Aim. Treatment algorithms for fracture-related nonunion depend on the presence or absence of bacterial infection. However, the manifestation of septic nonunion varies. Low-grade infections, unlike manifest infections, lack clinical signs of infection and present similarly to aseptic nonunion. The clinical importance of low-grade infection in nonunion is not entirely clear. Therefore, the aim of this study was to evaluate the clinical relevance of low-grade infection in the development and management of femoral or tibial nonunion. Method. A prospective, multicenter clinical study enrolled patients with nonunion and regular healed fractures. Preoperatively, complete blood count without differential, C-reactive protein (CRP), and procalcitonin were obtained, clinical signs of infection were recorded, and a suspected septic or aseptic diagnosis was made based on history and clinical examination. During surgical nonunion revision or routine implant removal, tissue samples were collected for microbiology and histopathology, and osteosynthesis material for sonication. Nonunion patients were followed for 12 months. Definitive diagnosis of “septic” or “aseptic” nonunion was made according to diagnostic criteria for fracture-related infection, considering the results of any further revision surgery during follow-up. Results. 34 patients with regular healed fractures were included. 62 nonunion patients were diagnosed as aseptic, 22 with manifest, and 23 with low-grade infection. The positive predictive value was 88% and the negative predictive value 72% for the suspected diagnosis. The nonunion groups had significantly higher CRP levels than the regular healer group. Differentiation between septic and aseptic nonunion based on blood values was not possible. Low-grade infection demonstrated less frequently histopathologic signs of infection than manifest infection (22% vs. 50%, p=0.048), with 15% of regular healers having histopathologic signs of infection. Cutibacterium acnes was less present in manifest compared to low-grade infection (p=0.042). Healing rates for septic nonunion involving C. acnes were significantly lower for manifest infection (20%) than for low-grade infection (100%, p=0.002). Patients with low-grade infection were treated with systemic antibiotics less frequently than patients with manifest infection (p=0.026), with no significant difference in healing rate (83% vs. 64%), which was slightly lower for low-grade infection than for aseptic nonunion (90%). Conclusions. Low-grade infections play a significant role in nonunion development and are difficult to diagnose preoperatively due to the lack of clinical signs of infection and unremarkable blood counts. However, our results imply that for low-grade infections, antibiotic therapy may not always be mandatory to heal the nonunion. This study was supported by the German Social Accident Insurance (FF-FR0276)

The purpose of this study was to develop a quality appraisal tool for the assessment of laboratory basic science biomechanical studies. Materials andScore development comprised of the following phases: item identification/development, item reduction, content/face/criterion validity, weighting, test-retest reliability and internal consistency. For item identification/development, the panel was asked to independently list criteria and factors they considered important for cadaver study and generate items that should be used to appraise cadaver study quality. For content validity, the content validity ratio (CVR) was calculated. The minimum accepted content validity index (CVI) was set to 0.85. For weighting, equal weight for each item was 6.7% [15 items]. Based on these figures the panel was asked to either upscale or downscale the weight for each item ensuring that the final sum for all items was 100%. Face validity was assessed by each panel member using a Likert scale from 1–7. Strong face validity was defined as a mean score of >5. Test-retest reliability was assessed using 10 randomly selected studies. Criterion validity was assessed using the QUACS scale as standard. Internal consistency was assessed using Cronbach's alpha. Five items reached a CVI of 1 and 10 items a CVI of 0.875. For weighting five items reached a final weight of 10% and ten items 5%. The mean score for face validity was 5.6. Test-retest reliability ranged from 0.78–1.00 with 9 items reaching a perfect score. Criterion validity was 0.76 and considered to be strong. Cronbach's alpha was calculated to be 0.71 indicating acceptable internal consistency. The new proposed quality score for basic science studies consists of 15 items and has been shown to be reliable, valid and of acceptable internal consistency. It is suggested that this score should be utilised when assessing basic science studies

The treatment of paediatric supracondylar humeral fractures is likely one of the first procedures involving X-ray guided wire insertion that trainee orthopaedic surgeons will encounter. Pinning is a skill that requires high levels of anatomical knowledge, spatial awareness, and hand-eye coordination. We developed a simulation model using silicone soft-tissue and 3D-printed bones to allow development and practice of this skill at no additional risk to patients. For this model, we have focused on reusability and lowering raw-material costs without compromising fidelity. To achieve this, the initial bone model was extracted from open-source computed tomography scans and modified from adult to paediatric size. Muscle of appropriate robustness was then sculpted around the bones using 3D modelling software. A cutaneous layer was developed to mimic oedema using clay sculpturing on a plaster-casted paediatric forearm. These models were then used for 3D-printing and silicone casting respectively. The bone models were printed with settings to imitate cortical and cancellous densities and give high-fidelity tactile feedback upon drilling. Each humerus costs NZD $0.30 in material to print and can be used 1–3 times. Silicone casting of the soft-tissue layers imitates differing relative densities between muscle and oedematous cutaneous tissue, thereby increasing skill necessary to accurately palpate landmarks. Each soft-tissue sleeve cost NZD $70 in material costs to produce and can be used 20+ times. The resulting model is modular, reusable, and replaceable, with each component standardised and easily reproduced. It can be used to practice land-mark palpation and Kirschner wire pinning and is especially valuable in smaller centres which may not be able to afford traditional Saw Bones models. This low-cost model thereby improves equity while maintaining quality of simulation training

