Background Understanding of the comprehensive hip-spine relationship may reduce total hip arthroplasty (THA) dislocation. However, the impact of sagittal spino-pelvic dynamics on three-dimensional implant orientation has not been investigated prospectively. This study aimed to assess hip-spine dynamics and changes in three-dimensional implant orientation in patients who have stable and unstable primary THAs. Methods In this prospective, case-control study, 23 adults who had a THA dislocation were matched to 23 patients who had a stable implant. Of the 23 dislocations, 17 sustained a posterior, and five sustained an anterior dislocation; one was unknown. Standing anterior-posterior and standing and sitting lateral pelvic radiographs were obtained. Sagittal spinopelvic morphology and orientation parameters, coronal and sagittal acetabular cup, and femoral component orientation parameters were measured. Transverse component orientation parameters were computed. Logistic regressions were conducted to determine the impact of demographics and hip-spine parameters on the likelihood for dislocation. Results The unstable THAs had significantly higher pelvic incidence (PI; 60 ± 13° versus 52 ± 10°, P = 0.015) and transverse version of the acetabular component (TV_Cup; 38 ± 11° versus 32 ± 8°, P = 0.042) compared to the stable THAs. Patients who have anterior dislocations had higher sagittal ante-inclination of the acetabular component (SAI_Cup) than posterior dislocations (48 ± 5° versus 34 ± 10°, P = 0.012). Based on logistic regression analyses, PI, TV_Cup, and the approach were significant predictors of THA dislocation. Conclusions By assessment of spino-pelvic characteristics, surgeons could identify patients at increased risk for THA dislocation preoperatively based on a high PI. Posterior dislocations seem to occur more in patients who have more TV_Cup and a postero-lateral approach, anterior dislocations seem to occur in patients who have more SAI_Cup, TV_Cup, and a direct anterior approach. This suggests implementing a patient-specific functional safe zone of the acetabular component may further reduce THA dislocation rates.

Indwelling medical implants are susceptible to developing biofilm-associated infections that are notoriously difficult to eradicate. These persistent infections often cannot be resolved with antibiotics alone and typically require surgical intervention for effective management. An alternative approach is radioimmunotherapy (RIT) which uses specific antibodies linked to radioisotopes to selectively destroy bacteria. This antimicrobial approach bypasses traditional antibiotic mechanisms, and RIT is hypothesized to enhance outcomes beyond antibiotic therapy alone. RIT bactericidal effects were studied in Wistar Han rats fitted with femoral rod implants covered by matured 3-day biofilms. The rats (six per group) were treated with either: RIT with 177Lu-labeled 4497 antibody to S. aureus teichoic wall acid (WTA) (116.6 MBq/kg), or vancomycin (88 mg/kg), or combination of RIT (116.8 MBq/kg) and vancomycin, or left untreated. To evaluate efficacy, bacterial counts were taken from the joint capsule, bone, and implant after 7 days. Uptake and biodistribution were assessed via non-invasive in vivo SPECT/CT imaging and ex vivo gamma counting. Single administration of RIT achieved a 2.7-log (99.78%) reduction of bacterial burden in the infected joint capsule, had no effect on the infected femur, and resulted in 72.5% reduction of bacterial burden on the infected implant when compared to untreated controls. RIT reduced bacterial burden and inflammation in experimental PJI with no side effects. These findings underscore the potential of RIT in the treatment of infected indwelling devices and warrant further study.

Objective: This study aimed to divide leg malalignment into different categories of valgus and varus of the femur, tibia, and intra-articular knee joint and investigates whether knee osteoarthritis (OA) patients are susceptible for changes of such leg deformities over time. Design: This study included 317 radiographs and CT-images on baseline and 24 months of 169 patients (median age 67, 78.2 % female) of the prospective European IMI-APPROACH cohort, enrolled for knee OA. Femoral, tibial, and intra-articular geometry was determined. Different categories were analysed based on varus or valgus in the femur, in the tibia, or within the intra-articular joint. Changes of these variables over time and their correlations were determined with mixed model analysis. Results: Femurs tended to become more varus-like over the two-year follow up (0.3°, 95 % CI 0.6°–0.1°, p = 0.02), bony valgus femurs became more varus shaped (1.1°, 95 % CI:1.7°–0.5°, p < 0.001). Patients with bone varus and a normal joint line convergence angle (JLCA) showed a significant increase in intra-articular joint varus, with a mean JLCA increase of 1.1°(95 % CI:0.4°–1.7°, p = 0.005). By two years, they reached the threshold for defining intra-articular joint varus deformity, with a JLCA of 2.0°. Conclusions: Substantial intra-articular joint and bone varus progression was observed within two years. This study shows that bone deformity is to some extent a dynamic process and there is a growing varus malalignment in the intra-articular knee joint and bones. Thereby this study emphasizes the importance of leg malalignment for progression of intra-articular knee joint changes in early OA.

