The management of periprosthetic distal femur fractures is an issue of increasing importance for orthopaedic surgeons. Because of the expanding indications for total knee arthroplasty (TKA) and an aging population with increasingly active lifestyles there has been a corresponding increase in the prevalence of these injuries. The management of these fractures is often complex because of issues with obtaining fixation around implants and dealing with osteopenic bone or compromised bone stock. In addition, these injuries frequently occur in frail, elderly patients, and the early restoration of function and ambulation is critical in these patients. There remains substantial controversy with respect to the optimal treatment of periprosthetic distal femur fractures, with some advocating for Locked Plating (LP), others Retrograde Intramedullary Nailing (RIMN) and finally those who advocate for Distal Femoral Replacement (DFR). The literature comparing these treatments, has been infrequent, and commonly restricted to single-center studies. The purpose of this study was to retrospectively evaluate a large series of operatively treated periprosthetic distal femur fractures from multiple centers and compare treatment strategies. Patients who were treated operatively for a periprosthetic distal femur fracture at 8 centers across North America between 2003 and 2018 were retrospectively identified. Baseline characteristics, surgical details and post-operative clinical outcomes were collected from patients meeting inclusion criteria. Inclusion criteria were patients aged 18 and older, any displaced operatively treated periprosthetic femur fracture and documented 1 year follow-up. Patients with other major lower extremity trauma or ipsilateral total hip replacement were excluded. Patients were divided into 3 groups depending on the type of fixation received: Locked Plating, Retrograde Intramedullary Nailing and Distal Femoral Replacement. Documented clinical follow-up was reviewed at 2 weeks, 3 months, 6 months and 1 year following surgery. Outcome and covariate measures were assessed using basic descriptive statistics. Categorical variables, including the rate of re-operation, were compared across the three treatment groups using Fisher Exact Test. In total, 121 patients (male: 21% / female: 79%) from 8 centers were included in our analysis. Sixty-seven patients were treated with Locked Plating, 15 with Retrograde Intramedullary Nailing, and 39 were treated with Distal Femoral Replacement. At 1 year, 64% of LP patients showed radiographic union compared to 77% in the RIMN group (p=0.747). Between the 3 groups, we did not find any significant differences in ambulation, return to work and complication rates at 6 months and 1 year (Table 1). Reoperation rates at 1 year were 27% in the LP group (17 reoperations), 16% in the DFR group (6 reoperations) and 0% in the RIMN group. These differences were not statistically significant (p=0.058). We evaluated a large multicenter series of operatively treated periprosthetic distal femur fractures in this study. We did not find any statistically significant differences at 1 year between treatment groups in this study. There was a trend towards a lower rate of reoperation in the Retrograde Intramedullary Nailing group that should be evaluated further with prospective studies. For any figures or tables, please contact the authors directly

Aims. Tuberculosis (TB) infection of bones and joints accounts for 6.7% of TB cases in England, and is associated with significant morbidity and disability. Public Health England reports that patients with TB experience delays in diagnosis and treatment. Our aims were to determine the demographics, presentation and investigation of patients with a TB infection of bones and joints, to help doctors assessing potential cases and to identify avoidable delays. Patients and Methods. This was a retrospective observational study of all adults with positive TB cultures on specimens taken at a tertiary orthopaedic centre between June 2012 and May 2014. A laboratory information system search identified the patients. The demographics, clinical presentation, radiology, histopathology and key clinical dates were obtained from medical records. Results. A total of 31 adult patients were identified. Their median age was 37 years (interquartile range (IQR): 29 to 53); 21 (68%) were male; 89% were migrants. The main sites affected were joints (10, 32%), the spine (8, 26%) and long bones (6, 19%); 8 (26%) had multifocal disease. The most common presenting symptoms were pain (29/31, 94%) and swelling (26/28, 93%). ‘Typical’ symptoms of TB, such as fever, sweats and weight loss, were uncommon. Patients waited a median of seven months (IQR 3 to 13.5) between the onset of symptoms and referral to the tertiary centre and 2.3 months (IQR 1.6 to 3.4.)) between referral and starting treatment. Radiology suggested TB in 26 (84%), but in seven patients (23%) the initial biopsy specimens were not sent for mycobacterial culture, necessitating a second biopsy. Rapid Polymerase Chain Reaction-based testing for TB using Xpert MTB/RIF was performed in five patients; 4 (80%) tested positive for TB. These patients had a reduced time between the diagnostic biopsy and starting treatment than those whose samples were not tested (median eight days versus 36 days, p = 0.016). Conclusion. Patients with bone and joint TB experience delays in diagnosis and treatment, some of which are avoidable. Maintaining a high index of clinical suspicion and sending specimens for mycobacterial culture are crucial to avoid missing cases. Rapid diagnostic tests reduce delays and should be performed on patients with radiological features of TB. Cite this article: Bone Joint J 2018;100-B:119–24

