Aims. To identify unanswered questions about the prevention, diagnosis, treatment, and rehabilitation and delivery of care of first-time soft-tissue knee injuries (ligament injuries, patella dislocations, meniscal injuries, and articular cartilage) in children (aged 12 years and older) and adults. Methods. The James Lind Alliance (JLA) methodology for Priority Setting Partnerships was followed. An initial survey invited patients and healthcare professionals from the UK to submit any uncertainties regarding soft-tissue knee injury prevention, diagnosis, treatment, and rehabilitation and delivery of care. Over 1,000 questions were received. From these, 74 questions (identifying common concerns) were formulated and checked against the best available evidence. An interim survey was then conducted and 27 questions were taken forward to the final workshop, held in January 2023, where they were discussed, ranked, and scored in multiple rounds of prioritization. This was conducted by healthcare professionals, patients, and carers. Results. The top ten included questions regarding prevention, diagnosis, treatment, and rehabilitation. The number one question was, ‘How urgently do soft-tissue knee injuries need to be treated for the best outcome?’. This reflects the concerns of patients, carers, and the wider multidisciplinary team. Conclusion. This validated process has generated ten important priorities for future soft-tissue knee injury research. These have been submitted to the National Institute for Health and Care Research. All 27 questions in the final workshop have been published on the JLA website. Cite this article: Bone Joint J 2024;106-B(3):232–239

The kinematic alignment (KA) approach to total knee arthroplasty (TKA) has recently increased in popularity. Accordingly, a number of derivatives have arisen and have caused confusion. Clarification is therefore needed for a better understanding of KA-TKA. Calipered (or true, pure) KA is performed by cutting the bone parallel to the articular surface, compensating for cartilage wear. In soft-tissue respecting KA, the tibial cutting surface is decided parallel to the femoral cutting surface (or trial component) with in-line traction. These approaches are categorized as unrestricted KA because there is no consideration of leg alignment or component orientation. Restricted KA is an approach where the periarthritic joint surface is replicated within a safe range, due to concerns about extreme alignments that have been considered ‘alignment outliers’ in the neutral mechanical alignment approach. More recently, functional alignment and inverse kinematic alignment have been advocated, where bone cuts are made following intraoperative planning, using intraoperative measurements acquired with computer assistance to fulfill good coordination of soft-tissue balance and alignment. The KA-TKA approach aims to restore the patients’ own harmony of three knee elements (morphology, soft-tissue balance, and alignment) and eventually the patients’ own kinematics. The respective approaches start from different points corresponding to one of the elements, yet each aim for the same goal, although the existing implants and techniques have not yet perfectly fulfilled that goal

Aims. Complex joint fractures of the lower extremity are often accompanied by soft-tissue swelling and are associated with prolonged hospitalization and soft-tissue complications. The aim of the study was to evaluate the effect of vascular impulse technology (VIT) on soft-tissue conditioning in comparison with conventional elevation. Methods. A total of 100 patients were included in this prospective, randomized, controlled monocentre study allocated to the three subgroups of dislocated ankle fracture (n = 40), pilon fracture (n = 20), and intra-articular calcaneal fracture (n = 40). Patients were randomized to the two study groups in a 1:1 ratio. The effectiveness of VIT (intervention) compared with elevation (control) was analyzed separately for the whole study population and for the three subgroups. The primary endpoint was the time from admission until operability (in days). Results. The mean length of time until operability was 8.2 days (SD 3.0) in the intervention group and 10.2 days (SD 3.7) in the control group across all three fractures groups combined (p = 0.004). An analysis of the subgroups revealed that a significant reduction in the time to operability was achieved in two of the three: with 8.6 days (SD 2.2) versus 10.6 days (SD 3.6) in ankle fractures (p = 0.043), 9.8 days (SD 4.1) versus 12.5 days (SD 5.1) in pilon fractures (p = 0.205), and 7.0 days (SD 2.6) versus 8.4 days (SD 1.5) in calcaneal fractures (p = 0.043). A lower length of stay (p = 0.007), a reduction in pain (p. preop. = 0.05; p. discharge. < 0.001) and need for narcotics (p. preop. = 0.064; p. postop. = 0.072), an increased reduction in swelling (p < 0.001), and a lower revision rate (p = 0.044) could also be seen, and a trend towards fewer complications (p = 0.216) became apparent. Conclusion. Compared with elevation, VIT results in a significant reduction in the time to achieve operability in complex joint fractures of the lower limb. Cite this article: Bone Joint J 2021;103-B(4):746–754