Hip resurfacing may be a useful surgical procedure when patient selection is correct and only implants with superior performance are used. In order to establish a body of evidence in relation to hip resurfacing, pseudotumour formation and its genetic predisposition, we performed a case-control study investigating the role of HLA genotype in the development of pseudotumour around MoM hip resurfacings. All metal-on-metal (MoM) hip resurfacings performed in the history of the institution were assessed. A total of 392 hip resurfacings were performed by 12 surgeons between February 1st 2005 and October 31st 2007. In all cases, pseudotumour was confirmed in the preoperative setting on Metal Artefact Reduction Sequencing (MARS) MRI. Controls were matched by implant (ASR or BHR) and absence of pseudotumour was confirmed on MRI. Blood samples from all cases and controls underwent genetic analysis using Next Generation Sequencing (NGS) assessing for the following alleles of 11 HLA loci (A, B, C, DRB1, DRB3/4/5, DQA1, DQB1, DPB1, DPA1). Statistical significance was determined using a Fisher's exact test or Chi-Squared test given the small sample size to quantify the clinical association between HLA genotype and the need for revision surgery due to pseudotumour. Both groups were matched for implant type (55% ASR, 45% BHR in both the case and control groups). According to the ALVAL histological classification described by Kurmis et al., the majority of cases (63%, n=10) were found to have group 2 histological findings. Four cases (25%) had group 3 histological findings and 2 (12%) patients had group 4 findings. Of the 11 HLA loci analysed, 2 were significantly associated with a higher risk of pseudotumour formation (DQB1*05:03:01 and DRB1*14:54:01) and 4 were noted to be protective against pseudotumour formation (DQA1*03:01:01, DRB1*04:04:01, C*01:02:01, B*27:05:02). These findings further develop the knowledge base around specific HLA genotypes and their role in the development of pseudotumour formation in MoM hip resurfacing. Specifically, the two alleles at higher risk of pseudotumour formation (DQB1*05:03:01 and DRB1*14:54:01) in MoM hip resurfacing should be noted, particularly as patient-specific genotype-dependent surgical treatments continue to develop in the future

Numerous prediction tools are available for estimating postoperative risk following spine surgery. External validation studies have shown mixed results. We present the development, validation, and comparative evaluation of novel tool (NZSpine) for modelling risk of complications within 30 days of spine surgery. Data was gathered retrospectively from medical records of patients who underwent spine surgery at Waikato Hospital between January 2019 and December 2020 (n = 488). Variables were selected a priori based on previous evidence and clinical judgement. Postoperative adverse events were classified objectively using the Comprehensive Complication Index. Models were constructed for the occurrence of any complication and significant complications (based on CCI >26). Performance and clinical utility of the novel model was compared against SpineSage (. https://depts.washington.edu/spinersk/. ), an extant online tool which we have shown in unpublished work to be valid in our local population. Overall complication rate was 34%. In the multivariate model, higher age, increased surgical invasiveness and the presence of preoperative anemia were most strongly predictive of any postoperative complication (OR = 1.03, 1.09, 2.1 respectively, p <0.001), whereas the occurrence of a major postoperative complication (CCI >26) was most strongly associated with the presence of respiratory disease (OR = 2.82, p <0.001). Internal validation using the bootstrapped models showed the model was robust, with an AUC of 0.73. Using sensitivity analysis, 80% of the model's predictions were correct. By comparison SpineSage had an AUC of 0.71, and in decision curve analysis the novel model showed greater expected benefit at all thresholds of risk. NZSpine is a novel risk assessment tool for patients undergoing acute and elective spine surgery and may help inform clinicians and patients of their prognosis. Use of an objective tool may help to provide uniformity between DHBs when completing the “clinician assessment of risk” section of the national prioritization tool

