Predictive Tool Use and Willingness for Surgery in Patients With Knee Osteoarthritis: A Randomized Clinical Trial.

Importance: Despite the increasing number of tools available to predict the outcomes of total knee arthroplasty (TKA), the effect of these predictive tools on patient decision-making remains uncertain. Objective: To assess the effect of an online predictive tool on patient-reported willingness to undergo TKA. Design, Setting, and Participants: This parallel, double-masked, 2-arm randomized clinical trial compared predictive tool use with treatment as usual (TAU). The study was conducted between June 30, 2022, and July 31, 2023. Participants were followed up for 6 months after enrollment. Participants were recruited from a major Australian private health insurance company and from the surgical waiting list for publicly funded TKA at a tertiary hospital. Eligible participants had unilateral knee osteoarthritis, were contemplating TKA, and had previously tried nonsurgical interventions, such as lifestyle modifications, physiotherapy, and pain medications. Intervention: The intervention group was provided access to an online predictive tool at the beginning of the study. This tool offered information regarding the likelihood of improvement in quality of life if patients chose to undergo TKA. The predictions were based on the patient's age, sex, and baseline symptoms. Conversely, the control group received TAU without access to the predictive tool. Main Outcomes and Measures: The primary outcome measure was the reduction in participants' willingness to undergo surgery at 6 months after tool use as measured by binomial logistic regression. Secondary outcome measures included participant treatment preference and the quality of their decision-making process as measured by the Knee Decision Quality Instrument. Results: Of 211 randomized participants (mean [SD] age, 65.8 [8.3] years; 118 female [55.9%]), 105 were allocated to the predictive tool group and 106 to the TAU group. After adjusting for baseline differences in willingness for surgery, the predictive tool did not significantly reduce the primary outcome of willingness for surgery at 6 months (adjusted odds ratio, 0.85; 95% CI, 0.42-1.71; P = .64). Conclusions and Relevance: Despite the absence of treatment effect on willingness for TKA, predictive tools might still enhance health outcomes of patients with knee osteoarthritis. Additional research is needed to optimize the design and implementation of predictive tools, address limitations, and fully understand their effect on the decision-making process in TKA. Trial Registration: ANZCTR.org.au Identifier: ACTRN12622000072718.

Radiotherapy versus limb-sparing surgery alone in low-grade soft-tissue sarcoma of the extremity and trunk wall: a systematic review and meta-analysis.

Current guidelines recommend the use of radiotherapy in the management of intermediate and high-grade soft-tissue sarcoma of the extremity and trunk wall. Its use in low-grade sarcoma is less clear. To date there have been no pooled data analyses regarding its role in this context. Its use is not without complications and therefore must be justified. We aim to assess the oncological impact of radiotherapy versus limb-sparing surgery alone in this subset of sarcoma. Medline, EMBASE and Cochrane's databases were searched from 1982 to present. Studies on or having a subgroup analysis of low-grade soft tissue sarcoma, with a radiotherapy and a surgery only arm were included. Outcomes included local recurrence and overall survival. Patients were at least 16 years of age with primary de-novo sarcoma who had not undergone prior resection or treatment. Those undergoing concomitant therapy were excluded. Data extraction was performed independently by two reviewers. Results were pooled using a random-effects model and presented as a forest plot. Primary outcome measures included local recurrence and overall survival. Eleven unique studies were included, consisting of two RCTs and nine non-randomized studies. Overall, there were 12 799 patients. Four studies were included in meta-analysis and the overall pooled effect showed a limited role of radiotherapy in overall survival outcomes when compared to limb-sparing surgery alone HR 1.00 [0.83-1.20] P = 0.41. Descriptive analysis suggests there is limited role of radiotherapy in improving local recurrence outcomes. This study suggests there is limited role for radiotherapy versus limb-sparing surgery alone in low-grade soft-tissue sarcoma. These findings strongly suggest there is lack of high-quality data and that further research must be undertaken prior to forming any strong conclusions regarding the management of low-grade soft-tissue sarcoma. Demonstrating a role for radiotherapy may help improve the quality of excisional margins and thus potentiate limb-sparing surgery.