Aim. Treatment recommendations for periprosthetic joint infections (PJI) include surgical debridement, antibiotic therapy or staged revision. In surgical related foot and ankle infections (SR-FAI), implant removal will lead to instability. Debridement is difficult because the implant is outside the joint. Recommendations regarding PJI treatment can therefore not be extrapolated to the treatment of SR-FAI. Method. We searched PubMed for the etiology and treatment of SR-FAI, taken into account the time of occurrence, causative microorganisms and surgical treatment options. We integrated this knowledge into a treatment algorithm for SR-FAI. Results. Within the first 6 weeks after surgery, it is difficult to distinguish acute osteomyelitis from surgical site infection in which infection is limited to the soft tissue. The predominantly causative microorganism is Staphylococcus aureus. No debridement can be performed, because of the diffuse soft tissue inflammation and the absence of a joint space. If early SR- FAI is suspected without signs of systemic symptoms, fistula or abscess, empirical antibiotic treatment covering Staphylococcus aureus is recommended. If there is suspicion of ongoing SR-FAI after 2 weeks of empirical treatment, samples for culture after an antibiotic free window should be obtained to identify the causative microorganisms. If SR-FAI is confirmed, but there is no consolidation yet, targeted antibiotic treatment is given for 12 weeks without initial implant removal. In all other cases, debridement and samples for culture should be obtained after an antibiotic free window. Staged revision surgery will be performed if there is still a nonunion. Conclusions. Treatment algorithm regarding PJI cannot be extrapolated to the treatment of SR-FAI. Until now, no treatment guideline for SR-FAI is available. We have introduced a treatment algorithm for the treatment of SR-FAI. The guideline will be validated during the next 2 years

Non-tuberculous mycobacterial (NTM) infection of the musculoskeletal tissue is a rare disease. An early and accurate diagnosis is often difficult because of the indolent clinical course and difficulty of isolating pathogens. Our goal was to determine the clinical features of musculoskeletal NTM infection and to present the treatment outcomes. A total of 29 patients (nine females, 20 males between 34 and 85 years old, mean age 61.7 years; 34 to 85) with NTM infection of the musculoskeletal system between 1998 to 2011 were identified and their treatment retrospectively analysed. Microbiological studies demonstrated NTM in 29 patients: the isolates were Mycobacterium intracellulare in six patients, M. fortuitum in three, M. abscessus in two and M. marinum in one. In the remaining patients we failed to identify the species. The involved sites were the hand/wrist in nine patients the knee in five patients, spine in four patients, foot in two patients, elbow in two patients, shoulder in one, ankle in two patients, leg in three patients and multiple in one patient. The mean interval between the appearance of symptoms and diagnosis was 20.8 months (1.5 to 180). All patients underwent surgical treatment and antimicrobial medication according to our protocol for chronic musculoskeletal infection: 20 patients had NTM-specific medication and nine had conventional antimicrobial therapy. At the final follow-up 22 patients were cured, three failed to respond to treatment and four were lost to follow-up. Identifying these diseases due the initial non-specific presentation can be difficult. Treatment consists of surgical intervention and adequate antimicrobial therapy, which can result in satisfactory outcomes. Cite this article: Bone Joint J 2014;96-B:1561–5

There is a significant positive association between hours of brace wear and rate of success in the treatment of Adolescent Idiopathic Scoliosis (AIS). The abandon rate reported in the literature averages 18%. In a recent randomized trial conducted at our center; the abandon rate was 4%. We aim to document the abandon rate towards brace treatment during the COVID-19 pandemic and its impact on AIS progression. We reviewed a database of AIS patients recruited between March and September 2020. Inclusion criteria were patients with AIS under brace treatment according to SRS criteria. The patients were divided in 2 cohorts: those with a self-reported good adherence to treatment and those who voluntarily abandoned treatment during follow-up. Patients with irregular adherence were excluded. Data analysis included age, gender, Risser stage, type of brace, Cobb angles at first visit and last follow-up (mean 11 months) and % of progression. Unpaired student tests were used for comparison. 154 patients met inclusion criteria. 20 patients were excluded due to irregular adherence. 89 patients (age: 12.1 y.o. ±1.4) reported good adherence to treatment, while 45 patients (age: 12.6 y.o. ±1.5) abandoned treatment, an abandon rate of 29%. The cohort of compliant patients started treatment with a mean main thoracic (MT) curve of 26° and finished with 27°. The mean difference between measurements was +0.65°±7.5; mean progression rate was −4.6%. However, patients who abandoned treatment started with a mean MT curve of 28° and finished with 33°, with a mean increase of +5°±8 and a mean progression rate of −11%. The differences between the 2 cohorts were statistically significant (p=0.002). Five (5) patients from the abandon group were offered for surgery because of curve progression. The abandon rate of brace treatment in AIS significantly increased during the first wave of COVID-19 pandemic. Patients who voluntarily discontinued treatment had significant increases in curve progression and surgical indication rates

