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The Bone & Joint Journal
Vol. 107-B, Issue 1 | Pages 65 - 71
1 Jan 2025
van Laarhoven SN Nota SPFT van Hellemondt GG Schreurs BW Wymenga AB Heesterbeek PJC

Aims

Tibial fixation in revision total knee arthroplasty (rTKA) can present surgical challenges. It has been suggested that appropriate fixation in at least two of the three anatomical zones (epiphysis, metaphysis, and diaphysis) is essential for implant survival. However, supporting clinical data are lacking. In this retrospective case-control study, we investigated the relationship between zonal fixation of hybrid rTKA tibial components and re-revision total knee arthroplasty for aseptic loosening (rrTKA-AL).

Methods

All consecutive rTKAs with hybrid tibial components (May 2006 to December 2020) were screened for subsequent rrTKA-AL. A control group was randomly selected from the remaining cohort. Postoperative radiographs of rTKAs were scored in random order by three blinded observers for zonal fixation in the epiphysis (bone resection level below, at, or above fibular head; 0 to 2), metaphysis (number of sufficiently cemented zones; 0 to 4), and diaphysis (canal filling ratio (CFR); %). The intraclass correlation coefficient (ICC) was calculated to quantify the agreement between observers. Multivariate logistic regression analysis was performed to assess the relationship between zonal fixation and rrTKA-AL.


Bone & Joint Research
Vol. 13, Issue 12 | Pages 779 - 789
16 Dec 2024
Zou H Hu F Wu X Xu B Shang G An D Qin D Zhang X Yang A

Aims

The involvement of long non-coding RNA (lncRNA) in bone marrow mesenchymal stem cell (MSC) osteogenic differentiation during osteoporosis (OP) development has attracted much attention. In this study, we aimed to disclose how LINC01089 functions in human mesenchymal stem cell (hMSC) osteogenic differentiation, and to study the mechanism by which LINC01089 regulates MSC osteogenesis.

Methods

Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blotting were performed to analyze LINC01089, miR-1287-5p, and heat shock protein family A (HSP70) member 4 (HSPA4) expression. The osteogenic differentiation of MSCs was assessed through alkaline phosphatase (ALP) activity, alizarin red S (ARS) staining, and by measuring the levels of osteogenic gene marker expressions using commercial kits and RT-qPCR analysis. Cell proliferative capacity was evaluated via the Cell Counting Kit-8 (CCK-8) assay. The binding of miR-1287-5p with LINC01089 and HSPA4 was verified by performing dual-luciferase reporter and RNA immunoprecipitation (RIP) experiments.


Bone & Joint Research
Vol. 13, Issue 12 | Pages 764 - 778
12 Dec 2024
Huang Q Zhuo Y Duan Z Long Y Wang J Zhang Z Fan S Huang Y Deng K Xin H

Aims. Mesenchymal stem cells (MSCs) are usually cultured in a normoxic atmosphere (21%) in vitro, while the oxygen concentrations in human tissues and organs are 1% to 10% when the cells are transplanted in vivo. However, the impact of hypoxia on MSCs has not been deeply studied, especially its translational application. Methods. In the present study, we investigated the characterizations of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in hypoxic (1%) and normoxic (21%) atmospheres with a long-term culture from primary to 30 generations, respectively. The comparison between both atmospheres systematically analyzed the biological functions of MSCs, mainly including stemness maintenance, immune regulation, and resistance to chondrocyte apoptosis, and studied their joint function and anti-inflammatory effects in osteoarthritis (OA) rats constructed by collagenase II. Results. We observed that long-term hypoxic culture surpassed normoxic atmosphere during hUC-MSCs culture in respect of promoting proliferation, anti-tumorigenicity, maintaining normal karyotype and stemness, inhibiting senescence, and improving immunoregulatory function and the role of anti-apoptosis in chondrocytes. Furthermore, we demonstrated that the transplantation of long-term hypoxic hUC-MSCs (Hy-MSCs) had a better therapeutic effect on OA rats compared with the hUC-MSCs cultured in the normoxic atmosphere (No-MSCs) in terms of the improved function and swelling recovery in the joints, and substantially inhibited the secretion of pro-inflammatory factors, which effectively alleviated cartilage damage by reducing the expression of matrix metallopeptidase 13 (MMP-13). Conclusion. Our results demonstrate that Hy-MSCs possess immense potential for clinical applications via promoting stemness maintenance and enhancing immunoregulatory function. Cite this article: Bone Joint Res 2024;13(12):763–777


Bone & Joint Research
Vol. 13, Issue 12 | Pages 703 - 715
3 Dec 2024
Raza IGA Snelling SJB Mimpen JY

Aims

Extracellular matrix (ECM) is a critical determinant of tissue mechanobiology, yet remains poorly characterized in joint tissues beyond cartilage in osteoarthritis (OA). This review aimed to define the composition and architecture of non-cartilage soft joint tissue structural ECM in human OA, and to compare the changes observed in humans with those seen in animal models of the disease.

