Aims. The aim of this study was to determine the consensus best practice approach for the investigation and management of children (aged 0 to 15 years) in the UK with musculoskeletal infection (including septic arthritis, osteomyelitis, pyomyositis, tenosynovitis, fasciitis, and discitis). This consensus can then be used to ensure consistent, safe care for children in UK hospitals and those elsewhere with similar healthcare systems. Methods. A Delphi approach was used to determine consensus in three core aspects of care: 1) assessment, investigation, and diagnosis; 2) treatment; and 3) service, pathways, and networks. A steering group of paediatric orthopaedic surgeons created statements which were then evaluated through a two-round Delphi survey sent to all members of the British Society for Children’s Orthopaedic Surgery (BSCOS). Statements were only included (‘consensus in’) in the final agreed consensus if at least 75% of respondents scored the statement as critical for inclusion. Statements were discarded (‘consensus out’) if at least 75% of respondents scored them as not important for inclusion. Reporting these results followed the Appraisal Guidelines for Research and Evaluation. Results. A total of 133 children’s orthopaedic surgeons completed the first survey, and 109 the second. Out of 43 proposed statements included in the initial Delphi, 32 reached ‘consensus in’, 0 ‘consensus out’, and 11 ‘no consensus’. These 11 statements were then reworded, amalgamated, or deleted before the second Delphi round of eight statements. All eight were accepted as ‘consensus in’, resulting in a total of 40 approved statements. Conclusion. In the many aspects of medicine where relevant evidence is not available for clinicians to base their practice, a Delphi consensus can provide a strong body of opinion that acts as a benchmark for good quality clinical care. We would recommend clinicians managing children with musculoskeletal infection follow the guidance in the consensus statements in this article, to ensure care in all medical settings is consistent and safe. Cite this article: Bone Joint J 2023;105-B(7):815–820

Aim. Prosthetic joint infections (PJI) and fracture related infections (FRI) are the most challenging complications in orthopaedic surgery. An interdisciplinary approach is mandatory not only to correctly diagnose and treat major musculoskeletal infections but also to address the comorbidities and impairments these patients are not rarely suffering from. Since, little data exists on cardiac complications following PJI and FRI revision surgery, this study aimed to investigate the risk of perioperative myocardial injury (PMI) and mortality. Method. We prospectively included consecutive patients at high cardiovascular risk (defined as expected postoperative hospital stay of >24 hours PLUS age >45 years with pre-existing coronary, peripheral or cerebrovascular artery disease OR age >65 years) undergoing major orthopaedic surgery between 2014 and 2016. All patients received a systematic screening to reliably detect PMI, using serial measurements of high-sensitivity cardiac troponin T (hs-cTnT). All-cause mortality was assessed at 30 days and one year. Multivariable logistic regression models were applied to compare incidence of PMI and mortality between patients undergoing septic revision surgery (for PJI/FRI) and patients receiving aseptic major bone and joint surgery. Results. In total 911 consecutive patients, with an overall PMI rate of 15.4% (n=140) were included. The PMI incidence in patients undergoing septic revision surgery was significantly higher compared to aseptic orthopaedic surgeries (29.2% vs 14.3%, p=0.001), also after multivariable adjustment (odds ratio 2.1, p=0.02). Mortality was higher at one year (16.9% vs. 8.3%, p=0.037) and numerically at 30 days (6.2% vs. 2.4%, p=0.085) in patients undergoing septic revision surgery. Virulence of the disease-causing pathogen showed no significant relationship with PMI incidence or mortality. Conclusions. Patients undergoing revision surgery for PJI or FRI were at a distinct higher risk of PMI and death compared to matched non-septic patients. In major bone and joint infections screening for PMI and treatment in specialized multidisciplinary units should be considered

Infection of the musculoskeletal (MSK) system is a dreaded complication that seems to be on the rise. Many factors, such as resistant bacteria or poor host factors, may influence such rise. This increase leads to greater resource consumption, especially due to antibiotic (ATB) prescription. Strategies must be created to detect patients at risk and prevent such infections. Hospital administrators should be made aware of the costs and impact of MSK infections in order to understand the need to prevent such complications.