Introduction: The anterior column of the spine is crucial for stability. In a dystrophic spine, the loss of multisegmental anterior spinal support can have devastating consequences. Since posterior instrumentation alone cannot take over the weight bearing capacity of the anterior column, structural anterior support must be created. Long bone struts are at risk for failure of engraftment and pseudoarthrosis. Patient-specific anterior support using 3D printing technology may be a better solution in these patients. Research question: Are patient-specific approaches using 3D printing technology a viable treatment option for multilevel anterior spinal support? Material and methods: Five patients received a custom-made anterior paravertebral titanium spinal strut prosthesis; one patient received a 3D shaped structural allograft. Cost assessment was made based on hours spent and production costs. Clinical outcomes were extracted from the medical records. Results: All six implantations went uneventful with adequate fit of the prostheses and allograft. The mean surgery time was 219 min, and mean blood loss was 850 ml. No implant subsidence or loosening occurred during follow-up (0.5–8 years). Complications observed were partial bronchial compression in one patient and a postoperative infection in another. The first cases were most costly due to the hours spent on design and regulatory compliance. These costs declined for subsequent cases. Discussion and conclusion: Custom-made prostheses appear to be a viable treatment option for multi-level anterior spinal support. No implant failure was observed up to 8 years postoperative. Close collaboration between an in-house 3D lab and the surgical team was essential for implementing custom-made prosthesis in clinical care.

Objective: Lower limb malalignment accelerates the progression of knee osteoarthritis (KOA). Knee realignment osteotomy is a well-established treatment for unicompartmental KOA with malalignment. Traditional planning in KOA patients corrects deformities with an osteotomy at the metaphysis but overlooks Paley’s approach, which targets the center of rotation angulation (CORA). Osteotomy at the metaphysis may induce secondary translational deformities, which remain unstudied in KOA patients. This study aims to identify the CORA in KOA patients with tibial malalignment. Methods: Thirty tibiae (10 varus, 10 neutral, 10 valgus) from the IMI-APPROACH cohort were analyzed using computed tomography (CT) scans. The CORA, defined as the intersection of the proximal and distal mechanical axes, was identified. Translational deformity was calculated by multiplying the CORA-to-osteotomy distance by the tangent of the correction angle. Results: Among the varus tibiae, 9 out of 10 CORAs were located in the diaphysis, while 8 out of 10 valgus tibiae had their CORA in the diaphysis. When osteotomies were performed in the proximal metaphysis instead of the CORA location, secondary translational deformities of up to 3 cm were induced. Conclusion: In KOA patients with tibial malalignment, the CORA is predominantly located in the diaphysis rather than in the proximal metaphysis, where osteotomies are typically performed. This discrepancy leads to iatrogenic translational deformities. Future research should investigate the clinical impact of these deformities to optimize osteotomy planning and potentially improve long-term surgical outcomes.