Methods

A systematic search strategy, devised using relevant matrix, tissue, and disease nomenclature, was run through the MEDLINE, Embase, and Scopus databases. Demographic, clinical, and biological data were extracted from eligible studies. Bias analysis was performed.


Bone & Joint 360
Vol. 13, Issue 6 | Pages 19 - 22
1 Dec 2024

The December 2024 Knee Roundup. 360. looks at: Unicompartmental knee arthroplasty and total knee arthroplasty in the same patient?; Lateral unicompartmental knee arthroplasty: is it a good option?; The fate of the unresurfaced patellae in contemporary total knee arthroplasty: early- to mid-term results; Tibial baseplate migration is not associated with change in PROMs and clinical scores after total knee arthroplasty; Unexpected positive intraoperative cultures in aseptic revision knee arthroplasty: what effect does this have?; Kinematic or mechanical alignment in total knee arthroplasty surgery?; Revision total knee arthroplasty achieves minimal clinically important difference faster than primary total knee arthroplasty; Outcomes after successful DAIR for periprosthetic joint infection in total knee arthroplasty


The Bone & Joint Journal
Vol. 106-B, Issue 12 | Pages 1426 - 1430
1 Dec 2024
Warne CN Ryan S Yu E Osmon DR Berry DJ Abdel MP

Aims. Cutibacterium acnes (C. acnes; previously known as Propionibacterium acnes or P. acnes) periprosthetic hip and knee infections are under-reported. While culture contamination with C. acnes occurs, true infections are important to recognize and treat. We sought to describe the demographics and treatment outcomes of patients with C. acnes periprosthetic joint infections (PJIs) of the hip and knee. Methods. Patients with C. acnes PJI between January 2005 and December 2018 were retrospectively reviewed utilizing the institutional total joint registry. Patients with monomicrobial PJI and two or more positive cultures were considered to have true C. acnes PJI. Patients with polymicrobial infection or with only one positive culture were excluded. This resulted in 35 PJIs (21 hips and 14 knees); the patients’ mean age was 63 years (35 to 84) and 15 (43%) were female. Mean follow-up was five years (1 to 14). Results. The median time to positive culture was five days (IQR 5 to 6) and median synovial fluid cell count was 22,583 cells (IQR 15,200 to 53,231). The median ESR was 25 mm/hr (IQR 7 to 37), and CRP was 15 mg/l (IQR 3 to 29). Of the 35 PJIs, 18 (51%) were treated with chronic antibiotic suppression without surgical intervention, and the remainder were treated with two-stage exchange arthroplasty. The two-year survival free of any revision was 94%. Four patients failed treatment due to symptomatic infection, with three treated with two-stage exchange and one treated with irrigation and debridement with modular component exchange for a survival rate of 89% and 83% at two and five years, respectively. Conclusion. Laboratory evidence of C. acnes PJI in this cohort was typical compared to more conventional organisms. Cultures grew more quickly than previously thought in patients with C. acnes PJI. Treatment with two-stage exchange or chronic antibiotic suppression alone both had few treatment failures at mid-term follow-up. Cite this article: Bone Joint J 2024;106-B(12):1426–1430


The Bone & Joint Journal
Vol. 106-B, Issue 12 | Pages 1443 - 1450
1 Dec 2024
Down B Ferguson J Loizou C McNally M Ramsden A Stubbs D Kendal A

Aims

Calcaneal osteomyelitis remains a difficult condition to treat with high rates of recurrence and below-knee amputation, particularly in the presence of severe soft-tissue destruction. This study assesses the outcomes of single-stage orthoplastic surgical treatment of calcaneal osteomyelitis with large soft-tissue defects.