Therefore, our goal is to characterize the infected orthopaedic patient and evaluate the cost associated with ATB prescription in such cases.

This is a retrospective and descriptive study, based on patient record analysis of all patients treated at our department, from January 2013 to March 2015.

We identified 177 patients with a MSK infection and an isolated infectious agent.

There was no predominance of either sex. Approximately 50% of patients were aged between 66 and 85 years old.

Most frequent agents were MSSA (30,2%) and MRSA (21,8%), followed by Streptococcus species (8,9%) and Pseudomonas aeruginosas (7,1%). Although most patients were infected by a single agent, 18,6% had two or more causative agents isolated in cultures. Of those, 69,7% had either MSSA or MRSA as one of the isolated agents.

Most commonly affected area was the hip (39,5%), followed by the knee (23,2%) and ankle (21,5%). Nearly all patients had had prior surgery, with arthroplasty and osteosynthesis as the most common procedures (52,4% and 33,3%, respectively).

Infection related admission was responsible for a total of 6.116 hospital bed-days, with the majority of patients staying in hospital for up to 30 days (77,3%).

Total cost of hospital ATB administration was 61.365,61€, with approximately 346,7€ spent in each patient. This corresponds to 42,6% of the total cost of medication during hospital stay (144.146,1€ of total cost, with 814,4€ per patient).

The typical infected orthopaedic patient is aged 66 to 85 years old, was operated to his hip or knee, and either an arthroplasty or osteosynthesis was performed. Staphylococcus aureus remains the most common agent.

MSK infections have significant costs associated with their treatment, and clinical departments should periodically re-evaluate discharged patients in order to understand what groups are at risk of developing such a complication.

Only a correct identification of all these factors makes it possible to create a targeted preventive strategy, in order to reduce costs to the institution.

Introduction

Accurate diagnosis of peri-prosthetic joint infection is critical to allow adequate treatment. Currently, the criteria of the Musculo-Skeletal Infection Society (MSIS) serve as a validated reference tool. More recently, these criteria have been modified for better accuracy. The goal of this study was to compare retrospectively the diagnostic accuracy of these two different tools in cases of known peri-prosthetic hip or knee infection or in aseptic cases and to analyze one additional criterion: presence of an early loosening (prior to 2 years after implantation).

Aim. Musculoskeletal infection is a serious complication, however literature is lacking prospective data on its impact on mental health. The study aimed to assess mental health in patients with musculoskeletal infections and how they experience the possible mental and physical impairment. Method. All patients treated in our unit for musculoskeletal infections between July 2020 and March 2022 were prospectively included. To assess specific patient reported outcomes the following questionnaires were used: World-Health-Organization Quality-Of-Life (WHOQOL)-BREF and the Veterans-RAND-12Item Health Survey (VR-12) for mental & physical health; Patient-Health-Questionnaire (PHQ-8) for depression symptoms; Generalized-Anxiety-Disorder-Scale-7 (GAD-7) for anxiety symptoms and Somatic-Symptom-Disorder-B Criteria Scale (SSD-12) for experience of mental & physical impairment. The surveys were conducted at baseline, 6 and 12-weeks and 1-year. Results. In total 199 patients were included (31 fracture-related infections, 80 prosthetic joint infections, 40 diabetic foot syndromes and 48 other musculoskeletal infections). Physical health was significantly worse 6 weeks after treatment compared to baseline (WHOQOL p=.002; VR-12 p<.001), but significantly better at 3-months (p<.001; p=.006) and 12-months (p=.003; p<.001). Mental health was significantly worse at 3-months (WHOQOL p=.002), but at final follow-up significantly better (VR-12 p=.046). Social relationships (domain of WHOQOL) were perceived significantly worse 6 weeks and 12 months after treatment initiation (p=.003; p=.007), as were environmental factors. At baseline moderate to severe depression symptoms (PHQ-8≥10) and moderate to severe anxiety symptoms (GAD-7≥10) were observed in 14.6%, respectively 10.6% of all patients. At 12-months these were 7.4% and 3%. Over the course of treatment, only patients with DFS showed a significant change in experienced psychological or physical impairment, which was perceived significantly less compared 6 weeks to 12 months (p=.042). Conclusions. Patients with musculoskeletal infections suffer from a considerable impact on their mental health. The greatest impairment in physical health was seen 6 weeks after beginning of treatment. The psychological well-being was worse at 3-months. Environmental factors, such as mobility, activities of daily living and dependence on medication or medical treatment were worst at 3-months. Also increasingly worse social relationships over the course of treatment was observed. Further studies are needed to identify psychological impairment and related factors, as well as to determine how patients cope with their disease and treatment. This could serve as a foundation to implement treatment algorithms in order to improve patient related outcome and quality of life