Aims. The primary objective of this study was to develop a validated classification system for assessing iatrogenic bone trauma and soft-tissue injury during total hip arthroplasty (THA). The secondary objective was to compare macroscopic bone trauma and soft-tissues injury in conventional THA (CO THA) versus robotic arm-assisted THA (RO THA) using this classification system. Methods. This study included 30 CO THAs versus 30 RO THAs performed by a single surgeon. Intraoperative photographs of the osseous acetabulum and periacetabular soft-tissues were obtained prior to implantation of the acetabular component, which were used to develop the proposed classification system. Interobserver and intraobserver variabilities of the proposed classification system were assessed. Results. The BOne trauma and Soft-Tissue Injury classification system in total Hip arthroplasty (BOSTI Hip) grades osseous acetabular trauma and periarticular muscle damage during THA. The classification system has an interclass correlation coefficient of 0.90 (95% CI 0.86 to 0.93) for interobserver agreement and 0.89 (95% CI 0.84 to 0.93) for intraobserver agreement. RO THA was associated with improved BOSTI Hip scores (p = 0.002) and more pristine osseous surfaces in the anterior superior (p = 0.001) and posterior superior (p < 0.001) acetabular quadrants compared with CO THA. There were no differences between the groups in relation to injury to the gluteus medius (p = 0.084), obturator internus (p = 0.241), piriformis (p = 0.081), superior gamellus (p = 0.116), inferior gamellus (p = 0.132), quadratus femoris (p = 0.208), and vastus lateralis (p = 0.135), but overall combined muscle injury was reduced in RO THA compared with CO THA (p = 0.023). Discussion. The proposed BOSTI Hip classification provides a reproducible grading system for stratifying iatrogenic bone trauma and soft-tissue injury during THA. RO THA was associated with improved BOSTI Hip scores, more pristine osseous acetabular surfaces, and reduced combined periarticular muscle injury compared with CO THA. Further research is required to understand if these intraoperative findings translate to differences in clinical outcomes between the treatment groups. Cite this article: Bone Joint J 2024;106-B(9):898–906

Aims. The aim of this study was to determine the rate of indocyanine green (ICG) staining of bone and soft-tissue tumours, as well as the stability and accuracy of ICG fluorescence imaging in detecting tumour residuals during surgery for bone and soft-tissue tumours. Methods. ICG fluorescence imaging was performed during surgery in 34 patients with bone and soft-tissue tumours. ICG was administered intravenously at a dose of 2 mg/kg over a period of 60 minutes on the day prior to surgery. The tumour stain rate and signal-to-background ratio of each tumour were post hoc analyzed. After tumour resection, the tumour bed was scanned to locate sites with fluorescence residuals, which were subsequently inspected and biopsied. Results. The overall tumour stain rate was 88% (30/34 patients), and specific stain rates included 90% for osteosarcomas and 92% for giant cell tumours. For malignant tumours, the overall stain rate was 94%, while it was 82% for benign tumours. The ICG tumour stain was not influenced by different pathologies, such as malignant versus benign pathology, the reception (or lack thereof) of neoadjuvant chemotherapies, the length of time between drug administration and surgery, the number of doses of denosumab for patients with giant cell tumours, or the tumour response to neoadjuvant chemotherapy. The overall accuracy rate of successfully predicting tumour residuals using fluorescence was 49% (23/47 pieces of tissue). The accuracy rate after en bloc resection was significantly lower than that after piecemeal resection (16% vs 71%; p < 0.001). Conclusion. A high percentage of bone and soft-tissue tumours can be stained by ICG and the tumour staining with ICG was stable. This approach can be used in both benign and malignant tumours, regardless of whether neoadjuvant chemotherapy is adopted. The technique is also useful to detect tumour residuals in the wound, especially in patients undergoing piecemeal resection. Cite this article: Bone Joint J 2023;105-B(5):551–558

