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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


The Bone & Joint Journal
Vol. 106-B, Issue 12 | Pages 1416 - 1425
1 Dec 2024
Stroobant L Jacobs E Arnout N Van Onsem S Tampere T Burssens A Witvrouw E Victor J

Aims. Approximately 10% to 20% of knee arthroplasty patients are not satisfied with the result, while a clear indication for revision surgery might not be present. Therapeutic options for these patients, who often lack adequate quadriceps strength, are limited. Therefore, the primary aim of this study was to evaluate the clinical effect of a novel rehabilitation protocol that combines low-load resistance training (LL-RT) with blood flow restriction (BFR). Methods. Between May 2022 and March 2024, we enrolled 45 dissatisfied knee arthroplasty patients who lacked any clear indication for revision to this prospective cohort study. All patients were at least six months post-surgery and had undergone conventional physiotherapy previously. The patients participated in a supervised LL-RT combined with BFR in 18 sessions. Primary assessments included the following patient-reported outcome measures (PROMs): Knee injury and Osteoarthritis Outcome Score (KOOS); Knee Society Score: satisfaction (KSSs); the EuroQol five-dimension five-level questionnaire (EQ-5D-5L); and the pain catastrophizing scale (PCS). Functionality was assessed using the six-minute walk Test (6MWT) and the 30-second chair stand test (30CST). Follow-up timepoints were at baseline, six weeks, three months, and six months after the start. Results. Six weeks of BFR with LL-RT improved all the PROMs except the sports subscale of the KOOS compared to baseline. Highest improvements after six weeks were found for quality of life (QoL) (mean 28.2 (SD 17.2) vs 19 (SD 14.7); p = 0.002), activities of daily living (mean 54.7 (SD 18.7) vs 42.9 (SD 17.3); p < 0.001), and KSSs (mean 17.1 (SD 8.8) vs 12.8 (SD 6.7); p < 0.001). PROMs improvements continued to be present at three-month and six-month follow-up compared to baseline. However, no significant differences were observed in the paired comparisons of the six-week, three-month, and six-month follow-up. The same trends are observed for the 6MWT and 30CST. Conclusion. The reported regime demonstrates improved QoL and function of dissatisfied knee arthroplasty patients. In light of this, the pathway described may provide a valuable and safe treatment option for dissatisfied knee arthroplasty patients for whom therapeutic options are limited. Cite this article: Bone Joint J 2024;106-B(12):1416–1425


The Bone & Joint Journal
Vol. 106-B, Issue 12 | Pages 1408 - 1415
1 Dec 2024
Wall L Bunzli S Nelson E Hawke LJ Genie M Hinwood M Lang D Dowsey MM Clarke P Choong PF Balogh ZJ Lohmander LS Paolucci F

Aims

Surgeon and patient reluctance to participate are potential significant barriers to conducting placebo-controlled trials of orthopaedic surgery. Understanding the preferences of orthopaedic surgeons and patients regarding the design of randomized placebo-controlled trials (RCT-Ps) of knee procedures can help to identify what RCT-P features will lead to the greatest participation. This information could inform future trial designs and feasibility assessments.

Methods

This study used two discrete choice experiments (DCEs) to determine which features of RCT-Ps of knee procedures influence surgeon and patient participation. A mixed-methods approach informed the DCE development. The DCEs were analyzed with a baseline category multinomial logit model.


Bone & Joint Research
Vol. 13, Issue 12 | Pages 695 - 702
1 Dec 2024
Cordero García-Galán E Medel-Plaza M Pozo-Kreilinger JJ Sarnago H Lucía Ó Rico-Nieto A Esteban J Gomez-Barrena E

Aims

Electromagnetic induction heating has demonstrated in vitro antibacterial efficacy over biofilms on metallic biomaterials, although no in vivo studies have been published. Assessment of side effects, including thermal necrosis of adjacent tissue, would determine transferability into clinical practice. Our goal was to assess bone necrosis and antibacterial efficacy of induction heating on biofilm-infected implants in an in vivo setting.