Aim. The intention of suppressive antimicrobial therapy (SAT) for prosthetic joint infection (PJI) is to minimise symptoms, maintain function and prevent further surgery in patients who cannot undergo further attempts at curative treatment(1). There is little high-quality evidence examining the role and efficacy of SAT for patients with PJI(1,2). The objective of this study was to describe the use of and outcomes after SAT in a large prospective PJI cohort. Methods. A pre-planned analysis of a prospective multi-centre cohort of patients with PJI. SAT was defined as antimicrobial therapy for PJI continuing 12-months after diagnosis or where there was an intention for chronic suppressive antibiotics. The primary outcome was treatment failure at 24 months, defined as any of the development of PJI symptoms, further surgery or death from PJI. Secondary outcomes included Oxford Hip and Knee Scores. Results. SAT was prescribed for 223 (31.0%) of the PJI cohort. Patients prescribed SAT for PJI were more likely to be older, have comorbidities, chronic PJI, higher CRP, a sinus tract and be treated with retention of their prosthesis than those not prescribed SAT. At 24-months, treatment failure was more common in the SAT group 75/185(40.1%) compared with the non-SAT group 85/447(19.0%). Propensity score adjusted analysis did not demonstrate an association between SAT and treatment failure in patients with chronic PJI (OR[95% CI] 1.57[0.63-3.91), late-acute PJI(1.87[0.90-3.87]), a sinus tract (2.74[0.89-8.39]), ongoing symptoms at day 90 (1.19[0.43-3.23]), treatment with DAIR(1.61[0.87-2.99]) or Staphylococcus aureus PJI (1.25[0.62-2.54]). There were similar improvements between SAT and non-SAT patients in functional joint scores (OHS median (IQR) +8.5(19.0) vs +7.0(22.0);p=0.78 and OKS +8.0(20.0) vs +7.0(22.0);p=0.53). Conclusion. SAT use for PJI is common. The lack of demonstrated evidence in this study for its benefit in controlling infection across multiple subgroups of patients but with some improvements in functional scores, suggest that the advantages of SAT are at best complex

Aim. To compare outcomes of PJI in relation to treatment method versus classification using the JS-BACH system. Method. Patients having surgery for EBJIS Criteria Confirmed PJI between 2010–2015 were included. Index surgical procedures were 1-stage or 2-stage revision or debridement and implant retention (DAIR). Patients completed the EuroQol EQ-5D-3L questionnaire and were followed clinically to a median of 4.7 years (IQR 2.7–6.7 years). Patients were stratified using the JS-BACH classification1 into either ‘Uncomplicated’, ‘Complex’ or having ‘Limited treatment options’, by two separate classifiers, blinded to clinical outcome. Results. 216 patients met the inclusion criteria. There were 51 patients classified as Uncomplicated (23.6%), 127 (58.8%) as Complex and 38 (17.6%) having Limited treatment options. Patients underwent either DAIR (n=97), 1-stage (n=35) or 2-stage (n=84) revision. Patients classified as Uncomplicated PJI had the lowest risk of recurrence or treatment failure, regardless of index procedure performed. Complex patients were significantly more likely than Uncomplicated patients to have recurrence following 2-stage revision (Odds Ratio 1.85; p=0.040) or DAIR (OR 1.83; p=0.037), but not 1-stage revision (OR 0.518; p=0.675). Limited treatment option patients had the highest recurrence risk regardless of index procedure (1-stage: OR 2.5 p=0.036; 2-stage: OR 3.3 p=0.004; DAIR: OR 3.40 p=0.006). At one year after surgery, Uncomplicated patients had the highest EQ-index scores (a marker of Quality of Life), with all treatments (EQ-5D-3L mean index scores; Uncomp 0.773, Complex 0.512, Limited Options 0.310: p<0.01). Differences in patient-reported outcomes were greater between the JS-BACH classification groups than between any methods of treatment. Conclusions. The JS-BACH classification effectively predicted outcome after three common PJI treatments. Comparing outcomes between treatments, without stratification of the patients, may be misleading as factors other than treatment method have a major effect on outcome. Classification may allow better allocation of individual treatments to provide optimal outcome for patients

Aim. Dalbavancin is a lipoglycopeptide with a broad antimicrobial spectrum against Gram-positive bacteria and effect against microorganisms in biofilm in vitro. Its pharmacokinetic properties, with an exceptionally long half-life of approximately 300 hours, allow for simplified administration that may be of value in the long-term treatment of bone and joint infections, such as prosthetic joint infections (PJIs). Several case reports and case series with “off-lable” treatment with dalbavancin of PJIs exist, but the optimal dosing regimen remains to be defined. Therapeutic drug monitoring (TDM) is recommended for treatment with >2 doses of dalbavancin. In the absence of TDM, the Swedish national guidelines for bone and joint infections (2023, . www.infektion.net. ) recommends a loading dose of dalbavancin 1,500 mg on day 1 and 1,500 mg on days 8 – 14, after which from day 28 1,000 mg is given biweekly or 500 mg every week. The aim of the present study was to determine trough levels of dalbavancin in patients with long-term treatment of PJIs according to the national guidelines. Method. Twelve patients with PJI were treated with at least 6 doses of dalbavancin, of which the first two doses were 1500 mg and the following doses were 1000 every second week, and prospectively sampled biweekly for determination of serum concentrations (trough levels) of dalbavancin which was measured by liquid chromatography coupled to electrospray tandem mass spectrometry (LC-MS/MS). The renal function was also examined. Results. The median serum concentration 14 days after the first dose of dalbavancin 1500 mg was 36.3 mg/L (range 6.6 – 62.4 mg/L). The median value 14 days after the second dose of 1500 mg (day 27 – 28) was 48.2 mg/L (range 12.2 – 77.3 mg/L). The trough value after the last dose of a total of 6 – 7 doses was as median 43.1 mg/L (range 26.2 – 97.5 mg/L). Three patients showed a tendency towards successive accumulation of dalbavancin during treatment. None of the patients, including those three with increasing through levels during treatment, showed any significant alteration in creatinine nor glomerular filtration rate. Conclusions. TDM during long-term treatment with dalbavancin is recommended to avoid the risk of accumulation and unnecessarily high trough values. With TDM, the dosing interval can be extended in several cases. In addition, with the support of TDM, subtherapeutic serum concentrations, with the risk of developing resistance, can be avoided