Aims. Intraoperative pressure sensors allow surgeons to quantify soft-tissue balance during total knee arthroplasty (TKA). The aim of this study was to determine whether using sensors to achieve soft-tissue balance was more effective than manual balancing in improving outcomes in TKA. Methods. A multicentre randomized trial compared the outcomes of sensor balancing (SB) with manual balancing (MB) in 250 patients (285 TKAs). The primary outcome measure was the mean difference in the four Knee injury and Osteoarthritis Outcome Score subscales (ΔKOOS. 4. ) in the two groups, comparing the preoperative and two-year scores. Secondary outcomes included intraoperative balance data, additional patient-reported outcome measures (PROMs), and functional measures. Results. There was no significant difference in ΔKOOS. 4. between the two groups at two years (mean difference 0.4 points (95% confidence interval (CI) -4.6 to 5.4); p = 0.869), and multiple regression found that SB was not associated with a significant ΔKOOS. 4. (0.2-point increase (95% CI -5.1 to 4.6); p = 0.924). There were no significant differences between groups in other PROMs. Six-minute walking distance was significantly increased in the SB group (mean difference 29 metres; p = 0.015). Four-times as many TKAs were unbalanced in the MB group (36.8% MB vs 9.4% SB; p < 0.001). Irrespective of group assignment, no differences were found in any PROM when increasing ICPD thresholds defined balance. Conclusion. Despite improved quantitative soft-tissue balance, the use of sensors intraoperatively did not differentially improve the clinical or functional outcomes two years after TKA. These results question whether a more precisely balanced TKA that is guided by sensor data, and often achieved by more balancing interventions, will ultimately have a significant effect on clinical outcomes. Cite this article: Bone Joint J 2022;104-B(5):604–612

Aims. Total knee arthroplasty (TKA) using functional alignment aims to implant the components with minimal compromise of the soft-tissue envelope by restoring the plane and obliquity of the non-arthritic joint. The objective of this study was to determine the effect of TKA with functional alignment on mediolateral soft-tissue balance as assessed using intraoperative sensor-guided technology. Methods. This prospective study included 30 consecutive patients undergoing robotic-assisted TKA using the Stryker PS Triathlon implant with functional alignment. Intraoperative soft-tissue balance was assessed using sensor-guided technology after definitive component implantation; soft-tissue balance was defined as intercompartmental pressure difference (ICPD) of < 15 psi. Medial and lateral compartment pressures were recorded at 10°, 45°, and 90° of knee flexion. This study included 18 females (60%) and 12 males (40%) with a mean age of 65.2 years (SD 9.3). Mean preoperative hip-knee-ankle deformity was 6.3° varus (SD 2.7°). Results. TKA with functional alignment achieved balanced medial and lateral compartment pressures at 10° (25.0 psi (SD 6.1) vs 23.1 psi (SD 6.7), respectively; p = 0.140), 45° (21.4 psi (SD 5.9) vs 20.6 psi (SD 5.9), respectively; p = 0.510), and 90° (21.2 psi (SD 7.1) vs 21.6 psi (SD 9.0), respectively; p = 0.800) of knee flexion. Mean ICPD was 6.1 psi (SD 4.5; 0 to 14) at 10°, 5.4 psi (SD 3.9; 0 to 12) at 45°, and 4.9 psi (SD 4.45; 0 to 15) at 90° of knee flexion. Mean postoperative limb alignment was 2.2° varus (SD 1.0°). Conclusion. TKA using the functional alignment achieves balanced mediolateral soft-tissue tension through the arc of knee flexion as assessed using intraoperative pressure-sensor technology. Further clinical trials are required to determine if TKA with functional alignment translates to improvements in patient satisfaction and outcomes compared to conventional alignment techniques. Cite this article: Bone Joint J 2021;103-B(3):507–514

