Current guidelines suggest that most lumps less than 5cm in size will not be malignant. We reviewed our experiences of small lumps at the Royal Orthopaedic Hospital, Birmingham, in order to try and identify factors associated with malignancy. All referrals to our clinic were included and data on size, symptoms, depth and diagnosis were analysed. We identified 325 patients, with 57 (17.5%) malignant and 268 (82.5%) benign lumps. Size >3cm was the most accurate predictor of malignancy (35.8% malignant vs 9.9% <3cm). 23.6% of lumps reported as increasing size were found to be malignant, compared to 8.6% of those that were not. Pain was found to be a poor predictor of malignancy, with only 15.5% of painful lumps found to be malignant and 18.9% of painless lumps found to be malignant. ‘Size >3cm’ has a sensitivity of 73.6% and a specificity of 56.3%, ‘Depth’ has a sensitivity of 73.6% and a specificity of 30.2%, ‘Increasing in Size’ a sensitivity of 71.4% and a specificity of 56.7% and ‘Pain’ a sensitivity of 33.3% and a specificity of 57.1%. If a lump has none of the above features then one can be 89.5% certain that it is not malignant. If it has 1 feature there is a 16.1% chance of its becoming malignant, 2 features a 58% chance, 3 features an 87% chance and if a lump has all 4 features there is a 93.5% chance of its being found to be malignant. The main limitation with this study is that the data set is skewed because all lumps referred to the Oncology Department are by their nature suspicious. This study identifies those factors which suggest malignancy in small lumps and provides the basis for carrying out a large, community-based study on all lumps, to identify features associated with malignancy

Introduction:. 25% of patients with an unknown primary tumour present to the orthopaedic surgeon with skeletal metastases. The onus is on the orthopaedic surgeon to establish the diagnosis, not only to decrease the patient's anxiety but also because the median survival increases from 6–9 months to 23 months when the primary is identified and allows for specific cancer treatment. The diagnostic work up of an unknown primary includes a multitude of special investigations. Since PET/CT has high sensitivity and specificity for detecting the primary tumours, we asked the question: Can you diagnose the unknown primary in patients with skeletal metastases with a PET/CT?. Method:. We included all PET/CT scans done in our institution between 2010 and 2013 for patients with malignancies known to metastasize to bone (melanoma, breast, lung, head and neck, GIT, other) and all scans done in patients with unknown primaries. After reviewing 686 PET/CT scans, 492 showed metastatic disease, with 78 of these having either spinal or skeletal metastases. Results:. Of these 78 patients, 68 primaries could be detected on the PET/CT scan. Thus the PET/CT detected the primary in 87% of cases. This number could possibly be higher as some were melanoma and breast cancer patients who had already undergone surgical resection. The most common primary detected was lung, followed by a group of other and unknown primaries which included cervical, kidney and thyroid carcinoma. Conclusion:. PET/CT scan is a good modality to use when looking for a primary malignancy in patients who present to the orthopaedic surgeon with bone metastases. We postulate that this might be a possible first line investigation when looking for the primary

Aim. Patient quality of life (QoL) in untreated bone infection was compared to other chronic conditions and stratified by disease severity. Method. Patients referred for treatment of osteomyelitis (including fracture related infection) were identified prospectively between 2019 and 2023. Patients with confirmed infection completed the EuroQol EQ-5D-5L questionnaire. Clinicians blinded to EQ-index score, grouped patients according to JS-BACH Classification into ‘Uncomplicated’, ‘Complex’ or ‘Limited treatment options’. A systematic review of the literature was performed of other conditions that have been stratified using EQ-index score. Results. 257 patients were referred, and 219 had suspected osteomyelitis. 196 patients had long bone infection and reported an average EQ-index score of 0.455 (SD 0.343). 23 patients with pelvic osteomyelitis had an average EQ-index score of 0.098 (SD 0.308). Compared to other chronic conditions, patients with long-bone osteomyelitis had worse QoL when compared to different types of malignancy (including bladder, oropharyngeal, colorectal, thyroid and myeloma), cardiorespiratory disease (including asthma, COPD and ischaemic heart disease), psychiatric conditions (including depression, pain and anxiety), endocrine disorders (including diabetes mellitus), neurological conditions (including Parkinson's disease, chronic pain and radiculopathy) and musculoskeletal conditions (including osteogenesis imperfecta, fibrous dysplasia and x-linked hypophosphataemic rickets). QoL in long-bone infection was similar to conditions such as Prada-Willi syndrome, Crohn's disease and juvenile idiopathic arthritis. Patients who had a history of stroke or multiple sclerosis reported worse QoL scores compared to long-bone infection. Patients who had pelvic osteomyelitis gave significantly lower QoL scores when compared to all other conditions that were available for comparison in the literature. In long bone infection, 41 cases (21.0%) were classified as ‘Uncomplicated’, 136 (69.4%) as ‘Complex’ and 19 (9.7%) as ‘Limited treatment options available’. Within classification stratification, patients with ‘Uncomplicated’ long bone infections reported a mean EQ-index score of 0.618 (SD 0.227) which was significantly higher compared to ‘Complex’ (EQ-index: 0.410 SD 0.359, p=0.004) and ‘Limited treatment options available’ (EQ-index: 0.400 SD 0.346, p=0.007). Conclusions. Bone and joint infections have a significant impact on patient quality of life. It is much worse when compared to other common chronic conditions, including malignancy, cardiovascular and neurological diseases. This has not been previously reported but may focus attention on the need for more investment in this patient group