Objective: To investigate the associations between whole joint cartilage and meniscal morphology on MRI and radiographic joint space width (JSW) measures and in knee osteoarthritis (KOA), to determine whether bicompartmental measures demonstrate stronger associations than unicompartmental ones, and to evaluate their correlations with Kellgren and Lawrence grading. Design: A cross-sectional analysis of baseline radiographs and MRIs from 262 KOA participants in the prospective, multicenter IMI-APPROACH cohort was conducted. Radiographic measures included minimum joint space width (mJSW), fixed location JSW (JSW(x)), mean JSW, and joint line convergence angle (JLCA), assessed using fully automated software. JSW was evaluated both unicompartmentally and bicompartmentally. Cartilage morphology, full-thickness cartilage loss, meniscal extrusion, tears, and maceration were assessed using the semi-quantitative MRI Osteoarthritis Knee Score to summarize whole-joint cartilage and meniscal morphology. Associations of radiographic measures with MRI outcomes were assessed using multivariable linear regression; Spearman correlations with Kellgren and Lawrence (KL) were also evaluated. Results: MRI-defined meniscal maceration was associated with unicompartmental and bicompartmental JSW measures. Full-thickness cartilage loss was associated with unicompartmental (95% CI [-0.16;-0.02]) and bicompartmental mJSW (95% CI [-0.14;-0.02]), and JLCA (95% CI [0.04;0.22]). Models explained 32–39% of variance for unicompartmental and 23–45% for bicompartmental measures (R²). Bicompartmental measures showed stronger correlations with KL grading than unicompartmental measures (95% CI: –0.31 to –0.02). Conclusions: Associations between whole-joint cartilage and meniscal degeneration are similar for uni- and bicompartmental JSW, with bicompartmental JSW showing stronger correlations with KL grades. These findings support including both compartments in radiographic assessment to improve structural evaluation in KOA.

Objectives: This study investigated the association between alpha angles of the hip and tibial genu varum in a healthy population with equal male-to-female distribution. It also examined sex-based differences, explored the impact of sports participation, and assessed the interplay between these conditions. Methods: Tibial, femoral, intra-articular knee deformities, and the alpha angle of the hip were analysed in 200 healthy volunteers (400 legs) aged 20–27 years using weight-bearing radiographs. The Tegner score was retrospectively collected and used to distinguish between high and low sports activity. Generalized estimating equations were used to examine the association between lower limb malalignment and alpha angle, accounting for side and gender. Results: Tibial alignment was associated with the alpha angle (β = −0.02, P = 0.002); tibial genu varum was associated with a higher alpha angle. Other deformities and their interaction with sports activity had no association with the alpha angle. Males exhibited a higher alpha angle (β = 0.19, P < 0.001, Δ = 9.0°) and more tibial genu varum (β = −0.95, P = 0.002, Δ = 1.1°) than females. High sports activity was associated with increased tibial genu varum (β = −0.75, P = 0.02) compared to low sports activity. Conclusion: This study found a significant association between alpha angle and tibial genu varum. Males exhibited higher alpha angles and more tibial genu varum than females. While higher sports activity was associated with tibial genu varum, no differences in alpha angle were seen across activity levels. These findings urge for future research to further explore mechanical load adjustments that prevent genu varum and primary cam morphology, reducing osteoarthritis risk.

Osteoimmunomodulation is a strategy to promote bone regeneration in implants by modifying the immune environment. CpG-containing oligonucleotides type C (CpG ODN C) and Polyinosinic:polycytidylic acid (Poly[I:C]) are analogs of microbial nucleic acids that have been studied for various immunotherapeutic applications. This research investigates the potential of CpG ODN C and Poly(I:C) as an osteoimmunomodulatory agent for bone regenerative purposes. We encapsulated each nucleic acid in a lipid-based nanoparticle to facilitate the delivery into intracellular pathogen recognition receptors in immune cells. The lipid-based nanoparticles were ±250 nm in size with a negative charge (−36 to −40 mV) and an encapsulation efficiency of ±60 %. Lipid-based nanoparticles containing nucleic acids, Lip/CpG ODN C and Lip/Poly(I:C), increased the production of TNF, IL-6, and IL-10 by primary human macrophages compared to free-form nucleic acids. Conditioned medium from macrophages treated with CpG ODN C (10 µg/ml) and Lip/CpG ODN C (0.1, 1, and 10 µg/ml) promoted osteoblast differentiation of human mesenchymal stromal cells by 2.6-fold and 3-fold, respectively; no effect was seen for Lip/Poly(I:C). Bone implants were prepared, consisting of a biphasic calcium phosphate scaffold, bone morphogenetic protein (BMP) 2, and lipid-based nanoparticles suspended in gelatin methacryloyl (GelMA) hydrogel. Implants were evaluated for de novo bone formation in an extra-skeletal implantation model in rabbits for 5 weeks. Based on the particles suspended in GelMA, six groups of implants were prepared: Lip/CpG ODN C, Lip/Poly(I:C), Lip (empty), CpG ODN C, Poly(I:C), and a control group consisting of empty GelMA. After 5 weeks, healthy bone tissue formed in all of the implants with active osteoblast and osteoclast activity, however, the amount of new bone volume and scaffold degradation were similar for all implants. We suggest that the working concentrations of the nucleic acids employed were inadequate to induce a relevant inflammatory response. Additionally, the dosage of BMP-2 used may potentially mask the immune-stimulatory effect. Lip/CpG ODN C holds potential as a bioactive agent for osteoimmunomodulation, although further in vivo demonstration should corroborate the current in vitro findings.

