Clinical research needs distributed infrastructures: efficient patient recruitment is a major bottleneck to clinical research, whereas quality of investigation, credibility of data, and compliance with regulation require professionalized support. The European Clinical Research Infrastructures Network (ECRIN) is designed to support multinational clinical research in the European Union. It is based on the connection of national hubs, each coordinating a national network of generic clinical research centres or of disease-oriented networks. Supported by the European Commission (FP7 Infrastructure programme) as an ESFRI roadmap infrastructure, it promotes multinational collaboration within the European Union, taking advantage of the EU population size and unlocking latent scientific potential. Building such a distributed, pan-European infrastructure requires addressing the challenge raised by the fragmentation of health and legislative systems. Networking of national clinical research infrastructures led to the development of common standards, of harmonised tools and practice. In addition, ECRIN provides integrated, ‘one-stop shop’ services to investigators and sponsors in multinational studies: patient recruitment and investigation, quality assurance, monitoring, ethical and regulatory requirements, adverse event reporting, circulation of medicinal products and of blood and tissue samples, data management. Information and consulting also help investigators prepare their study: ethical and regulatory requirement, insurance, centre selection, cost evaluation, funding opportunities. Access is given to users (mostly investigators and sponsors in the academic institutions that often lack the capacity to act as a sponsor in the conduct of EU-wide studies) after assessment of the protocol by the scientific board. Services provided by ECRIN are particularly relevant for research on rare diseases and neglected diseases, for clinical trials in elderly and paediatric populations, for academic clinical research institutions, and for clinical trials steered by biotechnology SMEs

Background. In Japan, idiopathic osteonecrosis of the femoral head (ONFH) is designated as a specified rare and intractable disease in patients for whom medical care is subsidized through the Specified Disease Treatment Research Program. Each patient is approved for the subsidy based upon a prefectural governmental review after filing an application together with a clinical research form documenting the patient's medical history, laboratory/clinical findings, and treatment. The purpose of this study was to conduct a fact-finding study of ONFH patients in the Fukuoka Prefecture based on clinical research forms of the Specified Disease Treatment Research Program. Methods. The distribution by gender and age of ONFH patients who filed an application for subsidy under this program between 1999 and 2008 was investigated on the basis of clinical research forms in the Fukuoka Prefecture. For comparative purposes, we also investigated the distribution by gender and age of ONFH patients who had a final diagnosis of ONFH at our institution during the past three years. Results. In the Fukuoka Prefecture, 1,244 ONFH patients (758 men, 61%; and 486 women, 39%) were identified during the 10-year period. The mean age was 48 years for men and 56 years for women. Men showed a normal age distribution with a peak in their fifties, whereas, women displayed a bimodal distribution with peaks in their fifties and seventies. The numbers of patients aged greater than 60 years were 162 (21.4%) for men and 218 (44.9%) for women. At our institution, there were 94 patients (61 men, 64.9%; and 33 women, 35.1%) who had a final diagnosis of ONFH based on radiology and pathology during the 3-year period. The mean age of these patients was 44 years for mrn and 45 years for women. Men showed a bimodal distribution with peaks in their thirties and fifties, whereas, women displayed a unimodal distribution with a peak in their fifties. The numbers of patients aged greater than 60 years were 7 (11.5%) for men and 6 (18.2%) for women. The age distribution of ONFH patients in the Fukuoka Prefecture was significantly higher, particularly for women, compared with patients at our institution. Conclusion. The present study, based on clinical research forms showed that 1,244 patients were identified as having ONFH in the Fukuoka Prefecture during a 10-year period, with a men-to-women ratio of 6:4. For women, approximately half were aged greater than 60 years of age

Using serial CT scans, this project aims to develop a clinical research tool that analyzes changes in vertebral density in spines involved with metastatic disease. Tracking of total vertebral body and tumor volume alone was investigated. A program was developed to semi-automate the segmentation of the region of interest followed by image registration to superimpose the segmentation onto spatially aligned serial scans. Based on analysis of a simulated metastatic vertebra, generating a voxel distribution histogram from the vertebral body best quantified density in serial scans. This quantification method may improve clinical decision-making and treatment options for patients with vertebral metastases. To develop a clinical research tool to serially track tumor involvement in vertebrae with metastatic disease by quantifying changes in CT attenuation. Segmentation of the vertebral body and analysis of the voxel distribution within the region provides the most accurate method of quantifying changes in tumor involvement for the metastatic spine. A quantitative method to assess the progression or regression of disease may improve clinical decision–making and treatment options for patients with spinal metastases. The vertebral body segmentation was more accurate at tracking tumor involvement (voxel distribution histogram: 96.8% +/− 0.75% accuracy, mean density error: 4.7% +/− 0.8%) than segmenting the tumor volume alone (voxel distribution histogram: 86.1% +/− 3.6% accuracy, mean density error: 14.1% +/− 4.8%). A program was developed to semi-automatically segment the total vertebral body and tumor volume alone from CT scans of metastatically involved vertebrae. Image registration through user-defined landmarks and surface matching was used to spatially align serial scans, and the initial segmentation was superimposed with the aligned scans. Changes within the segmentation between CT scans were tracked using mean density and a voxel distribution histogram. A cadaveric vertebra with a simulated tumor was scanned at five orientations with 20° offsets to determine the accuracy of the methods. Error primarily resulted from unavoidable re-sampling during alignment of the scans

Most long-term follow-up studies report retrospective data, the quality of which remains limited due to their inherent biases. Prospective databases may overcome these limitations, however, feasibility and costs limit their application. To date there exists a paucity of evidence-based literature on which recommendations can be made for the ideal length of follow-up for spinal deformity research. Therefore, our aim was to evaluate the added value of follow-up of patients beyond 2 years following surgery for AIS.

A database registry evaluating surgical outcomes for all consecutive AIS patients with post-op data-points of 6 months, 1 year, 2 year, and 5 year was analysed. Surgeon-reported complications, SRS-22 scores, and radiographic data were evaluated. Complications requiring surgical or medical intervention were compared between patients in whom complications developed within 2 years to those in which newly developed complications occurred between >2–5 years.

536 patients were analysed. SRS-22 scores significantly improved at 2 years post-op with no change at 5-year follow-up. Overall complication rate was 33.2% with majority occurring within 2 years (24.8%). The rate of complications occurring >2–5 years requiring intervention was significantly lower than those requiring intervention within 2 years of surgery (4.7% vs 9.7%, p=0.000), however was not negligible. The most common newly observed complication beyond 2 years was pain (1.9%), followed by surgical site infection (SSI) (1.3%) and implant issues (0.56%). There were no significant differences in the rates of crankshaft (p=0.48), implant issues (p=0.56), pseudarthrosis (p=0.19), and SSI (p=0.13) between the 2 time points.

Although majority of complications following AIS surgery occurs within 2 years, a non-negligible rate of newly observed complications occur at >2–5 years post-op. Specifically crankshaft, pseudarthrosis, implant issues, and SSI have similar rates of occurrence at these 2 time points.

Aims. The follow-up interval of a study represents an important aspect that is frequently mentioned in the title of the manuscript. Authors arbitrarily define whether the follow-up of their study is short-, mid-, or long-term. There is no clear consensus in that regard and definitions show a large range of variation. It was therefore the aim of this study to systematically identify clinical research published in high-impact orthopaedic journals in the last five years and extract follow-up information to deduce corresponding evidence-based definitions of short-, mid-, and long-term follow-up. Methods. A systematic literature search was performed to identify papers published in the six highest ranked orthopaedic journals during the years 2015 to 2019. Follow-up intervals were analyzed. Each article was assigned to a corresponding subspecialty field: sports traumatology, knee arthroplasty and reconstruction, hip-preserving surgery, hip arthroplasty, shoulder and elbow arthroplasty, hand and wrist, foot and ankle, paediatric orthopaedics, orthopaedic trauma, spine, and tumour. Mean follow-up data were tabulated for the corresponding subspecialty fields. Comparison between means was conducted using analysis of variance. Results. Of 16,161 published articles, 590 met the inclusion criteria. Of these, 321 were of level IV evidence, 176 level III, 53 level II, and 40 level I. Considering all included articles, a long-term study published in the included high impact journals had a mean follow-up of 151.6 months, a mid-term study of 63.5 months, and a short-term study of 30.0 months. Conclusion. The results of this study provide evidence-based definitions for orthopaedic follow-up intervals that should provide a citable standard for the planning of clinical studies. A minimum mean follow-up of a short-term study should be 30 months (2.5 years), while a mid-term study should aim for a mean follow-up of 60 months (five years), and a long-term study should aim for a mean of 150 months (12.5 years). Level of Evidence: Level I. Cite this article: Bone Jt Open 2021;2(5):344–350

While STS as a group represent a significant portion of all solid tumors in childhood, individual histologic entities are rare due to their extreme heterogeneity. This represents the principal obstacle to clinical trials. A compromise between clinical vs. statistical precision has been necessary in the majority of clinical trials on STS resulting in contradictory conclusions. Clinical trials have to reduce uncertainty but trials, which overlook clinical heterogeneity can even contribute to it. An example is many clinical trials, which have been carried out in the recent decades to answer the question of the role of adjuvant chemotherapy in “Non-RMS-STS”. Majority of these trials have overlooked clinically relevant subgroups. The result is that we still do not have certainty whether and which adjuvant chemotherapy is beneficial. In addition, most clinical trials of treatments for STS rely on the endpoints of survival or event-free survival, so results have taken years to accrue and even longer to report. However, in STS with well defined genetic abnormalities and strong preclinical rationale for activity of a molecular targeted therapy the demonstration of clinical activity in only a few cases might be sufficient. In dermatofibrosarcoma protuberans, a very rare entity, the demonstration of clinical activity of the molecular targeted therapy was very convincing and led to approval of the drug, although the number of cases was very low. International collaboration is necessary to obtain a sufficient number of patients but participation of many different centers with different expertise for a given rare tumor may compromise the quality of patient’s care. It is also difficult for many pediatric departments to open and maintain large numbers of trials with low accrual rates. In conclusion, new methods for clinical research in the field of STS especially surrogate outcome variables and novel technique for early assessment of response are urgently needed

In fractures of proximal humerus, stable fixation of osteoporotic bone fragments poses a significant problem, and wide surgical approach causes damage to blood supply of the humeral head, and to synovial bursae of the shoulder and tendons. These problems cause further permanent unfavourable changes in the shoulder. The least invasive surgical treatment is the percutaneous multi-plane fixation with a bundle of Kirschner wires monitored with fluoroscopy. Stability of these fixations and fixations by tension band, screws and Rush pins were examined in anatomical specimens of porcine humeri and in clinical evaluation. Experimental research concerned the primary stabilisation of various types of Kirschner wires inserted to the proximal part of a porcine humerus, later pulled out using a tensile testing machine, and fixations of 2-part fractures of a porcine proximal humerus fixed with Kirschner wires (various types), tension band, screws and Rush pins. The fixed bones were next torn apart with the same tensile testing machine to examine the strength of the junction. One type of Kirschner wires was designed by us. This type provided the maximum initial strength in the bone and maximum fixation strength, and was next used in surgical treatment of 21 proximal humerus fractures estimated as 2- and 3-part fractures in Neer classification. Follow-up covered a period from 18 months to 10 years. Results were estimated with Neer criteria. Reference comparison group was 50 patients, treated with different methods. Most of the very good and good results (86%) were obtained by fixation with the Kirschner wires of our design. These wires were threaded all over the part which entered the bone.