Tendinopathy is one of the most common orthopaedic pathological conditions characterized by tendon degenerative changes. Excessive mechanical loading is considered as a major causative factor in the development of tendinopathy, but the mechanisms of pathogenesis remain unclear. High mobility group box-1 (HMGB1), a potent inflammatory mediator when released into the matrix, has been identified in the early stage tendinopathy patients. Since the release and contribution of HMGB1 in tendinopathy development due to mechanical overloading is unknown, we investigated the role of HMGB1 in tendinopathy using a mouse intensive treadmill running (ITR) model and injection of glycyrrhizin (GL), a specific inhibitor of HMGB1. A total of 48 mice were divided into four groups, Cage Control group: The animals were allowed to move freely in their cage, GL group: The animals were received daily IP injection of GL (50 mg/kg body weight) for 24 weeks, ITR group: The animals ran on treadmill at 15 meters/min for three h/ day, five days a week for 12 or 24 weeks, GL+ITR group: The animals ran the same protocol as that of ITR group plus daily IP injection of GL for 12 or 24 weeks. Six mice/group were sacrificed at 12 or 24 weeks and the Achilles and patellar tendon tissues were harvested and used for histochemical staining and immunostaining. Mechanical overloading induced HMGB1 released from the cell nuclei to the matrix (Fig. 1a, b) caused tendon inflammation (Fig. 1c, d) and led to tendon degenerative changes (Fig. 1e-j). After 12 weeks of ITR, the tendon tissue near the bone insertion site showed typical tendinopathic changes in cell shape, accumulation of glycosaminoglycans (GAG) (Fig. 1e, f), and increase in SOX-9 staining (Fig. 1g-j). After 24 weeks ITR, the distal site of Achilles tendon showed considerable changes in cell shape (Fig. 2A, g, arrows), which is round compared to more elongated in the control and GL groups (Fig. 2A, e, f). However, daily treatment with GL prior to ITR blocked the cell shape change (Fig. 2A, h) and, ITR induced extensive GAG accumulation in ITR group (Fig. 2B, bottom panel). Furthermore, GL inhibited ITR-induced expression of chondrogenic markers (SOX-9 and collagen II) in the tendons (Fig. 3). Our results showed that mechanical overloading-induced HMGB1 plays a critical role in the development of tendinopathy by initiating tendon inflammation and eventual degeneration characterized by the presence of chondrocyte-like cells, accumulation of proteoglycans, high levels of collagen type II production, and chondrogenic marker SOX-9 expression. These results provide the first evidence for the role of HMGB1 as a therapeutic target to prevent tendinopathy before its onset and block further development at its early inflammation stages. The inhibition of tendinopathy development by GL administration in this study also suggests the putative therapeutic potential of this natural triterpene that is already in clinical use to treat other inflammation-related diseases. For any figures or tables, please contact authors directly

Aim. The aim of this study was to develop an in-house multiplex PCR real-time assay on the LightCycler 480 system (Roche, Basel, Switzerland) with the aim of rapid detection of common pathogens in prosthetic joint infections (PJI), followed by validation on clinical samples (sonication fluid and tissue biopsies) routinely collected for PJI diagnosis. Methods. Using the PrimerQuest and CLC WorkBench tool, we designed six primer sets with specific fluorescently labelled TaqMan probes for the nuc gene in different Staphylococcus species (S. aureus, S. epidermidis, S. capitis, S. lugdunensis, S. hominis, S. haemolyticus). In addition, primers previously developed by Renz et al. (2022) for C. acnes were integrated into our assay with internal control of isolation, leading to the development of specific mPCR assay with seven included targets. Analytical sensitivity and specificity were evaluated using reference bacterial strains. To determine the assay's limit of detection (LOD), we conducted serial dilutions of eluates containing known concentrations of bacterial DNA copies/µl. The overall LOD in spiked clinical samples, including sample preparation and DNA isolation on MagnaPure24, was measured through 10-fold serial dilutions (from 10. 9. to 10. -1. CFU/ml) including additional dilutions of 5000, 500, 50 and 5 CFU/ml. Results. The results with LOD in serial dilutions of eluates and spiked clinical samples, together with analytical sensitivity and specificity, are shown in Table 1. Conclusion. The mPCR assay showed excellent analytical sensitivity and specificity, but with considerably lower LOD after sample preparation and further DNA isolation in spiked clinical samples. Although still promising in diagnostics of acute infections, the use of mPCR could be challenging in chronic, low-grade infections with lower microbial burden. Nevertheless, PCR offers significant advantages in terms of speed and can shorten the time to result, especially for C. acnes infections. Additionally, it represents a promising complementary approach in patients with suspected PJI on antibiotic therapy with negative culture results. For any tables or figures, please contact the authors directly

