Aim. Periprosthetic joint infection (PJI) and periprosthetic fracture (PF) are one of the most devastating complications in arthroplasty. Each complication by itself is challenging to solve. Yet, simultaneously, both complications are inconceivably complex to deal with, while the treatment regimen of PJI and PF are contradictory. Chronic PJI most often requires implant removal, while PF requires stability, regularly achieved by stable osteosynthesis. This study aims to (1) analyse the success rate of PJI with following concomitant PF during the treatment course in total hip arthroplasties (THA) and (2) to determine the risk factors for reinfection and subsequent revision surgery after treatment of PJI and PF. Method. This restrospective study analyzed 41 patients with concomitant PJI and PF during the PJI treatment period from 2013 to 2022 involving THA. Patients were divided in two cohorts termed success and failure and were statistically compared. The median follow-up time was 66 months (>12 months). All patients were considered individually and treated according to their individual needs in fracture and infection treatment. Re-arthroplasty survival was analyzed using the Kaplan-Meier method. Relevant risk factors were analyzed using the Mann-Whitney test or Chi-square, depending on the variable's scale. Results. The overall success rate of our cohort was 70,7%. Twelve patients required re-operation due to reinfection, resulting in a cumulative 12-month-reinfection rate of 19,5%. The estimated cumulative reinfection free survival rate was 68,3%. Significance in risk factors for failure were found in pathogen virulence grade, Difficult to treat pathogen and number of debridement during interval. On average the Harris Hip score was 66 in the group of reinfection compared to 77 in the group of success. Conclusions. Reoperation and re-infection rate remains high in patients with simultaneous PJI and PF in THA. Due to the heterogeneity of the fractures, soft tissue conditions and pathogens found, treatment must be individualised to salvage the limb. However, small cohorts impact the statistical strength negatively due to instances of two rare complications

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

Aim. Biomaterial-associated infections (BAI) present a formidable clinical challenge. Bioactive glasses (BG) have proven highly successful in diverse clinical applications, especially in dentistry and orthopaedics. In this study, we aimed to determine the effect of three commonly used BG composition and particle sizes on cell and bacterial attachment and growth. Our focus is on understanding the changes in pH and osmotic pressure in the surrounding environment during glass degradation. Method. First, three different melt-derived glasses were characterized by analyzing particle size and glass network structure using Raman and NMR. The different glasses were then tested in vitro by seeding 4x 10. 4. cells/well (SaOS Cell line) in a 48 well plate. After a pre-incubation period of 72 hours, the different BGs and particle sizes were added to the cells and the pH value, ion release and live/dead staining was measured every hour. The effect of BG against bacteria (S. epidermidis) was analyzed after 24 and 72 hours of treatment by using XTT viability assay and CFU counting by plating out the treated aliquot agar to estimate the viable bacteria cells. Results. All three BG compositions tested showed a significant increase in pH, which was highest in BG composition 45S5 with a value of 11 compared to the other BG compositions 10 and 9 in S53P4 and 13-93 respectively. This strong increase in the pH in all BG samples tested results in a strongly reduced cell viability rate of more than 75% compared to the untreated control and 6-fold reduction in bacterial viability compared to the untreated control. The live/ dead assay also showed an increased cell viability with increasing glass particle size (i. e smallest glass particle < 25% viable cell and largest glass particle> 65% viable cell). The ion release concentration over 50 h showed an increase in sodium ions to 0.25 mol/L, calcium to 0.003 mol/L and a decrease in phosphorus. Conclusions. These results show that the composition of the bioactive glass and the choice of particle size have a major influence on subsequent applications. In addition to the different compositions of the BG, particle size and additional medium change also influence the pH and ion release, and therefore also on cells or bacteria viability. The sizes of the bioactive glass particle are inversely proportional to it. Further tests are necessary to develop custom design BG compositions, which simultaneously stimulate osteoblasts proliferation and prevent microbial adhesion