Does a consumer co-designed infographic increase knowledge of physical activity after total knee joint replacement? A randomised controlled trial.

PURPOSE: To determine if a consumer co-designed infographic increased knowledge of physical activity and self-efficacy for exercise after total knee joint replacement surgery. METHODS: Forty-four adults with primary knee joint replacement surgery were recruited from a public and a private hospital in Melbourne, Australia. Participants were randomly allocated to an experimental or control group. The experimental group received a consumer co-designed infographic. All participants received usual care. Primary outcome measures were knowledge of physical activity and self-efficacy for exercise. Outcomes were administered at baseline, week 1 and week 6. Semi-structured interviews with experimental group participants explored the acceptability, implementation and efficacy of the infographic. RESULTS: There were no between-group differences for knowledge of physical activity at week 1 (MD -0.02 units, 95% CI -0.9 to 0.9) or week 6 (MD 0.01 units, 95% CI -0.9 to 0.9). Self-efficacy for exercise increased at week 1 (MD 14.2 units, 95% CI 2.9-25.4) but was not sustained. Qualitative data showed that the infographic was embraced by some participants but not by others. CONCLUSIONS: A consumer co-designed infographic did not improve knowledge of physical activity but may have had a short-term positive effect on self-efficacy for exercise after knee joint replacement. Trial registration ACTRN12621000910808.

Mortality, patient-reported outcome measures, and the health economic burden of prosthetic joint infection.

Prosthetic joint infection (PJI) is one of the most devastating complications for a patient following arthroplasty. This scoping review aims to evaluate the burden of PJI on individual patients and the healthcare system regarding the mortality rate, patient-reported quality of life, and healthcare resource utilisation. Patients with PJI have up to a five-fold higher mortality rate than those who have undergone an uninfected primary arthroplasty. There is an increased use of ambulatory aids and reduced joint function scores in patients with PJI. Global quality of life is poorer, specifically measured by the EQ-5D. Direct hospitalisation costs are two- to five-fold higher, attributed to surgery and prostheses, antibiotics, and a prolonged inpatient stay. There is an immense clinical and health economic burden secondary to PJI worldwide. This is expected to rise exponentially due to the increasing number of primary procedures and an ageing population with comorbidities Improving preventative and treatment strategies is imperative for patients and the healthcare system.

Patients' Views on AI for Risk Prediction in Shared Decision-Making for Knee Replacement Surgery: Qualitative Interview Study.

BACKGROUND: The use of artificial intelligence (AI) in decision-making around knee replacement surgery is increasing, and this technology holds promise to improve the prediction of patient outcomes. Ambiguity surrounds the definition of AI, and there are mixed views on its application in clinical settings. OBJECTIVE: In this study, we aimed to explore the understanding and attitudes of patients who underwent knee replacement surgery regarding AI in the context of risk prediction for shared clinical decision-making. METHODS: This qualitative study involved patients who underwent knee replacement surgery at a tertiary referral center for joint replacement surgery. The participants were selected based on their age and sex. Semistructured interviews explored the participants' understanding of AI and their opinions on its use in shared clinical decision-making. Data collection and reflexive thematic analyses were conducted concurrently. Recruitment continued until thematic saturation was achieved. RESULTS: Thematic saturation was achieved with 19 interviews and confirmed with 1 additional interview, resulting in 20 participants being interviewed (female participants: n=11, 55%; male participants: n=9, 45%; median age: 66 years). A total of 11 (55%) participants had a substantial postoperative complication. Three themes captured the participants' understanding of AI and their perceptions of its use in shared clinical decision-making. The theme Expectations captured the participants' views of themselves as individuals with the right to self-determination as they sought therapeutic solutions tailored to their circumstances, needs, and desires, including whether to use AI at all. The theme Empowerment highlighted the potential of AI to enable patients to develop realistic expectations and equip them with personalized risk information to discuss in shared decision-making conversations with the surgeon. The theme Partnership captured the importance of symbiosis between AI and clinicians because AI has varied levels of interpretability and understanding of human emotions and empathy. CONCLUSIONS: Patients who underwent knee replacement surgery in this study had varied levels of familiarity with AI and diverse conceptualizations of its definitions and capabilities. Educating patients about AI through nontechnical explanations and illustrative scenarios could help inform their decision to use it for risk prediction in the shared decision-making process with their surgeon. These findings could be used in the process of developing a questionnaire to ascertain the views of patients undergoing knee replacement surgery on the acceptability of AI in shared clinical decision-making. Future work could investigate the accuracy of this patient group's understanding of AI, beyond their familiarity with it, and how this influences their acceptance of its use. Surgeons may play a key role in finding a place for AI in the clinical setting as the uptake of this technology in health care continues to grow.