Methods

Titanium-aluminium-vanadium (Ti6Al4V) screws were implanted in medial condyle of New Zealand giant rabbit knee. Study intervention consisted of induction heating of the screw head up to 70°C for 3.5 minutes after implantation using a portable device. Both knees were implanted, and induction heating was applied unilaterally keeping contralateral knee as paired control. Sterile screws were implanted in six rabbits, while the other six received screws coated with Staphylococcus aureus biofilm. Sacrifice and sample collection were performed 24, 48, or 96 hours postoperatively. Retrieved screws were sonicated, and adhered bacteria were estimated via drop-plate. Width of bone necrosis in retrieved femora was assessed through microscopic examination. Analysis was performed using non-parametric tests with significance fixed at p ≤ 0.05.


The Bone & Joint Journal
Vol. 106-B, Issue 12 | Pages 1377 - 1384
1 Dec 2024
Fontalis A Yasen AT Giebaly DE Luo TD Magan A Haddad FS

Periprosthetic joint infection (PJI) represents a complex challenge in orthopaedic surgery associated with substantial morbidity and healthcare expenditures. The debridement, antibiotics, and implant retention (DAIR) protocol is a viable treatment, offering several advantages over exchange arthroplasty. With the evolution of treatment strategies, considerable efforts have been directed towards enhancing the efficacy of DAIR, including the development of a phased debridement protocol for acute PJI management. This article provides an in-depth analysis of DAIR, presenting the outcomes of single-stage, two-stage, and repeated DAIR procedures. It delves into the challenges faced, including patient heterogeneity, pathogen identification, variability in surgical techniques, and antibiotics selection. Moreover, critical factors that influence the decision-making process between single- and two-stage DAIR protocols are addressed, including team composition, timing of the intervention, antibiotic regimens, and both anatomical and implant-related considerations. By providing a comprehensive overview of DAIR protocols and their clinical implications, this annotation aims to elucidate the advancements, challenges, and potential future directions in the application of DAIR for PJI management. It is intended to equip clinicians with the insights required to effectively navigate the complexities of implementing DAIR strategies, thereby facilitating informed decision-making for optimizing patient outcomes.

Cite this article: Bone Joint J 2024;106-B(12):1377–1384.


Bone & Joint Research
Vol. 13, Issue 11 | Pages 682 - 693
26 Nov 2024
Wahl P Heuberger R Pascucci A Imwinkelried T Fürstner M Icken N Schläppi M Pourzal R Gautier E

Aims. Highly cross-linked polyethylene (HXLPE) greatly reduces wear in total hip arthroplasty, compared to conventional polyethylene (CPE). Cross-linking is commonly achieved by irradiation. This study aimed to compare the degree of cross-linking and in vitro wear rates across a cohort of retrieved and unused polyethylene cups/liners from various brands. Methods. Polyethylene acetabular cups/liners were collected at one centre from 1 April 2021 to 30 April 2022. The trans-vinylene index (TVI) and oxidation index (OI) were determined by Fourier-transform infrared spectrometry. Wear was measured using a pin-on-disk test. Results. A total of 47 specimens from ten brands were included. The TVI was independent of time in vivo. A linear correlation (R. 2. = 0.995) was observed between the old and current TVI standards, except for vitamin E-containing polyethylene. The absorbed irradiation dose calculated from the TVI corresponded to product specifications for all but two products. For one electron beam-irradiated HXLPE, a mean dose of 241% (SD 18%) of specifications was determined. For another, gamma-irradiated HXLPE, a mean 41% (SD 13%) of specifications was determined. Lower wear was observed for higher TVI. Conclusion. The TVI is a reliable measure of the absorbed irradiation dose and does not alter over time in vivo. The products of various brands differ by manufacturing details and consequently cross-linking characteristics. Absorption and penetration of electron radiation and gamma radiation differ, potentially leading to higher degrees of cross-linking for electron radiation. There is a non-linear, inverse correlation between TVI and in vitro wear. The wear resistance of the HXLPE with low TVI was reduced and more comparable to CPE. Cite this article: Bone Joint Res 2024;13(11):682–693