Aim. Unexpected negative-cultures (UNC) are a common diagnostic problem in periprosthetic joint infection (PJI) of the hip and knee when using culture-based methods. A novel molecular approach (MC)1 based on the identification of the vast majority of bacterial species in a single assay using species-specific bacterial interspacing region length polymorphisms and phylum-specific 16S rDNA sequence polymorphisms has demonstrated clinical utility in PJI diagnostics (1). In addition, MC provides an estimate of the leukocyte concentration in the specimen analysed. The aim of this retrospective, blinded study was to evaluate the performance of MC in identifying the microbiological content and determining the leukocyte count in synovial fluid (SF) collected from hip and knee revision arthroplasty cases with UNC. It was also assessed whether antibiotic treatment would have been changed if the result from MC had been known. Method. A total of 89 SF samples from 70 patients (43 female; 27 male) who underwent revision arthroplasty (14 hip; 75 knee) were included. Using European and Bone Joint Infection Society (EBJIS) criteria, 82 cases were classified as infected (77 UNC and 5 septic culture-positive controls), five as non-infected (aseptic culture-negative controls), and two as likely infected, but infected by clinical observation. MC was performed and evaluated together with SF parameters. Antibiotic treatment, clinical outcome, patient demographics and surgical details were analysed. Results. Overall, 29.1% (23/79) of UNC had a positive yield by MC, of which 2/23 (8.7%) had two microorganisms detected simultaneously. Of the 25 microorganisms identified by MC, 12/25 (48%) were clinically relevant after re-evaluation of the patients’ microbiological history. The microorganisms detected were 5/25 (20%) Streptococcus pneumoniae/mitis, 4/25 (16%) Staphylococcus epidermidis, 3/25 (12%) Cutibacterium acnes, 3/25 (12%) Streptococcus agalactiae, 2/25 (8%) Streptococcus bovis, 2/25 (8%) Staphylococcus aureus, and 2/25 (8%) Haemophilus parainfluenzae. The prevalence of Enterococcus faecalis, Bacteroides fragillis, Staphylococcus lugdunensis, Corynebacterium striatum among all MC results was 1/25 (4%) each species. In total, 13/23 (56%) cases were associated with patients receiving antibiotic therapy at the time of SF collection. The yield for leukocyte counts provided the molecular technique was consistently much higher in the UNC and clearly septic groups than in the clearly aseptic group. Overall, 20/61 (32.8%) patients with UNC could have been managed differently and more accurately after MC assessment. Conclusions. MC shows clinical value in the diagnosis and management of PJI with UNC. The included leukocyte count shows promising results. Acknowledgments. This work was partially funded by Inbiome

Introduction. Three-dimensional (3D) morphological understanding of the hip joint, specifically the joint space and surrounding anatomy, including the proximal femur and the pelvis bone, is crucial for a range of orthopedic diagnoses and surgical planning. While deep learning algorithms can provide higher accuracy for segmenting bony structures, delineating hip joint space formed by cartilage layers is often left for subjective manual evaluation. This study compared the performance of two state-of-the-art 3D deep learning architectures (3D UNET and 3D UNETR) for automated segmentation of proximal femur bone, pelvis bone, and hip joint space with single and multi-class label segmentation strategies. Method. A dataset of 56 3D CT images covering the hip joint was used for the study. Two bones and hip joint space were manually segmented for training and evaluation. Deep learning models were trained and evaluated for a single-class approach for each label (proximal femur, pelvis, and the joint space) separately, and for a multi-class approach to segment all three labels simultaneously. A consistent training configuration of hyperparameters was used across all models by implementing the AdamW optimizer and Dice Loss as the primary loss function. Dice score, Root Mean Squared Error, and Mean Absolute Error were utilized as evaluation metrics. Results. Both the models performed at excellent levels for single-label segmentations in bones (dice > 0.95), but single-label joint space performance remained considerably lower (dice < 0.87). Multi-class segmentations remained at lower performance (dice < 0.88) for both models. Combining bone and joint space labels may have introduced a class imbalance problem in multi-class models, leading to lower performance. Conclusion. It is not clear if 3D UNETR provides better performance as the selection of hyperparameters was the same across the models and was not optimized. Further evaluations will be needed with baseline UNET and nnUNET modeling architectures