Aim. A substantial portion of periprosthetic joint infections (PJI) literature is comprised of observational studies. The Strengthening the Reporting of Observational Studies in Epidemiology guidelines emphasize the importance of clearly defining variables and providing diagnostic criteria. Well-defined variables in these studies play a crucial role in ensuring data consistency, fostering comparability among studies, and laying a robust foundation for evidence-based decision-making. We aimed to determine the definition of these variables and determine the objectivity of the definitions. Method. We reviewed observational studies on hip or knee PJI that focused on variables and their association with treatment outcomes. The inclusion criteria comprised studies from Jan 2017 to Jan 2023. We focused on 13 variables that were possibly subjective. These were smoking, alcohol use, diabetes mellitus, hypertension, lung disease, rheumatoid arthritis, liver diseases, kidney diseases, cardiovascular diseases, malignancy, immunosuppression, use of antibiotics, and type of infection. The reviewers examined the text of the articles, along with any available online supplements or protocols, for definitions of the selected variables. We classified a definition as objective if there was the presence of time element, severity, staging, frequencies, laboratory cut-off, medication dependence, among others. Chart review was deemed subjective. Results. We included 75 studies in the analysis. The most common factors studied were diabetes mellitus (79%), cardiovascular disease, smoking history, and rheumatoid arthritis (47% each). The variables that were objectively defined most often were antibiotic use (100%) and type of infection (95%). Smoking history (16%) and alcohol use (20%) were the least frequently objectively defined variables. Further analysis revealed that a considerable number of studies incorporated variables into their primary analyses without clear definitions. For instance, out of the 59 studies where diabetes was considered a variable, 41 studies (70%) included diabetes in their main analyses as a factor for PJI treatment outcomes, despite only 34 studies having defined this variable. Moreover, of the 34 provided definitions of diabetes mellitus, only 12 provided objective criteria for diagnosis. The rest of the provided definitions relied on “chart review” without further specification. Table 1 outlines the proportion of studies with variables defined and included in their analysis. Conclusions. Study variables were not clearly defined in most of the observational studies raising concerns about the reproducibility and reliability of findings. Our study underscores the vital need for standardized variable definitions in PJI research. Professional societies may play a crucial role in setting standards for the definition of variables. For any tables or figures, please contact the authors directly

Thrombelastography (TEG) is a point-of-care tool that can measure clot formation and breakdown using a whole blood sample. We have previously used serial TEG analysis to define hypercoagulability and increased venous thromboembolism (VTE) risk following a major fracture requiring surgical treatment. Additionally, we have used serial TEG analysis to quantify the prolonged hypercoagulable state and increased VTE risk that ensues following a hip fracture. Recently developed cartridge-based platelet mapping (PLM) using TEG analysis can be used to activate platelets at either the adenosine diphosphate (ADP) receptor or at the Thromboxane A2 (AA) receptor, in order to evaluate clot strength when platelets are activated only through those specific receptors. This study aim was to evaluate platelet contribution to hypercoagulability, in order to identify potential therapeutic targets for VTE prevention. We hypothesized that there would be a platelet-predominant contribution to hypercoagulability following a hip fracture. Patients aged 50 years or older with a hip fracture treated surgically were enrolled in this prospective cohort study. Exclusion criteria were: prior history of VTE, active malignancy, or pre-injury therapeutic dose anticoagulation. Serial TEG and PLM analyses were performed at admission, post-operative day (POD) 1, 3, 5, 7 and at 2-, 4-, 6- and 12-weeks post-operatively. All patients received thromboprophylaxis with low molecular weight heparin (LMWH) for 28 days post-operatively. Hypercoagulability was defined as maximal amplitude (MA; a measure of clot strength) over 65mm based on TEG analysis. Independent samples t-tests were used to compare MA values with this previously established threshold and a mixed effects linear regression model was used to compare MA values over time. Independent samples t-tests and Chi-sqaured analyses were used to compare between the surgical fixation and arthroplasty groups. Forty-six patients with an acute hip fracture were included, with a mean age of 77.1 (SD = 10.6) years, with 61% (N=11) being female. Twenty-six were treated with arthroplasty (56.5%), while the remainder underwent surgical fixation of their hip fractures. TEG analysis demonstrated post-operative hypercoagulability (mean MA over 65mm) at all follow-up timepoints until 12-weeks. PLM identified a platelet-mediated hypercoagulable state based on elevated ADP-MA and AA-MA, with more pronounced platelet contribution demonstrated by the AA pathway. Patients treated with arthroplasty had significantly increased AA-MA compared with ADP-MA at POD 3 and at the 12-week follow-up. Thrombelastography can be used to identify hypercoagulability and increased risk for VTE following a hip fracture. Platelet mapping analysis from this pilot study suggests a platelet-mediated hypercoagulable state that may benefit from thromboprophylaxis using an anti-platelet agent that specifically targets the AA platelet activation pathway, such as acetylsalicylic acid (ASA). This research also supports differences in hypercoagulability between patients treated with arthroplasty compared to those who undergo fracture fixation

The presence of metastatic bone disease (MBD) often necessitates major orthopaedic surgery. Patients will enter surgical care either through emergent or electively scheduled care pathways. Patients in a pain crisis or with an acute fracture are generally admitted via emergent care pathways whereas patients with identified high-risk bone lesions are often booked for urgent yet scheduled elective procedures. The purpose of this study is to compare the post-operative outcomes of patients who present through emergent or electively scheduled care pathways in patients in a Canadian health care system. We have conducted a retrospective, multicenter cohort study of all patients presenting for surgery for MBD of the femur, humerus, tibia or pelvis in southern Alberta between 2006 and 2021. Patients were identified by a search query of all patients with a diagnosis of metastatic cancer who underwent surgery for an impending or actual pathologic fracture in the Calgary, South and Central Alberta Zones. Subsequent chart reviews were performed. Emergent surgeries were defined by patients admitted to hospital via urgent care mechanisms and managed via unscheduled surgical bookings (“on call list”). Elective surgeries were defined by patients seen by an orthopaedic surgeon at least once prior to surgery, and booked for a scheduled urgent, yet elective procedure. Outcomes include overall survival from the time of surgery, hospital length of stay, and 30-day hospital readmission rate. We have identified 402 patients to date for inclusion. 273 patients (67.9%) underwent surgery through emergent pathways and 129 patients (32.1%) were treated through urgent, electively scheduled pathways. Lung, prostate, renal cell, and breast cancer were the most common primary malignancies and there was no significant difference in these primaries amongst the groups (p=0.06). Not surprisingly, emergent patients were more likely to be treated for a pathologic fracture (p<0.001) whereas elective patients were more likely to be treated for an impending fracture (p<0.001). Overall survival was significantly shorter in the emergent group (5.0 months, 95%CI: 4.0-6.1) compared to the elective group (14.9 months 95%CI: 10.4-24.6) [p<0.001]. Hospital length of stay was significantly longer in the emergent group (13 days, 95%CI: 12-16 versus 5 days, 95%CI: 5-7 days). There was a significantly greater rate of 30-day hospital readmission in the emergent group (13.3% versus 7.8%) [p=0.01]. Electively managed MBD has multiple benefits including longer post-operative survival, shorter length of hospital stay, and a lower rate of 30-day hospital readmission. These findings from a Canadian healthcare system demonstrate clinical value in providing elective orthopaedic care when possible for patients with MBD. Furthermore, care delivery interventions capable of decreasing the footprint of emergent surgery through enhanced screening or follow-up of patients with MBD has the potential to significantly improve clinical outcomes in this population. This is an ongoing study that will justify refinements to the current surgical care pathways for MBD in order to identify patients prior to emergent presentation. Future directions will evaluate the costs associated with each care delivery method to provide opportunity for health economic efficiencies