High ploidy large cytoplasmic megakaryocytes are hematopoietic stem cells regulators and essential for platelet production.

Megakaryocytes (MK) generate platelets. Recently, we and others, have reported MK also regulate hematopoietic stem cells (HSC). Here we show high ploidy large cytoplasmic megakaryocytes (LCM) are critical negative regulators of HSC and critical for platelet formation. Using a mouse knockout model (Pf4-Srsf3Δ/Δ) with normal MK numbers, but essentially devoid of LCM, we demonstrate a pronounced increase in BM HSC concurrent with endogenous mobilization and extramedullary hematopoiesis. Severe thrombocytopenia is observed in animals with diminished LCM, although there is no change in MK ploidy distribution, uncoupling endoreduplication and platelet production. When HSC isolated from a microenvironment essentially devoid of LCM reconstitute hematopoiesis in lethally irradiated mice, the absence of LCM increases HSC in BM, blood and spleen, and the recapitulation of thrombocytopenia. In contrast, following a competitive transplant using minimal numbers of WT HSC together with HSC from a microenvironment with diminished LCM, sufficient WT HSC-generated LCM regulates a normal HSC pool and prevents thrombocytopenia. Importantly, LCM are conserved in humans.

Research Buddy partnership in a MD-PhD program: lessons learned.

BACKGROUND AND AIMS: There is increasing recognition of the importance of patient involvement in research. In recent years, there has also been growing interest in patient partnerships with doctoral studies students. However, it can be difficult to know where to start and how to go about such involvement activities. The purpose of this perspective piece was to share experiential insight of the experience of a patient involvement program such that others can learn from this experience. BODY: This is a co-authored perspective piece centred on the experience of MGH, a patient who has had hip replacement surgery, and DG, a medical student completing a PhD, participating in a Research Buddy partnership over the course of over 3 years. The context in which this partnership took place was also described to facilitate comparison with readers' own circumstances and contexts. DG and MGH met regularly to discuss, and work together on, various aspects of DG's PhD research project. Reflexive thematic analysis was conducted on reflections from DG and MGH regarding their experience in the Research Buddy program to synthesise nine lessons which were then corroborated with reference to published literature on patient involvement in research. These lessons were: learn from experience; tailor the program; get involved early; embrace uniqueness; meet regularly; build rapport; ensure mutual benefit; broad involvement; regularly reflect and review. CONCLUSIONS: In this perspective piece, a patient and a medical student completing a PhD reflected upon their experience co-designing a Research Buddy partnership within a patient involvement program. A series of nine lessons was identified and presented to inform readers seeking to develop or enhance their own patient involvement programs. Researcher-patient rapport is foundational to all other aspects of the patient's involvement.

