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. 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

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

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

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

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. Smoking is known to impair wound healing and to increase the risk of peri-operative adverse events and is associated with orthopaedic infection and fracture non-union. Understanding the magnitude of the causal effect on orthopaedic infection recurrence may improve pre-operative patient counselling. Methods. Four prospectively-collected datasets including 1173 participants treated in European centres between 2003 and 2021, followed up to 12 months after surgery for clinically diagnosed orthopaedic infections, were included in logistic regression modelling with Inverse Probability of Treatment Weighting for current smoking status [1–3]. Host factors including age, gender and ASA score were included as potential confounding variables, interacting through surgical treatment as a collider variable in a pre-specified structural causal model informed by clinical experience. The definition of infection recurrence was identical and ascertained separately from baseline factors in three contributing cohorts. A subset of 669 participants with positive histology, microbiology or a sinus at the time of surgery, were analysed separately. Results. Participants were 64% male, with a median age of 60 years (range 18–95); 16% of participants experienced treatment failure by 12 months. 1171 of 1173 participants had current smoking status recorded. As expected for the European population, current smoking was less frequent in older participants (Table 1). There was no baseline association between Charlson score or ASA score and smoking status (p=0.9, p=1, Chi squared test). The estimated adjusted odds ratio for treatment failure at 12 months, resulting from current smoking at the time of surgery, was 1.37 for all participants (95% CI 0.75 to 2.50) and 1.53 for participants with recorded confirmatory criteria (95% CI 1.14 to 6.37). Conclusions. Smoking contributes to infection recurrence, particularly in people with unequivocal evidence of osteomyelitis or PJI. People awaiting surgery for orthopaedic infection should be supported to cease smoking, not only to reduce anaesthetic risk, but to improve treatment outcomes. Limitations of this study include unmeasured socioeconomic confounding and social desirability bias resulting in uncertainty in true smoking status, resulting in underestimated effect size

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

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

Aim. The treatment of fracture-related infections (FRI) focuses on obtaining fracture healing and eradicating infection to prevent osteomyelitis. Treatment guidelines include removal, exchange, or retention of the implants used according to the stability of the fracture and the time from the infection. Infection of a fracture in the process of healing with a stable fixation may be treated with implant retention, debridement, and antibiotics. Nonetheless, the retention of an intramedullary nail is a potential risk factor for failure, and it is recommended to exchange or remove the nail. This surgical approach implies additional life-threatening risks in elderly fragile hip fracture patients. Our study aimed to analyze the results of implant retention for the treatment of infected nails in elderly hip fracture patients. Methods. Our retrospective analysis included patients 65 years of age or older with an acute fracture-related infection treated with implant retention from 2012 to 2020 in 6 Spanish hospitals with a minimum 1-year follow-up. Patients that required open reduction during the initial fracture surgery were excluded. Variables included in our analysis were patient demographics, type of fracture, date of FRI diagnosis, causative microorganism, and outcome. Treatment success was defined as fracture healing with infection eradication without the need for further hospitalization. Results. A total of 48 patients were identified. Eight patients with open reduction were excluded and 11 did not complete a 1-year follow-up. Out of the 29 remaining patients, the mean age was 81.5 years, with a 21:9, female to male ratio. FRI was diagnosed between 10 and 48 days after initial surgery (mean 26 days). Treatment success was achieved in 24 patients (82.7%). Failure was objectivated in polymicrobial infections or infections caused by microorganisms resistant to antibiofilm antibiotics. Seven patients required more than one debridement with a success rate of 57%. Twelve patients had an infection diagnosed after 21 days from the initial surgery and implant retention was successful in all of them. Conclusion. Our results suggest implant retention is a valid therapeutic approach for fracture-related infection in elderly hip fracture patients treated by closed reduction and intramedullary nailing

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. 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

The Pavlik harness (PH) is commonly used to treat infantile dislocated hips. Variability exists in the duration of brace treatment after successful reduction of the dislocated hip. In this study we evaluate the effect of prescribed time in brace on acetabular index (AI) at two years of age using a prospective, international, multicenter database. We retrospectively studied prospectively enrolled infants with at least one dislocated hip that were initially treated with a PH and had a recorded AI at two-year follow-up. Subjects were treated at one of two institutions. Institution 1 used the PH until they observed normal radiographic acetabular development. Institution 2 followed a structured 12-week brace treatment protocol. Hip dislocation was defined as less than 30% femoral head coverage at rest on the pre-treatment ultrasound or IHDI grade III or IV on the pre-treatment radiograph. Fifty-three hips met our inclusion criteria. Hips from Institution 1 were treated with a brace 3x longer than hips from institution 2 (adjusted mean 8.9±1.3 months vs 2.6±0.2 months)(p < 0 .001). Institution 1 had an 88% success rate and institution 2 had an 85% success rate at achieving hip reduction (p=0.735). At 2-year follow-up, we observed no significant difference in AI between Institution 1 (adjusted mean 25.6±0.9˚) compared to Institution 2 (adjusted mean 23.5±0.8˚) (p=0.1). However, 19% of patients from Institution 1 and 44% of patients from Institution 2 were at or below the 50th percentile of previously published age- and sex- matched AI normal data (p=0.049). Also, 27% (7/26) of hips from Institution 1 had significant acetabular dysplasia, compared to a 22% (6/27) from Institution 2 (p=0.691). We found no correlation between age at initiation of bracing and AI at 2-year follow-up (p=0.071). Our findings suggest that prolonged brace treatment does not result in improved acetabular index at age two years. Hips treated at Institution 1 had the same AI at age two years as hips treated at Institution 2, while spending about 1/3 the amount of time in a brace. We recommend close follow-up for all children treated for dislocated hips, as ~1/4 of infants had acetabular index measurements at or above the 90th percentile of normal. Continued follow-up of this prospective cohort will be critical to determine how many children require acetabular procedures during childhood. The PH brace can successfully treat dislocated infant hips, however, prolonged brace treatment was not found to result in improved acetabular development at two-year follow-up