To date, few studies have investigated the feasibility of the loop-mediated isothermal amplification (LAMP) assay for identifying pathogens in tissue samples. This study aimed to investigate the feasibility of LAMP for the rapid detection of methicillin-susceptible or methicillin-resistant Staphylococcus aureus (MSSA or MRSA) in tissue samples, using a bead-beating DNA extraction method. Twenty tissue samples infected with either MSSA (n = 10) or MRSA (n = 10) were obtained from patients who underwent orthopedic surgery for suspected musculoskeletal infection between December 2019 and September 2020. DNA was extracted from the infected tissue samples using the bead-beating method. A multiplex LAMP assay was conducted to identify MSSA and MRSA infections. To recognize the Staphylococcus genus, S. aureus, and methicillin resistance, 3 sets of 6 primers for the 16S ribosomal ribonucleic acid (rRNA) and the femA and mecA genes were used, respectively. The limit of detection and sensitivity (detection rate) of the LAMP assay for diagnosing MSSA and MRSA infection were analyzed. The results of this study suggest that the LAMP assay performed with tissue DNA samples can be a useful diagnostic method for the rapid detection of musculoskeletal infections caused by MSSA and MRSA

Aim. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is commonly associated with serious cases of community-onset skin and musculoskeletal infections (Co-SMSI). Molecular epidemiology analysis of CA-MRSA recovered from skin and soft tissues specimens is lacking in Latin America. This study aimed to identify phenotypic and genotypic features of MRSA isolates recovered from patients presenting Co-SMSI. Methods. Consecutive MRSA isolates recovered from Co-SMSI of patients admitted from March 2022 to January 2023 in a Brazilian teaching hospital were tested for antimicrobial resistance and characterized by their genotypic features. Identification was carried out by automated method and through MALDI-TOF MS. Antimicrobial susceptibility was tested by disk diffusion, broth microdilution and E-test strips for determination of the minimal inhibitory concentration (MIC) according to recommendations from the Brazilian Committee on Antimicrobial Susceptibility Testing (BrCAST) and European Committee on Antimicrobial Susceptibility Testing (EUCAST). Gene mecA characterization and Sccmec typing were performed by multiplex polymerase chain reaction (PCR) assay, and gene lukF detection by single PCR. Patients were prospectively followed up for two months, in order to determine their clinical characteristics and outcomes. Results. Overall, 48 Staphylococcus aureus isolates were obtained from 68 samples recovered from patients with Co-SMSI. Twenty two (42%) were phenotypically characterized as MRSA, although mecA gene was only identified in 20 of those samples. Sccmec was untypable in 12 isolates, Sccmec was type II in 4 isolates and 2 were classified as type IVa. LukF gene was identified in 5 isolates. Antimicrobial resistance profile showed that all isolates were susceptible to linezolid and vancomycin with MIC = 1 and MIC = 2 in 66,7% and 33.3%, respectively. Susceptibility to quinolones was worryingly low and none of the isolates were sensitive to usual doses of ciprofloxacin and levofloxacin, and showed increased rates of resistance to increased exposure to these drugs, as well. Isolates were both susceptible to gentamicin and tetracycline in 85% and resistance to also Sulfamethoxazole/Trimethoprim occurred in only 2 isolates. Mortality rate evaluated within 1 month of the initial evaluation was 10% among MRSA isolates. Conclusions. Our results showed that CA-MRSA isolates causing Co-SMSI demonstrated an alarming pattern of multidrug resistance, including to β-lactam and quinolones, which have been commonly prescribed as empirical therapy for patients with skin, soft tissue and musculoskeletal infections