The aim of this study was to investigate surgeons’ reported change of treatment preference in response to the results and conclusion from a randomized controlled trial (RCT) and to study patterns of change between subspecialties and nationalities. Two questionnaires were developed through the Delphi process for this cross-sectional survey of surgical preference. The first questionnaire was sent out before the publication of a RCT and the second questionnaire was sent out after publication. The RCT investigated repair or non-repair of the pronator quadratus (PQ) muscle during volar locked plating of distal radial fractures (DRFs). Overall, 380 orthopaedic surgeons were invited to participate in the first questionnaire, of whom 115 replied. One hundred surgeons were invited to participate in the second questionnaire. The primary outcome was the proportion of surgeons for whom a treatment change was warranted, who then reported a change of treatment preference following the RCT. Secondary outcomes included the reasons for repair or non-repair, reasons for and against following the RCT results, and difference of preferred treatment of the PQ muscle between surgeons of different nationalities, qualifications, years of training, and number of procedures performed per year. Of the 100 surgeons invited for the second questionnaire, 74 replied. For the primary outcome, 6 of 32 surgeons (19%), who usually repaired the PQ muscle and therefore a change of treatment preference was warranted, reported a change of treatment preference based on the RCT publication. Of the secondary outcomes, restoring anatomy was the most common response for repairing the PQ muscle. The majority of the orthopaedic surgeons, where a change of treatment preference was warranted based on the results and conclusion of a RCT, did not report willingness to change their treatment preference

Introduction. Since the expanded war in Ukraine in 2022, explosives, mines, debris, blast waves, and other factors have predominantly caused injuries during artillery or rocket attacks. These injuries, such as those from shelling shrapnel, involve high-energy penetrating agents, resulting in extensive necrosis and notable characteristics like soft tissue defects and multiple fragmentary fractures with bone tissue defects and a high rate of infection complications caused by multi resistant gram-negative (MRGN) pathogens. Material and Methods. We conducted a prospective study at our center between March 2022 and December 2023. Out of the 56 patients from Ukraine, 21 met the inclusion criteria who had severe war injuries were included in the study. Each of these patients presented with multiple injuries to both bones and soft tissues, having initially undergone treatment in Ukraine involving multiple surgeries. The diagnosis of infection was established based on the EBJIS criteria. Prior to our treatment patients had undergone multiple revision surgeries, including debridement, biopsies, implant and fixator replacement. Additionally, soft tissue management required previously VAC therapy and flap reconstruction for successful treatment. Results. All 21 infections manifested as bone infections (11; 52%), followed by implant-associated infections (5; 24%), soft tissue infections (4; 19%), and septic arthritis (1; 5%). In all patients, the infection was polymicrobial, caused by 3- and 4-MRGN pathogens, as Klebsiella pneumonia 4MRGN, Proteus mirabilis 4MRGN, Enterobacter cloacae 4MRGN etc. Upon admission, all patients carried a diagnosis and exhibited signs indicative of chronic infection. 19 (90.5%) patients required complex antibiotic regimens combined with multiple wound revisions and debridements, changes of fixators and combination of systemic and local antibiotic therapy. In 6 patients (28%) high dosages of local antibiotics such as gentamycin, vancomycin and meropenem were incorporated into a carrier of bio-absorbable calcium sulfate, calcium sulfate/hydroxyapatite which were introduced into the hip joint, femoral canal or bone defect for dead space management during the surgery. When local antibiotics were administered at intervals, the microbiology results at implantation showed negative results. 2 (9%) patients had new infections (different site, different pathogens), 1 (4.8%) is still under the treatment. In 17 (81%) patients infection complications were treated successfully with no recurrence of infection. Conclusion. War injuries result in complex bone and soft-tissue infections caused by 3-, 4-MRGN pathogens. Addressing this challenge necessitates multidisciplinary approach with multiple, thorough surgical debridements, effective local, and systemic antimicrobial therapy. As for the outlook we can see potential in local antibiotic carriers

Aim. Dalbavancin is a lipoglycopeptide with a half-life of 14 days (range 6.1 to 18.4), significantly longer than other antimicrobials, which avoids the need for daily antibiotic dosing. This multi-centre observational study aims to describe the use of dalbavancin to facilitate discharge in treating bone and joint infections. Method. All adult patients treated with dalbavancin from January 2017 to September 2022 in four UK bone infection units were included. Data collected through a standardised data collection form included:. Clinical and microbiological characteristics. Hospital length of stay. Complications. Patient suitability for hypothetical treatment options, such as Outpatient Parenteral. Antibiotic Team (OPAT). Clinical outcome. Treatment-related costs were calculated for dalbavancin and the preferred hypothetical treatment option that would have been administered for the same duration. The costs were subtracted to calculate the cost difference. Clinical success was defined as the absence of definite failure in accordance with the OVIVA Trial protocol. Results. Thirty-six patients were included: 20 males and 16 females, with a median age of 53 (IQR 43–73): Thirteen were septic arthritis, twelve were prosthetic joints, seven were spondylodiscitis and five were other orthopaedic-related implant infections. In twenty cases the infecting organism was Staphylococcus aureus, fourteen were due to coagulase-negative staphylococci and two no cultured organism. Reasons for dalbavancin. The reasons for choosing dalbavancin over alternatives were due to either:. Necessity due to poor adherence (21), or lack of viable OPAT options due to antibiotic resistance or intolerance (7). OR. Convenience to avoid the need for OPAT (8). Dalbavancin was initiated at 1500mg after a median of 12 days (IQR 6–17) of in-hospital antimicrobial therapy. Subsequent dalbavancin doses were based on clinical decisions and ranged from 1000mg to 1500mg. Healthcare benefits. Switching to dalbavancin reduced treatment costs by a median of £3526 (IQR 1118 - 6251) compared with the preferred theoretical alternatives. A median of 31 hospital days (IQR 23–47) was avoided among patients who would have required a prolonged inpatient stay. Outcome. Overall, 20 patients (55.6%) were successfully treated after a median follow-up of 8 months (IQR, 5.8 – 18.4). No patients developed an adverse drug reaction. Conclusions. Dalbavancin can safely facilitate outpatient treatment in patients with limited oral options and in whom OPAT is unsuitable. Dalbavancin is cost-effective compared with the alternative of an inpatient stay