Aim. To develop a new system for antibacterial coating of joint prosthesis and osteosynthesis material. The new coating system was designed to release gentamicin immediately after insertion to eradicate surgical contamination. Method. Steel implants (2×15mm) were coated with a solid nanocomposite xerogel made from silica and the dendritic polymer, hyperbranched polyethyleneimine. The xerogel was anchored inside a porous surface made by pre-coating with titanium microspheres. Finally, gentamicin was encapsulated in the xerogel, i.e. no chemical binding. A total of 50 µg gentamicin was captured into each implant. The efficacy of the new coating was evaluated in a porcine model of implant associated osteomyelitis. In total, 30 female pigs were randomized into 3 study groups (n=10). Group A; plain implants + saline, Group B; plain implants + 10. 4. CFU of Staphylococcus aureus, and Group C; coated implants + 10. 4. CFU of S. aureus. Implant + inoculum was placed into a pre-drilled implant cavity of the right tibia and the pig was euthanized 5 days afterwards. Postmortem microbiology and pathology were performed. Two additional pigs were used in a pharmacokinetic study where microdialysis (MD) catheters were placed alongside coated implants. Extracellular fluid was sampled regularly for 24 hours from the MD catheters and analyzed for gentamicin content. Results. Within Groups A and C, all implants were found sterile by sonication and bacteria could not be identified within the surrounding bone tissue. In contrast, all Group B animals had S. aureus positive implant and tissue microbiology. Macroscopic and microscopic pathological examinations confirmed that Group A and C animals were complete identic, i.e. no pus around implants and only minor peri-implant inflammation related to insertion of implants per se. All Group B animals had pus around their implants and a massive peri-implant inflammatory response dominated by neutrophil granulocytes. Maximum gentamicin release (35 µg /mL) was measured in the first obtained MD sample, i.e. after 30 min, and the concentration stayed above the MIC level for the used S. aureus strain for 8 hours. Conclusions. The new xerogel coating prevented development of osteomyelitis. Prevention was due to a fast gentamicin release immediately following insertion and antimicrobial active concentrations were detectable several hours after implantation. This means that the critical time point of most relevant surgical procedures potentially could be protected by the novel coating. The new coating will be investigated on larger scale implants and full-size prosthesis in the future

Aim. There is an ongoing controversy whether the observed benefit of infection risk reduction by ALBC outweighs the risk of possible antimicrobial resistance development. Methods. The scientific & clinical literature in PubMed, Medline and Embase has been systematically reviewed with the keywords “antibiotic resistance”, “antibiotic loaded bone cement”, “local antibiotics”, “bacterial colonization” and “joint infection”. In total 28 relevant publications were found with the majority of them reporting laboratory results. Only 7 papers focused on clinical septic situations & patient data. Results. Although rare as consequence of the initially high drug concentrations in situ, experimental and clinical studies demonstrated survival of resistant bacteria on ALBC with subsequent bacterial re-colonisation of the biomaterial. This was most notable for coagulase-negative staphylococci (CoNS). Bacterial survival in presence of ALBC represents a selection process of already pre-existing high-level resistant mutants and not antibiotic resistance induction. The use of antibiotic combinations with gentamicin in bone cement is associated with a markedly lower risk of survival of resistant bacteria. This is particularly important in patients at high infection risks and in septic revision cases. There is no clinical evidence for a widespread increase of clinically important gentamicin resistancies in the orthopaedic ward because of routine use of ALBC. On an individual basis, the benefit of a lower infection probability with combined systemic & local antibiotic application should outweigh the risk of selecting pre-existing resistant bacteria. Each prevented infection case means that a complex and extended antibiotic therapy with risk of antibiotic resistance development over time has been avoided for a patient. In those cases where pre-existing resistant bacteria have survived the prophylactic exposure to antibiotics in bone cement, they remain in vast majority still susceptible to the clinically important antibiotics used for treatment of prosthetic joint infections. Conclusions. The benefit of a lower infection probability with ALBC should outweigh the risk of selecting resistant bacteria against the particular antibiotic used in bone cement. A trend towards broad resistance development which may complicate treatment of infection cases was not found