Osteoarthritis (OA) is a common degenerative inflammatory joint disease with progressive loss of articular cartilage that undermines patients’ quality of life. There are no regulatory-approved, disease-modifying OA medications, despite a great deal of studies done to elucidate OA pathogenesis. Until now, OA pharmacological treatment focused mainly on generalized inhibition of inflammation and pain. Currently, monoclonal antibodies and nucleic-acid aptamers emerge as targeted therapies offering potential alternatives by addressing the complex challenges posed by OA, such as specifically reducing inflammation and pain in the joint targeting specific molecular key players, instead of a systemic and generalized approach like with non-steroidal anti-inflammatory drugs. Aptamers’ properties, including structure versatility, reduced immunogenicity, and flexible administration methods, position them as high-potential candidates for OA treatment. This review summarizes results from clinical trials applying monoclonal antibodies to treat OA, preclinical research, and the development of aptamers as a new generation of targeting agents. Meanwhile, it provides a comprehensive comparison of the characteristics, advantages, and limitations of aptamers versus monoclonal antibodies. Notably, the promising applications of aptamers, demonstrated in other inflammatory and degenerative conditions, underscore their potential for OA therapy. We anticipate that the application of aptamer could offer a new way of OA pharmacological intervention.

Recent evidence indicates the potential of gamma-irradiated (γi) Staphylococcus aureus to be used as an osteo-immunomodulator for bone regeneration. This study aims at characterizing the inflammatory milieu caused by the stimulation of γi S. aureus in immune cells and investigates its effects on MSC osteogenic differentiation. Furthermore, we aimed to recreate the immune-modulatory response exhibited by γi S. aureus by using a mixture of various synthetic pathogen recognition receptor (PRR) ligands consisting of TLR2, TLR8, TLR9, and NOD2 agonists. Human peripheral blood mononuclear cells (hPBMCs), isolated from healthy human donors, were exposed to γi S. aureus or seven different ligand mixtures. After 24 h, the conditioned medium (CM) from the hPBMCs was collected and its effects on hMSC osteogenic differentiation were investigated by assessing alkaline phosphatase (ALP) activity and matrix mineralization. The hPBMCs and their CM were also analyzed by bulk RNA sequencing and for cytokine secretion. CM from the γi S. aureus and the mixture consisting of Pam3CSK4, C-class CpG oligodeoxynucleotide (CpG ODN C), and murabutide targeting TLR2, TLR9, and NOD2 showed a fivefold increase in ALP and matrix mineralization in a donor-dependent manner. These effects were due to the upregulation of inflammatory signaling pathways, which led to an increase in cytokines and chemokines TNF, interleukin (IL)-6, IFN-γ, IL-1α, CXCL10, CCL18, CCL17, CXCL1, and CCL5. Upregulation of genes like BMP2R, BMP6R, BGLAP, and others contributed to the upregulation of osteogenic pathways in the hPBMCs stimulated with γi S. aureus and the aforementioned mix. Thus, formulations with mixtures of PRR ligands may serve as immune-modulatory osteogenesis-enhancing agents.