Methods

A retrospective review was performed of all patients who underwent combined single-stage orthoplastic treatment of calcaneal osteomyelitis (01/2008 to 12/2022). Primary outcome measures were osteomyelitis recurrence and below-knee amputation (BKA). Secondary outcome measures included flap failure, operating time, complications, and length of stay.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 17 - 17
22 Nov 2024
Pedemonte G Reynaga E López V de los Rios JD Molinos S Larraza AV Hermoso JAH
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Aim. Haematogenous prosthetic joint infections account for 20-35% of total prosthetic infections. Debridement, antibiotics and implant retention (DAIR) is a well-accepted treatment for these infections and probably the most desired by surgeons, since it tries to maintain a functional and stable implant. However, the risk of DAIR failure is not negligible and some risk factors have been described, and also, different scores, such as CRIME80. Nonetheless, less is known about the impact of positive blood cultures may have on DAIR treatment. The aim of our study is to analyze whether the presence of a positive culture is a risk factor for DAIR failure. Method. A retrospective cohort study of 50 late acute haematogenous TKA infections was performed from 2015 to 2023. DAIR failure was defined as the need of a subsequent intervention either a new DAIR or a revision surgery. So, patients were divided into two groups depending on the surgical outcome: successful (SG) vs failure (FG). Demographic variables including age, gender, affected side and body mass index were collected. Patient's comorbidities were also collected including chronic obstructive pulmonary disease (COPD), diabetes, rheumatoid arthritis (RA), cirrhosis and chronic renal failure, etc. Other variables, such as ones included in CRIME80 (C-reactive protein (CRP) >150mg/dl and polyethylene exchange), were also collected. Results. 30 patients had a successful DAIR outcome (60%). Age and sex do not act as risk factors [OR 0.7 (0.2-2.6) and OR 0.4 (0.1-1.3)]. Neither do COPD [OR 3.3 (0.5-2.0), p=0.2]; RA [OR 0.8 (0.2-3.1), p=0.7]; CRP value [3.2 (0.9-11.2), p=0.06]; and polyethylene exchange [OR 0.4 (0.1-2.5), p= 0.3]. Thirty-five blood cultures (70%) were obtained before surgery (20 SG and 15 FG). Nine of the obtained blood cultures were positive (25.7%), being 7 from FG (46.7%) [OR 7.6 (1.3-4.8), p=0.02]. A logistic regression was performed where positive blood cultures were the only significant variable to predict DAIR failure (OR 12, 95% CI 1.1−18, p=0.049), after adjusting for all CRIME80 variables. Skin and soft tissue origin was described in 5 of the nine positive blood cultures (55.6%). Cardiovascular system was the second most common spread (22.2%), and then followed by urogenital and digestive tract. The most common microorganism in FG was Staphylococcus aureus (57.1%) [OR 6.4 (0.2-18.0), p=0.2]. Conclusions. Positive blood cultures may be another risk factor for DAIR failure. This can be important in diagnosis and it may be taken into account in antibiotic and surgical treatment strategies


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 20 - 20
22 Nov 2024
Elder A Wijendra A Hotchen A Wangrangsimakul T Young B Barrett L Ferguson J
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Aim. An instrumented blood culture system automatically flags when growth within the culture medium has been detected (‘work in progress’), and subsequently when the organism has been identified. We explore using this data to switch patients to oral therapy within 72 hours post-surgery, reducing costs and improving antimicrobial stewardship. Method. This retrospective review focused on clinically significant culture-positive bone and joint infections over a 5-month period in 2022. Two cohorts were defined as either having positive intraoperative microbiology at <72 hours or at ≥72 hours. Results. 150 patients were included. 133/150(88%) exhibited microbial growth <72hours. Of these, 98/133(74%) had all organisms identified <72-hours, and 34/133(26%) had additional organisms ≥72 hours. 19/151(12%) patients had their first positive cultures ≥72hrs from sampling. The most common isolates identified within 72 hours were S. aureus(30%), Enterobacteriaceae (26%), and Coagulase-negative Staphylococcus (CoNS)(19%). If no growth was observed by 48 hours, there was a 69.6% probability that subsequent growth wouldn't occur; this probability increases to 81.9% by 72 hours, 88.7% by 96 hours, 91.0% by 120 hours, and 95.0% by 144 hours (see figure 1). The most common isolates identified ≥72 hours were CoNS(28%), Cutibacterium acnes(16%) and S. aureus(12%). Assessing oral antibiotic regimes for isolates identified after 72 hours demonstrated that linezolid would cover isolates from 96% of patients, tetracyclines 92% of patients, clindamycin 85% of patients, and ciprofloxacin and rifampicin would cover 80% of patients. Vancomycin and meropenem, our standard empirical therapy, gave the best cover at 96% of patients. Conclusions. This study suggests there is sufficient microbiological information at 72 hours for most patients to allow transition to a targeted regimen. If there has been no detection of growth when using an instrumented blood culture system by 72 hours, it is likely that there will be no growth. For any tables or figures, please contact the authors directly