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 58 - 58
22 Nov 2024
Adan e Silva F dos Santos A Seixas J Rodrigues D Correia AL Cipriano A Abreu M Carvalho A Sousa R
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Aim. Successful management of native Joint septic arthritis (SA) hinges on the timely initiation of appropriate antibiotic therapy coupled with thorough joint debridement. Since 2018 we have implemented a protocol for empirical antibiotic in patients with suspected SA recommending amoxicillin/clavulanate (and cotrimoxazole in cases of beta-lactams allergy) based on local flora. Nevertheless we have recently found that institutional compliance to the protocol is only about 50% and many physicians are still choosing alternative wider spectrum regimens. The aim of this study is to assess whether current clinical and epidemiological characteristics of patients treated for this condition justify an update or whether previous recommendations are still valid. Method. All adult patients admitted to our institution with suspected SA between 2018-2022 were retrospectively reviewed. Data was collected from electronic medical records and then compared to similar data previously collected concerning the 2009-2017 period (that served as a basis for the aforementioned protocol). Results. A summary of available data from both time periods can be found in table 1. Overall, among the 35 patients with positive microbiology treated between 2018-2022, amoxicillin/clavulanate is appropriate for 30 (86%) of isolates (vs 88% in historic control). Analysing the whole cohort, we found that previous contact with healthcare services (hospital admission or prolonged ER stay) (p=0.0044) and antibiotic treatment for any infection (p= 0.0213) in the previous six months correlate with resistance to amoxicillin/clavulanate. In these patients, the proposed alternative cotrimoxazole is effective in 77% of cases. Conclusions. The institutional guideline for empirical antibiotic therapy in native joint SA remains adequate and there seems to be no justification to deviate from protocol except in cases of patients admitted to the hospital or antibiotic treatment in the previous six months. In these cases methicillin-resistance coverage is probably appropriate. Pseudomonal coverage is seldom required in SA. For any tables or figures, please contact the authors directly


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 9 - 9
22 Nov 2024
Wali R Miller C Harrison C Stafford G Hatton P
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Introduction. In specific conditions, infection may lead to bone loss and is difficult to treat. 1. Current clinical approaches rely on the introduction of antibiotics. While these may be effective, there are concerns regarding the rise of antimicrobial resistance. There is therefore interest in the development of antimicrobial bone graft substitutes for dental and trauma surgery. Aim & Objectives. The incorporation of zinc into biomaterials has been shown to confer broad spectrum antimicrobial activity, but this has not yet been applied to the development of a commercial bone graft substitute. The aim of this research was therefore to prepare and characterise a series of zinc-substituted nanoscale hydroxyapatite (nHA) materials, including evaluation of antimicrobial activity. Method. Zinc (Zn) substituted nHA materials were prepared (0, 5, 10, 15 & 20 mol.% Zn) using a wet chemical precipitation method with a rapid mixing. (2). The reaction was carried out using zinc hydroxide at pH 10. The suspension formed was washed and dried into both powder & paste forms. The resultant powders were characterized using transmission electron microscopy (TEM) and X-ray diffraction (XRD). The antimicrobial activity was evaluated against Staphylococcus aureus (S8650 strain - isolated from an osteomyelitis case), by two techniques. The Miles and Misra method was applied to determine the number of colony-forming units (CFUs) in bacterial suspensions incubated with pastes. Secondly, a biofilm initialization method was used to evaluate the capacity of the materials to prevent biofilm formation. One-way analysis of variance (ANOVA) was used for the statistical analysis and results with p-value < 0.05 were considered statistically significant. Results. XRD indicated the formation of pure hydroxyapatite with up to 10 mol.% Zn without any side products. However, when Zn was increased to 15 & 20 mol %, zinc oxide (ZnO) peaks were detected. The TEM showed nanoscale needle-like particles when Zn was increased compared to nHA particles. Regarding the antibacterial activity, ZnHA pastes at all concentrations caused a significant reduction in bacterial CFUs in a dose-dependent manner (50, 100 & 200 mg). Additionally, even the lowest zinc substitution (5 mol.%) significantly reduced biofilm formation. Conclusion. The results demonstrated a novel method to produce a Zn-substituted nHA that showed antimicrobial activity against a pathogen isolated from a bone infection


