Aim. Orthopedic implants play a tremendous role in fixing bone damages due to aging as well as fractures. However, these implants tend to get colonized by bacteria on the surface, leading to infections and subsequently prevention of healing and osteointegration. Recently, Roupie et al. showed that a nisin layer-by-layer based coating applied on biomaterials has both osteogenic and antibacterial properties. The Galleria mellonella larva is a well-known insect infection model that has been used to test the virulence of bacterial and fungal strains as well as for the high throughput screening of antimicrobial compounds against infections. Recently, we have developed an insect infection model with G. mellonella larvae to study implant-associated biofilm infections using Kirschner (K)-wires as implant material. Here, we would like to test the antibacterial capacity of nisin layer-by-layer based coatings on K-wires against Staphylococcus aureus in the G. mellonella larva implant infection model. Method. Prior to the implantation procedure, G. mellonella larvae are maintained at room temperature on wheat germ in an incubator. The larvae received bare titanium K-wires (uncoated), or either control-coated or nisin-coated K-wires. After one hour, the larvae were injected with 5×10. 5. S. aureus bacteria per larva (i.e., hematogenous implant infection model). Next, the larvae were incubated at 37. o. C in an incubator and the survival of the larvae was monitored for five days. Moreover, the number of bacteria on the implant surface and in the surrounding tissue was determined after 24h of incubation. Further, scanning electron microscopy (SEM) analyses were performed to study the effect of nisin on biofilm formation. Results. The larvae receiving the nisin-coated K-wires showed significantly higher survival rates compared to uncoated titanium K-wires, although not when compared to control-coated K-wires. A more than 1-log reduction in number of bacteria on the implant surface and in the surrounding tissue was observed in larvae receiving the nisin-coated K-wires, when compared to uncoated titanium K-wires SEM analysis showed reduced colonization of the bacteria nisin-coated K-wires compared to the controls. Conclusions. In conclusion, the antimicrobial nisin layer-by-layer based coating applied on titanium surfaces is able to prevent implant-related S. aureus biofilm infection in G. mellonella and is a promising antimicrobial strategy to prevent implant-related infections

Aim. Efficacious antibiotic treatment is crucial for managing and preventing orthopedic infections due to their complexity and associated risk of treatment failure. Previous reviews on antibiotic target tissue concentrations have primarily focused on static measurements, which may not accurately reflect the dynamic pharmacokinetic/pharmacodynamic (PK/PD) changes encountered in clinical settings. This review aimed to summarize the current literature on antibiotic distribution in orthopedically relevant tissues and settings using dynamic sampling methods. Method. In accordance with PRISMA guidelines, a literature search was conducted with a scientific librarian's assistance. PubMed and Embase databases were systematically searched using relevant MeSH terms, entries, and keywords. English-published studies between 2004 and 2023 involving systemic antibiotic administration and dynamic measurements were included. 4467 titles were identified. After title and abstract screening, 77 eligible studies remained. Results. The studies covered clinical and pre-clinical studies on both healthy and infected tissue. Dynamic measurements were obtained from various tissues including bone, intervertebral discs, joints, muscles, and subcutaneous tissue. Microdialysis was the predominant sampling method (98.70%, 76/77). Antibiotics like cefuroxime, linezolid, and vancomycin were extensively studied. Fluoroquinolones, tetracyclines, and most beta-lactams typically presented good tissue penetration in relation to relevant PK/PD-targets. In contrast, glycopeptides, macrolides, and flucloxacillin exhibited poorer penetration. Conclusions. This review provides valuable insights of antibiotic distribution in orthopedically relevant target tissues and settings, which may help improve dosing recommendations and treatment outcomes. Our findings are limited to the investigated dosing regimens and administration methods and depend on the chosen PK/PD target. Many antibiotics still require further research to address the significant knowledge gaps, such as the lack of dynamic evaluations for certain antibiotic types and further investigation across various orthopedic settings and tissues