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 73 - 73
22 Nov 2024
Erbeznik A Smrdel KS Kišek TC Cvitković-Špik V Triglav T Vodicar PM
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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


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 10 - 10
22 Nov 2024
Frank F Hotchen A Valand P Stubbs D Ferguson J McNally M
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Aim. This retrospective study evaluated the outcome of treatment for unhealed fracture-related infections (FRI). Methods. We identified a consecutive, single-centre cohort of patients having treatment for an FRI Consensus confirmed FRI. All fractures were unhealed at the time of treatment. Patients were followed up for at least one year. Successful outcome was a healed fracture without recurrent infection. Lack of union, persistent infection and/or unplanned reoperation defined failure. Results. Demographics: 183 patients (184 FRIs) with mean age 52.1 years (range 17-96) were treated and followed up for a mean of 2.8 years (range 1-9.4). Mean duration of FRI was 1.1 years with 65 (35.5 %) presenting within 6 months of injury. 118 patients had established infected non-union. FRI was most frequent in the tibia (74), femur (48) and humerus (24). 171 patients were BACH Complex. 75.5% of FRIs were culture positive, with Staph. aureus being the most frequent organism. Polymicrobial infection and Gram negative cultures were common (25.5% and 33.6%). Treatment: 98.3% of surgeries were performed in one stage with just 3 planned 2-stage procedures (2 endoprosthetic replacements and 1 free fibular flap). No bone graft was used in any surgery and all wounds were closed at first operation. 48 cases (26%) required flap coverage (29 free flaps and 19 local flaps). Local antibiotics were used in 124 cases (67.4%) of primary surgeries. All patients had sampling, debridement, systemic antibiotics and wound closure. 40 (21.7%) had DAIR, 31 (16.8%) had new internal fixation and 105 (57.1%) had external fixation (including 79 Ilizarov fixators). Outcomes: After primary surgery, 84.6% of all patients were infection-free and 77.2% had united. After further surgery, 98.8% were infection-free and 98.1% had united. External fixation techniques achieved infection eradication in 89.1% compared to 71.7% with any internal fixation (p=0.005). Primary internal fixation achieved union in 81.7% compared to 74.3% with external fixation (p=0.27). Secondary surgery after external fixation was mainly docking site fixation. Conclusion. Unhealed FRIs present a difficult challenge for treatment. This large series demonstrated that single-stage treatment, without bone grafting, gave acceptable results with few reoperations. Primary external fixation gave more certainty of infection eradication but required more reoperations to secure union. However, this difference in reoperation was not statistically significant. We strongly advocate managing these patients with a multidisciplinary team which can treat all aspects of the condition


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 77 - 77
22 Nov 2024
Vidal LS Auñon A García AB Cañete JG Parron R Esteban-Moreno J
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Aim. To evaluate the bacterial counts of sonicatied implants in patients with osteoarticular infections. Various studies have demostrated the usefulness of sonication of retrieved implants in order to provide an accurate microbiological diagnosis. Although cutoff values for original sonicate counts have been established, the use of centrifugation may influence these values. Method. A retrospective, single-center study, including sonication fluid samples from implants removed between January 2011 and October 2023, was performed. Patients were diagnosed with implant-associated infection based on the criteria available at the time of diagnosis. Osteoarticular implants were sonicated following the protocol described by Esteban et al. Sonicated fluid was centrifuged for 20 minutes at 3000 x g, and the sediment was resuspended in 5 mL of phosphate buffer solution. Ten µl of the sample were streaked onto each medium for quantitative culture. Bacterial counts exceeding 100,000 CFU/mL were considered as 100,000 CFU/mL for statistical analysis. Results. The study included 457 sonication fluid samples. Of these, 316 samples were from patients with prosthetic joint infection (PJI), with 26.3 % diagnosed with acute PJI and 73.7 % with chronic PJI. Additionally, 141 samples were from patients with osteosynthesis infection. The median CFU/ml in the sonication fluid was 40,000 CFU/mL (IQR 1,000 CFU/mL-100,000 CFU/mL). No statistically significant difference was observed between the different types of implants (prosthesis vs. osteosynthesis, p=0.218). A trend of higher counts was noted for acute PJI compared to chronic PJI (р=0.052). Most infections were monomicrobial, but 16.2% were polymicrobial. Statistically significant higher bacterial counts were observed in polymicrobial infections compared to monomicrobial infections (р<0.005). Among monomicrobial infections, no differences were found between Gram-negative and Gram-positive microorganisms (р=0.416). No differences were also found between joints (knee vs. hip) (p=0.353). Conclusions. Significant variability was observed in the number of colonies detected in all samples, regardless of the type of implant, the number of microorganisms or the species identified. Higher counts were detected in polymicrobial infections, and a trend was also noted for higher counts in acute infections