Objective To assess the relationship between cam morphology and the development of radiographic hip osteoarthritis (RHOA), overall and in subgroups based on age, biological sex and body mass index (BMI). Methods Hips with no RHOA at baseline and with available follow-up during 4–8 years were selected from the Worldwide Collaboration on Osteoarthritis PrediCtion for the Hip (World COACH) consortium. Alpha angles were uniformly measured on anteroposterior radiographs, with a threshold of 60° used to define cam morphology. Incident RHOA was defined as the transition from an RHOA-free state at baseline to definite diagnosis of RHOA at follow-up. The association between baseline cam morphology and the development of RHOA was assessed using a three-level mixed-effects logistic regression model, accounting for hip side, individual and cohort-level variation. Results A total of 23 886 hips were included (mean age: 62.2±8.4 years; 70.6% female; BMI: 27.4±4.5; mean time to follow-up: 6.1±3.0 years). Cam morphology was associated with RHOA (OR: 1.87, 95%CI 1.36 to 2.59), as was a greater alpha angle (OR 1.02, 95%CI 1.01 to 1.03 for every degree increase). The overall relative risk of developing RHOA in hips with cam morphology was 1.62 (95%CI 1.26 to 2.07), greatest for those aged 51–60 years (2.15, 95%CI 1.55 to 2.98) and higher in males (2.50, 95%CI 1.67 to 3.73), compared with females (1.75,95%CI 1.24 to 2.48). Conclusion Hips with cam morphology have higher odds of developing RHOA within 4–8 years compared with hips without cam morphology. The relative risk was highest in subgroups of participants aged 51–60 years and in males, making cam morphology a potential target for primary or secondary prevention of RHOA.

Advancements in biomaterials design increasingly focus on material-host immune interactions as one of the strategies to promote new bone formation, referred to as osteoimmunomodulation. Recent studies indicate that inflammatory stimuli can synergize with growth factors such as bone morphogenetic protein 2 (BMP-2) to promote bone formation. Pathogen-associated molecular patterns (PAMPs) are motifs expressed by microbes that are recognized by immune cells and induce an immune-stimulatory response. In this study, we combined PAMPs with low-dose BMP-2 on a biphasic calcium phosphate (BCP) scaffold and evaluated its effect on ectopic bone formation in a subcutaneous implantation model. The PAMPs tested include gamma-irradiated whole microbes (γi-Staphylococcus aureus and γi-Candida albicans), a vaccine (Bacillus Calmette-Guérin containing Mycobacterium bovis), bacterial cell wall components (peptidoglycan [PGN], lipopolysaccharide [LPS], lipoteichoic acid, and Pam3CysSerLys4), an exopolysaccharide (Curdlan), and nucleic acid analogues (polyinosinic:polycytidylic acid [Poly(I:C)] and Cytidine-phosphate-guanosine [CpG]-containing oligonucleotides type C). Implants consisting of BCP, PAMPs, and BMP-2 were placed subcutaneously in rabbits and evaluated for ectopic bone formation after 5 weeks. Implants with only BMP-2 served as controls. Of the PAMPs tested, only PGN and BMP-2 showed a positive bone volume compared with the control, with borderline significance (+4.4%, p = 0.08). Decreased bone volume was seen for LPS (−7.4%, p = 0.03) and Poly(I:C) (−6.3%, p = 0.04). Fluorochrome labeling at weeks 2 and 3 assessed mineralization onset, revealing no mineralization in the first 2 weeks and some implants showing onset at week 3. We observed variability in ectopic bone formation across animals, associated with higher osteoclast numbers in those where ectopic bone occurred versus those that did not (p = 0.004). PAMPs can modulate bone formation, but their effects are variable, requiring further refinement to harness their osteoimmunomodulatory properties effectively. Additionally, we highlight osteoclasts’ important role in stimulating ectopic bone formation.

Objective
To study the association between various radiographic definitions of acetabular dysplasia (AD) and incident radiographic hip osteoarthritis (RHOA), and to analyze in subgroups.

Methods
Hips free of RHOA at baseline and with follow-up within 4–8 years were drawn from the World COACH consortium. The Wiberg center edge angle (WCEA), acetabular depth width ratio (ADR), and the modified acetabular index (mAI) were calculated. AD was defined as WCEA≤25°, and for secondary analyses as WCEA≤20°, ADR ≤250, mAI ≥ 13°, and a combination. A logistic regression model with generalized mixed effects with 3 levels adjusted for age, biological sex, and body mass index (BMI) was used. Descriptive statistics stratified by age, biological sex and BMI were reported.