The Ponseti method is the gold standard treatment for clubfoot. It begins in early infancy with weekly serial casting for up to 3 months. Globally, a commonly reported barrier to accessing clubfoot treatment is increased distance patients must travel for intervention. This study aims to evaluate the impact of the distance traveled by families to the hospital on the treatment course and outcomes for idiopathic clubfoot. No prior studies in Canada have examined this potential barrier. This is a retrospective cohort study of patients managed at a single urban tertiary care center for idiopathic clubfoot deformity. All patients were enrolled in the Pediatric Clubfoot Research Registry between 2003 and April 2021. Inclusion criteria consisted of patients presenting at after percutaneous Achilles tenotomy. Postal codes were used to determine distance from patients’ home address to the hospital. Patients were divided into three groups based on distance traveled to hospital: those living within the city, within the Greater Metro Area (GMA) and outside of the GMA (non-GMA). The primary outcome evaluated was occurrence of deformity relapse and secondary outcomes included need for surgery, treatment interruptions/missed appointments, and complications with bracing or casting. A total of 320 patients met inclusion criteria. Of these, 32.8% lived in the city, 41% in the GMA and 26% outside of the GMA. The average travel distance to the treatment centre in each group was 13.3km, 49.5km and 264km, respectively. Over 22% of patients travelled over 100km, with the furthest patient travelling 831km. The average age of presentation was 0.91 months for patients living in the city, 1.15 months for those within the GMA and 1.33 months for patients outside of the GMA. The mean number of total casts applied was similar with 7.1, 7.8 and 7.3 casts in the city, GMA and non-GMA groups, respectively. At least one two or more-week gap was identified between serial casting appointments in 49% of patients outside the GMA, compared to 27% (GMA) and 24% (city). Relapse occurred in at least one foot in 40% of non-GMA patients, versus 27% (GMA) and 24% (city), with a mean age at first relapse of 50.3 months in non-GMA patients, 42.4 months in GMA and 35.7 months in city-dwelling patients. 12% of the non-GMA group, 6.8% of the GMA group and 5.7% of the city group underwent surgery, with a mean age at time of initial surgery of 79 months, 67 months and 76 months, respectively. Complications, such as pressure sores, casts slips and soiled casts, occurred in 35% (non-GMA), 32% (GMA) and 24% (city) of patients. These findings suggest that greater travel distance for clubfoot management is associated with more missed appointments, increased risk of relapse and treatment complications. Distance to a treatment center is a modifiable barrier. Improving access to clubfoot care by establishing clinics in more remote communities may improve clinical outcomes and significantly decrease the burdens of travel on patients and families

Bone turnover and the accumulation of microdamage are impacted by the presence of skeletal metastases which can contribute to increased fracture risk. Treatments for metastatic disease may further impact bone quality. The present study aims to establish a preliminary understanding of microdamage accumulation and load to failure in osteolytic vertebrae following stereotactic body radiotherapy (SBRT), zoledronic acid (ZA), or docetaxel (DTX) treatment. Twenty-two six-week old athymic female rats (Hsd:RH-Foxn1rnu, Envigo, USA) were inoculated with HeLa cervical cancer cells through intracardiac injection (day 0). Institutional approval was obtained for this work and the ARRIVE guidelines were followed. Animals were randomly assigned to four groups: untreated (n=6), spine stereotactic body radiotherapy (SBRT) administered on day 14 (n=6), zoledronic acid (ZA) administered on day 7 (n=5), and docetaxel (DTX) administered on day 14 (n=5). Animals were euthanized on day 21. T13-L3 vertebral segments were collected immediately after sacrifice and stored in −20°C wrapped in saline soaked gauze until testing. µCT scans (µCT100, Scanco, Switzerland) of the T13-L3 segment confirmed tumour burden in all T13 and L2 vertebrae prior to testing. T13 was stained with BaSO. 4. to label microdamage. High resolution µCT scans were obtained (90kVp, 44uA, 4W, 4.9µm voxel size) to visualize stain location and volume. Segmentations of bone and BaSO. 4. were created using intensity thresholding at 3000HU (~736mgHA/cm. 3. ) and 10000HU (~2420mgHA/cm. 3. ), respectively. Non-specific BaSO. 4. was removed from the outer edge of the cortical shell by shrinking the segmentation by 105mm in 3D. Stain volume fraction was calculated as the ratio of BaSO. 4. volume to the sum of BaSO. 4. and bone volume. The L1-L3 motion segments were loaded under axial compression to failure using a µCT compatible loading device (Scanco) and force-displacement data was recorded. µCT scans were acquired unloaded, at 1500µm displacement and post-failure. Stereological analysis was performed on the L2 vertebrae in the unloaded µCT scans. Differences in mean stain volume fraction, mean load to failure, and mean bone volume/total volume (BV/TV) were compared between treatment groups using one-way ANOVAs. Pearson's correlation between stain volume fraction and load to failure by treatment was calculated using an adjusted load to failure divided by BV/TV. Stained damage fraction was significantly different between treatment groups (p=0.0029). Tukey post-hoc analysis showed untreated samples to have higher stain volume fraction (16.25±2.54%) than all treatment groups (p<0.05). The ZA group had the highest mean load to failure (195.60±84.49N), followed by untreated (142.33±53.08N), DTX (126.60±48.75N), and SBRT (95.50±44.96N), but differences did not reach significance (p=0.075). BV/TV was significantly higher in the ZA group (49.28±3.56%) compared to all others. The SBRT group had significantly lower BV/TV than the untreated group (p=0.018). Load divided by BV/TV was not significantly different between groups (p=0.24), but relative load to failure results were consistent (ZA>Untreated>DTX>SBRT). No correlations were found between stain volume fraction and load to failure. Focal and systemic cancer treatments effect microdamage accumulation and load to failure in osteolytic vertebrae. Current testing of healthy controls will help to further separate the effects of the tumour and cancer treatments on bone quality