Aim. Bacteriophages, viruses specific of bacteria, are receiving substantial attention as alternative antibacterial agents to treat bacteria frequently multi-resistant to antibiotics and/or able to form biofilms, such as staphylococci. The latter are responsible for very difficult to treat bone and joint infections (BJIs). In this context, our consortium aims to develop a production of therapeutic phages in accordance with the will of ANSM (French National Agency for the Safety of Medicines and Health Products) to encourage the development of a national academic platform for phage therapy. We report the isolation and characterization of new anti-Staphylococcus phages as well as the evaluation of their activity on a collection of clinical strains of S. aureus (SA) and coagulase-negative staphylococci (CNS) in order to assess their therapeutic potential. Method. Seventeen phages were isolated from wastewater samples. Their identification was obtained by Illumina whole genome sequencing. To evaluate their spectrum of activity, 30 genetically characterized SA strains representative of the main genetic backgrounds as well as 32 strains belonging to 7 CNS species responsible for BJIs were included. The spot test technique, based on the determination of the Efficiency Of Plating ratio, was used (EOP, ratio between the phage titer obtained on a tested strain/titer on a reference strain, close to 1 if high sensitivity to the phage). Results. All isolated phages belonged to the Myoviridae family: 14/17 and 3/17 to the Kayvirus and Silviavirus genera respectively. Silviavirus phages were more active on SA strains (EOP>0.001 for 73–90% of strains) than Kayvirus phages (EOP>0.001 for 13–70% of strains, except for V1SA21: 80%). In total, 83% of strains were susceptible to the phage with the broadest spectrum in each genus, their combination representing a promising opportunity to prevent the emergence of resistance. Kayvirus phages had polyvalent activity on several CNS species (maximum 47% of tested strains), mainly S. lugdunensis, S. capitis and S. caprae, whereas Silviavirus phages were only active on 6–12% of the tested strains. Conclusions. We report the characterization of a large collection of novel phages with complementary spectra against a collection of SA and CNS strains. Further work is currently focused on i) the isolation of anti-S. epidermidis phages, bacterial species against which the present collection of phages was insufficiently active, while it is a major pathogen in this context, ii) the development of production and purification protocols in order to meet the requirements of ANSM for human use

Spinal stenosis is a condition resulting in the compression of the neural elements due to narrowing of the spinal canal. Anatomical factors including enlargement of the facet joints, thickening of the ligaments, and bulging or collapse of the intervertebral discs contribute to the compression. Decompression surgery alleviates spinal stenosis through a laminectomy involving the resection of bone and ligament. Spinal decompression surgery requires appropriate planning and variable strategies depending on the specific situation. Given the potential for neural complications, there exist significant barriers to residents and fellows obtaining adequate experience performing spinal decompression in the operating room. Virtual teaching tools exist for learning instrumentation which can enhance the quality of orthopaedic training, building competency and procedural understanding. However, virtual simulation tools are lacking for decompression surgery. The aim of this work was to develop an open-source 3D virtual simulator as a teaching tool to improve orthopaedic training in spinal decompression. A custom step-wise spinal decompression simulator workflow was built using 3D Slicer, an open-source software development platform for medical image visualization and processing. The procedural steps include multimodal patient-specific loading and fusion of Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) data, bone threshold-based segmentation, soft tissue segmentation, surgical planning, and a laminectomy and spinal decompression simulation. Fusion of CT and MRI elements was achieved using Fiducial-Based Registration which aligned the scans based on manually placed points allowing for the identification of the relative position of soft and hard tissues. Soft tissue segmentation of the spinal cord, the cerebrospinal fluid, the cauda equina, and the ligamentum flavum was performed using Simple Region Growing Segmentation (with manual adjustment allowed) involving the selection of structures on T1 and/or T2-weighted scans. A high-fidelity 3D model of the bony and soft tissue anatomy was generated with the resulting surgical exposure defined by labeled vertebrae simulating the central surgical incision. Bone and soft tissue resecting tools were developed by customizing manual 3D segmentation tools. Simulating a laminectomy was enabled through bone and ligamentum flavum resection at the site of compression. Elimination of the stenosis enabled decompression of the neural elements simulated by interpolation of the undeformed anatomy above and below the site of compression using Fill Between Slices to reestablish pre-compression neural tissue anatomy. The completed workflow allows patient specific simulation of decompression procedures by staff surgeons, fellows and residents. Qualitatively, good visualization was achieved of merged soft tissue and bony anatomy. Procedural accuracy, the design of resecting tools, and modeling of the impact of bone and ligament removal was found to adequately encompass important challenges in decompression surgery. This software development project has resulted in a well-characterized freely accessible tool for simulating spinal decompression surgery. Future work will integrate and evaluate the simulator within existing orthopaedic resident competency-based curriculum and fellowship training instruction. Best practices for effectively teaching decompression in tight areas of spinal stenosis using virtual simulation will also be investigated in future work