Results
A total of 18,807 hips from 9 studies were included. Baseline characteristics: age 61.84 (± 8.32) years, BMI 27.40 (± 4.49) kg/m², 70.1% women. 4766 hips (25.3%) had WCEA≤25°. Within 4–8 years (mean 5.8 ±1.6) follow-up, 378 hips (2.0%) developed incident RHOA. We found an association between AD and RHOA (adjusted OR [aOR] 1.80 95% confidence interval [CI] 1.40–2.34). In secondary analyses, all other definitions of AD were also associated with incident RHOA (aOR ranging from 1.52 95% CI 1.19–1.94 to 1.96 95% CI 1.26–3.02). Descriptive statistics showed that the relative risk (RR) in AD hips to develop RHOA was higher compared to non-AD hips in age group 61–70 (RR 1.70), BMI<25 (RR 1.66), and in female hips (RR 1.73).

Conclusion
AD was consistently associated with incident RHOA. Explorative analyses show that AD hips in women and age group 61–70 years seem to be more at risk of developing RHOA compared to non-AD hips.

Background: Lower limb malalignment increases the risk of unicompartmental knee osteoarthritis (KOA). This study investigates the association between knee cartilage quality, assessed via MRI-based T2 mapping, and lower limb malalignment. It also examines whether cartilage quality is more influenced by bony or intra-articular malalignment. Methods: In this cross-sectional analysis of 156 knees from the IMI-APPROACH cohort, tibiofemoral cartilage T2 values were measured using high-resolution MRI, distinguishing superficial and deep layers. Malalignment was categorized into entire leg, bony, and intra-articular malalignment (via the Joint Line Convergence Angle). Correlations between T2 values and alignment were assessed using Spearman's rho. A subgroup analysis evaluated cartilage quality in constitutional malalignment (malalignment without intra-articular deviation). Results: Cartilage T2 values were significantly associated with alignment. Varus knees showed significantly longer T2 in the superficial medial cartilage (ρ = –0.2, p = 0.04), and valgus knees in the lateral compartment (ρ = 0.1, p = 0.35). Associations were strongest for intra-articular malalignment (ρ = 0.3, p < 0.01). In constitutional varus, a non-significant medial T2 prolongation was observed (ρ = –0.2, p = 0.28); no changes were found in constitutional valgus. Conclusion: Lower limb malalignment, particularly intra-articular malalignment, is associated with compartment-specific lower cartilage quality, as reflected by longer T2 values. Distinguishing between bony and intra-articular malalignment, rather than overall limb alignment, should be a focus of future studies on malalignment. Future research should explore whether constitutional malalignment and early cartilage alterations may trigger cartilage degeneration and KOA progression.

Objective: To analyze and synthesize the information available from five pivotal, large-scale, multicenter, observational studies (CHECK, OAI, FNIH Biomarkers Consortium, IMI-APPROACH, and MOST) focusing on knee osteoarthritis (OA), which can be used to elucidate disease progression, risk factors, and the effectiveness of potential interventions. Design: For this narrative review, a comprehensive literature search and data extraction from official web pages and scientific databases were conducted to compare methodologies, in- and exclusion criteria, outcomes, and cohort characteristics across the studies. Thematic, comparative, and qualitative analyses were employed to identify trends, commonalities, and disparities among the findings. Results: The studies collectively enhanced understanding of the onset and progression of knee OA, and in several of the studies, hip OA, emphasizing the importance of both systemic and local risk factors. Advanced imaging and biomarkers are important components in all the cohorts, with the goal of aiding early diagnosis and tracking disease progression. All cohorts evaluated unique markers generally not available in the other cohorts, while other factors overlap, suggesting possibilities for combining or cross-validating between cohorts. Conclusions: The collaborative efforts of major OA research significantly advance our understanding of knee OA. These studies highlight the importance of a multifaceted approach, integrating advanced imaging, biomarkers, and longitudinal data to tackle the complexities of OA. By synthesizing findings and addressing knowledge gaps such as heterogeneity of patients and used measurements, and use of novel pain measures, future research can develop more effective diagnostic tools and treatments, ultimately enhancing the quality of life for OA patients.