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 24 - 24
22 Nov 2024
Veerman K Telgt D Rijnen W Donders R Kullberg BJ Wertheim H Goosen J
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Aim. Periprosthetic joint infection (PJI) is a severe complication after total joint arthroplasty. To prevent PJI, strict infection prevention measures are followed in combination with surgical antibiotic prophylaxis (SAP). To date, scientific reports concerning the optimal duration of SAP in revision arthroplasty are scarce. The aim of this multicenter open-label, randomized controlled trial in the Netherlands, is to investigate the superiority of 5 days (extended) versus a single dose of cefazolin to prevent PJI within the first year after revision arthroplasty of the hip and knee. Method. Included patients with an assumed aseptic hip or knee revision procedure received a single dose of 2 or 3 gram cefazolin preoperatively. Patients were randomly assigned in a 1:1 ratio to receive extended prophylaxis of cefazolin during 5 days postoperatively versus no prophylaxis after wound closure. Patients were excluded if evidence of PJI at revision. The primary endpoint was the incidence of PJI within one year after revision arthroplasty. PJI was defined according to the 2018 Philadelphia consensus criteria. With a sample size of 746 patients, an alpha of 5% and a power of 80%, superiority of the extended regimen would be shown if the lower boundary of the 95% confidence interval (CI) of the absolute between-group difference of the percentage of PJI is below −4%. Results. In total 751 patients were included for analysis: 379 in the single dose cefazolin group and 372 in the extended group. Within one year, PJI occurred in 2.6% (10/379) in the single dose group and 2.4% (9/372) in the extended group (risk difference, −0.2 percentage points; 95% CI, −2.5 to 2.0%), thus superiority was not shown. Adverse drug events were seen in 20 cases with extended and 7 cases with a single dose prophylaxis. Conclusions. Extended prophylaxis is not significantly superior to a single dose of cefazolin to prevent PJI within the first year after revision arthroplasty of the hip or knee. This is the first randomized controlled trail in which the duration of SAP in the selected group of patients undergoing revision arthroplasty was studied. Extending SAP after closure of the wound could increase the selection or induction of antimicrobial resistance, has an increased risk for adverse drug events, and is therefore not in line with the primary goal of antimicrobial stewardship, comprising optimizing clinical outcomes and ensuring cost-effective therapy while minimizing unintended consequences of antimicrobial use


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 66 - 66
22 Nov 2024
Ye Z van der Wildt B Vogely C Weinans H Poot A van der Wal B
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Aim. Prosthetic joint infections (PJI) remain a great challenge in orthopedic surgery with a high mortality rate. It is particularly complicated by biofilms and infections caused by Methicillin-resistant Staphylococcus aureus (MRSA). It concurrently shields bacteria from host immune responses and confers resistance to antibiotics. This study aims to investigate the efficacy of radioimmunotherapy as an innovative therapeutic modality to address the challenges posed by MRSA and its biofilm. Method. We induced specific monoclonal antibodies 4497-IgG1 as carriers, which target wall teichoic acids (WTA) existing on MRSA and its biofilm. Radionuclides actiniumr-225 (. 225. Ac, α-emitter) and lutetium-177 (. 177. Lu, β-emitter) were conjugated with mAbs using DOTA as chelator. Quality control was assessed using thin layer chromatography and immunoreactivity assays. . 225. Ac- and . 177. Lu-labelled 4497-IgG1 were employed to evaluate the susceptibility of MRSA and its biofilm to the radioimmunotherapy in vitro. Planktonic MRSA and biofilms, at concentrations of 10. 8. and 10. 7. CFU/mL, were incubated at 37°C for 60 minutes in PBS containing either . 225. Ac-mAb (0 - 14.8 kBq) or . 177. Lu-mAb (0 - 14.8 MBq). Radiolabelled dunituximab and free radionuclides serve as isotype-matched negative control. The bacterial viability and metabolic activity were subsequently quantified using CFU and XTT assays. Results. The radiochemical purity of the . 225. Ac-mAbs and . 177. Lu-mAbs complex were determined to be 95.4% and 96.16%. Immunoreactivity fractions of them were measured at 81.8% and 80.8%. . 225. Ac-mAbs and . 177. Lu-mAbs exhibited significant and dose-dependent antimicrobial effects on both planktonic MRSA and biofilm. . 225. Ac- and . 177. Lu-4497IgG1 at doses of 7.4 kBq and 7.4 MBq resulted in more than 4-log reduction in bacterial counts. In biofilms, 2-log reduction at the highest . 225. Ac radioactivity of 14,8kBq. The . 177. Lu complex showed a strong dose-dependent effect, with a reduction of up to 4-log. The XTT assay confirmed these findings, showing a decrease in metabolic activity corresponding to a decrease in bacterial counts, and a slight increase in metabolic activity at the lower dose. Conclusions. Our study demonstrates the efficacy of . 225. Ac and . 177. Lu-labelled 4497-IgG1 antibodies in mediating dose-dependent bactericidal effects against planktonic MRSA and biofilms in vitro. This indicates that radioimmunotherapy could be a potential targeted therapeutic strategy against MRSA and its biofilm. Further research in preclinical and clinical settings is warranted to validate and refine these findings on biofilm-associated implant infections