Introduction. The objective of the work is construction of a multi-bioactive scaffold based on that allows a space/time control over the regeneration of damaged bones by Medication-Related Osteonecrosis of the Jaw using a minimal invasive approach based on the injection of the fast-degrading pro neuro and angiogenic ELR (Elastin-Like Recombinamers) based hydrogels. Method. Chemical crosslinking facilitated the creation of multi-bioactive scaffolds using ELRs with reactive groups. Cell-loaded multi-bioactive scaffolds, prepared and incubated, underwent evaluation for adhesion, proliferation, angiogenic, and neurogenic potential. In vitro assessments utilized immunofluorescence staining and ELISA assays, while live-recorded monitoring and live-dead analysis ensured cytocompatibility. In rat and rabbit models, preformed scaffolds were subcutaneously implanted, and the regenerative process was evaluated over time. Rabbit models with MRONJ underwent traditional or percutaneous implantation, with histological evaluation following established bone histological techniques. Result. A 3D scaffold using ELR that combines various peptides with different degradation rates to guide both angiogenesis and neurogenesis has been developed. Notably, scaffolds with different degradation rates promoted distinct patterns of vascularization and innervation, facilitating integration with host tissue. This work demonstrates the potential for tailored tissue engineering, where the scaffold's bioactivities and degradation rates can control angiogenesis and neurogenesis. In an animal model of medication-related osteonecrosis of the jaw (MRONJ), the scaffold showed promising results in promoting bone regeneration in a necrotic environment, as confirmed by histological and imaging analyses. This study opens avenues for novel tissue-engineering strategies where precise control over vascularization and nerve growth is crucial. Conclusion. A groundbreaking dual approach, simultaneously targeting angiogenesis and innervation, addresses the necrotic bone in MRONJ syndrome. Vascularization and nerve formation play pivotal roles in driving reparative elements for bone regeneration. The scaffold achieves effective time/space control over necrotic bone regeneration. The authors are grateful for funding from the Spanish Government (PID2020-118669RA-I00)

Introduction. Bereft of their optimal tissue context, cells lose their phenotype, function and therapeutic potential during in vitro culture. Despite the fact that in vivo cells are exposed simultaneously to multiple signals, traditional ex vivo cultures are monofactorial. With these in mind, herein we assessed the combined effect of surface topography, substrate rigidity, collagen type I coating and macromolecular crowding in human tenocyte, skin fibroblast and bone marrow mesenchymal stromal cell cultures. Methods. Thermal imprinted was used to pattern (groove depth: 2,000 nm, groove width: 2,000 nm, line width: 2,000 nm) polydimethylsiloxane substrates of different rigidity (50 kPa, 130 kPa, 1,000 kPa). Grooved and planar substrates were subsequently coated with collagen type I and used to culture the aforementioned cell populations without and with macromolecular crowding (100 μg/ml carrageenan). After 3, 7 and 14 days in culture, cell morphology, viability, metabolic activity, proliferation, protein synthesis and deposition and gene expression analyses were conducted. Results. None of the variables assessed affected cell viability, metabolic activity and proliferation. Surface topography was found to be a potent regulator of cell morphology. Macromolecular crowding significantly increased extracellular matrix deposition, albeit in globular manner independently on whether grooved or planar substrates were used, possibly due to the low dimensionality of the grooves. Gene expression analysis made apparent that the 130 kPa and the 1,000 kPa grooved substrates under macromolecular crowding conditions maintained human tenocyte phenotype and directed human bone marrow mesenchymal stromal cells towards tendon-like lineage, respectively. None of the conditions assessed dramatically affected human skin fibroblast fate. Conclusions. Collectively, our data indicate that the physicochemical in vitro microenvironment modulators assessed herein are capable of maintaining human tenocyte phenotype and differentiating human bone marrow mesenchymal stromal cells towards tenogenic lineage, but not in trans-differentiating human skin fibroblasts