Background/Objectives: Tenosynovitis is a common feature of psoriatic arthritis (PsA) and is typically assessed using semi-quantitative magnetic resonance imaging (MRI) scoring. However, visual scoring s variability. This study evaluates a fully automated, deep-learning approach for ankle tenosynovitis segmentation and volume-based quantification from MRI in psoriatic arthritis (PsA) patients. Methods: We analyzed 364 ankle 3T MRI scans from 71 PsA patients. Four tenosynovitis pathologies were manually scored and used to create ground truth segmentations through a human–machine workflow. For each pathology, 30 annotated scans were used to train a deep-learning segmentation model based on the nnUNet framework, and 20 scans were used for testing, ensuring patient-level disjoint sets. Model performance was evaluated using Dice scores. Volumetric pathology measurements from test scans were compared to radiologist scores using Spearman correlation. Additionally, 218 serial MRI pairs were assessed to analyze the relationship between changes in pathology volume and changes in visual scores. Results: The segmentation model achieved promising performance on the test set, with mean Dice scores ranging from 0.84 to 0.92. Pathology volumes correlated with visual scores across all test MRIs (Spearman ρ = 0.52–0.62). Volume-based quantification captured changes in inflammation over time and identified subtle progression not reflected in semi-quantitative scores. Conclusions: Our automated segmentation tool enables fast and accurate quantification of ankle tenosynovitis in PsA patients. It may enhance sensitivity to disease progression and complement visual scoring through continuous, volume-based metrics.

Background: the primary challenge with implant infections is the formation of biofilm, which harbors dormant bacteria that reduce the effectiveness of antibiotics and amplify antibiotic resistance, exacerbating the global antimicrobial resistance crisis. A potential novel treatment strategy is radioimmunotherapy, which uses antibodies linked to radioisotopes to deliver targeted radiation to the bacteria and biofilm. We describe the first in vivo use of targeted radiation therapy, employing Actinium-225 (α-radiation) and Lutetium-177 (β-radiation) labeled antibodies to treat a Staphylococcus aureus biofilm-associated intramedullary implant infection. Untargeted radiation in the form of unbound radionuclide treatment was also evaluated. Methods: to assess therapeutic efficacy, bacterial counts were performed on implant and surrounding bone after seven days of follow-up. Biodistribution was evaluated using SPECT/CT and ex vivo gamma counting. Results: radioimmunotherapy using an antibody against wall teichoic acid which was labeled with Actinium-225 and Lutetium-177 achieved bacterial reductions between 45% and 93% on the implant and surrounding bone. Surprisingly, a similar antimicrobial effect was observed with unbound Actinium-225 treatment reducing the bacterial load by 80% on the implant and 98% in the surrounding bone. Indications of maximum tolerated dose (MTD) with Lutetium-177 labeled antibodies were observed through hepatic and renal function evaluations. Conclusions: These results should be interpreted in the context of the study’s constraints, particularly the limited animal sample size. Nonetheless, the results suggest that in vivo applied radiation may help reduce a biofilm-associated infection at the implant site as well as in the surrounding bone. These findings encourage further investigation into the use of targeted and non-targeted radiation, potentially combined with antibiotics, to develop effective strategies for eradicating biofilm-associated implant infections.

Objective: The objective is to determine the association and absolute risk of femoroacetabular impingement syndrome (FAIS) for the development of radiographic hip osteoarthritis (RHOA). Methods: This is a nationwide, multicentre prospective cohort study (Cohort Hip and Cohort Knee) with 1002 individuals aged between 45 and 65 years. Hips without definitive RHOA (Kellgren-Lawrence (KL) grade≤1) at baseline and with anteroposterior pelvic radiographs at baseline and 10-year follow-up available (n=1386 hips) were included. FAIS was defined by the baseline presence of a painful hip, limited internal hip rotation≤25° and cam morphology defined by an alpha angle>60°. The outcomes were incident RHOA (KL grade≥2 or total hip replacement (THR)) and incident end-stage RHOA (KL≥3 or THR) within 10 years. Results: Of the 1386 included hips (80% women; mean age 55.7±5.2 years), 21 hips fulfilled criteria for FAIS and 563 hips did not fulfil any of the FAIS criteria (reference group; no symptoms, no signs, no cam morphology). Within 10-year follow-up, 221 hips (38%) developed incident RHOA and 15 hips (3%) developed end-stage RHOA (including 9 hips with THR). Adjusted for sex, age and body mass index, FAIS with cam morphology resulted in an OR of 6.85 (95% CI 2.10 to 22.35) for incident RHOA and 47.82 (95% CI 12.51 to 182.76) for incident end-stage RHOA, compared with hips not having any FAIS criteria. The absolute risk of FAIS was 81% for incident RHOA and 33% for incident end-stage RHOA. Conclusion: FAIS was strongly associated with the development of RHOA within 10 years. Although the baseline prevalence of FAIS was low, the high absolute risk of FAIS for RHOA warrants further studies to determine preventive strategies.