Introduction. According to American Joint Replacement Registry, particle mediated osteolysis represents 13 % of the knee revision surgeries performed in the United States. The comprehension of mechanical and wear properties of materials envisioned for TJR is a key step in product development. Furthermore, the maintenance of UHMWPE mechanical properties after material modification is an important aspect of material success. Initial studies conducted by our research group demonstrated that the incorporation of ibuprofen in UHMWPE had a minor impact on UHMWPE physicochemical and mechanical properties. Drug release was also evaluated and resulted in an interesting profile as a material to be used as an anti-inflammatory system. Therefore, the present study investigated the effect of drug release on the mechanical and biological properties of ibuprofen-loaded UHMWPE. Experimental. UHMWPE resin GUR 1020 from Ticona was for sample preparation. Samples with drug concentrations of 3% and 5% wt were consolidated as well as samples without anti-inflammatory addition through compression molding at 150 °C and 5 MPa for 15 minutes. Mechanical properties were evaluated via the tensile strength experiment (ASTM D638) and dynamic mechanic tests. Wear resistance was measured using the pin on disc (POD) apparatus. Finally, cytotoxicity analysis was conducted based on ISO 10993–5. Results. Dynamic-mechanic analysis demonstrated no difference in flexion modulus and stress for all materials (Table 1). No difference was also verified during cyclical loading experiments (Table 1), which indicates that the drug concentration added to material composition did not affect these properties. POD experiments were proposed to evaluate wear resistance of ibuprofen-loaded UHMWPE samples considering the combination of materials similar to those employed in TJR. Results from POD tests are presented in Table 1. Volumetric wear was close to zero for all samples after 200 thousand cycles. Comprehension of the effect of drug release on mechanical properties is essential to estimate how the material will behave after implantation. Therefore, mechanical properties were assessed after 30 days of ibuprofen release and the results were compared with those obtained in samples as prepared (Table 2). Initial results demonstrated a decrease in elastic modulus in samples prepared with ibuprofen. However, no difference was verified between UHMWPE, UHMWPE 3% IBU and UHMWPE 5% IBU after ibuprofen release. Finally, cell viability of UHMWPE 3% IBU and UHMWPE 5% was found to be superior to 100% (Figure 1). Therefore, both materials can be considered nontoxic. Conclusions. Ibuprofen-loaded UHMWPE did not demonstrate a significant influence on the mechanical and biological behavior of UHMWPE. Dynamic-mechanical tests demonstrated constancy for all samples under analysis. Wear testing resulted in gravimetric wear close to zero, for all tested materials. Mechanical properties conducted after 30 days of ibuprofen release also had a positive outcome. Although presenting a difference in modulus prior and after release tests, modulus and tensile yield stress remained inside acceptable range indicated to UHMWPE used in orthopedic implants. Furthermore, after drug elution UHMWPE 3% IBU and UHMWPE 5% IBU recovered original UHMWPE properties. Cytotoxicity assessment was performed and both ibuprofen-based formulations were considered nontoxic according to ISO 10993–5. For any figures or tables, please contact the authors directly

BACKGROUND. Telerehabilitation has been shown to both promote effective recovery after shoulder arthroplasty and may improve adherence to treatment. Such systems require demonstration of feasibility, ease of use, efficacy, patient and clinician satisfaction, and overall cost of care, and much of this data has yet to be provided. Few augmented reality rehabilitation approaches have been developed to date. Evidence suggests augmented reality rehabilitation may be equivalent to conventional methods for adherence, improvement of function, and relief of pain seen in these musculoskeletal conditions. We proposed that the development of an augmented reality rehabilitation platform during the pre and postoperative period (including post-shoulder arthroplasty) could be used to track patient activity and range of motion as well as promote recovery. METHODS. A prototype augmented reality platform equipped with a motion sensor system optimised for the upper arm was developed to be used to validate 4 arcs of shoulder motion and complete directed upper arm exercises designed for post-shoulder arthroplasty rehabilitation was built and tested. This system combined augmented reality instructions and motion tracking to follow patients over the course of their therapy, along with a telehealth patient-clinician interface. FINDINGS. The augmented reality platform was tested to validate shoulder range of motion examination similar to that of standard goniometer measurements. Healthy test subjects without shoulder pain or prior shoulder surgery performed the arcs of motion for 5 repetitions as part of a home therapy program. Each motion was measured with angular measurements as a proof of concept with high degree precision (less than 5 degrees). Remote patient-clinician interface testing was also conducted along with a clinician established therapy plan. DISCUSSION. Augmented reality systems that track patients' complex movements, including clinical shoulder range of motion, suggest the promising future of telerehabilitation in arthroplasty, particularly in telemonitoring before and after surgery. As this technology continues to gain acceptance, further studies that evaluate the outcomes of augmented reality rehabilitation for long-term follow-up are needed

Aim

There is growing evidence that bacteria encountered in periprosthetic joint infections (PJI) form surface-attached biofilms on prostheses, as well as biofilm aggregates embedded in synovial fluid and tissues. However, models allowing the investigation of these biofilms and the assessment of their antimicrobial susceptibility in physiologically relevant conditions are currently lacking. To address this, we developed a synthetic synovial fluid (SSF) model and we validated this model in terms of growth, aggregate formation and antimicrobial susceptibility testing, using multiple PJI isolates.