Metastatic bone disease (MBD) is a significant contributor to diminished quality of life in cancer patients, often leading to pathologic fractures, hypercalcaemia, intractable bone pain, and reduced functional independence. Standard of care management for MBD patients undergoing orthopaedic surgery is multi-disciplinary, includes regular surgical follow-up, case by case assessment for use of bone protective medications, and post-operative radiation therapy to the operative site. The number of patients in southern Alberta receiving standard of care post-operative management is currently unclear. Our aim is to develop a database of all patients in southern Alberta undergoing orthopaedic surgery for MBD and to assess for deficiencies and opportunities to ensure standard of care for this complex patient population. Patients were identified for database inclusion by a search query of the Alberta Cancer Registry of all patients with a diagnosis of metastatic cancer who underwent surgery for an impending or pathologic fracture in the Calgary, South and Central Alberta Zones. Demographic information, primary cancer history, previous local and systemic treatments, anatomical location of MBD event(s), surgical fixation techniques, and post-operative care details were collected. The rate of standard of care post-operative treatment was evaluated. A comparison of outcomes between tertiary urban centres and rural centres was also completed. Survival was calculated from time of first operation to date of death. Univariate and multivariate analyses were performed to identify the impact of post-operative care variables on survival amongst patients surviving longer than one month. We identified 402 patients who have undergone surgical treatment for MBD in southern Alberta from 2006-2018. Median age at time of surgery was 66.3 years and 52.7% of patients were female. Breast, lung, prostate, renal cell and multiple myeloma were the most common primary malignancies (n=328, 81.6%). Median post-operative survival was 6.8 months (95%CI: 5.7-8.3). 203 patients (52.5%) were treated with post-operative radiotherapy and 159 patients (50.8%) had post-operative surgical follow-up. Only 39 patients (11.3%) received bone protective agents in the peri-operative period. On multivariate survival analysis, post-operative surgical follow-up was associated with improved survival (p<0.001). Patients were treated at nine hospitals across southern Alberta with most patients treated in an urban center (65.9%). Post-operative survival was significantly longer amongst patients treated in an urban center (9.0 months, 95%CI: 6.9-12.3 versus 4.3 months, 95%CI: 3.4-5.6, p<0.001). The burden of MBD is significant and increasing. With treatment occurring at multiple provincial sites, there is a need for standardized, primary disease-specific peri- and post-operative protocols to ensure quality and efficacious patient care. To provide evidence informed treatment recommendations, we have developed a database of all patients in southern Alberta undergoing orthopaedic surgery for MBD. Our results demonstrate that many patients were not treated according to post-operative standard of care recommendations. Notably, half of the included patients did not have documented surgical follow-up, post-operative radiation treatment was low and only 11% were actively treated with bone protective agents. This data justifies the need for established surgical MBD care pathways and provides reference data to benchmark prospective QA and QI outcomes in this patient population

Major orthopaedic fractures are an independent risk factor for the development of venous thromboembolism (VTE), which are significant causes of preventable morbidity and mortality in trauma patients. Despite thromboprophylaxis, patients who sustain a pelvic or acetabular fracture (PA) continue to have high rates of VTE (12% incidence). Thrombelastography (TEG) is a whole-blood, point-of-care test which provides an overview of the clotting process. Maximal amplitude (MA), from TEG analysis, is the measure of clot strength and values ≥65mm have been used to quantify hypercoagulability and increased VTE risk. Therefore, the primary aim was to use serial TEG analysis to quantify the duration of hypercoagulability, following surgically treated PA fractures. This is a single centre, prospective cohort study of adult patients 18 years or older with surgically treated PA fractures. Consecutive patients were enrolled from a Level I trauma centre and blood draws were taken over a 3-month follow-up period for serial TEG analysis. Hypercoagulability was defined as MA ≥65mm. Exclusion criteria: bleeding disorders, active malignancy, current therapeutic anticoagulation, burns (>20% of body surface) and currently, or expecting to become pregnant within study timeframe. Serial TEG analysis was performed using a TEG6s hemostasis analyzer (Haemonetics Corp.) upon admission, pre-operatively, on post-operative day (POD) 1, 3, 5, 7 (or until discharged from hospital, whichever comes sooner), then in follow-up at 2-, 4-, 6-weeks and 3-months post-operatively. Patients received standardized thromboprophylaxis with low molecular weight heparin for 28 days post-operatively. VTE was defined as symptomatic DVT or PE, or asymptomatic proximal DVT, and all participants underwent a screening post-operative lower extremity Doppler ultrasound on POD3. Descriptive statistics were used to determine the association between VTE events and MA values. For the primary outcome measure, the difference between the MA threshold value (≥65mm) and serial MA measures, were compared using one-sided t-tests (α=0.05). Twenty-eight patients (eight females, 29%) with a mean age of 48±18 years were included. Acetabular fractures were sustained by 13 patients (46%), pelvic fractures by 14 patients (50%), and one patient sustained both. On POD1, seven patients (25%) were hypercoagulable, with 21 patients (78%) being hypercoagulable by POD3, and 17 patients (85%) by POD5. The highest average MA values (71.7±3.9mm) occurred on POD7, where eight patients (89%) were hypercoagulable. At 2-weeks post-operatively, 16 patients (94%) were hypercoagulable, and at four weeks, when thromboprophylaxis was discontinued, six patients (40%) remained hypercoagulable. Hypercoagulability persisted for five patients (25%) at 6-weeks and for two patients (10%) by three months. There were six objectively diagnosed VTE events (21.4%), five were symptomatic, with a mean MA value of 69.3mm±4.3mm at the time of diagnosis. Of the VTE events, four occurred in participants with acetabular fractures (three male, 75%) and two in those with pelvic fractures (both males). At 4-weeks post-operatively, when thromboprophylaxis is discontinued, 40% of patients remained hypercoagulable and likely at increased risk for VTE. At 3-months post-operatively, 10% of the cohort continued to be hypercoagulable. Serial TEG analysis warrants further study to help predict VTE risk and to inform clinical recommendations following PA fractures