Aim. Irrigation and debridement with an irrigation solution are essential components of the surgical management of acute and chronic periprosthetic joint infection (PJI). Nevertheless, there is a lack of agreement regarding the most effective solution to use. The aim of the study was to perform a systematic review and meta-analysis of the current literature concerning the efficacy of different irrigation solutions over bacterial biofilm. Method. This study was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analysis extension for Network meta-analysis (PRISMA-NMA) checklist for systematic reviews and meta-analyses. A comprehensive literature search of PubMed, Cochrane Library, Web of Science and Scopus databases from inception to September 1, 2023. We combined terms related to PJI, biofilm and irrigation solutions studied in vitro. We performed a network meta-analysis to analyze which irrigation solution achieved a higher reduction of colony forming units (CFU) after specific exposure times, always with a maximum of five minutes, replicating intraoperative conditions. Effect-size was summarized with logarithmic response ratio (logRR) and 95% confidence intervals (95% CI). The rank probability for each treatment was calculated using the p-scores. Results. We screened 233 potential sources. Following deduplication, screening and full-text review, four studies with ten irrigation solutions for different duration of exposures were included, always less than five minutes, replicating intraoperative conditions. Solutions were studied over mature biofilms of most frequent bacteria grown over metal, bone cement or polyethylene surfaces. The highest effect was achieved with povidone iodine 10% during 5 minutes (logRR: −12.02; 95% CI: −14.04, −9.99). The best ranked solutions were povidone iodine 10% during five, three and one minute (respective p-scores: 0.977, 0.932, 0.887) and its combination with hydrogen peroxide for 3 minutes (p-score: 0.836). Povidone iodine 0.3% acting for 5 minutes completed the top 5 best ranked solutions in this study (p-score: 0.761). We assumed that there were no inconsistencies in our network because after examining both scenarios, with and without inconsistencies, the results were not significantly different. Conclusions. Our results show that 10% povidone-iodine is the best antiseptic solution when studied in vitro in the context of prosthetic joint infection. However, the included studies did not evaluate the possible cytotoxic effects of these solutions. This should also be taken into account before choosing the most appropriate antiseptic solution

Aim. Periprosthetic joint infection (PJI) is a serious complication after joint arthroplasty. Diagnosing PJI can be challenging as preoperative screening and conventional cultures may be inconclusive. Sonication fluid culturing stands out as a valuable adjunct technique to improve microbiological PJI diagnosis. This study aims to determine the clinical relevance of routinely using sonication for all septic and aseptic revisions. Method. All patients who underwent (partial) hip or knee revision arthroplasty for all causes between 2012 and 2021 at our institution were retrospectively reviewed. Based on the European Bone and Joint Society PJI criteria, we categorized them into three groups: infection confirmed, infection likely, and infection unlikely. We analyzed the clinical, laboratory, and radiological screening that could confirm or refute suspicion of PJI. We analyzed microbiology cultures and the most frequently detected microorganisms. Sensitivity and specificity were calculated for synovial fluid cultures (preoperative), tissue cultures, and sonication fluid cultures. We determined the clinical relevance of sonication as the percentage of patients for whom sonication confirmed (microbiological) PJI diagnosis. Results. 429 patients who underwent (partial) revision of hip (246 patients) or knee (183 patients) arthroplasty were included. Sensitivity and specificity were 69% and 99% for preoperative synovial fluid cultures, 76% and 92% for intraoperative tissue cultures, and 80% and 89% for sonication fluid cultures, respectively. Sonication fluid cultures improved tissue culture sensitivity and specificity to 83% and 99%, respectively. In 12 (11%) out of 110 PJIs, sonication fluid cultures were decisive for confirming the causative pathogen. This was applicable to acute and chronic infections. In 29 (9%) out of 319 aseptic cases, a negative sonication fluid culture could confirm contamination of tissue cultures. Conclusions. Routine sonication fluid cultures enhanced the sensitivity and specificity of PJI diagnostics. In 11% of PJI cases, causative pathogens were confirmed by sonication fluid culture results. Routine sonication may be helpful in confirming contamination of synovial fluid cultures and tissue cultures. Routine sonication fluid culture should be performed in all revision arthroplasties

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Osteoarthritis (OA) is a common degenerative disease. PA28γ is a member of the 11S proteasome activator and is involved in the regulation of several important cellular processes, including cell proliferation, apoptosis, and inflammation. This study aimed to explore the role of PA28γ in the occurrence and development of OA and its potential mechanism.

