ADAMTS4 as well as IL-8 were showed an increase in gene expression after LPS and peptidoglycan treatment compared to the non-treated control. Underlining these results, IL-8 protein was increased in treated groups, whereas peptidoglycan treated groups showed a dose dependence. Conclusion. This study demonstrates that Gram positive bacteria are present within the IVD. The exposure of NP cells to peptidoglycans indicates that bacterial components trigger a stress response. Conflicts of Interest: No conflict of interest. Sources of Funding: This project is part of the Disc4All Training network to advance integrated computational simulations in translational medicine, applies to intervertebral disc degeneration and funded by Horizon 2020 (H2020-MSCA-ITN-ETN-2020 GA: 955735)

Spinal surgery deals with the treatment of different pathological conditions of the spine such as tumors, deformities, degenerative disease, infections and traumas. Research in the field of vertebral surgery can be divided into two main areas: 1) research lines transversal to the different branches; 2) specific research lines for the different branches. The transversal lines of research are represented by strategies for the reduction of complications, by the development of minimally invasive surgical techniques, by the development of surgical navigation systems and by the development of increasingly reliable systems for the control of intra-operative monitoring. Instead, specific lines of research are developed within the different branches. In the field of oncological pathology, the current research concerns the development of in vitro models for the study of metastases and research for the study of targeted treatment methods such as electrochemotherapy and mesenchymal stem cells for the treatment of aneurysmal bone cysts. Research in the field of spinal deformities is focused on the development of increasingly minimally invasive methods and systems which, combined with appropriate pharmacological treatments, help reduce trauma, stress and post-operative pain. Scaffolds based on blood clots are also being developed to promote vertebral fusion, a fundamental requirement for improving the outcome of vertebral arthrodesis performed for the treatment of degenerative disc disease. To improve the management and the medical and surgical treatment of vertebral infections, research has focused on the definition of multidisciplinary strategies aimed at identifying the best possible treatment path. Thus, flow-charts have been created which allow to manage the patient suffering from vertebral infection. In addition, dedicated silver-coated surgical instrumentation and bone substitutes have been developed that simultaneously guarantee mechanical stability and reduce the risk of further local infection. In the field of vertebral traumatology, the most recent research studies have focused on the development of methods for the biostimulation of the bone growth in order to obtain, when possible, healing without surgery. Methods have also been developed that allow the minimally invasive percutaneous treatment of fractures by means of vertebral augmentation with PMMA, or more recently with the use of silicone which from a biomechanical point of view has an elastic modulus more similar to that of bone. It is clear that scientific research has changed clinical practice both in terms of medical and surgical management of patients with spinal pathologies. The results obtained stimulate the basic research to achieve even more. For this reason, new lines of research have been undertaken which, in the oncology field, aim at developing increasingly specific therapies against target receptors. Research efforts are also being multiplied to achieve regeneration of the degenerated intervertebral disc and to develop implants with characteristics increasingly similar to those of bone in order to improve mechanical stability and durability over time. Photodynamic therapies are being developed for the treatment of infections in order to reduce the use of antibiotic therapies. Finally, innovative lines of research are being launched to treat and regenerate damaged nerve structures with the goal, still far from today, of making patients with spinal cord injuries to walk