Surgical management for acute or impending pathologic fractures in metastatic bone disease (MBD) places patients at high-risk for post-operative venous thromboembolism (VTE). Due to the combination of malignancy, systemic cancer treatment, and surgical treatment, VTE-risk is increased 7-fold in patients with MBD compared to non-cancer patients undergoing the same procedure. The extent and duration of post-operative hypercoagulability in patients with MBD remains unknown and thromboprophylaxis guidelines were developed for non-cancer patients, limiting their applicability to address the elevated VTE-risk in cancer patients. Thrombelastography (TEG) analysis is a point-of-care test that measures clot formation, stabilization, and lysis in whole blood samples. The TEG parameter, maximal amplitude (MA), indicates clot strength and the threshold of ≥65 mm has been used to define hypercoagulability and predict VTE events in non-cancer patients requiring orthopaedic surgery. Therefore, this study aims to quantify the extent and duration of post-operative hypercoagulability in patients with MBD using serial TEG analysis. Consecutive adults (≥18 years) with MBD who required orthopaedic surgery for acute or impending pathologic fractures were enrolled into this single-centre, prospective cohort study. Serial TEG analysis was performed onsite using a TEG®6s haemostasis analyzer (Haemonetics Corporation, Boston, MA) on whole blood samples collected at seven timepoints: pre-operatively; on post-operative day (POD) 1, 3, and 5; and at 2-, 6-, and 12-weeks post-operatively. Hypercoagulability was defined as MA ≥65 mm. Participants received standardized thromboprophylaxis for four weeks and patient-reported compliance with thromboprophylaxis was recorded. VTE was defined as symptomatic DVT or PE, or asymptomatic proximal DVT, and all participants underwent a screening post-operative lower extremity Doppler ultrasound on POD3. Descriptive statistics were performed and difference between pre-operative MA values of participants with VTE versus no VTE was evaluated using Student's t-test (p≤0.05). Twenty-one participants (10 female; 47.6%) with a mean age of 70 ± 12 years were enrolled. Nine different primary cancers were identified amongst participants, with breast (23.8%), colorectal (19.0%), and lung cancer (14.3%) most frequently reported. Most participants (57.1%) were hypercoagulable pre-operatively, and nearly half remained hypercoagulable at 6- and 12-weeks post-operatively (47.1 and 46.7%, respectively). VTE occurred in 5 patients (23.8%) and mean MA was 68.1 ± 4.6 mm at the time of diagnosis. Mean pre-operative MA values were significantly higher (p=0.02) in patients who experienced VTE (68.9 ± 3.5 mm) compared to those who did not (62.7 ± 6.5 mm). VTE incidence was highest in the first week post-operatively, during which time four VTE events (80%) occurred. The proportion of patients in a hypercoagulable state increased at three consecutive timepoints, beginning on POD3 (85.0%), increasing on POD5 (87.5%), and peaking at 2-weeks post-operatively (88.9%). Current thromboprophylaxis guidelines do not consider cancer-associated risk factors that contribute to increased VTE incidence and prescription duration may be inadequate to address prolonged post-operative hypercoagulability in patients with MBD. The high rate of VTE events observed and sustained hypercoagulable state indicate that thromboprophylaxis may be prematurely terminated while patients remain at high risk for VTE. Therefore, extending thromboprophylaxis duration beyond 4-weeks post-operatively in patients with MBD warrants further investigation

Aim. To investigate self-reported quality of life (QoL) in patients with osteomyelitis referred to a specialist centre in the UK and investigate the relationship between QoL and BACH classification. Method. All patients newly referred to a specialist bone infection clinic at a single tertiary centre within the UK between January 2019 and February 2020 were prospectively included. Diagnosis of osteomyelitis was made according to the presence of clinical and radiological criteria for ≥6 months. An EQ-5D-5L questionnaire and visual analogue score (VAS) were completed during the initial clinic appointment. Long-bone osteomyelitis was classified by the attending orthopaedic surgeon using the BACH classification system as either uncomplicated, complex or with limited options available.1 Patients managed non-operatively were subclassified into those who were (i) unfit to receive an operation or (ii) fit and well with stable disease. EQ-5D index scores were compared to a published UK value set of 41 chronic health conditions within the UK.2. Results. 201 patients were referred during the study period, with 159 (79.1%) patients diagnosed with long-bone osteomyelitis and 16 (8.0%) with osteomyelitis of the pelvic bones. Patients with pelvic osteomyelitis reported lower EQ-5D index scores compared to long-bone osteomyelitis (EQ-5D: 0.097 vs. 0.435, p<0.001) but similar VAS (60.2 vs. 54.6, p=0.37). Long-bone and pelvic osteomyelitis gave the 40th and 41st lowest EQ-5D scores respectively when compared to 41 other chronic health conditions including stroke, chronic obstructive pulmonary disease, kidney disease, liver disease and malignancy. Patients classified as having uncomplicated long-bone osteomyelitis reported significantly higher QoL compared to those classified as complex osteomyelitis (EQ-5D: 0.527 vs. 0.401, p<0.05; VAS: 66.9 vs. 58.4, p<0.05). Patients who were not fit for surgery due to co-morbidity reported similar QoL scores compared to those patients with complex osteomyelitis (EQ-5D: 0.293, p=0.07; VAS: 46.6, p=0.06). Patients with stable disease who did not require surgery, gave significantly better QoL scores when compared to the other classifications of osteomyelitis (EQ-5D: 0.746, p<0.01; VAS: 81.9, p<0.01). Conclusions. Patient reported QoL in osteomyelitis correlates with disease complexity as classified according to the BACH classification system. Patients with pelvic and long-bone osteomyelitis rate their QoL lower than patients with other chronic diseases