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 84 - 84
22 Nov 2024
Unsworth A McNally M Scarborough M Young B
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Aim. Local antibiotics, delivered to the site of infection, achieve high tissue concentrations and are used as an adjunct to systemic therapy. Local gentamicin provides levels well above the minimum inhibitory concentration and may be sufficient on its own, however, the efficacy of single or combination local antibiotics has not been studied. This retrospective study evaluated the effect of combination aminoglycoside and vancomycin local antibiotic treatment compared to aminoglycoside alone in the surgical management of bone infection. Method. We studied patients with microbiologically confirmed osteomyelitis and fracture-related infection, who had implantation of antibiotic carriers as part of their surgical management. Data including patient demographics, type of surgery, microbiological characteristics, BACH score, duration of antibiotic treatment and clinical outcomes were collected. Failure of therapy was a composite of recurrence of infection, continued or new antimicrobial therapy, or reoperation with suspected or confirmed infection at one year after index surgery. Results. There were 266 patients who met the inclusion criteria. Nine patients died before the outcome endpoint at 12 months and five patients were lost to follow up so were excluded. 252 patients were included in the final analysis and were well matched with regard to demographics, BACH score and microbiology. 113 patients had treatment with aminoglycoside alone and 139 patients had combination aminoglycoside and vancomycin. There was no difference in the failure rate between groups; 10/113 (8.8%) in the aminoglycoside alone and 12/139 (8.6%) in the combination group, p = 0.934. There was no difference for reoperation, ongoing suppressive antibiotic use, or clinical suspicion of infection. Multivariate analysis showed that there was no added benefit of combination therapy (OR 1.54: 95%CI 0.59-4.04, p=0.38). BACH score and low BMI were associated with increased risk of failure (BACH OR 3.49: 95%CI 1.13-10.76, p=0.03; Low BMI OR 0.91: 95%CI 0.84-0.99, p-0.037). The form of the carrier material (pellets or injectable paste) had no effect on failure rate (p=0.434). Aminoglycoside resistance (confirmed and presumed) occurred in 39/113 (34.5%) of the aminoglycoside only group and 36/139 (25.9%) of the combination group (p=0.137). The presence of aminoglycoside resistance had no effect on failure rate (OR 0.39: 95%CI 0.05-3.01, p=0.37). Conclusions. Clinical outcome was not improved by the addition of vancomycin to aminoglycoside alone as local therapy for the management of osteomyelitis and FRI. Laboratory measured resistance, using currently accepted breakpoints, may not be relevant in local therapy


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 67 - 67
22 Nov 2024
Youf R Ruth S Mannala G Zhao Y Alt V Riool M
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Aim. In trauma surgery, the development of biomaterial-associated infections (BAI) is one of the most common complications affecting trauma patients, requiring prolonged hospitalization and the intensive use of antibiotics. Following the attachment of bacteria on the surface of the biomaterial, the biofilm-forming bacteria could initiate a chronic implant-related infection. Despite the use of conventional local and systemic antibiotic therapies, persistent biofilms involve various resistance mechanisms that contribute to therapeutic failures. The development of in vivo chronic BAI models to optimize antibiofilm treatments is a major challenge. Indeed, the biofilm pathogenicity and the host response need to be finely regulated, and compatible with the animal lifestyle. Previously, a Galleria mellonella larvae model for the formation of an early-stage biofilm on the surface of a Kirschner (K)-wire was established. In the present study, two models of mature biofilm using clinical Staphylococcus aureus strains were assessed: one related to contaminated K-wires (in vitro biofilm maturation) and the second to hematogenous infections (in vivo biofilm maturation). Rifampicin was used as a standard drug for antibiofilm treatment. Method. In the first model, biofilms were formed following an incubation period (up to 7 days) in the CDC Biofilm Reactor (CBR, BioSurface Technologies). Then, after implantation of the pre-incubated K-wire in the larvae, rifampicin (80 mg/kg) was injected and the survival of the larvae was monitored. In the second model, biofilm formation was achieved after an incubation period (up to 7 days) inside the larvae and then, after removing the K-wires from the host, in vitro rifampicin susceptibility assays were performed (according to EUCAST). Results. The first model indicate that in vitro biofilm maturation affects the bacterial pathogenicity in the host, depending on the S. aureus strain used. Furthermore, the more the biofilm is matured, the more the rifampicin treatment efficiency is compromised. The second model shows that, despite the fast in vivo biofilm formation in the host, the number of bacteria, either attached to the surface of the K-wire surface or in surrounding tissue of the larvae, was not increased over time. Conclusions. Altogether, these results allow the establishment of biofilm models using G. mellonella larvae in order to understand the impact of biofilm maturation on both the bacterial pathogenicity and the efficiency of antibiofilm treatments