Prediction tools are instruments which are commonly used to estimate the prognosis in oncology and facilitate clinical decision-making in a more personalized manner. Their popularity is shown by the increasing numbers of prediction tools, which have been described in the medical literature. Many of these tools have been shown to be useful in the field of soft-tissue sarcoma of the extremities (eSTS). In this annotation, we aim to provide an overview of the available prediction tools for eSTS, provide an approach for clinicians to evaluate the performance and usefulness of the available tools for their own patients, and discuss their possible applications in the management of patients with an eSTS. Cite this article: Bone Joint J 2022;104-B(9):1011–1016

Aims. The aim of this study was to identify factors associated with five-year cancer-related mortality in patients with limb and trunk soft-tissue sarcoma (STS) and develop and validate machine learning algorithms in order to predict five-year cancer-related mortality in these patients. Methods. Demographic, clinicopathological, and treatment variables of limb and trunk STS patients in the Surveillance, Epidemiology, and End Results Program (SEER) database from 2004 to 2017 were analyzed. Multivariable logistic regression was used to determine factors significantly associated with five-year cancer-related mortality. Various machine learning models were developed and compared using area under the curve (AUC), calibration, and decision curve analysis. The model that performed best on the SEER testing data was further assessed to determine the variables most important in its predictive capacity. This model was externally validated using our institutional dataset. Results. A total of 13,646 patients with STS from the SEER database were included, of whom 35.9% experienced five-year cancer-related mortality. The random forest model performed the best overall and identified tumour size as the most important variable when predicting mortality in patients with STS, followed by M stage, histological subtype, age, and surgical excision. Each variable was significant in logistic regression. External validation yielded an AUC of 0.752. Conclusion. This study identified clinically important variables associated with five-year cancer-related mortality in patients with limb and trunk STS, and developed a predictive model that demonstrated good accuracy and predictability. Orthopaedic oncologists may use these findings to further risk-stratify their patients and recommend an optimal course of treatment. Cite this article: Bone Joint J 2023;105-B(6):702–710

Aims. Current literature suggests that survival outcomes and local recurrence rates of primary soft-tissue sarcoma diagnosed in the very elderly age range, (over 90 years), are comparable with those in patients diagnosed under the age of 75 years. Our aim is to quantify these outcomes with a view to rationalizing management and follow-up for very elderly patients. Methods. Retrospective access to our prospectively maintained oncology database yielded a cohort of 48 patients across 23 years with a median follow-up of 12 months (0 to 78) and mean age at diagnosis of 92 years (90 to 99). Overall, 42 of 48 of 48 patients (87.5%) were managed surgically with either limb salvage or amputation. Results. A lower overall local recurrence rate (LRR) was seen with primary amputations compared with limb salvage (p > 0.050). The LRR was comparable between free (R0), microscopically (R1), and macroscopically positive (R2) resection margins in the limb salvage group. Amputation was also associated with longer survival times (p < 0.050). Overall median survival time was limited to 20 months (0 to 80). Conclusion. Early and aggressive treatment with appropriate oncological surgery confers the lowest LRR and a survival advantage versus conservative treatment in this cohort of patients. With limited survival, follow-up can be rationalized on a patient-by-patient basis using alternative means, such as GP, local oncology, and/or patient-led follow-up. Cite this article: Bone Joint J 2022;104-B(1):177–182