Aims. This study aimed to explore the role of small colony variants (SCVs) of Staphylococcus aureus in intraosseous invasion and colonization in patients with periprosthetic joint infection (PJI). Methods. A PJI diagnosis was made according to the MusculoSkeletal Infection Society (MSIS) for PJI. Bone and tissue samples were collected intraoperatively and the intracellular invasion and intraosseous colonization were detected. Transcriptomics of PJI samples were analyzed and verified by polymerase chain reaction (PCR). Results. SCVs can be isolated from samples collected from chronic PJIs intraoperatively. Transmission electron microscopy (TEM) and immunofluorescence (IF) showed that there was more S. aureus in bone samples collected from chronic PJIs, but much less in bone samples from acute PJIs, providing a potential mechanism of PJI. Immunofluorescence results showed that SCVs of S. aureus were more likely to invade osteoblasts in vitro. Furthermore, TEM and IF also demonstrated that SCVs of S. aureus were more likely to invade and colonize in vivo. Cluster analysis and principal component analysis (PCA) showed that there were substantial differences in gene expression profiles between chronic and acute PJI. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these differentially expressed genes were enriched to chemokine-related signal pathways. PCR also verified these results. Conclusion. Our study has shown that the S. aureus SCVs have a greater ability to invade and colonize in bone, resulting in S. aureus remaining in bone tissues long-term, thus explaining the pathogenesis of chronic PJI. Cite this article: Bone Joint Res 2022;11(12):843–853

Aims. Musculoskeletal infection is a devastating complication in both trauma and elective orthopaedic surgeries that can result in significant morbidity. Aim of this study was to assess the effectiveness and complications of local antibiotic impregnated dissolvable synthetic calcium sulphate beads (Stimulan Rapid Cure) in the hands of different surgeons from multiple centres in surgically managed bone and joint infections. Methods. Between January 2019 and December 2022, 106 patients with bone and joint infections were treated by five surgeons in five hospitals. Surgical debridement and calcium sulphate bead insertion was performed for local elution of antibiotics in high concentration. In all, 100 patients were available for follow-up at regular intervals. Choice of antibiotic was tailor made for each patient in consultation with microbiologist based on the organism grown on culture and the sensitivity. In majority of our cases, we used a combination of vancomycin and culture sensitive heat stable antibiotic after a thorough debridement of the site. Primary wound closure was achieved in 99 patients and a split skin graft closure was done in one patient. Mean follow-up was 20 months (12 to 30). Results. Overall, six out of 106 patients (5.6%) presented with sepsis and poorly controlled comorbid conditions, and died in the hospital within few days of index surgery. Out of the remaining 100 patients, control of infection was achieved in 95 patients (95%). Persistence of infection was noted in five (5%) patients. Out of these 95 patients that had good control of infection, four patients (4.2%) with gap nonunion needed Masquelet procedure to achieve union. Conclusion. Our multicentre experience confirmed that surgical debridement along with calcium sulphate bead insertion was effective in treating bone and joint infections without any side effects and complications. Cite this article: Bone Jt Open 2023;4(7):516–522

Acute Haematogenous Osteomyelitis (AHO) remains a cause of severe illness among children with the possibility of long-term consequences for growth and development. Previous research on sequelae from AHO rarely considers outcomes more than two years following treatment. This study aims to establish the quality of life of patients diagnosed with AHO in childhood up to 13 years after diagnosis, evaluating the impact on social, emotional, physical, and school function. Children treated for AHO between 2008–2018 at a tertiary referral centre in New Zealand were identified. PedsQL™ questionnaires were conducted via phone with either the child or primary caregiver and responses analysed. 40 patients met inclusion criteria, were contactable by phone, and consented to participate. The mean age was 7 years (range 0–15) and most were female (60%). Health related quality of life (HRQOL) was scored as a percentage with most participants scoring >80% (n=27). Those who do experience reduced quality of life following treatment for AHO were likely to complain of pain, stiffness, or anxiety. The impact of significant childhood illness on mental health was not adequately captured by the PedsQL™ but was highlighted in qualitative feedback. We conclude that the majority of children treated for AHO reported excellent health-related quality of life up to 13 years following treatment although an negative impact on mental health was reported using qualitative analysis. A refined scoring system is needed to assess the long-term impact of musculoskeletal infection