Bone turnover and the accumulation of microdamage are impacted by the presence of skeletal metastases which can contribute to increased fracture risk. Treatments for metastatic disease may further impact bone quality. The present study aims to establish a preliminary understanding of microdamage accumulation and load to failure in osteolytic vertebrae following stereotactic body radiotherapy (SBRT), zoledronic acid (ZA), or docetaxel (DTX) treatment. Twenty-two six-week old athymic female rats (Hsd:RH-Foxn1rnu, Envigo, USA) were inoculated with HeLa cervical cancer cells through intracardiac injection (day 0). Institutional approval was obtained for this work and the ARRIVE guidelines were followed. Animals were randomly assigned to four groups: untreated (n=6), spine stereotactic body radiotherapy (SBRT) administered on day 14 (n=6), zoledronic acid (ZA) administered on day 7 (n=5), and docetaxel (DTX) administered on day 14 (n=5). Animals were euthanized on day 21. T13-L3 vertebral segments were collected immediately after sacrifice and stored in −20°C wrapped in saline soaked gauze until testing. µCT scans (µCT100, Scanco, Switzerland) of the T13-L3 segment confirmed tumour burden in all T13 and L2 vertebrae prior to testing. T13 was stained with BaSO. 4. to label microdamage. High resolution µCT scans were obtained (90kVp, 44uA, 4W, 4.9µm voxel size) to visualize stain location and volume. Segmentations of bone and BaSO. 4. were created using intensity thresholding at 3000HU (~736mgHA/cm. 3. ) and 10000HU (~2420mgHA/cm. 3. ), respectively. Non-specific BaSO. 4. was removed from the outer edge of the cortical shell by shrinking the segmentation by 105mm in 3D. Stain volume fraction was calculated as the ratio of BaSO. 4. volume to the sum of BaSO. 4. and bone volume. The L1-L3 motion segments were loaded under axial compression to failure using a µCT compatible loading device (Scanco) and force-displacement data was recorded. µCT scans were acquired unloaded, at 1500µm displacement and post-failure. Stereological analysis was performed on the L2 vertebrae in the unloaded µCT scans. Differences in mean stain volume fraction, mean load to failure, and mean bone volume/total volume (BV/TV) were compared between treatment groups using one-way ANOVAs. Pearson's correlation between stain volume fraction and load to failure by treatment was calculated using an adjusted load to failure divided by BV/TV. Stained damage fraction was significantly different between treatment groups (p=0.0029). Tukey post-hoc analysis showed untreated samples to have higher stain volume fraction (16.25±2.54%) than all treatment groups (p<0.05). The ZA group had the highest mean load to failure (195.60±84.49N), followed by untreated (142.33±53.08N), DTX (126.60±48.75N), and SBRT (95.50±44.96N), but differences did not reach significance (p=0.075). BV/TV was significantly higher in the ZA group (49.28±3.56%) compared to all others. The SBRT group had significantly lower BV/TV than the untreated group (p=0.018). Load divided by BV/TV was not significantly different between groups (p=0.24), but relative load to failure results were consistent (ZA>Untreated>DTX>SBRT). No correlations were found between stain volume fraction and load to failure. Focal and systemic cancer treatments effect microdamage accumulation and load to failure in osteolytic vertebrae. Current testing of healthy controls will help to further separate the effects of the tumour and cancer treatments on bone quality