Introduction. Patients with external fixators are at risk of pin site infection. A more objective assessment of possible pin site infection is warranted, particularly for future home-based monitoring of pin sites. The aim was to determine if thermography can detect signs of inflammation around pin sites by 1) Establishing a maximum temperature cut-off value 2) Investigating the correlation between local temperature and visual signs of inflammation 3) Adjust for anatomical location and ambient room temperature. Method. This was a cross-sectional international multi-center study following STROBE guidelines. All patients with external ring-fixators scheduled for a visit in the out-patient clinic were eligible. Visual signs of inflammation were categorized using the Modified Gordon classification System (MGS, simplified sMGS). Thermographic imaging was done with an infrared camera (FLIR T540) and the maximum temperature within the ROI (MaxTp) was the primary outcome measure. Sample size and reliability were estimated. Cohen-Kappa, ROC-curve/AUC and Poisson regression were used for statistical analysis. Result. Data from 1970 pin sites were included. Inter-rater reliability of MGS was Kappa=0.79 and for MaxTp ICC=0.99 (95%CI: 0.99;0.99). Overall, a tendency of rising temperature with increasing sMGS was seen. The difference between sMGS=0 and sMGS>0 was significant. The performance of MaxTp as a screening tool to detect inflammation was reasonable with an AUC of 0.71 (95% CI: 0.65-0.76). The empirically optimal cut-off value was 34.1°C (Sensitivity=65%, Specificity=72%, Positive predictive value=23%, Negative Predictive value=94%). A 1°C increase in MaxTp increased the RR of visual signs of inflammation by a factor 1.5 (95% CI: 1.3; 1.7). Conclusion. We found a clinical positive association between the temperature at the pin site measured with thermography and visual signs of inflammation. The empirically optimal temperature cut-off value for inflammation screening was 34.1°C. Thermography may be a promising tool for a for a future point of care technology

Introduction. Approximately 20-25% of patients having joint replacement in the UK have moderate-severe frailty. Frailty is associated with poorer outcomes after joint replacement. Targeting frailty pre-operatively with exercise and protein supplementation could improve post-operative outcomes. Prior to conducting a randomised controlled trial (RCT), a feasibility study was necessary to inform trial design and delivery. Method. We conducted a randomised feasibility study with embedded qualitative work. Patients aged ≥65 years, frail and undergoing THR or TKR were recruited from three UK hospitals. Participants were randomly allocated on a 1:1 ratio to the intervention or usual care group. The intervention group had a 1:1 appointment with a physiotherapist and were provided with a home-based, tailored daily exercise programme and a daily protein supplement for 12 weeks before their operation, supported by six telephone calls from a physiotherapist. Questionnaires were administered at baseline and 12 weeks after randomisation. Interviews were conducted with 19 patients. Feasibility outcomes were eligibility and recruitment rates, intervention adherence, and acceptability of the trial and the intervention. Result. 411 patients were sent a screening pack. Of the 168 patients who returned a screening questionnaire, 79 were eligible and consented to participate, and 64 were randomised. Of the 33 participants randomised to the intervention, 26 attended the intervention appointment. Eighteen participants (69%) received all six intervention follow-up telephone calls. Nineteen participants completed an intervention adherence log; 13 (68%) adhered to the exercise programme and 11 (58%) adhered to the protein supplementation. The overall retention rate was 86% at 12 weeks. The 12-week follow-up questionnaire was returned by 84% of participants who were sent a questionnaire. Interviews found that the trial and intervention were generally acceptable, but areas of potential improvements were identified. Conclusion. This study demonstrated that a larger study is possible and has identified improvements to optimise the design of a RCT

Introduction. Knee Osteoarthritis (KOA) is a prevalent joint disease requiring accurate diagnosis and prompt management. The condition occurs due to cartilage deterioration and bone remodeling. Ultrasonography has emerged as a promising modality for diagnosing KOA. Medial meniscus extrusion (MME), characterized by displacement of medial meniscus beyond the joint line has been recognized as a significant marker of KOA progression. This study aimed to explore potentials Ultrasound findings in timely detection of MME and compare it to magnetic resonance imaging (MRI) as a reference standard. Method. A comprehensive literature search was performed in 4 databases from inception to May 1 2024. Two independent reviewers, initiated screening protocols and selected the articles based on inclusion and exclusion criteria and then extracted the data. Meta-analysis was conducted using R 4.3.2 packages mada and metafor. Result. A total of 2500 articles from 4 databases was retrieved; however, following the application of inclusion and exclusion criteria 23 articles were finally extracted. These studies collectively encompassed a total of 777 patients with mean age of 53.2±7.4. The mean BMI calculated for patients was 28.31 ± 2.45. All patients underwent non-weight bearing knee ultrasonography in supine position with 0° flexion. The reported medial meniscus extrusion was 2.58 mm for articles using MRI and 2.65 mm for those using Ultrasound (MD: 0.05 ± 0.12, P= 0.65, I. 2. : 54%). Our meta-analysis revealed insignificant difference between US and MRI. (SMD: 0.03, 95% CI: -0.18 _0.23, P= 0.77, I. 2. : 56%) Meta analysis for diagnostic accuracy measures yielded a pooled sensitivity and specificity of 90.8% and 77% (95% CI: 84.2% – 94.8%, 35.5% – 95.3%, respectively, I. 2. : 44%). Conclusion. Our results indicate a close alignment in the accuracy of measurements obtained using Ultrasound modality. The narrow range suggests a minimal discrepancy in MME values between MRI and ultrasound, highlighting their comparable precision in diagnostic assessments