Abstract. Background. Infections are rare and poorly studied complications of unicompartmental knee athroplasty (UKA) surgery. They are significantly less common compared to infections after total knee arthroplasties (TKAs). Optimal management of periprosthetic joint infections (PJIs) after a UKA is not clearly defined in the literature. We present the results of a multicentre retrospective series of UKA PJIs treated with Debridement, Antibiotics and Implant Retention (DAIR). Methodology. Patients presenting between January 2016 and December 2019 with early UKA infection were identified at three specialist centres using the Musculoskeletal Infection Society (MSIS) criteria. All patients underwent a standardized treatment protocol consisting of the DAIR procedure and antibiotic therapy comprising two weeks of intravenous (IV) antibiotics followed by six weeks of oral therapy. The main outcome measure was overall survivorship free from reoperation for infection. Results. A total of 3225 UKAs (2793 (86.2%) medial and 432 (13.8%) lateral UKAs) were performed between January 2016 and December 2019. Nineteen patients had early infections necessitating DAIR. The mean follow-up period was 32.5 months. DAIR showed an overall survivorship free from septic reoperation of 84.2%, with an overall survivorship free from all-cause reoperation of 78.95%. The most common bacteria were Coagulase-negative Staphylococci, Staphylococcus aureus and Group B Streptococci. Three patients required a second DAIR procedure but remained free from re-infection at follow-up obviating the need for more demanding, staged revision surgery. Conclusions. In infected UKAs, the DAIR procedure produces a high rate of success, with a high survivorship of the implant

Prosthetic joint infection (PJI) remains one of the most challenging complications to manage following total joint arthroplasty (TJA). There is a paucity of published data on the management of PJI in smaller, rural hospital settings. In this study, we investigate [1] the success rate of surgical management for PJI following TJA and [2] the microbiology of infecting organisms in this unique geographical environment. We performed a retrospective single-centre study at a rural hospital (Southland Hospital, Invercargill, New Zealand) over a 3-year period (2019 to 2022). All patients presenting with a first episode of PJI fulfilling Musculoskeletal Infection Society criteria after hip or knee arthroplasty were included. All patients had a minimum follow up of 6 months. Treatment success was defined eradication of infection. Twenty-one cases (14 hips and 7 knees) were identified. These were managed with Debridement, antibiotics, and implant retention (DAIR) procedure (n=14, 67%), single-stage revision (n=6, 29%), or long-term suppressive antibiotics (n=1, 4%). Of the DAIR patients, infection recurred in 50% and underwent subsequent revision. Of the single-stage revision patients, 17% failed and underwent subsequent revision. The overall success rate was 90%. Methicillin-sensitive Staphylococcus aureus (MSSA) was the most isolated pathogen (57%,) with no methicillin-resistance Staphylococcus aureus (MRSA) identified. Overall, 90% of infecting organisms were cefazolin sensitive. These results suggest that management of PJI is a safe and viable treatment option when performed in a rural hospital setting, with comparable treatment success rates to urban centres. The incidence of MRSA is low in this setting. Rates of antibiotic resistance were relatively low and most organisms were sensitive to cefazolin, the routine antibiotic used in prophylaxis