Aim. Fracture-related infection (FRI) is a severe post-traumatic complication which can be accompanied with a soft-tissue defect or an avital soft-tissue envelope. In these cases, a thoroughly planned orthoplastic approach is imperative since a vital soft-tissue envelope is mandatory to achieve fracture union and infection eradication. The aim of our study was to analyse plastic surgical aspects in the management of FRIs, including the type and outcome of soft-tissue reconstruction (STR), and to investigate the long-term outcome of FRI after STR. Method. Patients with a lower leg FRI requiring STR that were treated from 2010 to 2018 at our center were included in this retrospective analysis. STR involved the use of local, pedicled and free flaps. The primary outcome was the success rate of STR, and the secondary outcome was long-term fracture consolidation and cure of infection. Results. Overall, 145 patients with lower leg FRI were identified, of whom 58 (40%) received STR. Muscle flaps were applied in 38, fascio-cutaneous flaps in 19 and a composite osteo-cutaneous flap in one case. All patients underwent successful STR (primary STR in 51/58 patients, 7/58 patients needed secondary STR). A high Charlson Comorbidity Index Score was a significant risk factor for flap failure (p=0.011). Patients with free-flap STR developed significantly more severe complications and needed more surgical interventions (Clavien-Dindo ≥IIIa; p=0.001). Out of the 43 patients that completed long-term follow-up (mean 24 months), fracture consolidation was achieved in 32 and infection eradication in 31. Polymicrobial infection was a significant risk factor for fracture non-union (p=0.002). American Society of Anesthesiologists (ASA) classification of 3 or higher (p=0.040) was a risk factor for persistence or recurrence of infection. Conclusions. In our population, 58/145 patients with FRI required STR. STR was successful in all patients eventually, in 7/58 patients secondary STR was necessary. Therefore, STR should be sought even if primary STR fails. Despite successful STR, the long-term composite outcome showed a high rate of failed fracture consolidation and failed eradication of infection, which was independent of primary STR failure

Aim. Reconstruction of composite soft-tissue defects with extensor apparatus deficiency in patients with periprosthetic joint infection (PJI) of the knee is challenging. We present a single-centre multidisciplinary orthoplastic treatment concept based on a retrospective outcome analysis over 20 years. Method. One-hundred sixty-seven patients had PJI after total knee arthroplasty. Plastic surgical reconstruction of a concomitant perigenicular soft-tissue defect was indicated in 49 patients. Of these, seven presented with extensor apparatus deficiency. Results. One patient underwent primary arthrodesis and six patients underwent autologous reconstruction of the extensor apparatus. The principle to reconstruct missing tissue ‘like with like’ was thereby favoured: Two patients with a wide soft-tissue defect received a free anterolateral thigh flap with fascia lata; one patient with a smaller soft-tissue defect received a free sensate, extended lateral arm flap with triceps tendon; and three patients received a pedicled medial sural artery perforator gastrocnemius flap, of which one with Achilles tendon. Despite good functional results 1 year later, long-term follow-up revealed that two patients had to undergo knee arthrodesis because of recurrent infection and one patient was lost to follow-up. In parts, results have been published under doi: 10.7150/jbji.47018. Conclusions. A treatment concept and its rationale, based on a single-centre experience, is presented. It differentiates between various types of soft-tissue defects and shows reconstructive options following the concept to reconstruct ‘like with like’. Despite good results 1 year postoperatively, PJI of the knee with extensor apparatus deficiency remains a dreaded combination with a poor long-term outcome

In our database of 7935 patients referred for investigation of a soft-tissue mass, only 100 were found to have a soft-tissue metastasis (1.3%). Our aim was to define the clinical features of such patients and to identify the site of their primary tumour. The most common presentation was a painful lump, deep to the fascia, ranging between 2 cm and 35 cm (mean 8.3 cm) with 78% of the lumps located deep to the fascia. The mean age of the patients at presentation was 64 years (22 to 84) and there were almost equal numbers of men and women. Of 53 patients with a history of malignancy, 52 had metastases from the same primary (lung in 12, melanoma in ten, kidney in nine, gastrointestinal track in four, breast in five, bladder in four, and others in eight). The other 47 had no history of malignancy and the metastasis was the first presentation. The primary sites in these cases were the lung in 19, gastro-intestinal track in four, kidney in two, melanoma in nine, other in three, and unknown (despite investigations) in ten. There was no correlation between the site of the metastases and the primary tumour. Of the 7935 patients, 516 had a history of malignancy. Of these, only 10% had a soft-tissue metastasis, 29% had a benign diagnosis, 55% a soft-tissue sarcoma and 6% another malignancy. Patients with soft-tissue metastases have similar clinical features to those with soft-tissue sarcomas and should be considered for assessment at appropriate diagnostic centres for patients with suspicious soft-tissue lumps