Introduction. Selective screening of children at risk for developmental dysplasia of the hip (DDH) is based on clinical examination and risk factor identification. Two meta-analyses published in 2012 found breech presentation, family history of DDH, female sex and primiparity to increase the risk of DDH. However, the DDH definition, reference tests and age of the examined children vary considerably, complicating the translation of those findings to current screening guidelines. The aim of this meta-analysis was to evaluate the association of previously proposed risk factors to the risk of sonographically verified DDH. Method. We searched PubMed, EMBASE and Cochrane library to identify cohort, RCTs, case-control and cross-sectional studies from 1980 to 2023 in English language. Eligible studies included participants under three months of age, where the diagnosis of DDH was made by hip ultrasound using the gold standard Graf method and reported information on one or more of the proposed risk factors and final diagnosis was available. Result. Of 5363 studies screened, 20 studies (n=64543 children) were included. Breech presentation (OR: 4.2, 95%CI 2.6-6.6), family history (3.8, 95%CI 2.1-7.2), female sex (2.5, 95%CI 1.7-3.6), oligohydramnios (3.8, 95%CI 1.7-8.5) and high birthweight (2.0, 95%CI 1.6-2.5) significantly increased the risk of DDH. C-section, primiparity, multiple births, low birthweight and prematurity were not found to increase the risk for DDH, and there was only one study about clubfoot as a risk factor. Heterogeneity was high (I. 2. >75%) in all the tested factors except high birthweight (I. 2. =0%). Subgroup analysis was performed to investigate these heterogeneities. Conclusion. Family history of DDH and breech presentation are associated with significant increase of the risk of sonographic DDH in children aged three months. A similar risk increase was detected for oligohydramnios, which was not detected in previous meta-analyses. Additionally, the DDH risk increase of female sex was found to be lower than previously reported

Introduction. Chondrocytes are enveloped within the pericellular matrix (PCM), a structurally intricate network primarily demarcated by the presence of collagen type VI microfibrils and perlecan, resembling a protective cocoon. The PCM serves pivotal functions in facilitating cell mechanoprotection and mechanotransduction. The progression of osteoarthritis (OA) is associated with alterations in the spatial arrangement of chondrocytes, transitioning from single strings to double strings, small clusters, and eventually coalescing into large clusters in advanced OA stages. Changes in cellular patters coincide with structural degradation of the PCM and loss of biomechanical properties. Here, we systematically studied matrix metalloproteinases (MMPs), their distribution, activity, and involvement in PCM destruction, utilizing chondrocyte arrangement as an OA biomarker. Methods. Cartilage specimens were obtained from 149 osteoarthritis (OA) patients, and selected based on the predominant spatial pattern of chondrocytes. Immunoassays were employed to screen for the presence of various MMPs (-1, -2, -3, -7, -8, -9, -10, -12, -13). Subsequently, the presence and activity of elevated MMPs were further investigated through immunolabeling, western blots and zymograms. Enzymatic assays were utilized to demonstrate the direct involvement of the targeted MMPs in the PCM destruction. Results. Screening revealed increased levels of MMP-1, -2, -3, -7, and -13, with their expression profile demonstrating a distinct dependency on the stage of degeneration. We found that MMP-2 and -3 can directly compromise the integrity of collagen type VI, whereas MMP-3 and MMP-7 disrupt perlecan. Conclusions. Presence of both pro- and active forms of MMP-2, -3, and -7 in OA-induced patterns, along with their direct involvement in collagen type VI and perlecan degradation, underscores their crucial role in early PCM destruction. Given the early stages of the disease already exhibit heightened MMP expression, this understanding could inform early targeted therapies aimed at arresting abnormal PCM remodelling. Acknowledgments. Faculty of Medicine of the University of Tübingen (grant: 2650-0-0)