Non-invasive sampling of tumor-derived genetic material in circulation through liquid biopsy may be very beneficial for an accurate diagnosis and evaluation of response to treatment in patients with malignant and benign soft tissue tumors. We previously showed that tumor-derived genomic aberrations can be detected in plasma of patients with leiomyosarcoma (LMS) and leiomyoma (LM). In LMS patients, we also showed that the levels of circulating tumor DNA (ctDNA) correspond with response to treatment. We developed an approach tailored to genomic profile of LMS (characterized by intermediate levels of point mutations and copy number alterations, CNAs). Based on TCGA data, we designed a panel of 89 most frequently mutated genes in LMS, which we profiled in plasma DNA by deep sequencing. In parallel, plasma samples were analyzed by shallow whole genome sequencing for detection of CNAs. With this approach, we detected ctDNA in 71% (20/28) of samples from 6/7 patients with advanced disease with >98% specificity. The combination approach for orthogonal profiling of point mutations and CNAs proved to increase the sensitivity of ctDNA detection. Currently, we seek to further improve the sensitivity of ctDNA detection by refining our capture panel and tracking LMS-specific DNA methylation markers in circulation, in addition to point mutations and CNAs. The ultimate goals of our ctDNA studies are 1) to develop a highly sensitive assay for evaluation of response to therapy and long-term surveillance for patients with LMS, and 2) to develop a blood-based test for accurate pre-operative distinction between LMS and LM.

To identify LMS-specific DNA methylation markers, we analyzed a test cohort of 76 LM, 35 uterine LMS and 31 extra-uterine LMS by Illumina Infinium EPIC arrays. We identified differentially methylated CpGs between LM and uterine LMS, and between LM and all LMS using a newly developed custom pipeline in R. The results of this analysis are currently being validated in a new dataset of 41 LM and 153 LMS generated by our group. Recently published (PMID: 34301934) genomic data from new 53 LMS samples are used to refine the panel of the most frequently mutated genes that we identified previously in the LMS TCGA data.

Our preliminary analysis of test cohort revealed >270 differentially methylated CpGs between LM and uterine LMS, and >1000 differentially methylated CpGs between LM and all LMS. The preliminary analysis of genomic data shows that the initial panel of 89 frequently mutated genes could be substantially narrowed down to cover only selected tumor suppressor genes. Once validated, these results will be used to refine the ctDNA assay for LMS and LM.

Our results point to multiple epigenetic markers that could be used for ctDNA profiling, in addition to point mutations or CNAs. Further validation will allow us to select the most reliable LMS- and LM-specific DNA methylation markers and the most frequently mutated regions across independent datasets, and these markers will be incorporated into our new ctDNA test for a concurrent detection of point mutations, CNAs and DNA methylation markers in circulation.

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

Aims

Patients undergoing limb reconstruction surgery often face a challenging and lengthy process to complete their treatment journey. The majority of existing outcome measures do not adequately capture the patient-reported outcomes relevant to this patient group in a single measure. Following a previous systematic review, the Stanmore Limb Reconstruction Score (SLRS) was designed with the intent to address this need for an effective instrument to measure patient-reported outcomes in limb reconstruction patients. We aim to assess the face validity of this score in a pilot study.

Multiple organ failure (MOF) is a major cause of trauma mortality and morbidity. The role of surgical procedures in precipitating MOF remains unclear. Data on timing and duration of surgery was collated on 491 consecutive patients admitted to a Major Trauma Centre, who survived more than 48 hours and required Intensive Care Unit admission. MOF was defined according to the Denver Post Injury MOF Score, where MOF can occur only later than 48 hours after injury to exclude physiological derangements resulting from inadequate resuscitation. Overall, 268 patients (54.6%) underwent surgery within 48 hours of injury, with 110 (22.4%) requiring surgery within 6 hours of injury. Total mean intra-operative time (p=0.067) nor the need for an operation within the first 6 (p=0.069) or 48 hours (p=0.124) were associated with MOF development. Multivariate predictive modelling of MOF showed timing and duration of surgery had no significant predictive power for MOF development (Odds Ratio 0.72, 95% CI 0.47–1.10). Despite previous indication that early surgical intervention can precipitate MOF, current surgical strategy does not appear to impact MOF development