Objective: To study the effect in health status of telephone contact 2+10 weeks after total hip replacement (THR) during the first nine months after surgery. Not all of patient have improvement in their health status and quality of life, that the surgery benefits them.

Method: A randomised clinical trial enrolled 180 patients aged 65+ focusing on patients’ health status using SF-36, 4 weeks pre–to 3 and 9 months postoperative were carried out. Patients were randomised 4 weeks preoperative either to control or intervention group. Both groups received the conventional treatment. Furthermore the intervention group had postoperative telephone monitoring two and ten weeks after surgery Patients were given counselling by using an interview-guide within eight main themes referring to patients’ actual situation after THR.

Results: All patients experienced increase in their health status after THA. The intervention significantly reduced the time for patients to reach their habitual level as patients in the intervention group reached their habitual level at three months whereas patients in the control group reached this level after nine months.

Conclusion: Support by phone contact after THR seems to benefit patients’ outcome.

The presentation is based on the results of the nursing intervention program by using telephone contact to elderly patients with hip replacement after discharge.

Aims

To establish the utility of adding the laboratory-based synovial alpha-defensin immunoassay to the traditional diagnostic work-up of a prosthetic joint infection (PJI).

Traditionally, informed consent for clinical research involves the patient reading an approved Participant Information Sheet, considering the information presented and having as much time as they need to discuss the study information with their friends and relatives, their clinical care and the research teams. This system works well in the ‘planned’ or ‘elective’ setting. But what happens if the patient requires urgent treatment for an injury or emergency?

This article reviews the legal framework which governs informed consent in the emergency setting, discusses how the approach taken may vary according to the details of the emergency and the treatment required, and reports on the patients’ view of providing consent following a serious injury. We then provide some practical tips for managing the process of informed consent in the context of injuries and emergencies.

Cite this article: Bone Joint J 2017;99-B:147–150.

The aim was to examine the descriptive epidemiology of Slipped Capital Femoral Epiphysis, with respect to geography and time. We extracted all children with a diagnosis of Slipped Capital Femoral Epiphysis from the Clinical Practice Research Database between 1990 and 2014 (24 years). CPRD is the world's largest database of primary care, which encompasses 8% of the UK population. CPRD was linked to Hospital Episode Statistics, and a validation algorithm applied to maximise sensitivity and specificity of the cases finding methodology. Poisson confidence intervals were calculated, and poison regression used. 596 cases of SCFE were identified. The internal validation algorithm supported a SCFE diagnosis in 88% cases. The age and sex distribution of cases mirrored that in the literature, offering external validity to the cases identified. There was no significant change in the incidence of SCFE over the 24-year study period, with the overall incidence being 4.8 cases per 100,00 0–16 year olds. There was no significant geographic variation in SCFE within the UK. There was a positive association with rising socioeconomic deprivation (p<0.01). There was no seasonal variation in presentation. This study found no evidence to support the common belief that SCFE incidence is increasing, and for the first time demonstrated an association with socioeconomic deprivation. The results are important for considering the feasibility of intervention studies, and offer insights into the disease aetiology

Aims. The aim of this study was to develop a core outcome set of what to measure in all future clinical research on hand fractures and joint injuries in adults. Methods. Phase 1 consisted of steps to identify potential outcome domains through systematic review of published studies, and exploration of the patient perspective through qualitative research, consisting of 25 semi-structured interviews and five focus groups. Phase 2 involved key stakeholder groups (patients, hand surgeons, and hand therapists) prioritizing the outcome domains via a three-round international Delphi survey, with a final consensus meeting to agree the final core outcome set. Results. The systematic review of 160 studies identified 74 outcome domains based on the World Health Organization International Classification of Functioning, Disability, and Health. Overall, 35 domains were generated through thematic analysis of the patient interviews and focus groups. The domains from these elements were synthesised to develop 37 outcome domains as the basis of the Delphi survey, with a further four generated from participant suggestions in Round 1. The Delphi survey identified 20 outcome domains as ‘very important’ for the core outcome set. At the consensus meeting, 27 participants from key stakeholder groups selected seven outcomes for the core outcome set: pain/discomfort with activity, pain/discomfort with rest, fine hand use/dexterity, self-hygiene/personal care, return to usual work/job, range of motion, and patient satisfaction with outcome/result. Conclusion. This set of core outcome domains is recommended as a minimum to be reported in all clinical research on hand fractures and joint injuries in adults. While this establishes what to measure, future work will focus on determining how best to measure these outcomes. By adopting this patient-centred core outcome set, consistency and comparability of studies will be improved, aiding meta-analysis and strengthening the evidence base for management of these common and impactful injuries. Cite this article: Bone Jt Open 2023;4(2):87–95

Aims. Preprint servers allow authors to publish full-text manuscripts or interim findings prior to undergoing peer review. Several preprint servers have extended their services to biological sciences, clinical research, and medicine. The purpose of this study was to systematically identify and analyze all articles related to Trauma & Orthopaedic (T&O) surgery published in five medical preprint servers, and to investigate the factors that influence the subsequent rate of publication in a peer-reviewed journal. Methods. All preprints covering T&O surgery were systematically searched in five medical preprint servers (medRxiv, OSF Preprints, Preprints.org, PeerJ, and Research Square) and subsequently identified after a minimum of 12 months by searching for the title, keywords, and corresponding author in Google Scholar, PubMed, Scopus, Embase, Cochrane, and the Web of Science. Subsequent publication of a work was defined as publication in a peer-reviewed indexed journal. The rate of publication and time to peer-reviewed publication were assessed. Differences in definitive publication rates of preprints according to geographical origin and level of evidence were analyzed. Results. The number of preprints increased from 2014 to 2020 (p < 0.001). A total of 38.6% of the identified preprints (n = 331) were published in a peer-reviewed indexed journal after a mean time of 8.7 months (SD 5.4 (1 to 27)). The highest proportion of missing subsequent publications was in the preprints originating from Africa, Asia/Middle East, and South America, or in those that covered clinical research with a lower level of evidence (p < 0.001). Conclusion. Preprints are being published in increasing numbers in T&O surgery. Depending on the geographical origin and level of evidence, almost two-thirds of preprints are not subsequently published in a peer-reviewed indexed journal after one year. This raises major concerns regarding the dissemination and persistence of potentially wrong scientific work that bypasses peer review, and the orthopaedic community should discuss appropriate preventive measures. Cite this article: Bone Jt Open 2022;3(7):582–588

Aims. The extended wait that most patients are now experiencing for hip and knee arthroplasty has raised questions about whether reliance on waiting time as the primary driver for prioritization is ethical, and if other additional factors should be included in determining surgical priority. Our Prioritization of THose aWaiting hip and knee ArthroplastY (PATHWAY) project will explore which perioperative factors are important to consider when prioritizing those on the waiting list for hip and knee arthroplasty, and how these factors should be weighted. The final product will include a weighted benefit score that can be used to aid in surgical prioritization for those awaiting elective primary hip and knee arthroplasty. Methods. There will be two linked work packages focusing on opinion from key stakeholders (patients and surgeons). First, an online modified Delphi process to determine a consensus set of factors that should be involved in patient prioritization. This will be performed using standard Delphi methodology consisting of multiple rounds where following initial individual rating there is feedback, discussion, and further recommendations undertaken towards eventual consensus. The second stage will then consist of a Discrete Choice Experiment (DCE) to allow for priority setting of the factors derived from the Delphi through elicitation of weighted benefit scores. The DCE consists of several choice tasks designed to elicit stakeholder preference regarding included attributes (factors). Results. The study is co-funded by the University of Aberdeen Knowledge Exchange Commission (Ref CF10693-29) and a Chief Scientist Office (CSO) Scotland Clinical Research Fellowship which runs from 08/2021 to 08/2024 (Grant ref: CAF/21/06). Approval from the University of Aberdeen Institute of Applied Health Sciences School Ethics Review Board was granted 22/03/2022 - Reference number SERB/2021/12/2210. Conclusion. The PATHWAY project provides the first attempt to use patient and surgeon opinions to develop a unified approach to prioritization for those awaiting hip and knee arthroplasty. Development of such a tool will provide more equitable access to arthroplasty services, as well as providing a framework for developing similar approaches in other areas of healthcare delivery. Cite this article: Bone Jt Open 2022;3(10):753–758

The interleukin-6/gp130-associated Janus Kinases/STAT3 axis is known to play an important role in mediating inflammatory signals, resulting in production of matrix metalloproteinase-3 (MMP-3). The hip joints with rapidly destructive coxopathy (RDC) demonstrate rapid chondrolysis, probably by increased production of MMP-3 observed in the early stage of RDC. In the recent study, no apparent activation of STAT3 has been shown in the synovial tissues obtained from the osteoarthritic joint at operation. However, no data are currently available on STAT3 activation in the synovial tissues in the early stage of RDC. This study aimed to elucidate STAT3 activation in the synovial tissues in the early stage of RDC. Synovial tissues within 7 months from the disease onset were obtained from four RDC patients with femoral head destruction and high serum levels of MMP-3. RDC synovial tissues showed the synovial lining hyperplasia with an increase of CD68-positive macrophages and CD3-positive T lymphocytes. STAT3 phosphorylation was found in the synovial tissues by immunohistochemistry using anti-phospho-STAT3 antibody. The majority of phospho-STAT3-positive cells were the synovial lining cells and exhibited negative expression of macrophage or T cell marker. Treatment with tofacitinib, a Janus Kinase inhibitor, resulted in a decrease in phospho-STAT3-positive cells, especially with high intensity, indicating effective suppression of STAT3 activation in RDC synovial tissues. Inhibitory effect of tofacitinib could act through the Janus Kinase/STAT3 axis in the synovial tissues in the early stage of RDC. Therefore, STAT3 may be a potential therapeutic target for prevention of joint structural damage in RDC. Acknowledgements: This study was supported by Katakami Foundation for Clinical Research

Osteosarcoma is a highly malignant primary tumor of bone tissue. The 5-year survival rate of patients with metastasis is below 20% and this scenario is unchanged in the last two decades, despite great efforts in pre-clinical and clinical research. Traditional preclinical models of osteosarcoma do not consider the whole complexity of its microenvironment, leading to poor correlation between in vitro/in vivo results and clinical outcomes. Spheroids are a promising in vitro model to mimic osteosarcoma and perform drug-screening tests, as they (i) reproduce the microarchitecture of the tumor, (ii) are characterized by hypoxic regions and necrotic core as the in vivo tumor, (iii) and recapitulate the chemo-resistance phenomena. However, to date, the spheroid model is scarcely used in osteosarcoma research. Our aim is to develop a customized culture dish to grow and characterize spheroids and to perform advanced drug-screening tests. The resulting platform must be adapted to automated image acquisition systems, to overcome the drawbacks of commercial spheroids platforms. To this purpose, we designed and developed a micro-patterned culture dish by casting agarose on a 3D printed mold from a CAD design. We successfully obtained viable and reproducible homotypic osteosarcoma spheroids, with two different cells lines from osteosarcoma (i.e., 143b and MG-63). Using the platform, we performed viability assays and live fluorescent stainings (e.g., Calcein AM) with low reagent consumption. Moreover, the culture dish was validated as drug screening platform, administrating Doxorubicin at different doses, and evaluating its effect on OS spheroids, in terms of morphology and viability. This platform can be considered an attractive alternative to the highly expensive commercial spheroid platforms to obtain homogeneous and reproducible spheroids in a high-throughput and cost effective mode