Soft tissue sarcomas (STS) are rare, aggressive malignancies derived from connective tissues such as muscle and fat. Undifferentiated pleomorphic sarcoma (UPS) is one of the most common STS in adults. UPS is an aggressive, highly metastatic sarcoma, and is resistant to chemotherapy. New therapies for UPS are desperately needed. STS have an immune desert tumour immune microenvironment (TIME), characterized by a paucity of tumour infiltrating lymphocytes and subsequent resistance to immunotherapies such as immune checkpoint inhibitors. Strategies capable of creating an immune-rich, inflamed TIME may improve immunotherapy efficacies for sarcoma. Activation of the STING (stimulator of interferon genes) receptor can induce potent innate and adaptive immune responses within immunogenic solid tumours. However, this approach has never been attempted in immune-inert sarcomas. Purpose: To determine the therapeutic anti-tumour effects of STING activation in UPS tumours. We have developed an inducible, immune-competent mouse model of UPS. We evaluated intra-tumoural injection of the murine STING receptor agonist, DMXAA, into UPS-bearing immune-competent mice. DMXAA was injected into palpable UPS tumours of the hindlimb. Tumour volume and bioluminescence imaging was recorded bi-weekly. DMXAA treated UPS tumours were also evaluated for necrosis and immune infiltration at defined time points. UPS tumours developed necrosis and lymphocytic infiltration 72 hours after DMXAA treatment. A single intra-tumoural dose of DMXAA into UPS tumours resulted in durable cure in 50% of mice. All survivors rejected a re-challenge of the UPS tumours in both the contralateral hindlimb and lung, suggesting adaptive immunity. The therapeutic effects of DMXAA were mitigated in lymphocyte deficient Rag2 knockout mice. STING therapy is a promising immunotherapeutic opportunity for immune-inert sarcomas. Our data warrants further preclinical investigations in other sarcoma models and in combination with other immune-based therapies

Introduction. This study assesses self-reported quality of life (QoL) in patients with osteomyelitis referred to a specialist centre in the UK. Materials and Methods. All patients newly referred to a specialist tertiary bone infection clinic within the UK between January 2019 and February 2020 were prospectively included. Diagnosis of osteomyelitis was made according to the presence of clinical and radiological criteria for ≥6 months. An EQ-5D-5L questionnaire and visual analogue score (VAS) were completed during the initial clinic appointment. Long-bone osteomyelitis was classified by the attending orthopaedic surgeon using the BACH classification system as either uncomplicated, complex or with limited options available. Patients managed non-operatively were subclassified into those who were (i) unfit to receive an operation or (ii) fit and well with stable disease. EQ-5D index scores were compared to a published UK value-set of 41 chronic health conditions within the UK. Results. 201 new patients were referred during the study period. 159 (79.1%) met the criteria for long-bone osteomyelitis and 16 (8.0%) for osteomyelitis of the pelvic bones. Patients with pelvic osteomyelitis reported lower EQ-5D index scores compared to long-bone osteomyelitis (EQ-5D:0.097 vs. 0.435, p<0.001) but similar VAS (60.2 vs. 54.6, p=0.37). Long-bone and pelvic osteomyelitis gave the lowest EQ-5D scores respectively when compared to 41 other chronic health conditions including stroke, chronic obstructive pulmonary disease, kidney disease, liver disease and malignancy. Patients classified as having uncomplicated long-bone osteomyelitis reported significantly higher QoL compared to those classified as complex osteomyelitis (EQ-5D:0.527 vs. 0.401, p<0.05; VAS: 66.9 vs. 58.4, p<0.05). Patients not fit for surgery due to co-morbidity reported similar QoL scores compared to those patients with complex osteomyelitis (EQ-5D: 0.293, p=0.07; VAS: 46.6, p=0.06). Patients with stable disease who did not require surgery, gave significantly better QoL scores when compared to the other classifications of osteomyelitis (EQ-5D: 0.746, p<0.01; VAS: 81.9, p<0.01). Conclusions. Patient reported QoL in osteomyelitis correlates with disease complexity as classified according to the BACH classification system. Patients with pelvic and long-bone osteomyelitis rate their QoL lower than patients with other major chronic diseases