Introduction. Legg-Calve-Perthes (Perthes Disease) was first recognised by three physicians, Arthur Legg (1874–1939), Jacqui Calve (1875–1954) and George Perthes (1869 – 1927) in 1910. Perthes disease is a rare childhood condition that affects the hip. It occurs when the blood supply to the femoral head is disrupted. Without this blood supply, the bone cells die and avascular necrosis can occur. The Herring classification is used to diagnose the stages of Perthes Disease. It is an important prognostic factor. There are three classifications, Herring A, B and C. Herring A has no involvement of the lateral pillar with no density changes noted on x-ray. Herring B has at least 50% of the lateral pillar height maintained on x-ray. Herring C has less than 50% of the lateral pillar height on x-ray (Herring et al, 1992). Children with Perthes disease require specialist Limb Reconstruction team throughout their treatment journey, this includes Orthopaedic surgery and therapy (Physiotherapy and Occupational Therapy). The National Limb Reconstruction Therapy Team is based at the National Orthopaedic Hospital, Cappagh. The therapy team consists of 1 Clinical Specialist Physiotherapist, 1 Senior Physiotherapist and 1 Senior Occupational Therapist who provide input to this cohort. This study aims to analyse the importance of a comprehensive pre-operative assessment by the therapy team (Physiotherapist and Occupational Therapist) to maximise patient outcomes post operatively. Methodology. This is a quantitative research study conducted by the National Limb Reconstructive Therapy Service of the National Orthopaedic Hospital in Cappagh, Dublin. The inclusion criteria for this study consisted of:. Age – Patient must be part of the Paediatric Service, i.e., under the age of 16. Diagnosis – Patient must have a diagnosis of Perthes Disease with a Herring Classification documented. Application of a Hip Distractor Frame formed part of the patient's surgical management. Surgery was completed by Mr Connor Green. Surgery was completed between January 2021 and December 2022. Patient were required to have their external hip distractor frame removed by December 2022. Exclusion Criteria: Those not meeting the above inclusion criteria. Following the inclusion criteria, a number of cases were identified of which 10 cases were selected at random. A retrospective analysis of these samples was completed. The medical charts were reviewed as well as patient electronic healthcare records. Microsoft Excel was utilised to analyse the data and capture results. Results. From analysing the data, the following results were identified:. 80% of the sample cohort had a length of stay of 5 days following surgery. There were two outliers due to infection who had a length of stay of 14 days. 90% of the sample received a pre-operative Physiotherapy and Occupational Therapy assessment. This assessment included information gathering regarding the child's home and social environment; their functional baseline and anticipated post-operative needs. Standardised and non-standardised assessments were used. 88.89% of those who completed a pre-operative assessment required referral to community Occupational Therapy teams for equipment provision (wheelchair, transfer aids) to allow for timely discharge. On average, each patient in the sample required 17 physiotherapy outpatient sessions prior to handover to the community teams. 100% of our sample required post operation onward referral for MDT input in the community (Occupational Therapy and Physiotherapy). Conclusions. The importance of a multi-disciplinary approach towards family and children was highlighted in this study. A comprehensive pre-operative therapy assessment optimizes care for this cohort by preparing them in terms of equipment provisions, local team input and expectations for therapy. The data suggests future Limb Reconstruction team should include Physiotherapy and Occupational Therapy as part of the multi-disciplinary team, in the treatment of children with Perthe's Disease. We suggest an MDT pre-assessment is completed to optimize patient care, reduce length of stay and improve patient satisfaction in the acute hospital setting

Aims. The diagnosis of periprosthetic joint infection (PJI) continues to present a significant clinical challenge. New biomarkers have been proposed to support clinical decision-making; among them, synovial fluid alpha-defensin has gained interest. Current research methodology suggests reference methods are needed to establish solid evidence for use of the test. This prospective study aims to evaluate the diagnostic accuracy of high-performance liquid chromatography coupled with the mass spectrometry (LC-MS) method to detect alpha-defensin in synovial fluid. Methods. Between October 2017 and September 2019, we collected synovial fluid samples from patients scheduled to undergo revision surgery for painful total knee arthroplasty (TKA). The International Consensus Meeting criteria were used to classify 33 PJIs and 92 aseptic joints. LC-MS assay was performed to measure alpha-defensin in synovial fluid of all included patients. Sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristic curve (AUC) were calculated to define the test diagnostic accuracy. Results. The AUC was 0.99 (95% confidence interval (CI) 0.98 to 1.00). Receiver operating characteristic (ROC) analysis showed that the optimal cut-off value of synovial fluid alpha-defensin was 1.0 μg/l. The sensitivity of alpha-defensin was 100% (95% CI 96 to 100), the specificity was 97% (95% CI 90 to 98), the positive predictive value was 89.2% (95% CI 82 to 94), and negative predictive value was 100% (95% CI 96 to 100). ROC analysis demonstrated an AUC of 0.99 (95% CI 0.98 to 1.0). Conclusion. The present study confirms the utility of alpha-defensin in the synovial fluid in patients with painful TKA to select cases of PJI. Since LC-MS is still a time-consuming technology and is available in highly specialized laboratories, further translational research studies are needed to take this evidence into routine procedures and promote a new diagnostic approach. Cite this article: Bone Joint J 2022;104-B(9):1047–1051

Abstract. Introduction. Knee arthrodesis is one of the treatment options for limb salvage of a failed total knee replacement (TKR) when further revisions were contraindicated. The aim of this study is to determine patient outcomes after knee arthrodesis (KA) following a failed TKR. Methodology. A literature search was conducted for studies published from January 2000 through January 2022 via Medline, Web of Science, Embase and Cochrane databases. Only primary research studies were included with independent extraction of articles by two reviewers. Results were synthesised by narrative review according to PRISMA guidelines, with full tabulation of all included study results. Results. A total of 34 studies with 1,034 patients were included in the review; all were longitudinal observational studies, and none were conducted as randomised controlled trials. Reporting methods were very inconsistent in the included studies, and this heterogeneity led to pooled data totals that varied widely in different categories. The mean follow-up was 3.5 years. Overall, 72.0% (167 of 232) of patients used a walking stick and 12.5% (36 of 287) remained non-ambulatory after KA. Only 7.7% (58 of 752) of patients subsequently underwent above-knee amputation. Conclusion. KA is a potential limb salvage procedure after revision arthroplasties have been attempted in cases of failed TKR. Most patients were able to ambulate both at home and in the community, although with an increased rate of using a walking stick after the operation. However, in the absence of randomised controlled trials, these data may allow for a more accurate counselling and decision making