Aim. Diagnosis of prosthetic joint infection are often complicated by the presence of biofilm, which hampers bacteria dislodging from the implants, thus affecting sensitivity of cultures. In the last 20 years several studies have evidenced the usefulness of implant sonication to improve microbial recovery from biofilm formed on inert substrates. More recently, treatment of prosthetic joints and tissues with Dithiothreitol, a sulphur compound already used in routine diagnostic workflow for fluidification of respiratory samples, has proved to be not inferior to sonication in microbiological diagnosis of prosthetic joint infections. This study aimed to evaluate if the combination of the two treatments could further improve microbial retrieval from biofilm in an in vitro model. Method. Three isolates of Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus lugdunensis, Eschericha coli and Pseudomonas aeruginosa responsible of prosthetic joint infections were used. They were grown onto 3 titanium discs (20 mm diameter) and incubated in 3 sterile plastic containers with 15 mL of Triptyc Soy Broth. After overnight incubation, not adhered cells were removed and fresh broth was added to each sample. After 48 hours incubation, the exausted broth was removed and one sample was used for sonication, one for treatment with 0,1% (v:v) Dithiothreitol and one treated with Dithiothreitol followed by sonication. Treated fluids were plated on Muller Hinton Agar plates for colony count. One-way ANOVA analysis was performed to evidence statistical differences between treatments. Results. Similar colony counts were observed for the 3 treatments: 10.1± 0.77 log CFU/mL for Dithiothreitol, 10.0 ± 0.75 for sonication and 10.1 ±0.73 for dithiothreitol + sonication. No statistical differences between the 3 treatments were evidenced by ANOVA analysis. Conclusions. Results seems to confirm that treatment with dithiothreitol is equivalent to sonication in recovering bacteria from biofilm grown on inert surface. Combining dithiotreitol treatment with sonication does not significantly improve bacterial recovery in respect to each treatment alone

Giant cell tumors of bone (GCTs) are locally aggressive tumors with recurrence potential that represent up to 10% of primary tumors of the bone. GCTs pathogenesis is driven by neoplastic mononuclear stromal cells that overexpress receptor activator of nuclear factor kappa-B/ligand (RANKL). Treatment with specific anti-RANKL antibody (denosumab) was recently introduced, used either as a neo-adjuvant in resectable tumors or as a stand-alone treatment in unresectable tumors. While denosumab has been increasingly used, a percentage of patients do not improve after treatment. Here, we aim to determine molecular and histological patterns that would help predicting GCTs response to denosumab to improve personalized treatment. Nine pre-treatment biopsies of patients with spinal GCT were collected at 2 centres. In 4 patients denosumab was used as a neo-adjuvant, 3 as a stand-alone and 2 received denosumab as adjuvant treatment. Clinical data was extracted retrospectively. Total mRNA was extracted by using a formalin-fixed paraffin-embedded extraction kit and we determined the transcript profile of 730 immune-oncology related genes by using the Pan Cancer Immune Profiling panel (Nanostring). The gene expression was compared between patients with good and poor response to Denosumab treatment by using the nSolver Analysis Software (Nanostring). Immunohistochemistry was performed in the tissue slides to characterize cell populations and immune response in CGTs. Two out of 9 patients showed poor clinical response with tumor progression and metastasis. Our analysis using unsupervised hierarchical clustering determined differences in gene expression between poor responders and good responders before denosumab treatment. Poor responding lesions are characterized by increased expression of inflammatory cytokines as IL8, IL1, interferon a and g, among a myriad of cytokines and chemokines (CCL25, IL5, IL26, IL25, IL13, CCL20, IL24, IL22, etc.), while good responders are characterized by elevated expression of platelets (CD31 and PECAM), coagulation (CD74, F13A1), and complement classic pathway (C1QB, C1R, C1QBP, C1S, C2) markers, together with extracellular matrix proteins (COL3A1, FN1,. Interestingly the T-cell response is also different between groups. Poor responding lesions have increased Th1 and Th2 component, but good responders have an increased Th17 component. Interestingly, the checkpoint inhibitor of the immune response PD1 (PDCD1) is increased ~10 fold in poor responders. This preliminary study using a novel experimental approach revealed differences in the immune response in GCTs associated with clinical response to denosumab. The increased activity of checkpoint inhibitor PD1 in poor responders to denosumab treatment may have implications for therapy, raising the potential to investigate immunotherapy as is currently used in other neoplasms. Further validation using a larger independent cohort will be required but these results could potentially identify the patients who would most benefit from denosumab therapy

Introduction. Various biomaterials and bone graft substitute technologies for use in osteomyelitis treatment are currently used in clinal practice. They vary in mode of action (with or without antibiotics) and clinical application (one-stage or two-stage surgery). This systematic review aims to compare the clinical evidence of different synthetic antimicrobial bone graft substitutes and antibiotic-loaded carriers in eradicating infection and clinical outcome in patients with chronic osteomyelitis. Methods. Systematic review according to PRISMA statement on publications 2002-2023. MESH terms: osteomyelitis and bone substitutes. FREE terms: chronic osteomyelitis, bone infection. A standardized data extraction form was be used to extract data from the included papers. Results. Publications with increased methodological quality and clinical evidence for biomaterials in osteomyelitis treatment were published in the last decades. High 85-95% eradication rates of osteomyelitis were observed for various resorbable Ca-P and/or Ca-S biomaterials combined with antibiotics and S53P4 bioactive glass. Level of evidence varies significantly between products. Antibiotic pharmacokinetic release profiles vary between resorbable Ca-P and/or Ca-S biomaterials. Conclusion. Given the high 85-95% eradication rates of osteomyelitis by various resorbable Ca-P and/or Ca-S biomaterials combined with antibiotics and S53P4 bioactive glass, one-stage treatment is preferred. Surgeons should be aware of variations in mechanical properties and antibiotic pharmacokinetic release profiles between Ca-P and CA-s products. Mechanical, biological and antimicrobial properties of bioactive glass are formulation dependent. Currently, only S53P4 bioactive glass has proven antimicrobial properties. Based on this systematic review antibiotic loaded fleeces should be used with caution and restraint