The importance of patient involvement in research is gaining recognition. Existing research centres, as well as those that are just getting started, need to find their own way to involve patients and community members. However, learning from the experience of others is crucial to ensure every effort is made to do this in a fruitful way. Therefore, we aimed to share our experience and provide a list of lessons learned to help other researchers and patients get started and work together effectively. Our research centre developed a framework for involving patients in joint replacement research. Part of this framework is a 'Research Buddy' program, where a research student partners with a patient so that the research they conduct is more relevant and applicable to the target population. In our case, the research student partnered with someone who had a hip replacement to develop and test a questionnaire for an interview study about artificial intelligence in shared decision-making. The student and patient worked together and wrote this perspective piece outlining nine lessons so readers can learn from their experience of this program. The lessons were: learn from experience, tailor the program, get involved early, embrace uniqueness, meet regularly, build rapport, ensure mutual benefit, broad involvement, regularly reflect and review. People interested in starting, or improving, their own patient involvement activities can learn from our experience. These lessons will need to be adapted to fit the purpose and unique situation of other researchers and patients who have different needs and circumstances.

Penetration of Vancomycin into Noninfected Bone in Patients Undergoing Total Joint Arthroplasty Evaluated by a Minimal Physiologically Based Population Pharmacokinetic Modeling Approach.

Arthroplasty is a healthcare priority and represents high volume, high cost surgery. Periprosthetic joint infection (PJI) results in significant mortality, thus it is vital that the risk for PJI is minimized. Vancomycin is recommended for surgical prophylaxis in total joint arthroplasty (TJA) by current clinical practice guidelines endorsed by the Infectious Diseases Society of America. This study aimed to develop a new assay to determine vancomycin concentrations in serum and bone, and a minimal physiologically based population PK (mPBPK) model to evaluate vancomycin bone penetration in noninfected patients. Eleven patients undergoing TJA received 0.5-2.0 g intravenous vancomycin over 12-150 min before surgery. Excised bone specimens and four blood samples were collected per patient. Bone samples were pulverized under liquid nitrogen using a cryogenic mill. Vancomycin concentrations in serum and bone were analyzed by liquid chromatography-tandem mass spectrometry and subjected to mPBPK modeling. Vancomycin serum and bone concentrations ranged from 9.30 to 86.6 mg/L, and 1.94-37.0 mg/L, respectively. Average bone to serum concentration ratio was 0.41 (0.16-1.0) based on the collected samples. The population mean total body clearance was 2.12L/h/kg0.75. Inclusion of total body weight as a covariate substantially decreased interindividual variability in clearance. The bone/blood partition coefficient (Kpbone) was estimated at 0.635, reflecting the average bone/blood concentration ratio at steady-state. The model predicted median ratio of vancomycin area under the curve (AUC) for bone/AUC for serum was 44%. Observed vancomycin concentrations in bone were overall consistent with perfusion-limited distribution from blood to bone. An mPBPK model overall well described vancomycin concentrations in serum and bone.

Total joint replacement may be a valuable treatment for Aboriginal and Torres Strait Islander people with osteoarthritis, but uptake is low.

BACKGROUND: Despite bearing a higher burden of osteoarthritis, little research has examined disparities in the access, utilisation and surgical outcomes associated with total joint replacement (TJR) among Aboriginal and Torres Strait Islander people. METHODS: We conducted a retrospective cohort study to compare the sociodemographic and clinical characteristics of all Aboriginal and Torres Strait Islander and non-Aboriginal patients who underwent primary hip and knee replacement at St Vincent's Hospital Melbourne between 1996 and 2019. RESULTS: A total of 10 277 primary total knee or hip replacements were performed in the 1996-2019 study period, of which 49 (0.5%) patients identified as either Aboriginal and/or Torres Strait Islander. Aboriginal and Torres Strait Islander patients were younger (61.7 ± 11.8 vs. 68.3 ± 10.3 years; P < 0.001), recorded higher Body Mass Index scores (median (IQR), 36.0 (29.5-41.4) vs. 30.8 (27.0-35.3); P < 0.001) and were more likely to experience multiple co-morbidities at the time of surgery. Despite these findings, Aboriginal and Torres Strait Islander patients did not experience higher complication rates and experienced comparable, clinically meaningful quality of life improvements 12-months post-surgery. CONCLUSIONS: TJR appears to be a valuable treatment option for Aboriginal and Torres Strait Islander people with end-stage osteoarthritis. Our study was limited by the small number of procedures conducted in patients who identify as Aboriginal and Torres Strait Islander. Further research is needed to understand why uptake of TJR by Aboriginal and Torres Strait Islander people is low.