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 44 - 44
22 Nov 2024
De Bleeckere A Neyt J Vandendriessche S Boelens J Coenye T
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Aim. Fast and accurate identification of pathogens causing periprosthetic joint infections (PJI) is essential to initiate effective antimicrobial treatment. Culture-based approaches frequently yield false negative results, despite clear signs of infection. This may be due to the use of general growth media, which do not mimic the conditions at site of infection. Possible alternative approaches include DNA-based techniques, the use of in vivo-like media and isothermal microcalorimetry (ITC). We developed a synthetic synovial fluid (SSF) medium that closely resembles the in vivo microenvironment and allows to grow and study PJI pathogens in physiologically relevant conditions. In this study we investigated whether the use of ITC in combination with the SSF medium can improve accuracy and time to detection in the context of PJI. Methods. In this study, 120 synovial fluid samples were included, aspirated from patients with clinical signs of PJI. For these samples microbiology data (obtained in the clinical microbiology lab using standard procedures) and next generation sequencing (NGS) data, were available. The samples were incubated in the SSF medium at different oxygen levels (21% O. 2. , 3% O. 2. and 0% O. 2. ) for 10 days. Every 24h, the presence of growth was checked. From positive samples, cultures were purified on Columbia blood agar and identified using MALDI-TOF. In parallel, heat produced by metabolically active microorganisms present in the samples was measured using ITC (calScreener, Symcel), (96h at 37°C, in SSF, BHI and thioglycolate). From the resulting thermograms the ‘time to activity’ could be derived. The accuracy and time to detection were compared between the different detection methods. Results. So far, seven samples were investigated. Using conventional culture-based techniques only 14.3% of the samples resulted in positive cultures, whereas NGS indicated the presence of microorganisms in 57.1% of the samples (with 3/7 samples being polymicrobial). Strikingly, 100% of the samples resulted in positive cultures after incubation in the SSF medium, with time to detection varying from 1 to 9 days. MALDI-TOF revealed all samples to be polymicrobial after cultivation in SSF, identifying organisms not detected by conventional techniques or NGS. For the samples investigated so far, signals obtained with ITC were low, probably reflecting the low microbial load in the first set of samples. Conclusion. These initial results highlight the potential of the SSF medium as an alternative culture medium to detect microorganisms in PJI context. Further studies with additional samples are ongoing; in addition, the microcalorimetry workflow is being optimized


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 7 - 7
22 Nov 2024
Unsworth A McNally M Young B Scarborough M
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Aims. Bone and joint infections cause significant morbidity, often requiring combination medical and surgical treatment. The presence of foreign material reduces the number of organisms required to cause an infection. The aim of this study was to assess whether there was a difference in the species of organism identified on culture in osteomyelitis compared to prosthetic joint infection. Method. This was a retrospective observational cohort study of patients that had surgical intervention for prosthetic joint infection or osteomyelitis with positive microbial culture between 2019 and 2022. Data including patient demographics, site of injury, BACH score for osteomyelitis and JS-BACH score for prosthetic joint infection, organism classification and antibiotic resistance to vancomycin and gentamicin were extracted from the medical record. Logistic and multiple regressions were used to adjust for potential confounding variables. Results. A total of 445 patients were included in the study; 267 patients with osteomyelitis or fracture-related infection and 177 patients with prosthetic joint infection. The patients with prosthetic joint infection were older (Mean age 70 for PJI; IQR 60-77 vs 56 for OM/FRI; IQR 39-64), more likely to be female (55.6% vs 26.2%) and had a higher BMI and ASA compared to those with osteomyelitis. Symptom duration tended to be longer in osteomyelitis/FRI (p<0.001). Staphylococcus aureus was the most common pathogen isolated in both osteomyelitis (155/267 (58.1%)) and prosthetic joint infection (85/177 (48.9%), followed by other Gram negative pathogens with 77/267 (28.8%) in osteomyelitis and 48/177 (27.1%) in prosthetic joint infection. On multivariate analysis, there was no difference between the rate of Staphylococcus aureus infection between the two groups. The rate of polymicrobial infection was higher in patients with osteomyelitis (92/267 (34.5%)) compared to prosthetic joint infection (38/177 (23.7%), however after adjustment for confounders there was no difference, p = 0.842. There was no difference in the presence of gentamicin resistant organisms or vancomycin resistant Gram positive organisms in osteomyelitis compared to prosthetic joint infection. Conclusion. Causative pathogens are similar in these two common forms of bone and joint infection. There was no significant difference in the identification, presence of polymicrobial infection or gentamicin and vancomycin resistance in organisms isolated in osteomyelitis compared to prosthetic joint infection. This may have implications for empiric antibiotic choice and local antibiotic therapy in the management of bone and joint infection