Low back pain (LBP) is the main cause of disability worldwide and is primarily triggered by intervertebral disc degeneration (IDD). Although several treatment options exist, no therapeutic tool has demonstrated to halt the progressive course of IDD. Therefore, several clinical trials are being conducted to investigate different strategies to regenerate the intervertebral disc, with numerous studies not reaching completion nor being published. The aim of this study was to analyze the publication status of clinical trials on novel regenerative treatments for IDD by funding source and identify critical obstacles preventing their conclusion. Prospective clinical trials investigating regenerative treatments for IDD and registered on . ClinicalTrials.gov. were included. Primary outcomes were publication status and investigational treatment funding. Fisher's exact test was utilized to test the association for categorical variables between groups. 25 clinical trials were identified. Among these, only 6 (24%) have been published. The most common source of funding was university (52%), followed by industry (36%) and private companies (12%). Investigational treatments included autologous (56%) or allogeneic (12%) products alone or in combination with a carrier or delivery system (32%). The latter were more likely utilized in industry or privately funded studies (Fig. 1, p=0.0112). No significant difference was found in terms of funding regarding the publication status of included trials (Table 1, p=0.9104). Most clinical trials investigating regenerative approaches for the treatment of IDD were never completed nor published. This is likely due to multiple factors, including difficult enrollment, high dropout rate, and publication bias. 3. More accurate design and technical support from stakeholders and clinical research organization (CROs) may likely increase the quality of future clinical trials in the field. For any figures or tables, please contact the authors directly

Objectives. Open fracture classification systems are limited in their use. Our objective was to classify open tibia and femur fractures using the OTS classification system in a region with high incidence of gunshot fractures. One hundred and thirty-seven patients with diaphyseal tibia and femur open fractures were identified from a prospectively collected cohort of patients. This database contained all cases (closed and open fractures) of tibial and femoral intramedullary nailed patients older than 18 years old during the period of September 2017 to May 2021. Exclusion criteria included closed fractures, non-viable limbs, open fractures > 48 hours to first surgical debridement and patients unable to follow up over a period of 12 months (a total of 24). Open fractures captured and classified in the HOST study using the Gustilo-Anderson classification, were reviewed and reclassified using the OTS open fracture classification system, analysing gunshot fractures in particular. Ninety percent were males with a mean age of 34. Most common mechanism was civilian gunshot wounds (gsw) in 54.7% of cases. In 52.6% of cases soft tissue management was healing via secondary intention, these not encompassed in the classification. Fracture classification was OTS Simple in 23.4%, Complex B in 24.1% and 52.6% of cases unclassified. The OTS classification system was not comprehensive in the classification of open tibia and femur fractures in a setting of high incidence of gunshot fractures. An amendment has been proposed to alter acute management to appropriate wound care and to subcategorise Simple into A and B subdivisions; no soft tissue intervention and primary closure respectively. This will render the OTS classification system more inclusive to all open fractures of all causes with the potential to better guide patient care and clinical research

Establishing disease biomarkers has been a long-sought after goal to improve Osteoarthritis (OA) diagnosis, prognosis, clinical and pharmaceutical interventions. Given the role of the synovium in contributing to OA, a meta-analysis was performed to determine significant synovial biomarkers in human OA tissue, compared to non-OA patients. Outcomes will direct future research on marker panels for OA disease modelling in vitro/in vivo, aiding clinical research into OA disease targets. A PRISMA compliant search of databases was performed to identify potential biomarker studies analysing human, OA, synovial samples compared to non-OA/healthy participants. The Risk of Bias In Non-Randomised Studies of Interventions (ROBINS-I) tool assessed methodological quality, with outcome analysed by Grading of Recommendations Assessment, Development and Evaluation (GRADE). Meta-analyses were conducted for individual biomarkers using fixed or random effect models, as appropriate. Where three or more studies included a specific biomarker, Forest Plot comparisons were generated. 3230 studies were screened, resulting in 34 studies encompassing 25 potential biomarkers (1581 OA patients and 695 controls). Significant outcomes were identified for thirteen comparisons. Eleven favoured OA (IL-6, IL-10, IL-13, IP-10, IL-8, CCL4, CCL5, PIICP, TIMP1, Leptin and VEGF), two favoured non-OA controls (BMP-2 and HA). Notably, PIICP showed the largest effect (SMD 6.11 [3.50, 8.72], p <0.00001, I. 2. 99%), and TIMP1 resulted critically important (0.95 [0.65, 1.25], p <0.00001, I. 2. 82%). Leptin and CCL4 showed lower effects (SMD 0.81 [0.33, 1.28], p =0.0009; 0.59 [0.32, 0.86], p <0.0001, respectively). Thirteen significant synovial biomarkers showed links with OA bioprocesses including collagen turnover, inflammatory mediators and ECM components. Limitations arose due to bias risk from incomplete or missing data, publication bias of inconclusive results, and confounding factors from patient criteria. These findings suggest markers of potential clinical viability for OA diagnosis and prognosis that could be correlated with specific disease stages

Aim. Culture negative (CN) prosthetic joint infections (PJI) account for approximately 10% of all PJIs and present significant challenges for clinicians. We aimed to explore the significance of CN PJI within a large prospective cohort study, and to compare their characteristics and outcomes with culture positive cases. Methods. The Prosthetic joint Infection in Australia and New Zealand Observational (PIANO) study is a prospective, binational, multicentre observational cohort study conducted at 27 hospitals between July 2014 and December 2017. We compared baseline characteristics and outcomes of all patients with culture negative (CN) prosthetic joint infection (PJI) from the PIANO cohort with culture positive (CP) cases. “Treatment success” was defined as absence of clinical or microbiological signs of infection, no need for ongoing antibiotics, and no need for revision or resection arthroplasty since the end of the initial treatment. We also describe PJI diagnostic criteria in the CN cohort and apply internationally recognised PJI diagnostic guidelines. Results. Of the 650 patients eligible for inclusion, 55 (8.5%) were CN and 595 were CP. Compared with the CP cohort, CN patients were more likely to be female [32 (58.2%) vs 245 (41.2%); p=0.02], involve the shoulder joint [5 (9.1%) vs. 16 (2.7%); p=0.03] and have a lower mean C-reactive protein (142 mg/L vs. 187 mg/L; p=0.02). Overall, outcomes were superior in CN patients, with culture negativity an independent predictor of treatment success at 24 months (aOR 3.78; 95%CI 1.65 – 8.67). Of the 55 CN cases meeting Infectious Diseases Society of America (IDSA) diagnostic criteria, 45 (82%) met European Bone and Joint Infection Society (EBJIS) criteria (probable or definite) and 39 (71%) met the 2013 Musculoskeletal Infection Society (MSIS) criteria. Conclusions. Culture negativity is an independent predictor of treatment success in PJI. It is unclear whether this is because some of them are not actually infections, or for other reasons such as lower bacterial load or earlier effective antibiotic treatment. Diagnostic criteria for PJI vary substantially in their sensitivity, with MSIS criteria being the least sensitive. Acknowledgements. This work is being presented on behalf of the broader PIANO investigators and the Australasian Society for Infectious Diseases Clinical Research Network. The PIANO study received seed funding from Heraeus Medical and the John Hunter Hospital Charitable Trust Fund

Aims. This systematic review aims to compare the precision of component positioning, patient-reported outcome measures (PROMs), complications, survivorship, cost-effectiveness, and learning curves of MAKO robotic arm-assisted unicompartmental knee arthroplasty (RAUKA) with manual medial unicompartmental knee arthroplasty (mUKA). Methods. Searches of PubMed, MEDLINE, and Google Scholar were performed in November 2021 according to the Preferred Reporting Items for Systematic Review and Meta-­Analysis statement. Search terms included “robotic”, “unicompartmental”, “knee”, and “arthroplasty”. Published clinical research articles reporting the learning curves and cost-effectiveness of MAKO RAUKA, and those comparing the component precision, functional outcomes, survivorship, or complications with mUKA, were included for analysis. Results. A total of 179 articles were identified from initial screening, of which 14 articles satisfied the inclusion criteria and were included for analysis. The papers analyzed include one on learning curve, five on implant positioning, six on functional outcomes, five on complications, six on survivorship, and three on cost. The learning curve was six cases for operating time and zero for precision. There was consistent evidence of more precise implant positioning with MAKO RAUKA. Meta-analysis demonstrated lower overall complication rates associated with MAKO RAUKA (OR 2.18 (95% confidence interval (CI) 1.06 to 4.49); p = 0.040) but no difference in re-intervention, infection, Knee Society Score (KSS; mean difference 1.64 (95% CI -3.00 to 6.27); p = 0.490), or Western Ontario and McMaster Universities Arthritis Index (WOMAC) score (mean difference -0.58 (95% CI -3.55 to 2.38); p = 0.700). MAKO RAUKA was shown to be a cost-effective procedure, but this was directly related to volume. Conclusion. MAKO RAUKA was associated with improved precision of component positioning but was not associated with improved PROMs using the KSS and WOMAC scores. Future longer-term studies should report functional outcomes, potentially using scores with minimal ceiling effects and survival to assess whether the improved precision of MAKO RAUKA results in better outcomes. Cite this article: Bone Joint J 2022;104-B(5):541–548

The December 2022 Wrist & Hand Roundup. 360. looks at: Anti-tumour necrosis factor therapy for early-stage Dupuytren’s disease; Patient experiences of scaphoid waist fractures and their treatment; Postoperative complications following open a1 pulley release for a trigger finger or thumb; How certain are findings in distal radius fractures: a systematic review of randomized controlled trials; Partial wrist denervation in wrist osteoarthritis: patient-reported outcomes and objective function; Dorsal bridge plating versus bridging external fixation for management of complex distal radius fractures; How is reduction lost in distal radius fractures in females aged 50 years and older; The HAND-Q: psychometrics of a new patient-reported outcome measure for clinical and research applications

Tennis elbow (lateral epicondylitis or lateral elbow tendinopathy) is a self-limiting condition in most patients. Surgery is often offered to patients who fail to improve with conservative treatment. However, there is no evidence to support the superiority of surgery over continued nonoperative care or no treatment. New evidence also suggests that the prognosis of tennis elbow is not influenced by the duration of symptoms, and that there is a 50% probability of recovery every three to four months. This finding challenges the belief that failed nonoperative care is an indication for surgery. In this annotation, we discuss the clinical and research implications of the benign clinical course of tennis elbow. Cite this article: Bone Joint J 2023;105-B(2):109–111