Introduction. Despite the implementation of numerous preventive measures in recent years, the persistent challenge of periprosthetic infections remains. Among the various strategies, metallic modification of implants, particularly with silver, has emerged as a promising avenue. Silver's antimicrobial properties, coupled with its low human toxicity, render it an appealing option. However, ongoing debate surrounds its comparative efficacy in infection prevention when contrasted with titanium-coated prostheses. Methods. The PubMed database was systematically searched up to March 2024. Studies in English that met predetermined inclusion/exclusion criteria and utilized “Megaprosthesis AND infection” and “ silver-coated AND infection “ as key terms were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA) statement guided the article selection process. Results. From a pool of 1892 potential papers after literature screening, 11 studies with a total of 1419 patients were meticulously selected for analysis. Among these patients, 638 were treated with silver-coated implants, while 781 received titanium-coated implants, resulting in 166 recorded cases of infection. Remarkably, the infection rate stood at 9.2% for the silver-coated group, contrasting with 13.4% for the titanium-coated group. The subsequent analysis unveiled a notable discrepancy in proportions (P difference = -0.0473, 95%CI: -0.088 to -0.006), signaling a statistically significant decrease in infections within the silver-coated cohort. Furthermore, the I2 statistic, denoting heterogeneity in effect sizes, stood at 21.8% (95%CI: 0.0-66.9), indicating a modest degree of variability among the studies. Conclusion. In conclusion, our systematic review and meta-analysis shed light on the potential of silver-coated implants in mitigating periprosthetic infections. Despite the persistent challenge posed by such infections, our findings suggest a statistically significant decrease in infection rates among patients treated with silver-coated implants compared to those with titanium-coated ones

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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.

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Distal femoral osteotomies (DFOs) are commonly used for the correction of valgus deformities and lateral compartment osteoarthritis. However, the impact of a DFO on subsequent total knee arthroplasty (TKA) function remains a subject of debate. Therefore, the purpose of this study was to determine the effect of a unilateral DFO on subsequent TKA function in patients with bilateral TKAs, using the contralateral knee as a self-matched control group.

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Lower limb fractures are common in low- and middle-income countries (LMICs) and represent a significant burden to the existing orthopaedic surgical infrastructure. In high income country (HIC) settings, internal fixation is the standard of care due to its superior outcomes. In LMICs, external fixation is often the surgical treatment of choice due to limited supplies, cost considerations, and its perceived lower complication rate. The aim of this systematic review protocol is identifying differences in rates of infection, nonunion, and malunion of extra-articular femoral and tibial shaft fractures in LMICs treated with either internal or external fixation.

Aims. Reverse shoulder arthroplasty (RSA) has become the most common type of shoulder arthroplasty used in the UK, and a better understanding of the outcomes after revision of a failed RSA is needed. The aim of this study was to review the current evidence systematically to determine patient-reported outcome measures and the rates of re-revision and complications for patients undergoing revision of a RSA. Methods. MEDLINE, Embase, CENTRAL, and the Cochrane Database of Systematic Reviews were searched. Studies involving adult patients who underwent revision of a primary RSA for any indication were included. Those who underwent a RSA for failure of a total shoulder arthroplasty or hemiarthroplasty were excluded. Pre- and postoperative shoulder scores were evaluated in a random effects meta-analysis to determine the mean difference. The rates of re-revision and complications were also calculated. Results. The initial search elicited 3,166 results and, following removal of duplicates and screening, 13 studies with a total of 1,042 RSAs were identified. An increase in shoulder scores pre- to postoperatively was reported in all the studies. Following revision of a RSA to a further RSA, there was a significant increase in the American Shoulder and Elbow Surgeons Score (mean difference 20.78 (95% CI 8.16 to 33.40); p = 0.001). A re-revision rate at final follow-up ranging from 9% to 32%, a one-year re-revision rate of 14%, and a five-year re-revision rate of 23% were reported. The complication rate in all the studies was between 18.5% and 36%, with a total incidence of 29%. Conclusion. This is the largest systematic review of the outcomes following revision of a RSA. We found an improvement in functional outcomes after revision surgery, but the rates of re-revision and complications are high and warrant consideration when planning a revision procedure. Cite this article: Bone Joint J 2024;106-B(11):1293–1300

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Developmental cervical spinal stenosis (DcSS) is a well-known predisposing factor for degenerative cervical myelopathy (DCM) but there is a lack of consensus on its definition. This study aims to define DcSS based on MRI, and its multilevel characteristics, to assess the prevalence of DcSS in the general population, and to evaluate the presence of DcSS in the prediction of developing DCM.

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Machine learning (ML), a branch of artificial intelligence that uses algorithms to learn from data and make predictions, offers a pathway towards more personalized and tailored surgical treatments. This approach is particularly relevant to prevalent joint diseases such as osteoarthritis (OA). In contrast to end-stage disease, where joint arthroplasty provides excellent results, early stages of OA currently lack effective therapies to halt or reverse progression. Accurate prediction of OA progression is crucial if timely interventions are to be developed, to enhance patient care and optimize the design of clinical trials.

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This study examined the relationship between obesity (OB) and osteoporosis (OP), aiming to identify shared genetic markers and molecular mechanisms to facilitate the development of therapies that target both conditions simultaneously.

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This study aimed to demonstrate the promoting effect of elastic fixation on fracture, and further explore its mechanism at the gene and protein expression levels.