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 69 - 69
22 Nov 2024
De Vecchi E Riccardi M Mastroianni N
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Aim. Diagnosis of prosthetic joint infection are often complicated by the presence of biofilm, which hampers bacteria dislodging from the implants, thus affecting sensitivity of cultures. In the last 20 years several studies have evidenced the usefulness of implant sonication to improve microbial recovery from biofilm formed on inert substrates. More recently, treatment of prosthetic joints and tissues with Dithiothreitol, a sulphur compound already used in routine diagnostic workflow for fluidification of respiratory samples, has proved to be not inferior to sonication in microbiological diagnosis of prosthetic joint infections. This study aimed to evaluate if the combination of the two treatments could further improve microbial retrieval from biofilm in an in vitro model. Method. Three isolates of Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus lugdunensis, Eschericha coli and Pseudomonas aeruginosa responsible of prosthetic joint infections were used. They were grown onto 3 titanium discs (20 mm diameter) and incubated in 3 sterile plastic containers with 15 mL of Triptyc Soy Broth. After overnight incubation, not adhered cells were removed and fresh broth was added to each sample. After 48 hours incubation, the exausted broth was removed and one sample was used for sonication, one for treatment with 0,1% (v:v) Dithiothreitol and one treated with Dithiothreitol followed by sonication. Treated fluids were plated on Muller Hinton Agar plates for colony count. One-way ANOVA analysis was performed to evidence statistical differences between treatments. Results. Similar colony counts were observed for the 3 treatments: 10.1± 0.77 log CFU/mL for Dithiothreitol, 10.0 ± 0.75 for sonication and 10.1 ±0.73 for dithiothreitol + sonication. No statistical differences between the 3 treatments were evidenced by ANOVA analysis. Conclusions. Results seems to confirm that treatment with dithiothreitol is equivalent to sonication in recovering bacteria from biofilm grown on inert surface. Combining dithiotreitol treatment with sonication does not significantly improve bacterial recovery in respect to each treatment alone


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 70 - 70
22 Nov 2024
Jacob A Onsea J Bessems L Spoormans P Vles G Metsemakers W Depypere M
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Aim. The primary objective is to evaluate the diagnostic performance of inoculating homogenized tissue and bone biopsies in blood culture bottles (BCB) for patients with (suspected) orthopaedic device-related infections. As secondary objective the time to positivity (TTP) of BCB and Wilkins-Chalgren broth (conventional method) will be evaluated. Method. Patients undergoing revision surgery due to suspected or proven fracture-related infection (FRI) or periprosthetic joint infection (PJI) according to respectively Consensus definition and EBJIS definition are included. 1,2. A minimal of three macroscopic infected/inflamed tissue/bone samples are collected in a container with saline and glass beads. 1.5 mL of the homogenized suspension is inoculated in BacT/ALERT FA and FN Plus bottles for 14 days. The remaining suspension is inoculated in Wilkins-Chalgren broth for 10 days and subcultured when cloudy or after 10 days. TTP is defined as the time until definite identification of the pathogen in the Laboratory Information System. Results. Up to now, 25 patients have been included, 11 (44%) had concordant results in BCB and the CM. In 11 patients cultures showed negative results for both methods. Three patients tested positive with BCB but remained negative with the same pathogen in CM. In the first patient, the CM failed to identify anaerobic bacteria (i.e. Fusobacterium nucleatum). In the second patient, three BCB were positive with Staphylococcus capitis. The third patient showed an infection with Escherichia coli, which was detected in all samples from the BCB, while all cultures obtained with the CM remained negative. A possible explanation for this discrepancy could be that this patient already received antibiotic therapy. BCB contain resins, which are capable of neutralizing antibiotic activity. Another case illustrating superiority of BCB involved an infection with Cutibacterium acnes, which showed positivity in six BCB, while only three were positive using the CM. We observed the shortest TTP with BCB. The median TTP of BCB was 32.0 hours (IQR 29.8) compared to a median TTP of 77.5 hours (IQR 107.6) when culturing with the CM. Contamination was seen in three patients with both methods, in eight patients contamination was only seen with the CM. For the remaining 14 patients no contamination was found. Conclusions. The results in this ongoing study indicate that the recovery of pathogens and TTP is better using BCB compared to CM. In addition, contamination occurs less frequently with the BCB method. Culturing tissue or bone biopsies in BCB seems a promising and faster detection method