Elevated synovial leukocyte count is a minor criterion derived from the musculoskeletal infection society (MSIS) widely used in clinical practice for diagnosis of prosthetic joint infection. There is evidence to suggest analysis within 1 hour, preferentially within 30 minutes, of aspiration reduces the risk of ex vivo cell lysis occurring during prolonged transport. Multiple site working is more common practice and the availability of a lab on site to perform these tests is not always possible. We aimed to assess whether we could safely perform synovial leukocyte counts within our cold site in the diagnosis of prosthetic joint infection. We reviewed all orthopaedic synovial fluid aspirates within the lower limb arthroplasty unit from April 2021 – April 2022 performed at South Tees NHS Foundation Trust. We assessed time from aspirate to the lab using electronic data resources. This information was compared with the labs ability to perform a synovial leukocyte count to determine the impact of delays on testing. 110 patients (34.5% hips and 63.6% knees) were identified between two sites. Time from aspirate to lab ranged from 0 mins to 26 hrs 34 mins. Mean time to processing was 3hrs 10 mins. 50% of all samples had a synovial leukocyte count performed. 67% of patients had a cell differential performed. There was no difference in the ability to perform a synovial leukocyte count between samples process in < 2hours vs > 6 hours. We conclude that it is safe practice to perform joint aspirates for the work up of periprosthetic joint infections in sites where no laboratory is immediately available as the delay to processing synovial fluid does not alter the ability to perform a synovial leukocyte count. This study will provide evidence to enable the work up of periprosthetic joint infections in cold centres and therefore reduce the delay in diagnosis and proceeding management

Aim. Predicting success of a Debridement, Antibiotics and Implant Retention (DAIR) procedure for Periprosthetic Joint Infection (PJI) remains a challenge. A failed DAIR might adversely affect the outcome of any future revision surgery for PJI. Hence, the ability to identify and optimise factors predictive of DAIR success would help target the procedure to the appropriate patient cohort and avoid unnecessary surgery for patients where a DAIR is unlikely to eradicate infection. Method. A retrospective review of our prospective Bone Infection Group database was performed to identify all patients who underwent a DAIR of their hip or knee arthroplasty. Diagnosis of PJI was confirmed using the Musculoskeletal Infection Society (MSIS) 2013 and the European Bone and Joint Infection Society (EBJIS) 2021 classification systems. DAIR surgery was grouped into “successful” or “unsuccessful” outcomes as per the MSIS working group outcome-reporting tool. Results. Sixty-Four consecutive patients with an acute PJI underwent a DAIR procedure between 2009 and 2020. Treatment was successful in 44 (69%). The chance of a successful DAIR was significantly greater if performed within one week of symptom onset compared to greater than one week duration (adjusted odds ratio (OR 0.11; p=0.027; 95% CI [0.02- 0.78]). The chances of a successful DAIR was not influenced by whether the surgeon was an arthroplasty or non-arthroplasty surgeon (OR 0.28; p=0.13; 95% CI [0.05- 1.48]). Isolated Streptococcus infection had a success rate of 100%; followed by Coagulasenegative Staphylococci 71% and Methicillin-susceptible Staphylococcus Aureus 65%. Polymicrobial infection had the worst outcome with a success rate of 47%. Conclusions. In our experience DAIR surgery performed within one week of symptom onset, significantly increased chances of successful infection eradication. Collaborative work is required to ensure arthroplasty patients access prompt appropriate surgical decision-making, remove barriers to early assessment and minimise delays to surgery

Introduction. Identification of the causative pathogen in musculoskeletal infection is critical as it directs further treatment. Fracture-related infection is often associated with ‘no growth’ in standard culture. We investigated the efficiency of two alternate methods to identify the causative pathogen, namely extended bacterial culture and 16Sr RNA gene sequence analysis with next generation sequencing (NGS) in ‘culture negative’ fracture related infections. Method. Patients were diagnosed as having fracture related infection based on the MSIS criteria (n=120). All patients had samples taken for culture and sensitivity. All samples which were culture negative by standard culture methods formed the study group. These samples were subjected to further extended culture in both aerobic and anaerobic medium for 14 days to improve recovery of pathogens. Further, DNA isolated from implants from a sub-group of these culture negative patients were subjected to 16SrRNA gene amplification followed by Sanger sequencing. Subsequent sequencing analysis was performed using the Illumina NGS platform which identified and detected the most abundant genera/species present in those samples more precisely. Result. 57 culture negative samples formed the study group. Eight samples (14%) converted to positivity after 14 days of culture. Bacteroides fragilis was the commonest yield. 14 samples underwent 16SrRNA gene amplification followed by Sanger sequencing. Acinetobacter baumannii, Enterococcus faecalis, Pseudomonas aeruginosa were identified as common pathogens. Next generation sequencing (n=12) not only identified common pathogens like as Staphylococcus, Acinetobacter baumannii, but also many uncultivable species. Conclusion. Positive results from extended bacterial culture are about 15%. The delay in definite identification of pathogens in extended culture may be critical in certain clinical situations. Molecular methods are quicker and have additional yield in culture negative infections. The exact role of all microorganisms identified by molecular methods in the pathogenesis of infection is unknown