Introduction. Osteoarthritis (OA) often results from joint misloading, which affects chondrocyte calcium signaling through mechano-sensitive receptors such as Piezo1, -2, and TRPV4. Activation of Piezo1, especially under inflammatory conditions, can trigger premature chondrocyte apoptosis. Intra-articular glucocorticoid therapy, while beneficial against inflammation and pain in osteoarthritis, may induce oxidative stress and chondrotoxicity at higher doses. This study aims to assess the effects of glucocorticoids, particularly triamcinolone, on chondrocyte elasticity and mechanosignaling. Method. Chondrocytes isolated from articular condyles obtained from patients undergoing knee replacement surgery (n= 5) were cultured for 7 days in triamcinolone acetonide (TA) at different concentrations (0.2µM – 2mM). Cytoskeletal changes were assessed by F-actin labeling. Cell elasticity was measured using atomic force microscopy (AFM). Labeling cells (n=6 patients) with the calcium-sensitive dye (Fluo-4) enabled monitoring changes in intracellular calcium fluorescence intensity during guided single-cell mechanical indentation (500 nN) by AFM. Result. Cell exposure to 2 mM TA led to cell death and crystallization of TA in the cell culture media. However, the concentration of TA for intra-articular application is 46 times higher at 92.1 mM (40 mg/ml). The maximal pharmacological effect on viable cells was observed at 0.2 mM. AFM results showed a significant decrease of elasticity (p<0.001), alongside significantly higher calcium intensities both prior to and during mechanical stimulation in the TA-treated samples (p<0.05). Conclusion. Administration of TA significantly impacts the mechanical properties of chondrocytes, reducing cellular elasticity while simultaneously enhancing calcium-dependent mechanosensitivity. This data suggests a correlation between glucocorticoid-induced changes in cell elasticity and cell mechanosensitivity. Finding ways to minimize the effect of glucocorticoids on cell mechanosensitivity could help to make future therapies safer and reduce side effects

Aims. 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. Methods. The inclusion criteria consisted of patients who underwent simultaneous or staged bilateral TKA after prior unilateral DFO between 1972 and 2023. The type of osteotomy performed, osteotomy hardware fixation, implanted TKA components, and revision rates were recorded. Postoperative outcomes including the Forgotten Joint Score-12 (FJS-12), Tegner Activity Scale score, and subjective knee preference were also obtained at final follow-up. Results. A total of 21 patients underwent bilateral TKA following unilateral DFO and were followed for a mean of 31.5 years (SD 11.1; 20.2 to 74.2) after DFO. The mean time from DFO to TKA conversion was 13.1 years (SD 9.7) with 13 (61.9%) of DFO knees converting to TKA more than ten years after DFO. There was no difference in arthroplasty implant systems employed in both the DFO-TKA and TKA-only knees (p > 0.999). At final follow-up, the mean FJS-12 of the DFO-TKA knee was 62.7 (SD 36.6), while for the TKA-only knee it was 65.6 (SD 34.7) (p = 0.328). In all, 80% of patients had no subjective knee preference or preferred their DFO-TKA knee. Three DFO-TKA knees and two TKA-only knees underwent subsequent revision following index arthroplasty at a mean of 12.8 years (SD 6.9) and 8.5 years (SD 3.8), respectively (p > 0.999). Conclusion. In this self-matched study, DFOs did not affect subsequent TKA function as clinical outcomes, subjective knee preference, and revision rates were similar in both the DFO-TKA and TKA-only knees at mean 32-year follow-up. Cite this article: Bone Jt Open 2024;5(11):1013–1019

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We sought to compare functional outcomes and survival between non-smokers, former smokers, and current smokers who underwent anatomical total shoulder arthroplasty (aTSA) in a large cohort of patients.

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The aim of this study was to review the provision of total elbow arthroplasties (TEAs) in England, including the incidence, the characteristics of the patients and the service providers, the types of implant, and the outcomes.