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 22 - 22
22 Nov 2024
Söderquist B Möller M Salihovic S
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Aim. Dalbavancin is a lipoglycopeptide with a broad antimicrobial spectrum against Gram-positive bacteria and effect against microorganisms in biofilm in vitro. Its pharmacokinetic properties, with an exceptionally long half-life of approximately 300 hours, allow for simplified administration that may be of value in the long-term treatment of bone and joint infections, such as prosthetic joint infections (PJIs). Several case reports and case series with “off-lable” treatment with dalbavancin of PJIs exist, but the optimal dosing regimen remains to be defined. Therapeutic drug monitoring (TDM) is recommended for treatment with >2 doses of dalbavancin. In the absence of TDM, the Swedish national guidelines for bone and joint infections (2023, . www.infektion.net. ) recommends a loading dose of dalbavancin 1,500 mg on day 1 and 1,500 mg on days 8 – 14, after which from day 28 1,000 mg is given biweekly or 500 mg every week. The aim of the present study was to determine trough levels of dalbavancin in patients with long-term treatment of PJIs according to the national guidelines. Method. Twelve patients with PJI were treated with at least 6 doses of dalbavancin, of which the first two doses were 1500 mg and the following doses were 1000 every second week, and prospectively sampled biweekly for determination of serum concentrations (trough levels) of dalbavancin which was measured by liquid chromatography coupled to electrospray tandem mass spectrometry (LC-MS/MS). The renal function was also examined. Results. The median serum concentration 14 days after the first dose of dalbavancin 1500 mg was 36.3 mg/L (range 6.6 – 62.4 mg/L). The median value 14 days after the second dose of 1500 mg (day 27 – 28) was 48.2 mg/L (range 12.2 – 77.3 mg/L). The trough value after the last dose of a total of 6 – 7 doses was as median 43.1 mg/L (range 26.2 – 97.5 mg/L). Three patients showed a tendency towards successive accumulation of dalbavancin during treatment. None of the patients, including those three with increasing through levels during treatment, showed any significant alteration in creatinine nor glomerular filtration rate. Conclusions. TDM during long-term treatment with dalbavancin is recommended to avoid the risk of accumulation and unnecessarily high trough values. With TDM, the dosing interval can be extended in several cases. In addition, with the support of TDM, subtherapeutic serum concentrations, with the risk of developing resistance, can be avoided