No consistent association between patient-reported outcome measures and coronal alignment following total knee arthroplasty: a narrative review.

BACKGROUND: Total knee arthroplasty is a common procedure for treating knee conditions; however, significant proportions of patients report dissatisfaction post-operatively. Recent data suggests accurate coronal alignment may not be essential for optimizing prosthesis functionality and survivorship. This narrative review utilized a systematic approach to analyse the literature comparing post-operative coronal alignment and PROMs following knee replacement. METHODS: A systematic search of MEDLINE was utilized to identify publications that directly compare the relationship between coronal alignment and PROMs. RESULTS: Thirty-one eligible publications were identified. Variability in both study design and findings were observed, with no studies being without risk of bias. CONCLUSION: Given this variability and lack of consensus among the reported publications, current literature is ill-equipped to describe the exact nature of the relationship between coronal alignment and PROMs following TKA. Further research would ideally utilize both validated generic, and knee-specific PROMs, make use of pre-operative outcome data, and standardized follow-up to develop reliable assessments of coronal alignment and its impact upon both functionality and quality of life.

A Nomogram for Predicting Non-Response to Surgery One Year after Elective Total Hip Replacement.

Background: Total hip replacement (THR) is a common and cost-effective procedure for end-stage osteoarthritis, but inappropriate utilization may be devaluing its true impact. The purpose of this study was to develop and test the internal validity of a prognostic algorithm for predicting the probability of non-response to THR surgery at 1 year. Methods: Analysis of outcome data extracted from an institutional registry of individuals (N = 2177) following elective THR performed between January 2012 and December 2019. OMERACT-OARSI responder criteria were applied to Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain and function scores at pre- and 1 year post-THR, to determine non-response to surgery. Independent prognostic correlates of post-operative non-response observed in adjusted modelling were then used to develop a nomogram. Results: A total of 194 (8.9%) cases were deemed non-responders to THR. The degree of contribution (OR, 95% CI) of each explanatory factor to non-response on the nomogram was, morbid obesity (1.88, 1.16, 3.05), Kellgren−Lawrence grade <4 (1.89, 1.39, 2.56), WOMAC Global rating per 10 units (0.86, 0.79, 0.94) and the following co-morbidities: cerebrovascular disease (2.39, 1.33, 4.30), chronic pulmonary disease (1.64; 1.00, 2.71), connective tissue disease (1.99, 1.17, 3.39), diabetes (1.86, 1.26, 2.75) and liver disease (2.28, 0.99, 5.27). The concordance index for the nomogram was 0.70. Conclusion: We have developed a prognostic nomogram to calculate the probability of non-response to THR surgery. In doing so, we determined that both the probability of and predictive prognostic factors for non-response to THR differed from a previously developed nomogram for total knee replacement (TKR), confirming the benefit of designing decision support tools that are both condition and surgery site specific. Future external validation of the nomogram is required to confirm its generalisability.

Metastatic giant cell tumour of bone: a narrative review of management options and approaches.

Giant cell tumour of bone (GCTB) is a locally aggressive bone neoplasm with a rare tendency to metastasise, most commonly to the lungs. The management of metastatic GCTB (metGCTB) is controversial due to its unpredictable behaviour. Asymptomatic patients should be monitored radiologically and undergo treatment only when disease progression occurs. Surgery is recommended for resectable metGCTB. Denosumab, a monoclonal antibody which inhibits receptor activator of nuclear factor-κB ligand, is recommended for unresectable metGCTB with evidence from phase II trials demonstrating its safety and efficacy. Relapse after denosumab withdrawal may occur and prolonged treatment may be associated with serious adverse events, thus further research is warranted to inform a maintenance regimen with reduced dosing and frequency. Combined denosumab and bisphosphonate therapy has the potential to achieve sustained disease control or remission in unresectable metGCTB without requiring long-term treatment and should be evaluated in prospective trials. Various novel agents have demonstrated in vitro and anecdotal efficacy and warrant further evaluation.