Aims. To identify a suite of the key physical, emotional, and social outcomes to be employed in clinical practice and research concerning Perthes' disease in children. Methods. The study follows the guidelines of the COMET-Initiative (Core Outcome Measures in Effectiveness Trials). A systematic review of the literature was performed to identify a list of outcomes reported in previous studies, which was supplemented by a qualitative study exploring the experiences of families affected by Perthes’ disease. Collectively, these outcomes formed the basis of a Delphi survey (two rounds), where 18 patients with Perthes’ disease, 46 parents, and 36 orthopaedic surgeons rated each outcome for importance. The International Perthes Study Group (IPSG) (Dallas, Texas, USA (October 2018)) discussed outcomes that failed to reach any consensus (either ‘in’ or ‘out’) before a final consensus meeting with representatives of surgeons, patients, and parents. Results. In total, 23 different outcome domains were identified from the systematic review, and a further ten from qualitative interviews. After round one of the Delphi survey, participants suggested five further outcome domains. A total of 38 outcomes were scored in round two of the Delphi. Among these, 16 outcomes were scored over the prespecified 70% threshold for importance (divided into six main categories: adverse events; life impact; resource use; pathophysiological manifestations; death; and technical considerations). Following the final consensus meeting, 14 outcomes were included in the final Core Outcome Set (COS). Conclusion. Core Outcome Sets (COSs) are important to improve standardization of outcomes in clinical research and to aid communication between patients, clinicians, and funding bodies. The results of this study should be a catalyst to develop high-quality clinical research in order to determine the optimal treatments for children with Perthes’ disease. Cite this article: Bone Joint J 2020;102-B(5):611–617

Aims. Hip disease is common in children with cerebral palsy (CP) and can decrease quality of life and function. Surveillance programmes exist to improve outcomes by treating hip disease at an early stage using radiological surveillance. However, studies and surveillance programmes report different radiological outcomes, making it difficult to compare. We aimed to identify the most important radiological measurements and develop a core measurement set (CMS) for clinical practice, research, and surveillance programmes. Methods. A systematic review identified a list of measurements previously used in studies reporting radiological hip outcomes in children with CP. These measurements informed a two-round Delphi study, conducted among orthopaedic surgeons and specialist physiotherapists. Participants rated each measurement on a nine-point Likert scale (‘not important’ to ‘critically important’). A consensus meeting was held to finalize the CMS. Results. Overall, 14 distinct measurements were identified in the systematic review, with Reimer’s migration percentage being the most frequently reported. These measurements were presented over the two rounds of the Delphi process, along with two additional measurements that were suggested by participants. Ultimately, two measurements, Reimer’s migration percentage and femoral head-shaft angle, were included in the CMS. Conclusion. This use of a minimum standardized set of measurements has the potential to encourage uniformity across hip surveillance programmes, and may streamline the development of tools, such as artificial intelligence systems to automate the analysis in surveillance programmes. This core set should be the minimum requirement in clinical studies, allowing clinicians to add to this as needed, which will facilitate comparisons to be drawn between studies and future meta-analyses. Cite this article: Bone Jt Open 2023;4(11):825–831

Aims. The aim of this study was to estimate the clinical and economic burden of dislocation following primary total hip arthroplasty (THA) in England. Methods. This retrospective evaluation used data from the UK Clinical Practice Research Datalink database. Patients were eligible if they underwent a primary THA (index date) and had medical records available 90 days pre-index and 180 days post-index. Bilateral THAs were excluded. Healthcare costs and resource use were evaluated over two years. Changes (pre- vs post-THA) in generic quality of life (QoL) and joint-specific disability were evaluated. Propensity score matching controlled for baseline differences between patients with and without THA dislocation. Results. Among 13,044 patients (mean age 69.2 years (SD 11.4), 60.9% female), 191 (1.5%) had THA dislocation. Two-year median direct medical costs were £15,333 (interquartile range (IQR) 14,437 to 16,156) higher for patients with THA dislocation. Patients underwent revision surgery after a mean of 1.5 dislocations (1 to 5). Two-year costs increased to £54,088 (IQR 34,126 to 59,117) for patients with multiple closed reductions and a revision procedure. On average, patients with dislocation had greater healthcare resource use and less improvement in EuroQol five-dimension index (mean 0.24 (SD 0.35) vs 0.44 (SD 0.35); p < 0.001) and visual analogue scale (0.95 vs 8.85; p = 0.038) scores, and Oxford Hip Scores (12.93 vs 21.19; p < 0.001). Conclusion. The cost, resource use, and QoL burden of THA dislocation in England are substantial. Further research is required to understand optimal timing of revision after dislocation, with regard to cost-effectiveness and impact on QoL. Cite this article: Bone Joint J 2022;104-B(7):811–819

Critical size bone defects deriving from large bone loss are an unmet clinical challenge1. To account for disadvantages with clinical treatments, researchers focus on designing biological substitutes, which mimic endogenous healing through osteogenic differentiation promotion. Some studies have however suggested that this notion fails to consider the full complexity of native bone with respect to the interplay between osteoclast and osteoblasts, thus leading to the regeneration of less functional tissue2. The objective of this research is to assess the ability of our laboratory's previously developed 6-Bromoindirubin-3’-Oxime (BIO) incorporated guanosine diphosphate crosslinked chitosan scaffold in promoting multilineage differentiation of myoblastic C2C12 cells and monocytes into osteoblasts and osteoclasts1, 3, 4. BIO addition has been previously demonstrated to promote osteogenic differentiation in cell cultures5, but implementation of a co-culture model here is expected to encourage crosstalk thus further supporting differentiation, as well as the secretion of regulatory molecules and cytokines2. Biocompatibility testing of both cell types is performed using AlamarBlue for metabolic activity, and nucleic acid staining for distribution. Osteoblastic differentiation is assessed through quantification of ALP and osteopontin secretion, as well as osteocalcin and mineralization staining. Differentiation into osteoclasts is verified using SEM and TEM, qPCR, and TRAP staining. Cellular viability of C2C12 cells and monocytes was maintained when cultured separately in scaffolds with and without BIO for 21 days. Both scaffold variations showed a characteristic increase in ALP secretion from day 1 to 7, indicating early differentiation but BIO-incorporated sponges yielded higher values compared to controls. SEM and TEM imaging confirmed initial aggregation and fusion of monocytes on the scaffold's surface, but BIO addition appeared to result in smoother cell surfaces indicating a change in morphology. Late-stage differentiation assessment and co-culture work in the scaffold are ongoing, but initial results show promise in the material's ability to support multilineage differentiation. Acknowledgements: The authors would like to acknowledge the financial support of the Collaborative Health Research Program (CHRP) through CIHR and NSERC, as well as Canada Research Chair – Tier 1 in Regenerative Medicine and Nanomedicine, and the FRQ-S

Aims. The aims of this systematic review were to assess the learning curve of semi-active robotic arm-assisted total hip arthroplasty (rTHA), and to compare the accuracy, patient-reported functional outcomes, complications, and survivorship between rTHA and manual total hip arthroplasty (mTHA). Methods. Searches of PubMed, Medline, and Google Scholar were performed in April 2020 in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Search terms included “robotic”, “hip”, and “arthroplasty”. The criteria for inclusion were published clinical research articles reporting the learning curve for rTHA (robotic arm-assisted only) and those comparing the implantation accuracy, functional outcomes, survivorship, or complications with mTHA. Results. There were 501 articles initially identified from databases and references. Following full text screening, 17 articles that satisfied the inclusion criteria were included. Four studies reported the learning curve of rTHA, 13 studies reported on implant positioning, five on functional outcomes, ten on complications, and four on survivorship. The meta-analysis showed a significantly greater number of cases of acetabular component placement in the safe zone compared with the mTHA group (95% confidence interval (CI) 4.10 to 7.94; p < 0.001) and that rTHA resulted in a significantly better Harris Hip Score compared to mTHA in the short- to mid-term follow-up (95% CI 0.46 to 5.64; p = 0.020). However, there was no difference in infection rates, dislocation rates, overall complication rates, and survival rates at short-term follow-up. Conclusion. The learning curve of rTHA was between 12 and 35 cases, which was dependent on the assessment goal, such as operating time, accuracy, and team working. Robotic arm-assisted total hip arthroplasty was associated with improved accuracy of component positioning and functional outcome, however no difference in complication rates or survival were observed at short- to mid-term follow-up. Overall, there remains an absence of high-quality level I evidence and cost analysis comparing rTHA and mTHA. Cite this article: Bone Joint J 2021;103-B(6):1009–1020

Introduction. In 2015, the healthcare system transitioned from International Classification of Diseases, Ninth Revision (ICD-9) coding to the Tenth Revision (ICD-10). Given that administrative claims are used for quality initiatives, risk adjustment models and clinical research, we sought to determine the effect of new, more detailed coding on the incidence of complications following primary total knee arthroplasty (TKA). Methods. The Humana administrative claims database was queried from 2-years prior to October 1, 2015 (ICD-9 cohort) and for 1-year after this date (ICD-10 cohort) to identify all primary TKA procedures. Each TKA was then tracked for occurrence of an arthroplasty specific post-operative complication within 6 months of surgery using the respective coding systems. Laterality and joint specific codes were utilized for the ICD-10 cohort to ensure complications occurred on the same side and joint as the index procedure. Incidence of each complication was compared between cohorts using risk ratios (RR) and 95% confidence intervals. Results. There were 19,009 TKAs in the ICD-10 cohort and 38,172 TKAs in the ICD-9 cohort. The incidence of each post-operative complication analyzed was significantly higher in the ICD-9 cohort relative to the ICD-10 cohort (Figure 1). Comparing ICD-9 cohort to ICD-10 cohort, PJI occurred in 1.9% vs 1.3% (RR 1.5), loosening in 0.3% vs 0.1% (RR 2.7), periprosthetic fracture in 0.3% vs 0.1% (RR 3.0) and other mechanical complications in 0.7% vs 0.4% (RR 2.0), respectively (p < 0.05 for all). These findings remained significant when subgroup analyses were performed to control for seasonal variation between groups. Conclusion. The transition from ICD-9 to ICD-10 coding has dramatically altered the reported incidence of complications following TKA. These results are likely due to the added complexity of ICD-10 which is joint and laterality specific. It is important to quantify and understand the differences between coding systems as this data is used for quality initiatives, risk adjustment models and clinical research. Thoughtful methodology will be necessary for future research if both ICD-9 and ICD-10 data are being analyzed simultaneously. Furthermore, additional studies are needed to compare the hospital billing data for complex diagnoses or revision procedures to coding performed by skilled researchers in the field. For figures, tables, or references, please contact authors directly

Bone is one of the most highly adaptive tissues in the body, possessing the capability to alter its morphology and function in response to stimuli in its surrounding environment. The ability of bone to sense and convert external mechanical stimuli into a biochemical response, which ultimately alters the phenotype and function of the cell, is described as mechanotransduction. This review aims to describe the fundamental physiology and biomechanisms that occur to induce osteogenic adaptation of a cell following application of a physical stimulus. Considerable developments have been made in recent years in our understanding of how cells orchestrate this complex interplay of processes, and have become the focus of research in osteogenesis. We will discuss current areas of preclinical and clinical research exploring the harnessing of mechanotransductive properties of cells and applying them therapeutically, both in the context of fracture healing and de novo bone formation in situations such as nonunion. Cite this article: Bone Joint Res 2019;9(1):1–14