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 37 - 37
14 Nov 2024
Zderic I Kraus M Axente B Dhillon M Puls L Gueorguiev B Richards G Pape HC Pastor T Pastor T
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Introduction. Distal triceps tendon rupture is related to high complication rates with up to 25% failures. Elbow stiffness is another severe complication, as the traditional approach considers prolonged immobilization to ensure tendon healing. Recently a dynamic high-strength suture tape was designed, implementing a silicone-infused core for braid shortening and preventing repair elongation during mobilization, thus maintaining constant tissue approximation. The aim of this study was to biomechanically compare the novel dynamic tape versus a conventional high-strength suture tape in a human cadaveric distal triceps tendon rupture repair model. Method. Sixteen paired arms from eight donors were used. Distal triceps tendon rupture tenotomies and repairs were performed via the crossed transosseous locking Krackow stitch technique for anatomic footprint repair using either conventional suture tape (ST) or novel dynamic tape (DT). A postoperative protocol mimicking intense early rehabilitation was simulated, by a 9-day, 300-cycle daily mobilization under 120N pulling force followed by a final destructive test. Result. Significant differences were identified between the groups regarding the temporal progression of the displacement in the distal, intermediate, and proximal tendon aspects, p<0.001. DT demonstrated significantly less displacement compared to ST (4.6±1.2mm versus 7.8±2.1mm) and higher load to failure (637±113N versus 341±230N), p≤0.037. DT retracted 0.95±1.95mm after each 24-hour rest period and withstood the whole cyclic loading sequence without failure. In contrast, ST failed early in three specimens. Conclusion. From a biomechanical perspective, DT revealed lower tendon displacement and greater resistance in load to failure over ST during simulated daily mobilization, suggesting its potential for earlier elbow mobilization and prevention of postoperative elbow stiffness


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 36 - 36
14 Nov 2024
Zderic I Kraus M Rossenberg LV Gueorguiev B Richards G Pape HC Pastor T Pastor T
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Introduction. Tendon ruptures are a common injury and often require surgical intervention to heal. A refixation is commonly performed with high-strength suture material. However, slipping of the thread is unavoidable even at 7 knots potentially leading to reduced compression of the sutured tendon at its footprint. This study aimed to evaluate the biomechanical properties and effectiveness of a novel dynamic high-strength suture, featuring self-tightening properties. Method. Distal biceps tendon rupture tenotomies and subsequent repairs were performed in sixteen paired human forearms using either conventional or the novel dynamic high-strength sutures in a paired design. Each tendon repair utilized an intramedullary biceps button for radial fixation. Biomechanical testing aimed to simulate an aggressive postoperative rehabilitation protocol stressing the repaired constructs. For that purpose, each specimen underwent in nine sequential days a daily mobilization over 300 cycles under 0-50 N loading, followed by a final destructive test. Result. After the ninth day of cyclic loading, specimens treated with the dynamic suture exhibited significantly less tendon elongation at both proximal and distal measurement sites (-0.569±2.734 mm and 0.681±1.871 mm) compared to the conventional suture group (4.506±2.169 mm and 3.575±1.716 mm), p=0.003/p<0.002. Gap formation at the bone-tendon interface was significantly lower following suturing using dynamic suture (2.0±1.6 mm) compared to conventional suture (4.5±2.2 mm), p=0.04. The maximum load at failure was similar in both treatment groups (dynamic suture: 374± 159 N; conventional suture: 379± 154 N), p=0.925. The predominant failure mechanism was breakout of the button from the bone (dynamic suture: 5/8; conventional suture: 6/8), followed by suture rupturing, suture unraveling and tendon cut-through. Conclusion. From a biomechanical perspective, the novel dynamic high-strength suture demonstrated higher resistance against gap formation at the bone tendon interface compared to the conventional suture, which may contribute to better postoperative tendon integrity and potentially quicker functional recovery in the clinical setting


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 45 - 45
14 Nov 2024
Kjeldsen T Thorgaard Skou S Dalgas U Tønning L Birch S Frydendal T Varnum C Garval M G Ingwersen K Mechlenburg I
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Introduction. Exercise is recommended as first-line treatment for patients with hip osteoarthritis (OA). Interestingly, content and dose of exercise interventions seem to be important for the effect of exercise interventions, but the optimal content and dose is unknown. This warrants randomized controlled trials providing evidence for the optimal exercise program in Hip OA. The aim of this trial was to investigate whether progressive resistance training (PRT) is superior to neuromuscular exercise (NEMEX) for improving functional performance, hip pain and hip-related quality of life in patients with hip OA. Method. This was a multicenter, cluster-randomized, controlled, parallel-group, assessor-blinded, superiority trial. 160 participants with clinically diagnosed hip OA were recruited from hospitals and physiotherapy clinics and randomly assigned to twelve weeks of PRT or NEMEX. The PRT intervention consisted of 5 high-intensity resistance training exercises targeting muscles at the hip and knee joints. The NEMEX intervention included 10 exercises and emphasized sensorimotor control and functional stability. The primary outcome was change in the 30-second chair stand test (30s-CST). Key secondary outcomes were changes in scores on the pain and hip-related quality of life (QoL) subscales of the Hip Disability and Osteoarthritis Outcome Score (HOOS). Result. The mean changes from baseline to 12-week follow-up in the 30s-CST were 1.5 (95% CI, 0.9 to 2.1) chair stands with PRT and 1.5 (CI, 0.9 to 2.1) chair stands with NEMEX (difference, 0.0 [CI, 0.8 to 0.8] chair stands). For the HOOS pain subscale, mean changes were 8.6 (CI, 5.3 to 11.8) points with PRT and 9.3 (CI, 5.9 to 12.6) points with NEMEX. For the HOOS QoL subscale, mean changes were 8.0 (CI, 4.3 to 11.7) points with PRT and 5.7 (CI, 1.9 to 9.5) points with NEMEX. Conclusion. In patients with hip OA, PRT is not superior to NEMEX for improving functional performance, hip pain, or hip-related QoL