Low grade of radiographic osteoarthritis predicts unsatisfactory response of the contralateral knee replacement in two-stage bilateral total knee arthroplasty.

PURPOSE: It is difficult to counsel patients with bilateral osteoarthritis who are unsatisfied with their first knee replacement as to whether they are likely to have a better outcome after the contralateral knee is replaced. The purpose of this study was to determine whether predictive factors can be found to prognosticate outcome of the second-side knee replacement when a patient has an unsatisfactory response to the first, with the hypothesis that predictors, such as prosthetic factors and radiographic level of osteoarthritis, may be able to predict a satisfactory response to the contralateral knee replacement. MATERIALS AND METHODS: An analysis of staged bilateral knee replacements performed at a tertiary arthroplasty centre from 2012 to 2018 was undertaken. A total of 550 knee replacements in 275 patients were included in this study. The primary variable measured was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. Satisfactory response to surgery was defined as a WOMAC score improved by 17 points or more, and 56 or greater. Patients who did not achieve a satisfactory response with their first knee replacement were further analysed for predictive factors (age, sex, pre-operative score, mental score, socioeconomic status, type of prosthesis, use of navigation, patella resurfacing and radiographic osteoarthritis) of an unsatisfactory response for their contralateral knee replacement. RESULTS: Overall, 44 (16%) patients failed to achieve a satisfactory response from both their first and contralateral knee replacements. The factor most predictive of an unsatisfactory response to their first knee replacement was pre-operative mental health score. However, in patients who did not achieve a satisfactory response with their first knee replacement, radiographic osteoarthritis, as measured by the Kellgren-Lawrence (KL) score was the main predictor of satisfactory response for their contralateral knee replacement. Only patients with KL grade 4 osteoarthritis were likely to have a satisfactory response with their contralateral knee replacements (KL4 versus KL3, Odds ratio 3.57 (CI 1.26-10.03) p = 0.016*). Patients with KL grade 3 osteoarthritis were unlikely to have a satisfactory response, and in this series, no patient with KL grade 2 osteoarthritis had a satisfactory response. CONCLUSION: In a patient who has an unsatisfactory response to their first knee replacement, the best predictor of achieving a satisfactory response to his/her contralateral knee replacement is the level of radiographic osteoarthritis in that knee. LEVEL OF EVIDENCE: IV: Retrospective Cohort study.

Matured Myofibers in Bioprinted Constructs with In Vivo Vascularization and Innervation.

For decades, the study of tissue-engineered skeletal muscle has been driven by a clinical need to treat neuromuscular diseases and volumetric muscle loss. The in vitro fabrication of muscle offers the opportunity to test drug-and cell-based therapies, to study disease processes, and to perhaps, one day, serve as a muscle graft for reconstructive surgery. This study developed a biofabrication technique to engineer muscle for research and clinical applications. A bioprinting protocol was established to deliver primary mouse myoblasts in a gelatin methacryloyl (GelMA) bioink, which was implanted in an in vivo chamber in a nude rat model. For the first time, this work demonstrated the phenomenon of myoblast migration through the bioprinted GelMA scaffold with cells spontaneously forming fibers on the surface of the material. This enabled advanced maturation and facilitated the connection between incoming vessels and nerve axons in vivo without the hindrance of a scaffold material. Immunohistochemistry revealed the hallmarks of tissue maturity with sarcomeric striations and peripherally placed nuclei in the organized bundles of muscle fibers. Such engineered muscle autografts could, with further structural development, eventually be used for surgical reconstructive purposes while the methodology presented here specifically has wide applications for in vitro and in vivo neuromuscular function and disease modelling.

Life or limb: an international qualitative study on decision making in sarcoma surgery during the COVID-19 pandemic.