The surgical community is plagued with a reputation for both failing to engage and to deliver on clinical research. This is in part due to the absence of a strong research culture, however it is also due to a multitude of barriers encountered in clinical research; particularly those involving surgical interventions. ‘Trauma’ amplifies these barriers, owing to the unplanned nature of care, unpredictable work patterns, the emergent nature of treatment and complexities in the consent process. This review discusses the barriers to clinical research in surgery, with a particular emphasis on trauma. It considers how barriers may be overcome, with the aim to facilitate future successful clinical research. Cite this article: Bone Joint Res 2014;3:123–9

To estimate the clinical and economic burden of primary total hip arthroplasty (THA) dislocation in England. Retrospective propensity score-matched evaluation of patients with and without dislocation following primary THA using the UK Clinical Practice Research Datalink linked and Hospital Episode Statistics datasets with a 2-year follow-up. 13,044 patients with total hip replacements met the inclusion criteria (mean age 69.2, 60.9% female) of which 154 (1.18%) suffered at least one postoperative hip dislocation. The mean number of dislocations per patient was 1.44 with a maximum of 4. Approximately one-third of the patients with dislocation (32.5%) had more than one dislocation. Among patients with a hip dislocation 148 patients (96.7%) had at least one closed reduction and 20 patients (13.1%) had revision surgery. Two-year median direct medical costs were £14,748 (95% confidence interval [CI] £12,028 to £20,638) higher with vs. without dislocation (+227%). On average, patients with a dislocation had significantly greater healthcare resource utilization and significantly less improvement in EuroQol-5D (EQ-5D) index (0.24 vs. 0.45; p<0.001) and Visual Analogue Scale (VAS) (1.58 vs. 11.23; p=0.010) scores and Oxford Hip Scores (13.02 vs. 21.98; p<0.001). This is the first study to estimate the economic burden of dislocation in the UK throughout the entire patient pathway. Dislocation following total hip replacement is a costly complication, both in terms of economic costs and to the functional quality of life of the patient. Efforts to reduce the risks of dislocation should remain at the forefront of hip research

Aim. We aimed to assess the incidence and the outcome of Gram-negative prosthetic-joint infections (PJI) in 3 international tertiary hospital. Method. We included patients with Gram-negative PJI at Humanitas Clinical and Research Hospital (Milan, Italy), Centre Hospitalier Universitaire Vaudois (Lausanne, Switzerland) and Hospital Parc de Salut Mar (Barcelona, Spain) between 2014 and 2018 in a retrospective cohort. We described the treatment's success rate according to Gram-negative species and type of surgical procedure. Results. In the present cohort we have 780 PJI out of which 71 (9.1%) were caused by Gram-negative bacteria (polymicrobial infection 30%, Escherichia coli 25%, Pseudomonas aeruginosa 20%, Proteus spp. 4%, Klebsiella spp. 3%, Morganella morganii 3%, Enterobacter 3%, others 12%). Gram-negative PJI were more common in females (60%) than males (40%). Sixty percent had a hip infection, 40% a knee infection, the median age was 74 years and the median ASA score was 3. It was a chronic infection in 60% of the cases and an acute one in 40%. Two-step exchange was performed in 55%, débridement and retention (DAIR) in 30%, one-step exchange in 11% and implant removal without replacement in 4% of the patients. The overall treatment success rate was 89%. The success rate was better for two-step exchange (95%) compared to DAIR (81%) and one-step exchange (87%) (p=0.068). The median antibiotic duration was 68 days and ciprofloxacin was used in 70% of the cured patients versus in 88% of the failures (p=0.388). Infections caused by Escherichia coli were associated with a lower success rate (83%) especially compared to Pseudomonas aeruginosa (93%) and polymicrobial infections (90%) (p=0.358). Finally, the success rate was better in knee PJI compared to hip PJI (97% versus 83%, p=0.121) and in females compared to males (93% versus 82%, p=0.121). Conclusions. The treatment's success of Gram-negative PJI is comparable to reported rates for all bacteria. However, our results suggest that surgical management with two-step exchange might be useful in selected patients’ groups such as those with Escherichia coli PJI. Moreover, ciprofloxacin use seems not to improve cure rate

Objectives. This review aims to summarize the outcomes used to describe effectiveness of treatments for paediatric wrist fractures within existing literature. Method. We searched the Cochrane Library, Scopus, and Ovid Medline for studies pertaining to paediatric wrist fractures. Three authors independently identified and reviewed eligible studies. This resulted in a list of outcome domains and outcomes measures used within clinical research. Outcomes were mapped onto domains defined by the COMET collaborative. Results. Our search terms identified 4,262 different papers. Screening of titles excluded 2,975, leaving 1,287 papers to be assessed for eligibility. Of this 1,287, 30 studies were included for full analysis. Overall, five outcome domains, 16 outcome measures, and 28 measurement instruments were identified as outcomes within these studies. 24 studies used at least one measurement pertaining to the physiological/clinical outcome domain. The technical, life impact, and adverse effect domains were recorded in 23, 20, and 11 of the studies respectively. Within each domain it was common for different measurement instruments to be used to assess each outcome measure. The most commonly reported outcome measures were range of movement, a broad array of “radiological measures” and pain intensity, which were used in 24, 23, and 12 of the 30 studies. Conclusion. This study highlights the heterogeneity in outcomes reported within clinical effectiveness studies of paediatric wrist fractures. We provided an overview of the types of outcomes reported in paediatric wrist fracture studies and identified a list of potentially relevant outcomes required for the development of a core outcome set

Aims. Dual plating of distal femoral fractures with medial and lateral implants has been performed to improve construct mechanics and alignment, in cases where isolated lateral plating would be insufficient. This may potentially compromise vascularity, paradoxically impairing healing. This study investigates effects of single versus dual plating on distal femoral vascularity. Methods. A total of eight cadaveric lower limb pairs were arbitrarily assigned to either 1) isolated lateral plating, or 2) lateral and medial plating of the distal femur, with four specimens per group. Contralateral limbs served as matched controls. Pre- and post-contrast MRI was performed to quantify signal intensity enhancement in the distal femur. Further evaluation of intraosseous vascularity was done with barium sulphate infusion with CT scan imaging. Specimens were then injected with latex medium and dissection was completed to assess extraosseous vasculature. Results. Quantitative MRI revealed a mean reduction of 21.2% (SD 1.3%) of arterial contribution in the lateral plating group and 25.4% (SD 3.2%) in the dual plating group (p = 0.051); representing a mean decrease in arterial contribution of 4.2%. The only significant difference found between both experimental groups was regionally, at the lateral aspect of the distal femur with a mean drop in arterial contribution in the lateral plating group of 18.9% (SD 2.6%) versus 24.0% (SD 3.2%) in the dual plating group (p = 0.048), representing a mean decrease in arterial contribution of 5.1%. Gross dissection revealed complete destruction of periosteal vessels underneath either medial or lateral plates in both groups. The network of genicular branches contributing to the posterior and distal femoral condyles was preserved in all specimens. A medial vascular pedicle was found dividing from the superficial femoral artery at a mean 12.7 cm (SD 1.7) proximal to the medial epicondyle and was undisrupted in the dual plating group. Conclusion. Lateral locking-plate application resulted in mean 21.2% reduction in distal femur vascularity. Addition of medial plates did not further markedly decrease vascularity. As such, the majority of the vascular insult occurred with lateral plating alone. Supplemental medially based fixation did not lead to marked devascularization of the distal femur, and should therefore be considered in the setting of comminution and poor bone stock in distal femoral fractures. Further clinical research is required to confirm the results of this study. Cite this article: Bone Joint J 2020;102-B(4):530–538

Due to limitations of existing pharmacological therapies for the management of chronic pain in osteoarthritis (OA), surgical interventions remain a major component of current standard of care, with total joint replacements (TJRs) considered for people who have not responded adequately to conservative treatment. This study aimed to quantify the economic burden of moderate-to-severe chronic pain in patients with OA in England prior to TJR. A retrospective, longitudinal cohort design was employed using Clinical Practice Research Datalink GOLD primary care data linked to Hospital Episode Statistics secondary care data in England. Patients (age ≥18 years) with an existing OA diagnosis of any anatomical site (Read/ICD-10) were indexed (Dec-2009 to Nov-2017) on a moderate-to-severe pain event (which included TJR) occurring within an episode of chronic pain. 5-year TJR rates from indexing were assessed via Kaplan-Meier estimates. All-cause healthcare resource utilisation and direct medical costs were evaluated in the 1–12 and 13–24 months prior to the first TJR experienced after index. Statistical significance was assessed via paired t-tests. The study cohort comprised 5,931 eligible patients (57.9% aged ≥65 years, 59.2% female). 2,176 (36.7%) underwent TJR (knee: 54.4%; hip: 42.8%; other: 2.8%). The 5-year TJR rate was 45.4% (knee: 24.3%; hip: 17.5%; other: 6.8%). Patients experienced more general practitioner consultations in 1–12 months pre-TJR compared with 13–24 months pre-TJR (means: 12.13 vs. 9.61; p<0.0001), more outpatient visits (6.68 vs. 3.77; p<0.0001), more hospitalisations (0.74 vs. 0.62; p=0.0032), and more emergency department visits (0.29 vs. 0.25, p=0.0190). Total time (days) spent as an inpatient was higher in 1–12 months pre-TJR (1.86 vs. 1.07; p<0.0001). Mean total per-patient cost pre-TJR increased from £1,771 (13–24 months) to £2,621 (1–12 months) (p<0.0001). Resource-use and costs incurred were substantially greater in the 12 months immediately prior to TJR, compared with 13–24 months prior. Reasons for increased healthcare and economic burden in the pre-TJR period deserve further exploration as potential targets for efforts to improve patient experience and efficiency of care

Purpose of study and background. Clinical researchers use Pfirrmann classification for grading intervertebral disc degeneration radiologically. Basic researchers have access to morphology and instead use the Thompson score. The aim of this study was to assess the inter-observer reliability of both classifications, along with their correlation. Methods and Results. We obtained T2-weighted MR images of 80 human lumbar intervertebral discs with various stages of degeneration to assess the Pfirrmann-score. Then the discs were dissected midsagittally to obtain the Thompson-score. The observers were typical users of both grading systems: a spine surgeon, radiology resident, orthopaedic resident, and a basic scientist, all experts on intervertebral disc degeneration. Cohen's kappa (CK) was used to determine inter-observer reliability, and intra-class correlation (ICC) as a measure for the variation between the outcomes. For the Thompson score, the average CK was 0.366 and ICC score 0.873. The average inter-observer reliability for the Pfirrmann score was 0.214 (CK) and 0.790 (ICC). Comparing the grading systems, the intra-observer agreement was 0.240 (CK) and 0.685 (ICC). Conclusion. With substantial variation between observers, the inter-observer agreements for the Pfirrmann and Thompson grading systems were moderate. This may explain the poor relationship between radiological and clinical observations in patients and raises questions about the validity of the Pfirrmann score. The mediocre intra-observer agreement between the Pfirrmann and Thompson score shows that there is no clear definition of intervertebral disc degeneration. The field is in need for a new, objective and quantitative classification system to better define and evaluate disc degeneration. There are no conflicts of interest. Funded in part by Annafonds Netherlands and Dutch Spine Society