Aims. Early large treatment effects can arise in small studies, which lessen as more data accumulate. This study aimed to retrospectively examine whether early treatment effects occurred for two multicentre orthopaedic randomized controlled trials (RCTs) and explore biases related to this. Methods. Included RCTs were ProFHER (PROximal Fracture of the Humerus: Evaluation by Randomisation), a two-arm study of surgery versus non-surgical treatment for proximal humerus fractures, and UK FROST (United Kingdom Frozen Shoulder Trial), a three-arm study of two surgical and one non-surgical treatment for frozen shoulder. To determine whether early treatment effects were present, the primary outcome of Oxford Shoulder Score (OSS) was compared on forest plots for: the chief investigator’s (CI) site to the remaining sites, the first five sites opened to the other sites, and patients grouped in quintiles by randomization date. Potential for bias was assessed by comparing mean age and proportion of patients with indicators of poor outcome between included and excluded/non-consenting participants. Results. No bias in treatment effect was observed overall for the CI site, or the first five sites, compared with the remaining sites in either trial. An early treatment effect on the OSS was observed for the first quintile of participants recruited to ProFHER only (clinically relevant difference of seven points). Selection bias for age was observed in the ProFHER trial only, with slightly younger patients being recruited into the study. Both trials showed some selection bias for markers of poor prognosis, although these did not appear to change over time. Conclusion. No bias in treatment effects overall were found at the CI or early sites set-up. An early treatment effect was found in one of the two trials, which was likely a chance effect as this did not continue during the study. Selection bias was observed in both RCTs, however this was minimal and did not impact on outcome. Cite this article: Bone Jt Open 2023;4(2):96–103

Aim. Patients with late acute periprosthetic joint infections (PJI) and treated with surgical debridement have a high failure rate. Previous studies have shown that rheumatoid arthritis (RA) is an independent risk factor for treatment failure. We conducted a case-control study to identify predictors for failure in late acute PJI treatment in RA patients. We hypothesize that patients with RA have a higher failure rate compared to controls due to the use of immunosuppressive drugs. Method. Data of an international multicenter retrospective observational study was used. Late acute PJI was defined as a sudden onset of symptoms and signs of a PJI, more than 3 months after implantation. Failure of treatment was defined as persistent signs of infection, relapse with the same or reinfection with a different micro-organism, need for prosthesis removal or death. Cases with RA were matched with cases without RA based on the affected joint. A Cox survival analyses, stratified for RA, was used to calculate hazard ratio's (HR) for failure. Subgroup analyses were used to explore other predictors for treatment failure in RA patients. Results. A total of 40 patients with RA and 80 controls without RA were included. Treatment failure occurred in 65% patients with RA compared to 45% for controls (p= .052). 68% of patients with RA used immunosuppressive drugs at time of PJI diagnosis. The use or continuation of immunosuppressive drugs in PJI was not associated with a higher failure rate; neither were the duration of symptoms and causative microorganism. The time between implantation of the prosthetic joint and diagnosis of infection was longer in RA patients: median 110 (IQR 41-171) vs 29 months (IQR 7.5–101.25). Exchange of mobile components was associated with a lower risk of treatment failure (HR 0.489, 95% CI 0.242–0.989, p-value .047). Conclusions. The use of immunosuppressive drugs does not seem to be associated with a higher failure rate in patients with RA. Mobile exchange in RA patients is associated with a lower risk of failure. This might be due to the significantly older age of the prosthesis in RA patients. Future studies are needed to explore these associations and its underlying pathogenesis

Aim. This study assessed quality of life (QoL) in patients having external fixation for treatment of osteomyelitis and fracture-related infection (OM/FRI). Method. Patients who had surgery for OM/FRI and who completed the EuroQoL EQ-5D-5L or EQ-5D- 3L questionnaires, were identified between 2010 and 2020. Patients were followed-up for 2 years after surgery. QoL was compared between patients who had either an Ilizarov frame or a monolateral external fixator with those who did not receive external fixation. Results. 165 patients were included. Of these, 37 (22.4%) underwent application of external fixation which included 23 circular frames and 14 monolateral external fixators. Patients in the frame group had more BACH ‘Complex’ infections (34/37; 91.9%), compared to non-frame patients (57/81; 70.3%). Pre-operatively, the mean EQ-index score for patients planned to receive a frame (0.278 SD 0.427) was worse compared to other treatments (0.453 SD 0.338, p=0.083). At 6 weeks after surgery, the EQ-index score remained significantly lower in frame patients compared to non-frame patients (frame: 0.379 SD 0.363; no frame: 0.608 SD 0.326, p=0.016). By 6 months, 26/37 patients had undergone frame removal. The patients who had frames in situ at 6 months had lower EQ-index scores when compared to patients who had their frames removed (frame in situ: 0.187 SD 0.213; frame removed 0.674 SD 0.206, p=0.076). At one year, 36/37 (97.3%) patients had their frame removed. QoL had greatly improved, to levels similar to non-frame patients (no frame: 0.652 SD 0.357; frame removed: 0.657 SD 0.247, p=0.949). Conclusions. Frame treatment leads to significant improvement in Quality of Life in patients suffering from osteomyelitis, with similar results in EQ5D scores after 1 year compared to patients who did not need an external fixator. These effects cannot be felt until after the frame has been removed with impaired QoL during frame treatment, especially in those patients with frames in situ for more than 6 months. This underlines the need for close and professional patient support during frame treatment for bone infection