OBJECTIVES: The COVID-19 pandemic is unprecedented as a global crisis over the last century. How do specialist surgeons make decisions about patient care in these unprecedent times? DESIGN: Between April and May 2020, we conducted an international qualitative study. Sarcoma surgeons from diverse global settings participated in 60 min interviews exploring surgical decision making during COVID-19. Interview data were analysed using an inductive thematic analysis approach. SETTING: Participants represented public and private hospitals in 14 countries, in different phases of the first wave of the pandemic: Australia, Argentina, Canada, India, Italy, Japan, Nigeria, Singapore, Spain, South Africa, Switzerland, Turkey, UK and USA. PARTICIPANTS: From 22 invited sarcoma surgeons, 18 surgeons participated. Participants had an average of 19 years experience as a sarcoma surgeon. RESULTS: 17/18 participants described a decision they had made about patient care since the start of the pandemic that was unique to them, that is, without precedence. Common to 'unique' decisions about patient care was uncertainty about what was going on and what would happen in the future (theme 1: the context of uncertainty), the impact of the pandemic on resources or threat of the pandemic to overwhelm resources (theme 2: limited resources), perceived increased risk to self (theme 3: duty of care) and least-worst decision making, in which none of the options were perceived as ideal and participants settled on the least-worst option at that point in time (theme 4: least-worst decision making). CONCLUSIONS: In the context of rapidly changing standards of justice and beneficence in patient care, traditional decision-making frameworks may no longer apply. Based on the experiences of surgeons in this study, we describe a framework of least-worst decision making. This framework gives rise to actionable strategies that can support decision making in sarcoma and other specialised fields of surgery, both during the current crisis and beyond.

Circulating tumor DNA for malignant peripheral nerve sheath tumors in neurofibromatosis type 1.

PURPOSE: The leading cause of early death in patients with neurofibromatosis type 1 (NF1) is malignant peripheral nerve sheath tumor (MPNST). The principles of management include early diagnosis, surgical clearance and close monitoring for tumor recurrence. Current methods for diagnosis, detection of residual disease and monitoring tumor burden are inadequate, as clinical and radiological features are non-specific for malignancy in patients with multiple tumors and lack the sensitivity to identify early evidence of malignant transformation or tumor recurrence. Circulating tumor DNA (ctDNA) is a promising tool in cancer management and has the potential to improve the care of patients with NF1. In the following article we summarise the current understanding of the genomic landscape of MPNST, report on the previous literature of ctDNA in MPNST and outline the potential clinical applications for ctDNA in NF1 associated MPNST. Finally, we describe our prospective cohort study protocol investigating the utility of using ctDNA as an early diagnostic tool for MPNSTs in NF1 patients.

The need for improved patient reported outcome measures in patients with extremity sarcoma: a narrative review.

BACKGROUND: Extremity sarcoma causes impairments to functionality and quality of life. Patient-reported outcome measures (PROMS) assess patient perspectives relating to domains of health and quality of life. METHODS: To describe PROMs utilised in extremity sarcoma, the available literature was screened for studies that utilised PROMs to evaluate outcomes in extremity sarcoma following surgery. RESULTS: Seventy articles met eligibility criteria; six PROMs were identified. The Toronto Extremity Salvage Score, The Short-Form 36, The EORTC QLQ-C30, The Disabilities of the Arm, Shoulder and Hand questionnaire, the Reintegration to Normal Living index and the Patient-Reported Outcomes Measurement Information System. Most sarcoma patients score well in these tools, with bone sarcoma, and extent of resection being predictors of poor outcomes. CONCLUSION: TESS is the only sarcoma-specific PROM, and though a valid assessment of functionality, it has difficulty differentiating patients with minor functional impairments. The absence of a disease-specific measure of health is concerning, as generic tools do not account for the unique experiences sarcoma patients face and may impair their accuracy in analysing intervention effectiveness.

The Impact of Enhanced Recovery After Surgery on Total Joint Arthroplasty: Protocol for a Systematic Review and Meta-analysis.