Aim. Evaluate if Neutrophil Extracellular Traps related biomarkers (citrullinated histone H3 [H3Cit], cellfree DNA [cfDNA], and myeloperoxidase) are increased in synovial fluid of patients with PJI and investigate the diagnostic accuracy of NET formation biomarkers for PJI. Method. Patients who underwent hip or knee revision total joint arthroplasty were categorised into two groups according to the Second International Consensus Meeting on Musculoskeletal Infection (2018) criteria. Sixteen patients were classified as infected and 16 as non-infected. cf-DNA, myeloperoxidase and H3Cit were measured in synovial fluid collected during surgery. Sensitivity, specificity, and receiver operating characteristic (ROC) curve were calculated. Results. Patients with PJI presented significantly higher levels of synovial fluid cf-DNA (105.5 ng/ml ± 58.3 vs 1.9 ± 1.2, p>0.0001), myeloperoxidase (1575 pg/ml ± 826 vs 50.16 ± 100, p<0.0001) and citrullinated histone H3 (1.688 ± 1.214 vs 13.88 ± 24.4, p < 0.0001). In the ROC curve analyses, the area under the curve for cf-DNA, myeloperoxidase and H3cit were 1 [0.89 – 1], 0.98 [0.86 – 1], and 0.94 [0.8 – 0.99], respectively. The sensitivity for detecting PJI using synovial fluid was 100% for cf-DNA, 93,7% for myeloperoxidase, and 87,5% for H3cit. The sensitivity for cf-DNA and myeloperoxidase was 100%, and 87,5 % for H3cit. Conclusions. Our results show that neutrophils within periprosthetic microenvironment release NETs as part of the bactericidal arsenal to fight infection. These results allow a better understanding of the cellular and molecular processes that occur in this microenvironment, enabling the design of more assertive strategies for the identification of new biomarkers and for a better use of the available ones. Furthermore, novel studies are needed to define whether and how NET-related biomarkers can be useful for the diagnosis of PJI

Survival of sepsis has been documented worldwide, but little is documented about the long-term health outcomes of multifocal sepsis from acute musculoskeletal infection - the first study of its kind in New Zealand. Children admitted to the Paediatric Intensive Care Unit (PICU) from 1. st. January 2002 to 31. st. December 2017 with a musculoskeletal focus of infection were identified from hospital coding data. Notes review from discharge to present day determined survival and morbidity. Present-day clinical assessment of the musculoskeletal and respiratory systems along with questionnaires on health-related quality of life, mental health and sleep were performed. Seventy patients were studied. Seven children died acutely (five Pasifika and two Māori children) indicating 10% mortality. Long-term survival was favourable with no recorded deaths after discharge. Recurrence/chronic infection occurred in 23%, a mean of 1.1 year after discharge. Growth disturbance occurred in 18%, a mean of 3 years after discharge. The hip joint and proximal femur have the worst complications. Children under 2 years are most at risk of long-term disability. No patients had chronic respiratory illness beyond 90 days. Fifteen children had symptoms of acute neurological impairment, three of whom had permanent brain injury. Twenty-six survivors (41%) were assessed a mean of 8.2 years after discharge. Health-related quality of life scores were on par with normative data. Six patients and eight parents screened positive for moderate to severe post-traumatic stress disorder. Paediatric multifocal musculoskeletal sepsis can result in complex illness with long hospital stay and multi-organ complications. Māori and Pasifika children, those under two and those involving the proximal femur/or hip are most at risk. Other outcomes are favourable with no evidence of chronic lung disease or poor quality of life. A period of rehabilitation for children with identified acquired brain injury should be part of discharge planning