Aims. 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. Methods. Using weighted gene co-expression network analysis (WGCNA), we analyzed datasets from the Gene Expression Omnibus (GEO) database to identify co-expressed gene modules in OB and OP. These modules underwent Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interaction analysis to discover Hub genes. Machine learning refined the gene selection, with further validation using additional datasets. Single-cell analysis emphasized specific cell subpopulations, and enzyme-linked immunosorbent assay (ELISA), protein blotting, and cellular staining were used to investigate key genes. Results. WGCNA revealed critical gene modules for OB and OP, identifying the Toll-like receptor (TLR) signalling pathway as a common factor. TLR2 was the most significant gene, with a pronounced expression in macrophages. Elevated TLR2 expression correlated with increased adipose accumulation, inflammation, and osteoclast differentiation, linking it to OP development. Conclusion. Our study underscores the pivotal role of TLR2 in connecting OP and OB. It highlights the influence of TLR2 in macrophages, driving both diseases through a pro-inflammatory mechanism. These insights propose TLR2 as a potential dual therapeutic target for treating OP and OB. Cite this article: Bone Joint Res 2024;13(10):573–587

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This study examined windswept deformity (WSD) of the knee, comparing prevalence and contributing factors in healthy and osteoarthritic (OA) cohorts.

Acetabular fractures present a challenge. Anatomical reduction can be achieved by open reduction and internal fixation (ORIF). However, in elderly patients with complex fracture patterns and osteoporotic bone stock, “fix and replace” has become an option in the management of these injuries. This involves ORIF of the acetabulum to enable insertion of a press fit cup and subsequent cemented femoral stem at the index surgery.

A Retrospective analysis of all operatively managed acetabular fractures by a regional Pelvic and Acetabular Trauma service (01/01/2018-30/05/2023) STATA used for analysis. 34 patients undergoing “fix and replace” surgery. Of the 133 patients managed with ORIF, 21 subsequently required Total Hip Arthroplasty (THA). Mean follow up was 2.7 years versus 5.1. There was no statistical significance between the two groups with regards to BMI or sex. Mean age in the “fix and replace” group was 68 compared to 48 in the ORIF and subsequent THA group. This reached statistical significance between the two groups (p=0.001).ASA and Charlson Comorbidity Index (3 and 3 in “fix and replace” and 2 and 1.2 in ORIF to THA group) and Charlson Comorbidity Index both were statistically significantly different (p=0.006 and p=0.027, respectively). High energy mechanism of injury accounted for 56% of the “fix and replace” group compared to 48% in the ORIF to THA. 74% of “fix and replace” were associated fractures compared to 53% of ORIF to THA. Wait to surgery was 3 days for “fix and replace” while 186 days was the mean wait time from listing to THA for the ORIF to THA group. Complication rate was 41% versus 43% in the two groups. 14% in the ORIF to THA group developed PJI versus 6% in “fix and replace”.

Fix and replace allows early mobilisation in frailer, elderly patients. Our results show fewer returns to theatre and less PJI in patients having arthroplasty as part of “fix and replace” than subsequent to Open reduction internal fixation.

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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.

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The optimum type of antibiotics and their administration route for treating Gram-negative (GN) periprosthetic joint infection (PJI) remain controversial. This study aimed to determine the GN bacterial species and antibacterial resistance rates related to clinical GN-PJI, and to determine the efficacy and safety of intra-articular (IA) antibiotic injection after one-stage revision in a GN pathogen-induced PJI rat model of total knee arthroplasty.

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We aimed to determine the concentrations of synovial vancomycin and meropenem in patients treated by single-stage revision combined with intra-articular infusion following periprosthetic joint infection (PJI), thereby validating this drug delivery approach.

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The aim of this study was to evaluate the kinematics of the elbow following increasing length of the radius with implantation of radial head arthroplasties (RHAs) using dynamic radiostereometry (dRSA).

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The risk factors for recurrent instability (RI) following a primary traumatic anterior shoulder dislocation (PTASD) remain unclear. In this study, we aimed to determine the rate of RI in a large cohort of patients managed nonoperatively after PTASD and to develop a clinical prediction model.

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The influence of metabolic syndrome (MetS) on the outcome after hip and knee arthroplasty is debated. We aimed to investigate the change in patient-reported outcome measure (PROM) scores after hip and knee arthroplasty, comparing patients with and without MetS.