BACKGROUND: The number of total joint arthroplasties (TJAs) being performed is increasing worldwide. To match this increasing demand, there has been focus on hastening patients' recovery of function. This effort has culminated in the formulation of enhanced recovery after surgery (ERAS) strategies. However, with evolving ERAS programs and new recommendations, a review of current evidence is required to provide clinicians with up-to-date information about its effect on outcomes for TJA. OBJECTIVE: The objective of this study is to assess the utility of ERAS programs on patient, health service, and economic outcomes for primary, elective total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: A systematic search will be conducted in Medline (Ovid), EMCARE (Ovid), EMBASE (Ovid), Web of Science, CINAHL, National Health Service Economic Evaluations Database, and the Cochrane Library. Analytical, observational, and experimental designs will be included in this systematic review. Only studies including patients undergoing primary TKA and THA comparing ERAS programs with conventional surgery and postoperative care will be included. Data related to patient outcomes, health service outcomes, safety, and economic evaluation will be extracted. RESULTS: The search terms and primary database searches have been finalized. Findings will be reported in narrative and tabular form. Where appropriate, random effects meta-analyses will be conducted for each outcome, and heterogeneity quantified with Cochran Q test and I2 statistic. Measures of effect or mean differences will be reported with 95% confidence intervals. The results of this systematic review will be disseminated in a peer-reviewed journal. CONCLUSIONS: This protocol will guide a systematic review assessing outcomes associated with ERAS surgery in primary THA and TKA. TRIAL REGISTRATION: Open Science Framework osf.io/y4bhs; https://osf.io/y4bhs. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/25581.

Addressing surgical inequity for Aboriginal and Torres Strait Islander people in Australia's universal health care system: a call to action.

Aboriginal and Torres Strait Islander people continue to experience health inequity within the Australian health care system. Little research has examined how disparities in surgical care access and outcomes contribute to Aboriginal health. In this narrative review and call to action, we discuss five care points along the journey to high-quality surgical care: health care seeking, primary health care services, specialist services, surgery and surgical outcomes. We highlight barriers and disparities that exist along this journey, drawing examples from the field of joint replacement surgery. Finally, we present opportunities for change at the health system, health service and clinician level, calling upon researchers, clinicians and policy makers to confront the surgical disparities experienced by Aboriginal and Torres Strait Islander people.

Placebo Surgery Controlled Trials: Do They Achieve What They Set Out To Do? A Systematic Review.

OBJECTIVE: To explore whether placebo surgery controlled trials achieve what they set out to do by investigating discrepancy between projected and actual design aspects of trials identified through systematic review methods. SUMMARY BACKGROUND: Interest in placebo surgery controlled trials is growing in response to concerns regarding unnecessary surgery and the societal cost of low-value healthcare. As questions about the justifiability of using placebo controls in surgery have been addressed, attention is now being paid to more practical concerns. METHODS: Six databases were searched from inception - May 2020 (MEDLINE, Embase, Emcare, APA PsycInfo, CINAHL, Cochrane Library). Placebo surgery controlled trials with a published protocol were included. Three authors extracted "projected" design aspects from protocols and "actual" design aspects from main findings papers. Absolute and relative difference between projected and actual design aspects were presented for each trial. Trials were grouped according to whether they met their target sample size ("completed") and were concluded in a timely fashion. Pairs of authors assessed risk of bias. RESULTS: Of 24 trials with data available to analyse; 3 were completed and concluded within target timeframe; 10 were completed and concluded outside the target timeline; 4 were completed without clear target timeframes; 2 were incomplete and concluded within the target framework; 5 were incomplete and concluded outside the target timeline. Trials which reached the recruitment target underestimated trial duration by 88% and number of recruitment sites by 87%. CONCLUSIONS: Trialists need to factor additional time and sites into future placebo surgery controlled trials. A robust reporting framework of projected and actual trial design is imperative for trialists to learn from their predecessors. REVIEW REGISTRATION: PROSPERO (CRD42019133296).