Aims. The aim of this study was to evaluate the surgical management and outcome of patients with an acral soft-tissue sarcoma of the hand or foot. Patients and Methods. We identified 63 patients with an acral soft-tissue sarcoma who presented to our tertiary referral sarcoma service between 2000 and 2016. There were 35 men and 28 women with a mean age of 49 years (. sd. 21). Of the 63 sarcomas, 27 were in the hands and 36 in the feet. The commonest subtypes were epithelioid sarcoma in the hand (n = 8) and synovial sarcoma in the foot (n = 11). Results. In 41 patients (65%), the tumour measured less than 5 cm in its largest dimension (median size 3 cm (٢ to ٦)); 27 patients (43%) were diagnosed after inadvertent excision prior to their referral to the specialist sarcoma unit. After biopsy and staging, primary surgical intervention at the sarcoma unit was excision and limb salvage in 43 (68%), partial (digit or ray) amputation in 14 (22%), and more proximal amputation in six (10%). At final follow up, local recurrence had been treated by one partial amputation and six amputations, resulting in a partial amputation rate of 24% and a proximal amputation rate of 19%. The five-year survival rate was 82%. Patients who underwent inadvertent excision showed no statistically significant difference in survival or local recurrence, but were more likely to undergo amputation (p = 0.008). Large tumour size (> 5 cm) was associated with lower survival (p = 0.04) and a higher risk of local recurrence (p = ٠.٠٠٩). Conclusion. Most acral soft-tissue sarcomas measure less than 5 cm at presentation, indicating that while size can be a useful prognostic factor, it should not be used as a diagnostic threshold for referral. Increased tumour size is associated with a higher rate of local recurrence and reduced survival. Sarcoma excision with limb preservation does not result in an increased risk of local recurrence. Cite this article: Bone Joint J 2018;100-B:1518–23

Introduction/Aim. Mid-flexion instability is a well-documented, but often poorly understood cause of failure of TKA. NAVIO robotic-assisted TKA (RA-TKA) offers a novel, integrative approach as a planning, execution as well as an evaluation tool in TKA surgery. RA-TKA provides a hybrid planning technique of measured resection and gap balancing- generating a predictive soft-tissue balance model, prior to making cuts. Concurrently, the system uses a semi-active robot to facilitate both the execution and verification of the plan, as it pertains to both the static and dynamic anatomy. The goal of this study was to assess the ability of the NAVIO RA-TKA to plan, execute and deliver an individualized approach to the soft-tissue balance of the knee, specifically in the “mid-flexion” arc of motion. Materials and Methods. Between May and September 2018, 50 patients underwent NAVIO RA-TKA. Baseline demographics were collected, including age, gender, BMI, and range of motion. The NAVIO imageless technique was used to plan the procedure, including: surface-mapping of the static anatomy; objective assessment of the dynamic, soft-tissue anatomy; and then application of a hybrid of measured-resection and gap-balancing technique. Medial and lateral gaps as predicted by the software were recorded throughout the entire arc of motion at 15° increments. After executing the plan and placing the components, actual medial and lateral gaps were recorded throughout the arc of motion. Results. In the assessment of coronal-plane balance, the average deviation from the predicted plan between 0–90° was 0.9mm in both the medial and lateral compartments (range 0.5–1.2mm). In the mid-flexion arc (15–75°), final soft-tissue stability was within 1.0mm of the predictive plan (range 0.9–1.2mm). Discussion/Conclusions. In this study, NAVIO RA-TKA demonstrated a highly accurate and reproducible surgical technique to plan, execute and verify a balanced a soft-tissue envelope in TKA. Objective soft-tissue balancing of the TKA can now be performed, including the mid-flexion arc of motion. Further analysis can determine if these objective measurements will translate into improved patient-reported outcome scores