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 87 - 87
14 Nov 2024
Savaş S Konya M Yılmaz BK Kağa S Kağa E Demirel HH
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Introduction. The Achilles tendon is the thickest and strongest tendon in the human body. Even though the tendon is so strong, it is one of the most frequently injured tendons. Treatment of patients after rupture is planned conservatively and surgically. Conservative treatment is generally applied to elderly patients with sedentary lives. If the treatment is surgical, it can be planned as open surgery or percutaneous surgery. In our study with rabbits, we wrapped a membrane made of plga (polylactic-co-glycolic acid) nanotubes impregnated with type 1 collagen around the tendon in rabbits that underwent open Achilles tendon repair surgery. After surgery, biomechanical and histological tests were performed on the tendons. Method. In the study consisting of 24 rabbits, 2 groups were created by random distribution. In the study group, after the Achilles tendon rupture was created, a type 1 collagen-impregnated plga-based membrane was placed around the tendon after the repair of 1 modified Kesslerr suture. In the control group, after the Achilles tendon rupture was created, 1 modified Kessler suture and Tendon repair was performed with the application of 3 primary sutures. At the end of the 6th week of the study, the rabbits in 2 groups were randomly distributed and histological examination was performed. Additionally, biomechanical testing was performed. Bonar and Movın scoring were used in histological examinations. Result. As a result of biomechanical tests, it was seen that the resistance of the tendon against rupture was higher in the study group than in the control group. In addition, it was observed that the tendon rupture time was longer in the study group than in the control group. Histological examinations gave supportive results from biomechanical tests. Conclusion. We think that the use of collagen-impregnated plga-based nanotubes in the surgical treatment of Achilles tendon ruptures has a positive healing effect. Although we think that the return to normal life after surgery may be faster, we believe that more clinical studies are needed


Bone & Joint Research
Vol. 13, Issue 11 | Pages 647 - 658
12 Nov 2024
Li K Zhang Q

Aims

The incidence of limb fractures in patients living with HIV (PLWH) is increasing. However, due to their immunodeficiency status, the operation and rehabilitation of these patients present unique challenges. Currently, it is urgent to establish a standardized perioperative rehabilitation plan based on the concept of enhanced recovery after surgery (ERAS). This study aimed to validate the effectiveness of ERAS in the perioperative period of PLWH with limb fractures.

Methods

A total of 120 PLWH with limb fractures, between January 2015 and December 2023, were included in this study. We established a multidisciplinary team to design and implement a standardized ERAS protocol. The demographic, surgical, clinical, and follow-up information of the patients were collected and analyzed retrospectively.


Bone & Joint Research
Vol. 13, Issue 11 | Pages 632 - 646
7 Nov 2024
Diaz Dilernia F Watson D Heinrichs DE Vasarhelyi E

Aims

The mechanism by which synovial fluid (SF) kills bacteria has not yet been elucidated, and a better understanding is needed. We sought to analyze the antimicrobial properties of exogenous copper in human SF against Staphylococcus aureus.

Methods

We performed in vitro growth and viability assays to determine the capability of S. aureus to survive in SF with the addition of 10 µM of copper. We determined the minimum bactericidal concentration of copper (MBC-Cu) and evaluated its sensitivity to killing, comparing wild type (WT) and CopAZB-deficient USA300 strains.