Aim. Evaluate the metabolites composition of the synovial fluid from patients with PJI or aseptic failure of total knee arthroplasties. Method. The synovial fluids from 21 patients scheduled for revision total knee arthroplasty (11 with the diagnosis of PJI and 10 with aseptic failures) were analyzed using 1D 1H NMR spectroscopy. Univariate and multivariate statistical analyses were used to identify metabolites that were differentially abundant between those groups. Results. A total of 28 metabolites were identified and five of them found to be differentially abundant between infected and non-infected synovial fluids. Lactate, acetate and 3-hydroxybutyrate were found to be in a higher concentration, and glucose and creatine were found reduced in the synovial fluid from PJI patients. Conclusions. Synovial fluid from patients with PJI exhibit a distinct metabolic profile, possibly reflecting metabolic adaptation that occurs in the infected periprosthetic microenvironment. Further research and studies are warranted to gain a broader insight into the metabolic pathways engaged by both pathogen and immune cells in the context of a PJI

Breast cancer is the most frequent malignancy in women with an estimation of 2.1 million new diagnoses in 2018. Even though primary tumours are usually efficiently removed by surgery, 20–40% of patients will develop metastases in distant organs. Bone is one of the most frequent site of metastases from advanced breast cancer, accounting from 55 to 58% of all metastases. Currently, none of the therapeutic strategies used to manage breast cancer bone metastasis are really curative. Tailoring a suitable model to study and evaluate the disease pathophysiology and novel advanced therapies is one of the major challenges that will predict more effectively and efficiently the clinical response. Preclinical traditional models have been largely used as they can provide standardization and simplicity, moreover, further advancements have been made with 3D cultures, by spheroids and artificial matrices, patient derived xenografts and microfluidics. Despite these models recapitulate numerous aspects of tumour complexity, they do not completely mimic the clinical native microenvironment. Thus, to fulfil this need, in our study we developed a new, advanced and alternative model of human breast cancer bone metastasis as potential biologic assay for cancer research. The study involved breast cancer bone metastasis samples obtained from three female patients undergoing wide spinal decompression and stabilization through a posterior approach. Samples were cultured in a TubeSpin Bioreactor on a rolling apparatus under hypoxic conditions at time 0 and for up to 40 days and evaluated for viability by the Alamar Blue test, gene expression profile, histology and immunohistochemistry. Results showed the maintenance and preservation, at time 0 and after 40 days of culture, of the tissue viability, biological activity, as well as molecular markers, i.e. several key genes involved in the complex interactions between the tumour cells and bone able to drive cancer progression, cancer aggressiveness and metastasis to bone. A good tis sue morphological and microarchitectural preservation with the presence of lacunar osteolysis, fragmented trabeculae locally surrounded by osteoclast cells and malignant cells and an intense infiltration by tumour cells in bone marrow compartment in all examined samples. Histomorphometrical data on the levels of bone resorption and bone apposition parameters remained constant between T0 and T40 for all analysed patients. Additionally, immunohistochemistry showed homogeneous expression and location of CDH1, CDH2, KRT8, KRT18, Ki67, CASP3, ESR1, CD8 and CD68 between T0 and T40, thus further confirming the invasive behaviour of breast cancer cells and indicating the maintaining of the metastatic microenvironment. The novel tissue culture, set-up in this study, has significant advantages in comparison to the pre-existent 3D models: the tumour environment is the same of the clinical scenario, including all cell types as well as the native extracellular matrix; it can be quickly set-up employing only small samples of breast cancer bone metastasis tissue in a simple, ethically correct and cost-effective manner; it bypasses and/or decreases the necessity to use more complex preclinical model, thus reducing the ethical burden following the guiding principles aimed at replacing/reducing/refining (3R) animal use and their suffering for scientific purposes; it can allow the study of the interactions within the breast cancer bone metastasis tissue over a relatively long period of up to 40 days, preserving the tumour morphology and architecture and allowing also the evaluation of different biological factors, parameters and activities. Therefore, the study provides for the first time the feasibility and rationale for the use of a human-derived advanced alternative model for cancer research and testing of drugs and innovative strategies, taking into account patient individual characteristics and specific tumour subtypes so predicting patient specific responses