Aims. Surgical site infection (SSI) after soft-tissue sarcoma (STS) resection is a serious complication. The purpose of this retrospective study was to investigate the risk factors for SSI after STS resection, and to develop a nomogram that allows patient-specific risk assessment. Methods. A total of 547 patients with STS who underwent tumour resection between 2005 and 2021 were divided into a development cohort and a validation cohort. In the development cohort of 402 patients, the least absolute shrinkage and selection operator (LASSO) regression model was used to screen possible risk factors of SSI. To select risk factors and construct the prediction nomogram, multivariate logistic regression was used. The predictive power of the nomogram was evaluated by receiver operating curve (ROC) analysis in the validation cohort of 145 patients. Results. LASSO regression analysis selected possible risk factors for SSI, including age, diabetes, operating time, skin graft or flap, resected tumour size, smoking, and radiation therapy. Multivariate analysis revealed that age, diabetes, smoking during the previous year, operating time, and radiation therapy were independent risk factors for SSI. A nomogram was developed based on the results of multivariate logistic regression analysis. In the development cohort, the incidence of SSI was 4.5% in the low-risk group (risk score < 6.89) and 26.6% in the high-risk group (risk score ≥ 6.89; p < 0.001). In the validation cohort, the incidence of SSI was 2.0% in the low-risk group and 15.9% in the high-risk group (p = 0.004). Conclusion. Our nomogram will enable surgeons to assess the risk of SSI in patients with STS. In patients with high risk of SSI, frequent monitoring and aggressive interventions should be considered to prevent this. Cite this article: Bone Joint J 2024;106-B(5):492–500

Introduction. Autologous fat grafting has favourable potential as a regenerative strategy and is the current gold-standard to repair large contour defects, as needed in breast reconstruction after mastectomy and traumatic soft tissue reconstruction. Clinically, there is a limit on the volume of lipoaspirate which can be utilised to repair a soft-tissue defect. Surgical complications are the result of poor structural fidelity of lipoaspirate and graft resorption as a filling material and are hindered further by poor graft vascularisation. This study aims to develop injectable lipoaspirate-derived adipose tissue grafts with enhanced biologically and clinically-admissible structural and functional properties adopting light photocrosslinking of unmodified lipoaspirate. Methods. Patient-derived lipoaspirate was harvested and crosslinked using novel photoinitiator and exposure to visible light (wavelength 450nm) in surgery, establishing bonds between extracellular matrix (ECM) proteins within the material. The degree of crosslinking was tuned (photoinitiator concentration, light exposure, light intensity) and covalent bond formation measured using mass spectrometry. To predict patient response, SWATH-MS was used to identify differences in patient ECM and crosslinked grafts were implanted in vivo using a subcutaneous mouse model. Functional vessel formation and resorption were quantified using micro-CT and tissue-remodelling was assessed via histology. Results. There was an increase in the relative abundance of covalent bonds present with increasing degree of crosslinking. When injected, crosslinked lipoaspirate had better shape fidelity compared with native lipoaspirate – demonstrated by a smaller fibre diameter. Crosslinked lipoaspirate remained viable over long term culture and resulted in more predictable resorption profiles when implanted in vivo. Conclusions. The crosslinking approach described here is tunable and functional across different patient samples. Improving the structural properties of lipoaspirate through minimal manipulation has clinical utility for the delivery of grafts with higher shape fidelity and therefore increased graft survival when implanted

Aims. Time to treatment initiation (TTI) is generally defined as the time from the histological diagnosis of malignancy to the initiation of first definitive treatment. There is no consensus on the impact of TTI on the overall survival in patients with a soft-tissue sarcoma. The purpose of this study was to determine if an increased TTI is associated with overall survival in patients with a soft-tissue sarcoma, and to identify the factors associated with a prolonged TTI. Methods. We identified 23,786 patients from the National Cancer Database who had undergone definitive surgery between 2004 and 2015 for a localized high-grade soft-tissue sarcoma of the limbs or trunk. A Cox proportional hazards model was used to examine the relationship between a number of factors and overall survival. We calculated the incidence rate ratio (IRR) using negative binomial regression models to identify the factors that affected TTI. Results. Patients in whom the time to treatment initiation was prolonged had poorer overall survival than those with a TTI of 0 to 30 days. These were: 31 to 60 days (hazard ratio (HR) 1.08, p = 0.011); 61 to 90 days (HR 1.11, p = 0.044); and 91 days (HR 1.22; p = 0.003). The restricted cubic spline showed that the hazard ratio increased substantially with a TTI longer than 50 days. Non-academic centres (vs academic centres; IRR ranging from 0.64 to 0.86; p < 0.001) had a shorter TTI. Those insured by Medicaid (vs private insurance; IRR 1.34), were uninsured (vs private insurance; IRR 1.17), or underwent a transition in care (IRR 1.62) had a longer TTI. Conclusion. A time to treatment initiation of more than 30 days after diagnosis was independently associated with poorer survival. The hazard ratio showed linear increase, especially if the TTI was more than 50 days. We recommend starting treatment within 30 days of diagnosis to achieve the highest likelihood of cure for localized high-grade soft-tissue sarcomas in the limbs and trunk, even when a patient needs to be referred to a specialist centre. Cite this article: Bone Joint J 2021;103-B(6):1142–1149