Aim. Magnetic resonance imaging (MRI) and 2-[. 18. F]-fluoro-2-deoxy-D-glucose (. 18. F-FDG) Positron Emission Tomography, paired with Computed Tomography (PET/CT) are two indicated advanced imaging modalities in the complicated diagnostic work-up of osteomyelitis. PET/MRI is a relatively novel hybrid modality with suggested applications in musculoskeletal infection imaging. The goal of this study was to assess the value of hybrid . 18. F-FDG PET/MRI for chronic osteomyelitis diagnosis and surgical planning. Method. Five suspected chronic osteomyelitis patients underwent a prospective . 18. F-FDG single-injection/dual-imaging protocol with hybrid PET/CT and hybrid PET/MR. Diagnosis and relevant clinical features for the surgeon planning treatment were compared. Subsequently, 36 patients with . 18. F-FDG PET/MRI scans for suspected osteomyelitis were analysed retrospectively. Sensitivity, specificity, and accuracy were determined with the clinical assessment as the ground truth. Standardized uptake values (SUV) were measured and analysed by means of receiver operating characteristics (ROC). Results. The consensus diagnosis was identical for PET/CT and PET/MRI in the prospective cases, with PET/CT missing one clinical feature. The retrospective analysis yielded a sensitivity, specificity, and accuracy of 78%, 100%, and 86% respectively. Area under the ROC curve was .736, .755, and.769 for the SUVmax, target to background ratio, and SUVmax_ratio respectively. These results are in the same range and not statistically different compared to diagnostic value for . 18. F-FDG PET/CT imaging of osteomyelitis in literature. Conclusions. Based on our qualitative comparison, reduced radiation dose, and the diagnostic value that was found, the authors propose . 18. F-FDG PET/MRI as an alternative to . 18. F-FDG PET/CT in osteomyelitis diagnosis, if available

Aim. Antimicrobial peptides occur naturally in our intrinsic immune system. PLG0206 is a novel, engineered, 24-amino acid peptide which has broad-spectrum antimicrobial activity, including in biofilm and against multi-drug resistant pathogens (1,2). This is the first clinical study to evaluate the safety and tolerability of PLG0206 when administered via an irrigation solution in patients with periprosthetic joint infections (PJI) following total knee arthroplasty (TKA) during debridement, antibiotics, and implant retention (DAIR). Secondary objectives were to evaluate pharmacokinetics (PK), biomarkers and initial clinical efficacy at one year post-DAIR procedure. Method. This prospective, multicenter, open-label, interventional study assessed two dose levels of PLG0206. Fourteen patients underwent revision for PJI after TKA. At the end of debridement, they received a single intra-articular irrigation of PLG0206 into the wound cavity lasting 15 minutes at concentrations of 3 mg/mL (n=7) or 10 mg/mL (n=7). Patients received post-operative care and intravenous/oral antimicrobial therapy as per their institutional guidelines. Patients were monitored for safety and signs of relapse or persistent infection for 12 months post study drug administration and PK and blood biomarkers were assessed. Results. All patients completed their final study assessment at Day 365. Over the 1-year follow-up, only one recurrence (7%) was noted at Day 169 in the low-dose cohort. Following dosing, nine patients (64.3%) had limited systemic exposure; maximum plasma concentration occurred 1-hour post-administration and declined rapidly to undetectable levels by 24 hours following treatment in all patients. The incidence of drug related treatment-emergent adverse events (TEAEs) was low. Two patients, both in the higher dose cohort, experienced a transient drug related TEAE; one of hypertransaminasaemia and one of neuralgia. Both events were moderate in severity and resolved within two weeks of onset. Conclusions. A single 15-minute irrigation of PLG0206 into the wound cavity of patients undergoing a DAIR procedure for PJI following TKA, is safe and well tolerated by patients. This new antimicrobial peptide offers a promising therapeutic option in musculoskeletal infection. The initial clinical efficacy is encouraging but now needs to be investigated in a much larger clinical trial