Introduction Implant infections caused by Staphylococcus aureus are responsible for high mortality and morbidity worldwide. Treatment of these infections can be difficult especially when bacterial biofilms are involved. In this study we investigate the potential of infrared photoimmunotherapy to eradicate staphylococcal infection in a mouse model. Methods A monoclonal antibody that targets Wall Teichoic Acid surface components of both S. aureus and its biofilm (4497-IgG1) was conjugated to a photosensitizer (IRDye700DX) and used as photoimmunotherapy in vitro and in vivo in mice with a subcutaneous implant pre-colonized with biofilm of Staphylococcus aureus. A dose of 400 μg and 200 μg of antibody-photosensitizer conjugate 4497-IgG–IRDye700DXwas administered intravenously to two groups of 5 mice. In addition, multiple control groups (vancomycin treated, unconjugated IRDye700DX and IRDye700DX conjugated to a non-specific antibody) were used to verify anti-microbial effects. Results In vitro results of 4497-IgG-IRDye700DX on pre-colonized (biofilm) implants showed significant (p<0.01) colony-forming units (CFU) reduction at a concentration of 5 μg of the antibody-photosensitizer conjugate. In vivo, treatment with 4497-IgG-IRDye700DX showed no significant CFU reduction at the implant infection. However, tissue around the implant did show a significant CFU reduction with 400 μg 4497-IgG-IRDye700DX compared to control groups (p = 0.037). Conclusion This study demonstrated the antimicrobial potential of photoimmunotherapy for selectively eliminating S. aureus in vivo. However, using a solid implant instead of a catheter could result in an increased bactericidal effect of 4497-IgG-IRDye700DX and administration locally around an implant (per operative) could become valuable applications in patients that are difficult to treat with conventional methods. We conclude that photoimmunotherapy could be a potential additional therapy in the treatment of implant related infections, but requires further improvement.

Background: Addressing prosthetic joint infections poses a significant challenge within orthopedic surgery, marked by elevated morbidity and mortality rates. The presence of biofilms and infections attributed to Staphylococcus aureus (S. aureus) further complicates the scenario. Objective: To investigate the potential of radioimmunotherapy as an innovative intervention to tackle biofilm-associated infections. Methods: Our methodology involved employing specific monoclonal antibodies 4497-IgG1, designed for targeting wall teichoic acids found on S. aureus and its biofilm. These antibodies were linked with radionuclides actinium-225 (²²⁵Ac) and lutetium-177 (¹⁷⁷Lu) using DOTA as a chelator. Following this, we evaluated the susceptibility of S. aureus and its biofilm to radioimmunotherapy in vitro, assessing bacterial viability and metabolic activity via colony-forming unit enumeration and xylenol tetrazolium assays. Results: Both [²²⁵Ac]4497-IgG1 and [¹⁷⁷Lu]4497-IgG1 exhibited a noteworthy dose-dependent reduction in S. aureus in planktonic cultures and biofilms over a 96-h exposure period, compared to non-specific antibody control groups. Specifically, doses of 7.4 kBq and 7.4 MBq of [²²⁵Ac]4497-IgG1 and [¹⁷⁷Lu]4497-IgG1 resulted in a four-log reduction in planktonic bacterial counts. Within biofilms, 14.8 kBq of [²²⁵Ac]4497-IgG1 and 14.8 Mbq [¹⁷⁷Lu]4497-IgG1 led to reductions of two and four logs, respectively. Conclusion: Our findings underscore the effectiveness of [²²⁵Ac]4497-IgG1 and [¹⁷⁷Lu]4497-IgG1 antibodies in exerting dose-dependent bactericidal effects against planktonic S. aureus and biofilms in vitro. This suggests that radioimmunotherapy might serve as a promising targeted treatment approach for combating S. aureus and its biofilm.