Proximal junctional kyphosis (PJK) is defined as adjacent segment kyphosis >10° between the upper instrumented vertebrae and the vertebrae 2 levels above following scoliosis surgery. There are few studies investigating the predictors and clinical sequelae involved with this relatively common complication. Our purpose was to determine the radiographic predictors of post-op PJK and to examine the association between PJK and pain/HRQOL following surgery for AIS. The Post-Operative Recovery after Scoliosis Correction: Home Experience (PORSCHE) study was a prospective multicenter cohort of AIS patients undergoing spinal fusion surgery. Pre-op and minimum 2 year f/u scoliosis and sagittal spinopelvic parameters (thoracic kyphosis–TK, lordosis–LL, pelvic tilt-PT, sacral slope-SS, pelvic incidence-PI) were measured and compared to numeric rating scale for pain (NRS) score, SRS-30 HRQOL and to the presence or absence of PJK (proximal junctional angle >100). Continuous and categorical variables were assessed using logistic regression and binomial variables were compared to binomial outcomes using chi-square. 163 (137 females) patients from 8 Canadian centers met inclusion criteria. At final f/u, PJK was present in 27 patients (17%). Pre-op means for PJK vs No PJK: Age 14.1 vs 14.7yr; females 85 vs 86%; scoliosis 57±22 vs 62±15deg; TK 28±18 vs 19±16deg ∗, LL 62±11 vs 60±12deg, PT 8±12 vs 10±10deg, SS 39±8 vs 41±9deg, PI 47±14 vs 52±13deg, SVA −9±30 vs −7±31mm. Final f/u for PJK vs No PJK: Scoliosis 20±11 vs 18±8deg, final TK 26±12 vs 19±10deg∗, LL 60±11 vs 57±12deg, PT 9±12 vs 12±13deg, SS 39±9 vs 41±9deg, PI 48±17 vs 52±14deg, SVA −23±26 vs −9±32mm∗. Significant findings: Pre-op kyphosis >40deg has an odds ratio (OR) of 4.41 (1.50–12.92) for developing PJK∗. The presence of PJK was not associated with any significant differences in NRS or SRS-30. ∗denotes p<0.05. This prospective multicenter cohort of AIS patients demonstrated a 17% risk of developing PJK. Pre-op thoracic kyphosis >40deg was associated with the development of PJK; however, the presence of PJK was not associated with increased pain or decreased HRQOL

Aim. This study aimed to identify risk factors for development of deep periprosthetic joint infection (PJI) in patients following surgical treatment of neck of femur fracture. Method. This study identified a consecutive series of 2,822 (2,052 female, 73%) patients who underwent either hemiarthroplasty (n=1,825, 65%) or fixation (DHS) (n=997, 35%) for fractured neck of femur performed between January 2009 and June 2015 at our institution. Full patient demographics, co-morbidity and peri-operative complication data were determined. The majority of patients were either ASA 2 (n=663, 23%) or ASA 3 (n=1,521, 54%), mean age = 81.3 years (SD 10.3). All patients were followed up post-operatively by a dedicated surgical site infection (SSI) monitoring team in order to identify patients who developed a PJI within 1 year. A stepwise multivariable logistic regression model was used to identify patient and surgical factors associated with increased risk of infection. Predictors with a p-value of <0.20 in the univariate analysis were included in the multivariate analysis. Results. Thirty-nine (39) cases of deep periprosthetic infection were identified (hemiarthroplasty n=35, DHS n=4) representing an overall deep infection rate of 1.4% (hemiarthroplasty 1.9%, DHS 0.4%). The most common infecting pathogen was a pure growth of coagulase negative Staphylococcus (n=9, 23%) followed by a pure growth of Staphylococcus aureus (n=7, 18%). An increased risk of PJI was observed in patients who underwent hemiarthroplasty compared to those treated by fixation (odds ratio (OR) 6.50, 95%CI 2.26 – 18.7, p=0.001). Of patient factors, only blood transfusion within 30 days (OR 3.51, 95%CI 1.72 – 7.13, p=0.001) and the presence or development of pressure sores on or during admission (OR 2.99, 95%CI 1.24 – 7.19, p=0.015) were significantly associated with an increased risk of development of PJI. Use of high-dose dual antibiotic cement (gentamicin and clindamycin) was associated with a two-fold reduction in the risk of PJI (OR 0.39, 95%CI 0.20 – 0.76, p=0.005) vs standard dose gentamicin antibiotic cement. Conclusions. This study found: 1) a deep infection rate similar to that reported earlier from large number studies from the UK, 2) a six-fold higher deep infection rate in hemiarthroplasties, compared to internal fixations, and 3) a three-fold higher infection rate in patients who suffer concomitant pressure sores or receive a blood transfusion up to 30 days post-operatively