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 28 - 28
22 Nov 2024
Boyce S Nichol T Smith T Le Maitre C
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Aim. Periprosthetic joint infections follow 1-3% of arthroplasty surgeries, with the biofilm nature of these infections presenting a significant treatment challenge. 1. Prevention strategies include antibiotic-loaded bone cement; however, increases in cementless procedures means there is an urgent need for alternative local antimicrobial delivery methods. 2. A novel, ultrathin, silica-based sol-gel technology is evaluated in this research as an anti-infective coating for orthopaedic prosthetic devices, providing local antibiotic release following surgery. Method. Reduction in clinically relevant microbial activity and biofilm reduction by antimicrobial sol-gel coatings, containing a selection of antibiotics, were assessed via disc diffusion and microdilution culture assays using the Calgary biofilm device. 3. Proliferation, morphology, collagen, and calcium production by primary bovine osteoblasts cultured upon antibiotic sol-gel surfaces were examined, and cytotoxicity evaluated using Alamar blue staining and lactate dehydrogenase assays. Concentrations of silica, calcium and phosphorus compounds within the cell layer cultured on sol-gel coatings and concentrations eluted into media, were quantified using ICP-OES. Furthermore, cellular phenotype was assessed using alkaline phosphatase activity with time in culture. Results. Low antibiotic concentrations within sol-gel had an inhibitory effect on clinically relevant biofilm growth, for example 0.8 mg ml. -1. tobramycin inhibited clinically isolated S. aureus (MRSA) growth with an 8-log reduction in viable colony forming units. There was no significant difference in metabolic activity between untreated and sol-gel exposed primary bovine osteoblasts in elution-based assays. Reduction (2-fold) in metabolic activity in direct contact assays after 48 hours exposure was likely to be due to increased osteoinduction, whereas no impact upon cell proliferation were observed (p=0.92 at 14 days culture). The morphology of primary osteoblasts was unaffected by culture on sol-gel coatings and collagen production was maintained. Calcium containing nodule production within bovine osteoblastic cells was increased 16-fold after 14 days culture upon sol-gel. Conclusions. The ultrathin sol-gel coating showed low cytotoxicity, strong biofilm reducing activity and antimicrobial activity, which was comparable to antibiotics alone, demonstrating that sol-gel delivery of antibiotics could provide local antimicrobial effects to inhibit PJI growth without the need for bone cement. Future work will develop and evaluate sol-gel performance in an ex vivo explant bone infection model which will reduce the need for animal experimentation


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 41 - 41
22 Nov 2024
Copier B Visser D van Oldenrijk J Bos K Veltman W
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Aim. Periprosthetic joint infection (PJI) is a devasting complication after total hip arthroplasty. Joint aspiration and preoperative biopsy can be helpful diagnostics for PJI. The aim of this study is to evaluate the diagnostic value of preoperative biopsies after inconclusive or dry tap aspiration of the hip in patients undergoing revision hip arthroplasty. Secondarily we will evaluate the diagnostic value of synovial fluid aspiration cultures and peroperative tissue cultures for diagnosing or ruling out PJI. Methods. Patients who underwent diagnostic aspiration and subsequent preoperative biopsy and/or revision surgery between January 2015 and January 2024 were included in the study. Synovial fluid aspirations and tissue samples obtained from biopsy and revision surgery were interpreted using the European Bone and Joint Infection Society criteria for PJI and in close consultation with the microbiologist. Results. 207 Patients were included with 231 synovial fluid aspirations. Sensitivity and specificity of synovial fluid aspiration cultures were 76% and 98%. In 62 patients tissue biopsies were performed, of which 40 after a dry tap. The tissue biopsies after a dry tap aspiration had a sensitivity of 50.0% and a specificity of 95.8%. In 21% tissue biopsies led to the confirmation of PJI in patient with a high suspicion of PJI after dry tap aspiration. In patients with an inconclusive synovial fluid aspiration result the addition of tissue biopsies led to a change in treatment in 14%. In 212 cases revision surgery was performed, intraoperative tissue cultures had a sensitivity and specificity of 83.3% and 99.3%. Conclusions. Diagnosing PJI can be troublesome, especially if synovial fluid aspiration provides a dry tap. Tissue biopsy cultures in patients with a high suspicion of PJI after dry tap aspiration is a feasible way to confirm PJI, in 21% of patients PJI could be confirmed after dry tap aspiration. Ruling out PJI by means of a biopsy after a dry tap aspiration is less successful due to its low sensitivity. Tissue biopsies after an inconclusive aspiration leads to clinically important treatment changes