Myxoid or Myxoid Round Cell liposarcoma (MLS) is a mesenchymal malignancy with adipocyte differentiation accounting for 15–20% of liposarcomas and 5% of all adult soft tissue sarcomas (STS). Like other STS, treatment of MLS is generally by wide surgical resection in conjunction with radiotherapy and this approach is associated with low rates of local recurrence [1]. However, most MLS are located between muscles so wide local excision(WLE) can be quite morbid with adverse functional results. MLS are known to be extremely sensitive to radiotherapy which has led to development of treatment protocols utilizing neoadjuvant radiation. Given the radiosensitivity of MLS, we hypothesize that resection with marginal margins (1mm) does not result in higher rates of local recurrence or disease-free survival if performed following pre-operative radiotherapy. We identified all patients with localized MLS who underwent preoperative radiation and surgical resection between January 2000 and January 2018 from a prospectively collected sarcoma database. We calculated the ellipsoid tumour volume(ETV=h x w x d x ()) at diagnosis and after radiation, and documented the necrosis percentage of the tumour and margin status following resection based on histological analysis [2]. Marginal resection was identified by the operative report describing no or only very minimal resection of muscle surrounding the tumour, and a negative surgical margin 0.1cm/1mm as defined histologically. In comparison, WLE was defined if the operative note described an attempt to remove the tumour with a cuff of surrounding muscle, and the final histology reported a negative margin 0.1cm/1mm which included skeletal muscle. The third group for analysis included patients with positive resection margins. There were 91 patients with MLS of mean age 48 years (range 18–88) with 69% male and 31% female. The mean pre-radiotherapy ETV was 507cm. 3. (16.1cm. 3. to 6961cm. 3. ) and decreased to 361cm. 3. (8.7cm. 3. to 5695cm. 3. ) following radiation, with an average percentage reduction in ETV of −45%(+129%to-99%). Mean patient follow-up was 7.3 years (0.2–18) with no differences between margin groups(p=0.284). Only 10(11%) patients had positive margins, of which 43(47%) underwent marginal resection and 38(42%) WLE. Overall the mean necrosis as measured histologically following preoperative radiation was 69% (range 0–100%) with no differences between the 3 resection groups(p-0.151). Similarly, there was no significant difference in reduction in mean ETV between the three resection groups(p=0.311), there was no significant difference between the three treatment groups in 5-year LR-free survival (p=0.469), metastasis-free survival (p=0.841) or overall survival (p=0.873). Most patients with MLS experienced significant reduction in tumour size and necrosis following preoperative radiation. We found no differences in the risk of local recurrence or survival based on the type of surgical approach for patients with MLS. Based on these results, we conclude that MLS can be safely removed by marginal resection following preoperative radiotherapy with high rates of local tumour control. Even following a positive margin resection, local recurrence remains uncommon after preoperative radiation. A marginal surgical approach for patients with MLS reduces the need for major muscle resection and is associated with improved functional outcomes with less complications

A clinical evaluation of the effect of MRI scan to bring about a change in surgical management of elderly patients who present with hip fracture with no history of trauma or a suspicious looking lesion on x-rays. Many of these patients present with or without history of previous malignancy or bone disorder. We evaluated that if the delay in treatment within 36 hours as per national guide lines is justified to benefit patients. Methods. A clinical review of six hundred hip fracture patients where one hundred and four patients who had MRI scan of hip for fracture with either no history of trauma or a fracture with suspected pathological features with or without history of malignancy or bone disorder. The final outcome of hundred patients who had MRI scans 32 male and 68 female with median age of 65 years. Four patients were excluded as were unable to tolerate the MRI scan. Statistical analysis software SAS/STAT® was used to conduct data collation and analyses. A further radiological analysis of MRI scans with positive lesion to the plain X-rays to correlate the finding of a lesion on femoral side on MRI scan to a lesion on acetabular side. Results. Out of hundred patients who had MRI scan for a suspected metastatic or pathological lesion only 12 showed a metastatic lesion despite the fact 31 had previous history of malignancy, CI 4.03; 101.91, P < 0.0003. No primary lesion detected in any patient. We also found if the acetabular side was not seen to be involved on pain x-ray, MRI scan did not detect any acetabular lesion, contingency coefficient 0.5632, P < .0001. Conclusion. Delay in surgery to obtain an MRI scan does not change any management plans and hence best avoided for benefit of patients and compliance with guide lines

Aim. We present the long-term surgical outcomes, complications, implant survival and causes of implant failure in patients treated with the modified Harrington procedure using antegrade large diameter pins. Patients and Methods. A cohort of 50 consecutive patients who underwent the modified Harrington procedure along with cemented THA for peri-acetabular metastasis or haematological malignancy between 1990 and April 2018 were studied. The median follow-up time for all patients was 14 years (interquartile range, 9 – 16 years). Results. The 5-year overall survival rate was 33% for all the patients. However, implant survival rates were 100% and 46% at 5 and 10 years respectively. Eight patients survived beyond 5 years. There was no immediate peri-operative mortality or complications. Fifteen late complications occurred in 11 patients (22%). Five (10%) patients required additional surgeries to treat complications. The most frequent complication was pin breakage without evidence of acetabular loosening (6%). Two patients (4%) underwent revision for aseptic loosening at 6.5 and 8.9 years after surgery. Ambulatory status improved in 83%. Conclusions. The modified Harrington procedure for acetabular destruction showed low complication rates, good functional outcome and improved pain relief in selected patients. Long-term results are acceptable in this high risk group of patients. The described procedure using antegrade fully threaded large diameter pins combined with standard arthroplasty showed low rates of complications in this high risk cohort of patients with significant improvement in mobility and pain. This method of reconstruction remains robust for at least 5 years in appropriately selected group of patients