Objectives. Preclinical data showed poly(methyl methacrylate) (PMMA) loaded with microsilver to be effective against a variety of bacteria. The purpose of this study was to assess patient safety of PMMA spacers with microsilver in prosthetic hip infections in a prospective cohort study. Methods. A total of 12 patients with prosthetic hip infections were included for a three-stage revision procedure. All patients received either a gentamicin-PMMA spacer (80 g to 160 g PMMA depending on hip joint dimension) with additional loading of 1% (w/w) of microsilver (0.8 g to 1.6 g per spacer) at surgery 1 followed by a gentamicin-PMMA spacer without microsilver at surgery 2 or vice versa. Implantation of the revision prosthesis was carried out at surgery 3. Results. In total, 11 of the 12 patients completed the study. No argyria or considerable differences in laboratory parameters were detected. Silver blood concentrations were below or around the detection limit of 1 ppb in ten of the 11 patients. A maximum of 5.6 ppb at 48 hours after implantation of the silver spacer, which is below the recommended maximum level of 10 ppb, was found in one patient. No silver was detected in the urine. Drainage fluids showed concentrations between 16.1 ppb and 23.3 ppb at 12 hours after implantation of the silver spacers, and between 16.8 ppb to 25.1 ppb at 48 hours after implantation. Pathohistological assessment of the periprosthetic membrane did not reveal any differences between the two groups. Conclusion. Microsilver-loaded gentamicin-PMMA spacers showed good biocompatibility and the broad antimicrobial activity warrants further clinical research to assess its effectivity in reducing infection rates in prosthetic joint infection. Cite this article: V. Alt, M. Rupp, K. Lemberger, T. Bechert, T. Konradt, P. Steinrücke, R. Schnettler, S. Söder, R. Ascherl. Safety assessment of microsilver-loaded poly(methyl methacrylate) (PMMA) cement spacers in patients with prosthetic hip infections: Results of a prospective cohort study. Bone Joint Res 2019;8:387–396. DOI: 10.1302/2046-3758.88.BJR-2018-0270.R1

Stem cells are defined by their potential for self-renewal and the ability to differentiate into numerous cell types, including cartilage and bone cells. Although basic laboratory studies demonstrate that cell therapies have strong potential for improvement in tissue healing and regeneration, there is little evidence in the scientific literature for many of the available cell formulations that are currently offered to patients. Numerous commercial entities and ‘regenerative medicine centres’ have aggressively marketed unproven cell therapies for a wide range of medical conditions, leading to sometimes indiscriminate use of these treatments, which has added to the confusion and unpredictable outcomes. The significant variability and heterogeneity in cell formulations between different individuals makes it difficult to draw conclusions about efficacy. The ‘minimally manipulated’ preparations derived from bone marrow and adipose tissue that are currently used differ substantially from cells that are processed and prepared under defined laboratory protocols. The term ‘stem cells’ should be reserved for laboratory-purified, culture-expanded cells. The number of cells in uncultured preparations that meet these defined criteria is estimated to be approximately one in 10 000 to 20 000 (0.005% to 0.01%) in native bone marrow and 1 in 2000 in adipose tissue. It is clear that more refined definitions of stem cells are required, as the lumping together of widely diverse progenitor cell types under the umbrella term ‘mesenchymal stem cells’ has created confusion among scientists, clinicians, regulators, and our patients. Validated methods need to be developed to measure and characterize the ‘critical quality attributes’ and biological activity of a specific cell formulation. It is certain that ‘one size does not fit all’ – different cell formulations, dosing schedules, and culturing parameters will likely be required based on the tissue being treated and the desired biological target. As an alternative to the use of exogenous cells, in the future we may be able to stimulate the intrinsic vascular stem cell niche that is known to exist in many tissues. The tremendous potential of cell therapy will only be realized with further basic, translational, and clinical research. Cite this article: Bone Joint J 2019;101-B:361–364

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.

Aims

A core outcome set for adult, open lower limb fracture has been established consisting of ‘Walking, gait and mobility’, ‘Being able to return to life roles’, ‘Pain or discomfort’, and ‘Quality of life’. This study aims to identify which outcome measurement instruments (OMIs) should be recommended to measure each core outcome.

Aims

In this study, we aimed to visualize the spatial distribution characteristics of femoral head necrosis using a novel measurement method.

The August 2024 Research Roundup³⁶⁰ looks at: Effect of vitamin D deficiency on periprosthetic joint infection and complications after primary total joint replacement; Postoperative angiotensin receptor blocker use associated with decreased rates of manipulation under anaesthesia in patients undergoing total knee arthroplasty; Central sensitization: the missing link between psychological distress and poor outcome following primary total knee arthroplasty; Thromboprophylaxis for the trauma and orthopaedic surgeon; Life expectancy after treatment of metastatic bone disease: an international trend analysis.

Aims. High-quality clinical research in children’s orthopaedic surgery has lagged behind other surgical subspecialties. This study used a consensus-based approach to identify research priorities for clinical trials in children’s orthopaedics. Methods. A modified Delphi technique was used, which involved an initial scoping survey, a two-round Delphi process and an expert panel formed of members of the British Society of Children’s Orthopaedic Surgery. The survey was conducted amongst orthopaedic surgeons treating children in the United Kingdom and Ireland. Results. A total of 86 clinicians contributed to both rounds of the Delphi process, scoring priorities from one (low priority) to five (high priority). Elective topics were ranked higher than those relating to trauma, with the top ten elective research questions scoring higher than the top question for trauma. Ten elective, and five trauma research priorities were identified, with the three highest ranked questions relating to the treatment of slipped capital femoral epiphysis (mean score 4.6/ 5), Perthes’ disease (4.5) and bone infection (4.5). Conclusion. This consensus-based research agenda will guide surgeons, academics and funders to improve the evidence in children’s orthopaedic surgery and encourage the development of multicentre clinical trials. Cite this article: Bone Joint J 2018;100-B:680–4

The importance of registries has been brought into focus by recent UK national reports focusing on implant (Cumberlege) and surgeon (Paterson) performance. National arthroplasty registries provide real-time, real-world information about implant, hospital, and surgeon performance and allow case identification in the event of product recall or adverse surgical outcomes. They are a valuable resource for research and service improvement given the volume of data recorded and the longitunidal nature of data collection. This review discusses the current value of registry data as it relates to both clinical practice and research.

Cite this article: Bone Joint J 2023;105-B(4):356–360.

Aims

Acetabular fractures are associated with long-term morbidity. Our prospective cohort study sought to understand the recovery trajectory of this injury over five years.

Aims

This study aims to determine difference in annual rate of early-onset (≤ 90 days) deep surgical site infection (SSI) following primary total knee arthroplasty (TKA) for osteoarthritis, and to identify risk factors that may be associated with infection.

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The primary aim of this study is to assess the survival of the uncemented hydroxyapatite (HA) coated Trident II acetabular component as part of a hybrid total hip arthroplasty (THA) using a cemented Exeter stem. The secondary aims are to assess the complications, joint-specific function, health-related quality of life, and radiological signs of loosening of the acetabular component.

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Ankle fractures are common, mainly affecting adults aged 50 years and over. To aid recovery, some patients are referred to physiotherapy, but referral patterns vary, likely due to uncertainty about the effectiveness of this supervised rehabilitation approach. To inform clinical practice, this study will evaluate the effectiveness of supervised versus self-directed rehabilitation in improving ankle function for older adults with ankle fractures.

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During total knee replacement (TKR), surgeons can choose whether or not to resurface the patella, with advantages and disadvantages of each approach. Recently, the National Institute for Health and Care Excellence (NICE) recommended always resurfacing the patella, rather than never doing so. NICE found insufficient evidence on selective resurfacing (surgeon’s decision based on intraoperative findings and symptoms) to make recommendations. If effective, selective resurfacing could result in optimal individualized patient care. This protocol describes a randomized controlled trial to evaluate the clinical and cost-effectiveness of primary TKR with always patellar resurfacing compared to selective patellar resurfacing.

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

Benefits of early stabilization of femoral shaft fractures, in mitigation of pulmonary and other complications, have been recognized over the past decades. Investigation into the appropriate level of resuscitation, and other measures of readiness for definitive fixation, versus a damage control strategy have been ongoing. These principles are now being applied to fractures of the thoracolumbar spine, pelvis, and acetabulum. Systems of trauma care are evolving to encompass attention to expeditious and safe management of not only multiply injured patients with these major fractures, but also definitive care for hip and periprosthetic fractures, which pose a similar burden of patient recumbency until stabilized. Future directions regarding refinement of patient resuscitation, assessment, and treatment are anticipated, as is the potential for data sharing and registries in enhancing trauma system functionality.

Cite this article: Bone Joint J 2023;105-B(4):361–364.

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Treatment of Weber B ankle fractures that are stable on weightbearing radiographs but unstable on concomitant stress tests (classified SER4a) is controversial. Recent studies indicate that these fractures should be treated nonoperatively, but no studies have compared alternative nonoperative options. This study aims to evaluate patient-reported outcomes and the safety of fracture treatment using functional orthosis versus cast immobilization.

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Unicompartmental knee arthroplasty (UKA) is the preferred treatment for anterior medial knee osteoarthritis (OA) owing to the rapid postoperative recovery. However, the risk factors for UKA failure remain controversial.

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Perthes' disease (PD) is a relatively rare syndrome of idiopathic osteonecrosis of the proximal femoral epiphysis. Treatment for Perthes' disease is controversial due to the many options available, with no clear superiority of one treatment over another. Despite having few evidence-based approaches, many patients with Perthes' disease are managed surgically. Positive outcome reporting, defined as reporting a study variable producing statistically significant positive (beneficial) results, is a phenomenon that can be considered a proxy for the strength of science. This study aims to conduct a systematic literature review with the hypothesis that positive outcome reporting is frequent in studies on the treatment of Perthes' disease.

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To evaluate mid-to long-term patient-reported outcome measures (PROMs) of endoprosthetic reconstruction after resection of malignant tumours arising around the knee, and to investigate the risk factors for unfavourable PROMs.

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Isolated fractures of the ulnar diaphysis are uncommon, occurring at a rate of 0.02 to 0.04 per 1,000 cases. Despite their infrequency, these fractures commonly give rise to complications, such as nonunion, limited forearm pronation and supination, restricted elbow range of motion, radioulnar synostosis, and prolonged pain. Treatment options for this injury remain a topic of debate, with limited research available and no consensus on the optimal approach. Therefore, this trial aims to compare clinical, radiological, and functional outcomes of two treatment methods: open reduction and internal fixation (ORIF) versus nonoperative treatment in patients with isolated ulnar diaphyseal fractures.

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This study aims to identify the top unanswered research priorities in the field of knee surgery using consensus-based methodology.