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 86 - 86
22 Nov 2024
Lentini A Djoko J Putineanu D Tribak K Coyette M Yombi J Cornu O
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Aim. Bone infections often manifest with soft tissue complications such as severe scarring, fistulas, or ulcerations. Ideally, their management involves thorough debridement of infected bone and associated soft tissues, along with achieving stable bone structure, substantial tissue coverage, and long-term antibiotic therapy. The formation of a multidisciplinary team comprising orthopedic surgeons, plastic surgeons, and infectious disease specialists is essential in addressing the most complex cases. Method. We conducted a retrospective study during six years (2018-2023) at our university center. Focusing on the most challenging cases, we included patients with bone infections in the leg and/or foot requiring free flap reconstruction. Each patient underwent simultaneous bone debridement and reconstruction by the orthopedic team, alongside soft tissue debridement and free flap reconstruction by the plastic surgery team. Targeted antibiotic therapy for either 6 weeks (acute) or 12 weeks (chronic osteitis) was initiated based on intraoperative cultures. Additional procedures such as allografts, arthrodesis, or autografts were performed if necessary. We analyzed the rates of bone union, infection resolution, and limb preservation. Results. Forty-five patients were enrolled. Twenty-four patients (53.3%) had urgent indications (e.g., open infected fractures, osteitis, acute osteoarthritis, or wound dehiscence), while 21 (46.7%) underwent elective surgery (e.g., septic pseudarthrosis or chronic osteitis). Two patients underwent amputation due to flap failure (4.4%), and one patient was lost to follow-up. Follow-up of the remaining 42 patients averaged 28 months (range: 6–60 months). During this period, 35 patients (83.4%) experienced no recurrence of infection. Similarly, 35 patients (83.4%) achieved bone union. Overall, the rate of lower limb preservation was 93.3%. Conclusions. Managing bone infection coupled with soft tissue defects brings significant challenges. Although the majority of patients treated here belong to a complex framework based on the BACH classification, the outcomes achieved here appear to align with those of the simpler cases, thanks to optimal care with a dedicated septic ortho-plastic team. Our study demonstrates a notable success rate in treating infection, achieving bone consolidation, and preserving lower limb function


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 15 - 15
22 Nov 2024
Liew-Littorin C Davidsson S Nilsdotter-Augustinsson Å Brueggemann H Söderquist B
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Aim. Cutibacterium acnes is a major skin commensal that may also act as an opportunistic pathogen. Findings of C. acnes in tissue cultures obtained during arthroplasty revision surgery are difficult to interpret, since they may represent true infection or contamination. This study investigated whether C. acnes isolates obtained from prosthetic joint infections (PJIs) were related and shared common genomic traits that might correlate with clinical courses and patient outcomes. Method. C. acnes isolates from revision surgery of patients with PJIs of the hip, shoulder, and knee were characterized using molecular methods to determine sequence type (ST) and the presence of virulence determinants (CAMP factors, dermatan sulfate-binding adhesion 1, hyaluronidase lyase, and linear plasmid). A standardized review of the patients’ medical charts was performed. Results. The study included 37 patients with C. acnes culture-positive tissue samples where multiple isolates of C. acnes belonged to the same ST. Most of the isolates belonged to phylotype IA. 1. Phylogenetic analysis of virulence determinants revealed no shared pattern among PJI isolates. Seven patients had a polymicrobial infection. Exchange revision was performed in 70% of the patients, and >50% of all patients received antibiotic treatment for ≥3 months. Failure was noted in seven patients, all of whom had shoulder PJIs. Conclusions. No specific ST or any identifiable unique feature among virulence determinants were found among C. acnes isolated from PJIs of hips and shoulders. The majority of all included patients had low inflammatory markers and were treated successfully, even when the infection consisted of a polymicrobial infection