Currently 180 days is the target maximum wait time set by all Canadian provinces for elective joint replacement surgery. In Nova Scotia however, only 34% of Total Knee Arthroplasties (TKA) and 51% of Total Hip Arthroplasties (THA) met this benchmark in 2017. Surgery performed later in the natural history of disease is shown to have significant impact on pain, function and Health related Quality of Life at the time of surgery and potentially affect post-operative outcomes. The aim of this study is to describe the association between wait time and acute hospital Length of Stay (LOS) during elective hip and knee arthroplasty in province of Nova Scotia. Secondarily we aim to describe risk factors associated with variations in LOS. Data from Patient Access Registry Nova Scotia (PAR-NS) was linked to the hospital Discharge Access Database (DAD) for primary hip and knee arthroplasty spanning 2009 to 2017. There were 23,727 DAD observations and 21,329 PARNS observations identified. Observations were excluded based on missing variables, missing linkages, revision status and emergency cases. Percentage difference in LOS, risk factors and outcomes were analyzed using Poisson regression for those waiting more than 180 days compared to those waiting equal or less than 180 days. For primary TKA, 11,833 observations were identified with mean age of 66 years, mean wait time of 348 days and mean LOS of 3.6 days. After adjusting for controls, patients waiting more than 180 days for elective TKA have a 2.5% longer acute care LOS (p < 0.028). Risk factors identified for prolonged LOS are advanced age, female gender, higher surgical priority indicator, required blood transfusion, dementia, peptic ulcer disease, cerebrovascular disease, heart failure, chronic kidney disease, malignancy, ischemic heart disease and diabetes. Factors associated with decreased LOS are surgical year, use of local anesthetic, peripheral location of hospital and admission to hospital from home. For primary THA, 6626 observations were identified with mean age of 66 years, mean wait time of 267 days and mean LOS of 4 days. Patients waiting more than 180 days for THA did not show a statistically significant association with LOS. Risk factors and protective factors are the same with exception of CVD and use of local anesthetic. Our findings suggest a positive and statistically significant association for patients waiting more than 180 days for TKA and longer acute care LOS. Longer LOS may be due to deteriorating health status while placed on a surgical waitlist and may represent a delayed and indirect cost to the patient and the healthcare system. Ultimately with projected increase in demand for elective joint replacement surgeries, our findings are aimed to inform physicians and policy makers in management of surgical waitlist efficiency and cost effectiveness. For any reader inquiries, please contact . shahriar-s@hotmail.com

Advances in cancer therapy have prolonged patient survival even in the presence of disseminated disease and an increasing number of cancer patients are living with metastatic bone disease (MBD). The proximal femur is the most common long bone involved in MBD and pathologic fractures of the femur are associated with significant morbidity, mortality and loss of quality of life (QoL). Successful prophylactic surgery for an impending fracture of the proximal femur has been shown in multiple cohort studies to result in longer survival, preserved mobility, lower transfusion rates and shorter post-operative hospital stays. However, there is currently no optimal method to predict a pathologic fracture. The most well-known tool is Mirel's criteria, established in 1989 and is limited from guiding clinical practice due to poor specificity and sensitivity. The ideal clinical decision support tool will be of the highest sensitivity and specificity, non-invasive, generalizable to all patients, and not a burden on hospital resources or the patient's time. Our research uses novel machine learning techniques to develop a model to fill this considerable gap in the treatment pathway of MBD of the femur. The goal of our study is to train a convolutional neural network (CNN) to predict fracture risk when metastatic bone disease is present in the proximal femur. Our fracture risk prediction tool was developed by analysis of prospectively collected data of consecutive MBD patients presenting from 2009–2016. Patients with primary bone tumors, pathologic fractures at initial presentation, and hematologic malignancies were excluded. A total of 546 patients comprising 114 pathologic fractures were included. Every patient had at least one Anterior-Posterior X-ray and clinical data including patient demographics, Mirel's criteria, tumor biology, all previous radiation and chemotherapy received, multiple pain and function scores, medications and time to fracture or time to death. We have trained a convolutional neural network (CNN) with AP X-ray images of 546 patients with metastatic bone disease of the proximal femur. The digital X-ray data is converted into a matrix representing the color information at each pixel. Our CNN contains five convolutional layers, a fully connected layers of 512 units and a final output layer. As the information passes through successive levels of the network, higher level features are abstracted from the data. The model converges on two fully connected deep neural network layers that output the risk of fracture. This prediction is compared to the true outcome, and any errors are back-propagated through the network to accordingly adjust the weights between connections, until overall prediction accuracy is optimized. Methods to improve learning included using stochastic gradient descent with a learning rate of 0.01 and a momentum rate of 0.9. We used average classification accuracy and the average F1 score across five test sets to measure model performance. We compute F1 = 2 x (precision x recall)/(precision + recall). F1 is a measure of a model's accuracy in binary classification, in our case, whether a lesion would result in pathologic fracture or not. Our model achieved 88.2% accuracy in predicting fracture risk across five-fold cross validation testing. The F1 statistic is 0.87. This is the first reported application of convolutional neural networks, a machine learning algorithm, to this important Orthopaedic problem. Our neural network model was able to achieve reasonable accuracy in classifying fracture risk of metastatic proximal femur lesions from analysis of X-rays and clinical information. Our future work will aim to externally validate this algorithm on an international cohort

Advances in cancer therapy have prolonged cancer patient survival even in the presence of disseminated disease and an increasing number of cancer patients are living with metastatic bone disease (MBD). The proximal femur is the most common long bone involved in MBD and pathologic fractures of the femur are associated with significant morbidity, mortality and loss of quality of life (QoL). Successful prophylactic surgery for an impending fracture of the proximal femur has been shown in multiple cohort studies to result in patients more likely to walk after surgery, longer survival, lower transfusion rates and shorter post-operative hospital stays. However, there is currently no optimal method to predict a pathologic fracture. The most well-known tool is Mirel's criteria, established in 1989 and is limited from guiding clinical practice due to poor specificity and sensitivity. The goal of our study is to train a convolutional neural network (CNN) to predict fracture risk when metastatic bone disease is present in the proximal femur. Our fracture risk prediction tool was developed by analysis of prospectively collected data for MBD patients (2009–2016) in order to determine which features are most commonly associated with fracture. Patients with primary bone tumors, pathologic fractures at initial presentation, and hematologic malignancies were excluded. A total of 1146 patients comprising 224 pathologic fractures were included. Every patient had at least one Anterior-Posterior X-ray. The clinical data includes patient demographics, tumor biology, all previous radiation and chemotherapy received, multiple pain and function scores, medications and time to fracture or time to death. Each of Mirel's criteria has been further subdivided and recorded for each lesion. We have trained a convolutional neural network (CNN) with X-ray images of 1146 patients with metastatic bone disease of the proximal femur. The digital X-ray data is converted into a matrix representing the color information at each pixel. Our CNN contains five convolutional layers, a fully connected layers of 512 units and a final output layer. As the information passes through successive levels of the network, higher level features are abstracted from the data. This model converges on two fully connected deep neural network layers that output the fracture risk. This prediction is compared to the true outcome, and any errors are back-propagated through the network to accordingly adjust the weights between connections. Methods to improve learning included using stochastic gradient descent with a learning rate of 0.01 and a momentum rate of 0.9. We used average classification accuracy and the average F1 score across test sets to measure model performance. We compute F1 = 2 x (precision x recall)/(precision + recall). F1 is a measure of a test's accuracy in binary classification, in our case, whether a lesion would result in pathologic fracture or not. Five-fold cross validation testing of our fully trained model revealed accurate classification for 88.2% of patients with metastatic bone disease of the proximal femur. The F1 statistic is 0.87. This represents a 24% error reduction from using Mirel's criteria alone to classify the risk of fracture in this cohort. This is the first reported application of convolutional neural networks, a machine learning algorithm, to an important Orthopaedic problem. Our neural network model was able to achieve impressive accuracy in classifying fracture risk of metastatic proximal femur lesions from analysis of X-rays and clinical information. Our future work will aim to validate this algorithm on an external cohort