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Ankle fracture is one of the most common musculoskeletal injuries sustained in the UK. Many patients experience pain and physical impairment, with the consequences of the fracture and its management lasting for several months or even years. The broad aim of ankle fracture treatment is to maintain the alignment of the joint while the fracture heals, and to reduce the risks of problems, such as stiffness. More severe injuries to the ankle are routinely treated surgically. However, even with advances in surgery, there remains a risk of complications; for patients experiencing these, the associated loss of function and quality of life (Qol) is considerable. Non-surgical treatment is an alternative to surgery and involves applying a cast carefully shaped to the patient’s ankle to correct and maintain alignment of the joint with the key benefit being a reduction in the frequency of common complications of surgery. The main potential risk of non-surgical treatment is a loss of alignment with a consequent reduction in ankle function. This study aims to determine whether ankle function, four months after treatment, in patients with unstable ankle fractures treated with close contact casting is not worse than in those treated with surgical intervention, which is the current standard of care.

Osteoarthritis (OA) is mainly caused by ageing, strain, trauma, and congenital joint abnormalities, resulting in articular cartilage degeneration. During the pathogenesis of OA, the changes in subchondral bone (SB) are not only secondary manifestations of OA, but also an active part of the disease, and are closely associated with the severity of OA. In different stages of OA, there were microstructural changes in SB. Osteocytes, osteoblasts, and osteoclasts in SB are important in the pathogenesis of OA. The signal transduction mechanism in SB is necessary to maintain the balance of a stable phenotype, extracellular matrix (ECM) synthesis, and bone remodelling between articular cartilage and SB. An imbalance in signal transduction can lead to reduced cartilage quality and SB thickening, which leads to the progression of OA. By understanding changes in SB in OA, researchers are exploring drugs that can regulate these changes, which will help to provide new ideas for the treatment of OA.

Cite this article: Bone Joint Res 2023;12(9):536–545.

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Current diagnostic tools are not always able to effectively identify periprosthetic joint infections (PJIs). Recent studies suggest that circulating microRNAs (miRNAs) undergo changes under pathological conditions such as infection. The aim of this study was to analyze miRNA expression in hip arthroplasty PJI patients.

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This study aimed to investigate the clinical characteristics and outcomes associated with culture-negative limb osteomyelitis patients.

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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.

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The aim of this study was to compare the functional and radiological outcomes and the complication rate after nail and plate fixation of unstable fractures of the ankle in elderly patients.

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This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA.

The October 2023 Research Roundup³⁶⁰ looks at: Gut microbiota in high-risk individuals for rheumatoid arthritis associated with disturbed metabolome and initiates arthritis by triggering mucosal immunity imbalance; International Consensus on Anaemia Management in Surgical Patients (ICCAMS); Sleep disturbance trends in the short-term postoperative period for patients undergoing total joint replacement; Achilles tendon tissue turnover before and immediately after an acute rupture; Quadriceps or hip exercises for patellofemoral pain? A randomized controlled equivalence trial; Total-body MRI for screening in patients with multiple osteochondromas.

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Computer-assisted 3D preoperative planning software has the potential to improve postoperative stability in total hip arthroplasty (THA). Commonly, preoperative protocols simulate two functional positions (standing and relaxed sitting) but do not consider other common positions that may increase postoperative impingement and possible dislocation. This study investigates the feasibility of simulating commonly encountered positions, and positions with an increased risk of impingement, to lower postoperative impingement risk in a CT-based 3D model.

The June 2023 Shoulder & Elbow Roundup³⁶⁰ looks at: Proximal humerus fractures: what does the literature say now?; Infection risk of steroid injections and subsequent reverse shoulder arthroplasty; Surgical versus non-surgical management of humeral shaft fractures; Core outcome set needed for elbow arthroplasty; Minimally invasive approaches to locating radial nerve in the posterior humeral approach; Predictors of bone loss in anterior glenohumeral instability; Does the addition of motor control or strengthening exercises improve rotator cuff-related shoulder pain?; Terminology and diagnostic criteria used in patients with subacromial pain syndrome.

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Fractures of the humeral shaft represent 3% to 5% of all fractures. The most common treatment for isolated humeral diaphysis fractures in the UK is non-operative using functional bracing, which carries a low risk of complications, but is associated with a longer healing time and a greater risk of nonunion than surgery. There is an increasing trend to surgical treatment, which may lead to quicker functional recovery and lower rates of fracture nonunion than functional bracing. However, surgery carries inherent risk, including infection, bleeding, and nerve damage. The aim of this trial is to evaluate the clinical and cost-effectiveness of functional bracing compared to surgical fixation for the treatment of humeral shaft fractures.

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To review the evidence and reach consensus on recommendations for follow-up after total hip and knee arthroplasty.

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The primary aim of this study was to assess the feasibility of recruiting and retaining patients to a patient-blinded randomized controlled trial comparing corticosteroid injection (CSI) to autologous protein solution (APS) injection for the treatment of subacromial shoulder pain in a community care setting. The study focused on recruitment rates and retention of participants throughout, and collected data on the interventions’ safety and efficacy.

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Frailty greatly increases the risk of adverse outcome of trauma in older people. Frailty detection tools appear to be unsuitable for use in traumatically injured older patients. We therefore aimed to develop a method for detecting frailty in older people sustaining trauma using routinely collected clinical data.

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Previous studies have suggested that selenium as a trace element is involved in bone health, but findings related to the specific effect of selenium on bone health remain inconclusive. Thus, we performed a meta-analysis by including all the relevant studies to elucidate the association between selenium status (dietary intake or serum selenium) and bone health indicators (bone mineral density (BMD), osteoporosis (OP), or fracture).

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Scoliosis is a lateral curvature of the spine with associated rotation, often causing distress due to appearance. For some curves, there is good evidence to support the use of a spinal brace, worn for 20 to 24 hours a day to minimize the curve, making it as straight as possible during growth, preventing progression. Compliance can be poor due to appearance and comfort. A night-time brace, worn for eight to 12 hours, can achieve higher levels of curve correction while patients are supine, and could be preferable for patients, but evidence of efficacy is limited. This is the protocol for a randomized controlled trial of ‘full-time bracing’ versus ‘night-time bracing’ in adolescent idiopathic scoliosis (AIS).

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To determine whether platelet-rich plasma (PRP) injection improves outcomes two years after acute Achilles tendon rupture.

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The management of fractures of the medial epicondyle is one of the greatest controversies in paediatric fracture care, with uncertainty concerning the need for surgery. The British Society of Children’s Orthopaedic Surgery prioritized this as their most important research question in paediatric trauma. This is the protocol for a randomized controlled, multicentre, prospective superiority trial of operative fixation versus nonoperative treatment for displaced medial epicondyle fractures: the Surgery or Cast of the EpicoNdyle in Children’s Elbows (SCIENCE) trial.

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Transcription factor nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of chronic inflammatory diseases in all organ systems. Despite its importance, NF-κB targeted drug therapy to mitigate chronic inflammation has had limited success in preclinical studies. We hypothesized that sex differences affect the response to NF-κB treatment during chronic inflammation in bone. This study investigated the therapeutic effects of NF-κB decoy oligodeoxynucleotides (ODN) during chronic inflammation in male and female mice.

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To develop prediction models using machine-learning (ML) algorithms for 90-day and one-year mortality prediction in femoral neck fracture (FNF) patients aged 50 years or older based on the Hip fracture Evaluation with Alternatives of Total Hip arthroplasty versus Hemiarthroplasty (HEALTH) and Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trials.

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The Open-Fracture Patient Evaluation Nationwide (OPEN) study was performed to provide clarity in open fracture management previously skewed by small, specialist centre studies and large, unfocused registry investigations. We report the current management metrics of open fractures across the UK.

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A number of anti-retroviral therapies (ART) have been implicated in potentially contributing to HIV-associated bone disease. The aim of this study was to evaluate the effect of combination ART on the fracture healing process.

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To explore individuals’ experience of a scaphoid waist fracture and its subsequent treatment.

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Although absorbable sutures for the repair of acute Achilles tendon rupture (ATR) have been attracting attention, the rationale for their use remains insufficient. This study prospectively compared the outcomes of absorbable and nonabsorbable sutures for the repair of acute ATR.

Investigator-Driven Clinical Trials (IDCT) form a key part of patient-oriented clinical research, the basis for continually improving patient care. Such research is under strain in Europe for a multiplicity of reasons, and because of this the European Medical Research Councils (EMRC) of the ESF has undertaken in 2007 a Forward Look exercise. This Forward Look represents what is probably the most comprehensive examination of IDCT in Europe in recent years. A thorough analysis of the problems faced by academic investigators conducting IDCT was carried out through a series of workshops covering different themes and attended by active and acknowledged experts in the field. These workshops identified specific issues that need to be addressed:. - Categories and Design of Investigator-Driven Clinical Trials. - Regulatory and Legal Issues, Intellectual Property Rights and Data Sharing. - Management of Investigator-Driven Clinical Trials. - Education, Training, Career Tracks and Authorship. - Funding and Models of Partnership. - Status of Investigator-Driven Clinical Trials in Central and Eastern European Countries. A range of possible solutions were proposed and five among the 26 recommendations as ranked by the consensus conference, held on 29–30 September 2008, were considered as top priorities to strengthen IDCT in Europe:. To improve the education, training and career structure for scientists involved in patient-oriented clinical research. To increase levels of funding for IDCT. To adopt a ‘risk-based’ approach to the regulation of IDCT. To streamline procedures for obtaining authorisation for IDCT. To ensure that IDCT are carried out with an appropriate number of patients to produce statistically reliable results – that the trials are ‘correctly powered’. To help implement the recommendations expressed in the report for strengthening patient oriented research in Europe a broad dissemination to the four stakeholder groups identified as key players will be assured.We clearly think that if we can collaborate on this important issue and improve conditions for clinical research, we can contribute to bringing better health and prosperity to Europe

Study aim. There is an ever increasing demand for quality clinical trials in surgery. Surgeons' co-operation and enthusiasm to participate are important, if not crucial in success of such studies, especially if they are multi-centred. Clinician's individual uncertainty (equipoise) about a case has been often cited as an ethical basis for inviting a patient to take part in a clinical trial. This study aims to establish current attitudes of surgeons participating in a national multi-centred randomised controlled trial and explores an on line tool for instant assessment of collective uncertainty (equipoise) for individual clinical cases eligible for a trial. Study design. Surgeons taking part in the UK Heel Fracture Trial were invited to take part. If agreed, they were asked to evaluate treatment prognosis for eligible for the trial anonymised cases of calcaneal fractures online by means of specially designed system. The cases were published on a password protected website on ad-hoc basis during the three years course of the trial. Their responses were submitted instantly on line. Results. 16 out of 24 surgeons agreed to participate. The participating surgeons were emailed links to cases (normally in butches of three) less than once a month. It took them 10-15 min to assess all three cases via interactive interface. Of those who agreed 12 submitted their opinion at least once. 7 voted consistently during the course of the trial. Seventy one cases had been published. The data collected from responses allowed to assess individual and collective uncertainty about clinical cases. 4 surgeons demonstrated tendency towards individual uncertainty, balanced by 4 who did not accept it. However, sufficient collective uncertainty was demonstrated in 84.5% of cases. Discussion. Level of surgeons' enthusiasm towards clinical research appears to be moderate in a selected population of orthopaedic surgeons who already agreed to take part in a randomised clinical trial, despite a very low research time burden of this study. It is important to continue to promote multi-centred studies in order to improve surgeons' attitude towards quality clinical research. Extra efforts by academic clinicians to develop further low research time burden methodologies may increase acceptance and volume of multi-centred clinical research. This study supports previously expressed view that individual uncertainty is a very unreliable and unnecessary justification to offer a subject to take part in a clinical trial. The system used in the study offers surgeons to express their opinions and preferences freely. The instant on line comparison of opinions provides a clear assessment of collective uncertainty, which can be returned to a treating surgeon and a patient him/herself within 48 hours. In absence of collective uncertainty it would be ethical to offer a patient the best treatment according to current opinion. These cases can then be followed up as part of an inclusive trial, if a subject agrees. We believe that using the system may improve decision making process in randomised controlled trials, for example in selected challenging cases