Aims. Cell-free DNA (cfDNA) and circulating tumour DNA (ctDNA) are used for prognostication and monitoring in patients with carcinomas, but their utility is unclear in sarcomas. The objectives of this pilot study were to explore the prognostic significance of cfDNA and investigate whether tumour-specific alterations can be detected in the circulation of sarcoma patients. Methods. Matched tumour and blood were collected from 64 sarcoma patients (n = 70 samples) prior to resection of the primary tumour (n = 57) or disease recurrence (n = 7). DNA was isolated from plasma, quantified, and analyzed for cfDNA. A subset of cases (n = 6) underwent whole exome sequencing to identify tumour-specific alterations used to detect ctDNA using digital droplet polymerase chain reaction (ddPCR). Results. Cell-free was present in 69 of 70 samples above 0.5 ng/ml. Improved disease-free survival was found for patients with lower cfDNA levels (90% vs 48% at one-year for ≤ 6 ng/ml and > 6 ng/ml, respectively; p = 0.005). Digital droplet PCR was performed as a pilot study and mutant alleles were detectable at 0.5% to 2.5% of the wild type genome, and at a level of 0.25 ng tumour DNA. Tumour-specific alterations (ctDNA) were found in five of six cases. Conclusion. This work demonstrates the feasibility and potential utility of cfDNA and ctDNA as biomarkers for bone and soft-tissue sarcomas, despite the lack of recurrent genomic alterations. A larger study is required to validate these findings. Cite this article: Bone Joint Res 2021;10(9):602–610

Aims. Urgent referral to a specialist centre for patients with a soft-tissue sarcoma (STS) has been recommended by the National Institute for Health and Care Excellence (NICE) in the UK since 2006. However, the impact of this recommendation on the prognosis for these patients remains unclear. We aimed to determine the impact of the NICE guidelines on the disease-specific survival (DSS) of patients with an STS. Methods. A total of 2,427 patients with an STS referred to a supraregional centre in the ten-year periods before (n = 1,386) and after (n = 1,041) the issue of the NICE guidelines were evaluated. Results. The mean size of the tumour was significantly smaller at the time of diagnosis (10.3 cm (SD 6.5) vs 9.1 cm (SD 6.2); p < 0.001) and the number of patients who had undergone an inadvertent excision significantly decreased (28% (n = 389) vs 20% (n = 204); p < 0.001) following the introduction of the NICE guidelines. The five-year DSS was 63% in the pre-NICE and 71% in post-NICE groups (p < 0.001). The improved survival was more significant for those with a high-grade tumour (pre-NICE, 48%; post-NICE, 68%; p < 0.001). In those with a high-grade tumour, the mean size of the tumour (11.6 cm (SD 6.2) vs 9.6 cm (SD 5.8); p < 0.001) and the number of patients with metastasis at the time of diagnosis (15% (n = 124 vs 10% (n = 80); p = 0.007) significantly decreased in the post-NICE group. Conclusion. An improvement in survival was seen after the introduction of the NICE guidelines, especially in patients with a high-grade STS. More patients were referred at an earlier stage, indicating a clearer pathway after the issue of national policy for the management of STSs in the UK. Cite this article: Bone Joint J 2021;103-B(3):569–577