Computer assisted total knee arthroplasty helps in accurate and reproducible implant positioning, bony alignment, and soft-tissue balancing which are important for the success of the procedure. In TKR, there are two surgical techniques one is measured resection in which bony landmarks are used to guide the bone cuts and the other is gap balancing which equal collateral ligament tension in flexion and extension is done before and as a guide to final bone cuts. Both these procedures have their own advantages and disadvantages. We retrospectively collected the data of 128 consecutive patients who underwent computer-assisted primary TKA using either a gap-balancing technique or measured resection technique. All the operations were performed by a single surgeon using computer navigation system available during a period between June 2016 to October 2016. Inclusion criteria were all patients requiring a primary TKA, male or female patients, and who have given informed consent for participation in the study. All patients requiring revision surgery of a previous implanted TKA or affected by active infection or malignancy, who presented hip ankylosis or arthrodesis, neurological deficit or bone loss or necessity of more constrained implants were excluded from the study. Two groups measured resection and gap balancing was randomly selected. At 1-year follow-up, patients were assessed by a single orthopaedic registrar blinded to the type of surgery using the Knee Society score (KSS) and functional Knee Society score (FKSS). Outcomes of the 2 groups were compared using the paired t test. All the obtained data were analysed. Statistical analysis was performed using SPSS 11.5 statistical software (SPSS Inc. Chicago). Inter-class correlation coefficient (ICC) and paired t-test were used and statistical significance was set at P = 0.05. In the measured resection group, the mean FKSS increased from 48.8769 (SD, 2.3576), to 88.5692 (SD, 2.7178) respectively. In the gap balancing group, the respective scores increased from 48.9333 (SD, 3.6577) to 89.2133(SD, 7.377). Preoperative and Postoperative increases in the respective scores were slightly better with the gap balancing technique; the respective p values were 0.8493 and 0.1045. The primary goal of TKA is restoration of mechanical axis and soft-tissue balance. Improper restoration leads to poor functional outcome and premature prosthesis loosening. Computer navigation enables precise femoral and tibial cuts and controlled soft-tissue release. Well balanced and well aligned knee is important for good results. Mechanical alignment and soft-tissue balance are interlinked and corrected by soft tissue releases and precise proximal tibial and distal femoral cuts. The 2 common techniques used are measured resection and gap balancing techniques. In our study, knee scores of the 2 groups at 1-year follow-up were compared, as most of the improvement occurs within one year, with very little subsequent improvement. Some surgeons favour gap balancing technique, as it provides more consistent soft-tissue tension in TKA

Aim. There is a theoretical advantage for immediate postoperative start of rifampicin after debridement, antibiotics and implant retention (DAIR). Anti-biofilm treatment may be mostly needed during the first postoperative days in order to prevent new biofilm formation. However, there are concerns with regard to development of rifampicin resistance if rifampicin is started too early. Rifampicin monotherapy will rapidly result in rifampicin resistance, but this may not occur when prescribed as part of combination antimicrobial therapy and after thorough surgical debridement. We hypothesized that in this setting the probability of development of rifampicin resistance is very low. We evaluated the frequency of development of rifampicin resistance in patients with acute staphylococcal PJI who were treated with DAIR followed by immediate postoperative start of rifampicin in combination with a betalactam or glycopeptide. Method. During 2003–2014, all patients with an acute staphylococcal PJI were treated with five days of high-dose rifampicin (600mg bid) in combination with at least 6 weeks of betalactam or glycopeptide antibiotics, both started immediately postoperative after DAIR. Clinical outcome and development of rifampicin resistance in patients who failed were monitored. Susceptibility testing for rifampicin was performed by Vitek 2 (Biomerieux). Until 2014, Clinical and Laboratory Standards Institute (CLSI) criteria for rifampicin resistance were applied (S ≤ 1), from 2014 EUCAST criteria (S ≤ 0.06) were applied. Results. Forty-one patients with acute staphylococcal hip (22) of knee (19) PJI were included. Comorbidities were rheumatoid arthritis (22%), diabetes (10%), a tumor prosthesis due to malignancy (34%) and corticosteroid use (27%). Fifteen patients (37%) developed a failure after DAIR. Eight failures were caused by the same staphylococcal species as the initial PJI (six Staphylococcus aureus, two Coagulase-negative staphylococci). In all failures, rifampicin susceptibility of the isolate had not changed. One patient was started on chronic suppressive treatment (not including rifampicin) and had a prosthetic joint removal 18 months later. In this patient, one out of five positive cultures with S. aureus from the removed prosthesis showed a rifampicin resistant strain. In all failures, mean duration between the initial DAIR and failure was 208 days (range 7–636 days). Conclusions. Immediate postoperative start of high-dose rifampicin in combination with betalactam or glycopeptide did not result in rifampicin resistant staphylococci among patient who had a failure with the same staphylococci. These results strongly indicate that immediate postoperative start of rifampicin is safe. Larger studies are needed to prove the clinical benefit of this strategy