Successful reconstruction of bone defects requires an adequate filling material that supports regeneration and formation of new bone within the treated defect in an optimal fashion. Currently available synthetic bone graft substitutes cannot fulfill all requirements of the highly complex biological processes involved in physiological bone healing. Due their unphysiologically asynchronous biodegradation properties, their specific foreign material-mediated side effects and complications and their relatively modest overall osteogenic potential, their overall clinical performance typically lags behind conventional bone grafts of human origin. However, defect- and pathology specific combination of synthetic bone graft substitutes exhibiting appropriate carrier properties with therapeutic agents and/or conventional bone graft materials allows creation of biologically enhanced composite constructs that can surpass the biological and therapeutic limits even of autologous bone grafts. This presentation introduces a bone defect reconstruction concept based on biological enhancement of optimal therapeutic agent-carrier composites and provides a rationale for an individual, requirement-specific adaptation of a truly patient-specific reconstruction of bone defects. It represents the pinnacle of the bone defect reconstruction pyramid, founded on the basic principles and prerequisites of complete elimination of the underlying pathology, preservation, augmentation or restoration of mechanical stability of the treated bone segment and creation of a biodegradable scaffold with adequate mechanical integrity. It summarises the current body of relevant experimental and clinical research, presents clinical case examples illustrating the various aspects of the proposed concept as well as early clinical results. The author hopes that the theoretical and conceptual framework provided, will help guide future research as well as clinical decision making with respect to this particular field

Introduction. Manual chart review is labor-intensive and requires specialized knowledge possessed by highly-trained medical professionals. The cost and infrastructure challenges required to implement this is prohibitive for most hospitals. Natural language processing (NLP) tools are distinctive in their ability to extract critical information from raw text in the electronic health records (EHR). As a simple proof-of-concept, for the potential application of this technology, we examined its ability to discriminate between a binary classification (periprosthetic fracture [PPFFx] vs. no PPFFx) followed by a more complex classification of the same problem (Vancouver). Methods. PPFFx were identified among all THAs performed at a single academic institution between 1977 and 2015. A training cohort (n = 90 PPFFx) selected randomly by an electronic program was utilized to develop a prototype NLP algorithm and an additional randomly-selected 86 PPFFx were used to further validate the algorithm. Keywords to identify, and subsequently classify, Vancouver type PPFFx about THA were defined. The algorithm was applied to consult and operative notes to evaluate language used by surgeons as a means to predict the correct pathology in the absence of a listed, precise diagnosis (e.g. Vancouver B2). Validation statistics were calculated using manual chart review as the gold standard. Results. In distinguishing between 2983 cases of PPFFx, 2898 cases of no PPFFx, and 85 cases of index THA performed for fracture, the NLP algorithm demonstrated an accuracy of 99.8%. Among 73 PPFFx test cases, the algorithm demonstrated a sensitivity of 87.1%, specificity of 78.6%, PPV of 75.0%, and NPV of 89.1% in determining the correct Vancouver classification. Overall Vancouver classification accuracy was moderate at 82.2%. Conclusion. NLP-enabled algorithms are a promising alternative to the current gold standard of manual chart review for evaluating outcomes of large data sets in orthopedics. Despite their immaturity with respect to orthopedic applications, NLP algorithms applied to surgeon notes demonstrated excellent accuracy (99.8%) in delineating a simple binary outcome, in this case the presence or absence of PPFFx. However, accuracy of the algorithm was attenuated when trying to predict a Vancouver classification subtype given the wide variability in surgeon dictation styles and precision of language. Nevertheless, this study provides a proof-of-concept for use of this technology in clinical research and registry development endeavors as it can reliably extract certain select data of interest in an expeditious and cost-effective manner. Summary. NLP-enabled algorithms are a promising alternative to the current gold standard of manual chart review for the extraction and evaluation of large data sets in orthopedics

Aims

Periprosthetic joint infections (PJIs) and fracture-related infections (FRIs) are associated with a significant risk of adverse events. However, there is a paucity of data on cardiac complications following revision surgery for PJI and FRI and how they impact overall mortality. Therefore, this study aimed to investigate the risk of perioperative myocardial injury (PMI) and mortality in this patient cohort.

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The aim of the HIPGEN consortium is to develop the first cell therapy product for hip fracture patients using PLacental-eXpanded (PLX-PAD) stromal cells.

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Bone turnover markers (BTMs) follow distinct trends after fractures and limited evidence suggests differential levels in BTMs in patients with delayed healing. The effect of vitamin D, and other factors that influence BTMs and fracture healing, is important to elucidate the use of BTMs as surrogates of fracture healing. We sought to determine whether BTMs can be used as early markers of delayed fracture healing, and the effect of vitamin D on BTM response after fracture.

Background and purpose of the study. Patients with sciatica experience high levels of disability and poor outcomes and treatment has demonstrated, at best, only modest success. To be effective, management strategies must be informed by patients' perceptions about ‘what matters’ about experiencing this condition. The aim of this paper is to explore the lived experience of sciatica and to consider the implications for clinical practice. Methods and results. In this qualitative study, based on the principles of interpretative phenomenological analysis, 14 participants with a clinical presentation of sciatica of likely nerve root origin were purposively recruited from an NHS, Primary Care Musculoskeletal Service in the UK. Individual, semi-structured interviews were used to collect data, which were audio-recorded and transcribed verbatim. Data were managed using a framework approach and analysed thematically. Sciatica was experienced as a protracted journey of acute exacerbations of uncontrolled and incapacitating symptoms that were overwhelming and difficult to make sense of. Adversely affecting almost all aspects of life, participants struggled to maintain their physical, functional and financial independence; their important relationships; social networks and the roles and activities that provided joy and purpose. The impact of sciatica was a ‘life on hold’; an altered sense of self and an uncertain future. For three participants, the experience of sciatica was sufficiently distressing for them to contemplate suicide. Conclusions. This paper reveals the severity and devastating impact of the symptoms and effects of sciatica. Important practice and research implications have been identified regarding managing symptoms and the need to align treatment strategies with patients' complex and multifaceted needs. Conflicts of interest: None. Funding acknowledgements: This study was funded by an NIHR Masters in Clinical Research Fellowship awarded to CR. LR is funded, in part, by an NIHR Senior Clinical Lecturer award (Round 3)

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Treatment for delayed wound healing resulting from peripheral vascular diseases and diabetic foot ulcers remains a challenge. A novel surgical technique named ‘tibial cortex transverse transport’ (TTT) has been developed for treating peripheral ischaemia, with encouraging clinical effects. However, its underlying mechanisms remain unclear. In the present study, we explored the potential biological mechanisms of TTT surgery using various techniques in a rat TTT animal model.

Background and purpose of the study. Uncertainty remains regarding the optimal method of diagnosing sciatica. Clinical guidelines currently recommend that investigations be used only when they are likely to change management. In clinical practice, considerable variation can occur between patient and clinician, regarding the perceived importance of investigations such as MRI scans. The aim of this study was to explore patients' experiences of investigations and to consider the impact of concordance between clinical presentation and investigation findings. Methods and results. In this qualitative study, based on the principles of interpretative phenomenological analysis, 14 participants with a clinical presentation of sciatica of likely nerve root origin, who had recently undergone investigations, were purposively recruited from an NHS, Primary Care Musculoskeletal Service in the UK. Individual, semi-structured interviews were used to collect data, which were audio-recorded and transcribed verbatim. Data were managed using a framework approach and analysed thematically. Although patients reported wanting investigations to understand the cause of symptoms and inform management, access to them was difficult and protracted. When investigations revealed potentially relevant findings, patients experienced relief, validation, empowerment and decisive decision-making. Disappointment emerged, however, regarding treatment waiting times and options, and long-term prognosis. When investigations failed to identify relevant findings, patients were unable to make sense of their symptoms, move forward in their management or relinquish their search to identify the cause. Conclusion. This study provides the first reported in-depth interpretation of patients' experience of undergoing investigations for sciatica. Important policy and practice implications have been identified for investigation referral criteria; shared-decision-making; information sharing; aligning expectations and managing disappointment. No conflicts of interest. This study was funded by an NIHR Masters in Clinical Research Fellowship awarded to CR. LR is funded, in part, by an NIHR Senior Clinical Lecturer award (Round 3)

Introduction. Despite decades of clinical research in artificial joints and underlying failure mechanisms, systematical and reproducible identification of reasons for complications in total knee replacements (TKR) remains difficult. Due to the complex dynamic interaction of implant system and biological situs, malfunction eventually leading to failure is multifactorial and remains not fully understood. The aim of present study was to evaluate different TKR designs and positions with regard to joint kinematics and stability under dynamic conditions by using a robot-based hardware-in-the-loop (HiL) setup. Material & methods. An industrial 6-axis robot with 6-axis force-torque sensor mounted into its end-effector moved and loaded real, commercially available TKR (bicondylar, cruciate-retaining) that were in virtual interaction with a subject-specific computational multibody model representing the anatomical situs of the knee joint while performing passive seated deep knee flexion. The subject-specific musculoskeletal multibody model (MMB) included rigid bones of the lower right extremity. Bone and cartilage geometries were reconstructed from MRT/ CT data sets preserving anatomical landmarks and allowing for the calculation of inertial properties. M. quadriceps femoris was modeled as single passive tensile force elements. Knee ligaments were modelled as elastic spring elements with a nonlinear force-displacement characteristic. Providing the flexion angle, the robot moved and loaded the mounted femoral implant component with respect to the tibial component while being in continuous interaction with the MMB. Several influencing parameters like implant position (internal/external rotation, varus/valgus alignment) and design (fixed vs. mobile bearing, tibia-insert height) as well as ligament insufficiency and joint loading on joint kinematics and stability was systematically analysed. Results. Improper implant positioning caused joint instability, which was demonstrated in higher magnitudes of the relative kinematics. Negative effects by incorrect implant positioning could be partially compensated by a mobile bearing design. However, this was accompanied with an increase in tibiofemoral contact forces. High correlation of tibia-insert height on ligament and contact force was found. After releasing ligament structures, lower tibiofemoral contact forces and joint opening during deep knee flexion were observed. Conclusion. By means of HiL simulation different clinical and technical parameters of TKR were evaluated in a systematical and reproducible fashion under physiological-like boundary conditions with regard to joint kinematics and stability. The proposed HiL test setup combining robot-based testing with MMBs can contribute to deeper understanding of knee joint function and improvement of total knee implant systems. Acknowledgement. The authors would like to thank the Deutsche Forschungsgemeinschaft (grant numbers: WO WO 452/8-1, BA 3347/3-1 and KL 2327/4-1) for supporting the project