Aim. Debridement, antibiotics, and implant retention (DAIR) is a viable treatment option for acute periprosthetic joint infections (PJI). The landmark DATIPO trial of Bernard et al. concluded that six weeks is not non-inferior to 12-week antibiotic therapy for DAIR. However, it is unknown if suppressive antibiotic treatment (SAT) would improve patient outcomes. Therefore, our study aims to evaluate the utility of SAT after 12 weeks of therapy. Method. We performed a retrospective study of patients with acute hip or knee PJI managed with DAIR at five institutions; in the U.S. (n=1), Netherlands (n=3), and Spain (n=1) from 2005–2020. We analyzed the effect of SAT using a Cox model among patients after 12 weeks of antibiotic treatment. The primary covariate of interest was whether the patient was on antibiotics after week 12, which was coded as a time-varying covariate. We decided a-priori to control for the clinically important risk factors such as age, sex, type of infection, modular exchange, joint, and presence of bacteremia and Staphylococcus aureus. We excluded patients who died, had treatment failure, or were lost to follow-up before 12 weeks. We defined treatment failure as infection recurrence (same or different organism), unexpected reoperation, or death due to infection. Results. There were 504 patients included in the study. The majority were female (58%, n=292), with a mean age of 70 years ago (SD 11). Hips and knees were equally proportioned. Primary arthroplasties represented 69% of the total cohort (n=349). Treatment failure was 11.9% in the total cohort (n=60). There was no statistically significant association between SAT after 12 weeks and treatment failure (HR 1.25, p=0.45, 95% CI 0.70–2.24). This finding was consistent across different subgroups, including hip or knee joints, early or late acute infections, cohort, and a subgroup of knee joints after 180 days. Conclusions. SAT after 12 weeks of antibiotic treatment for acute PJI managed with DAIR does not appear to improve patient outcomes

Introduction. Non-union is an unfortunate outcome of the fracture healing process for some patients; with an estimated annual incidence of 17.4- 18.9 per 100,00. The management of these patients depicts a significant clinical challenge for surgeons and financial burden to health services. External ultrasound stimulation devices (Exogen. TM. ) have been highlighted as a novel non invasive therapy to achieve union in cases of delayed and non-union. The aim of the current study was to assess the rate of union in patients using Exogen. TM. therapy for delayed fracture union in a district general hospital. Materials & Methods. This is a single centre retrospective continuous cohort study. Patients were identified from a prospective database of all patients prescribed Exogen. TM. therapy between June 2013- September 2021 in a district general hospital. Patient data was collected retrospectively using electronic patient records. Fracture union was assessed both clinically and radiographically and recorded in patient records. Failure of treatment was defined as progression to operative treatment due to lack of progression with ultrasound therapy or established asymptomatic non-union. Patient were excluded from the study if Exogen. TM. therapy was prescribed within 6 weeks of injury. Results. 142 potential patient were identified from the database. 35 patients were excluded from the data set (17 patients due to insufficient data available, 9 lost to follow up, 4 died and 5 excluded due to early application of Exogen. TM. therapy). 58 Patients progressed to union with an average time to union of 41 weeks. 49 cases failed to progress to union, of which 7 cases had conversion to operative management prior to completion of single course of Exogen. TM. therapy and were excluded from all other data review. 12% of cases that failed to unite with ultrasound therapy required multiple operations to establish union. Conclusions. A union rate of 58% was reported by the current study, which is lower than previously published. This likely reflects the heterogenous nature of the patient population and fracture distribution included. However, this is potentially a more reflective union rate for the general population than previously published. There were no adverse events associated with the use of Exogen. TM. therapy in the current study. Therefore supporting its use as a first line management to promote union in delayed fracture union in the general population. Additionally, failure to achieve fracture union with utilisation of Exogen. TM. therapy was associated with risk for requirement of multiple surgeries to achieve union. This could serve as an indicator for surgeon to consider the requirement additional measures at the initial surgical procedure