Background: Early postoperative implant infections are difficult to diagnose due to overlapping symptoms with inflammation. However, prompt surgical intervention for an implant infection can prevent the need for repeated surgeries and improve the overall success of the treatment and preserving the implant. The primary objective of this study was to assess the sensitivity and specificity of a novel immuno-PET radiotracer for detecting Staphylococcus aureus bacteria and their biofilms in a preclinical rat model. Results: An antibody against wall teichoic acid a common surface component of S. aureus, was labeled with Zirconium-89- as the PET tracer. Wistar Han rats underwent surgery with a S. aureus-related biofilm-infected femoral implant on one side and a sterile femoral implant on the contralateral side. The diagnostic efficacy of this imaging modality was compared with clinically established nuclear imaging techniques for implant infections, including [^99mTc]Tc-MDP SPECT/CT, [¹⁸F]FDG PET/CT, and [¹⁸F]NaF PET/CT. Furthermore, co-injection of unlabeled (“cold”) antibodies was performed to evaluate their impact on biodistribution. All animals with a biofilm-associated femoral implant infection showed significantly higher uptake of the novel ImmunoPET tracer in the infected side compared to the sterile side throughout the 13-day postoperative study duration. A dose-dependent increase in tracer accumulation was observed with co-injection of cold antibody, suggesting its potential to improve biodistribution. Conclusions: ImmunoPET with Zirconium-89-labeled antibodies specific for wall teichoic acid antigen demonstrates sensitive and specific diagnostic capabilities compared to conventional nuclear imaging modalities, offering a promising tool for early detection of postoperative chronic low-grade infections and septic implant loosening.

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: 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.

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.

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.

Introduction: Hip dysplasia, characterized by an insufficient acetabular coverage of the femoral head, increases hip joint stress and predisposes to degenerative changes. A novel 3D-printed, patient-specific extracapsular shelf implant was developed to increase femoral head coverage. Accurate implant placement is crucial. This cadaveric study compared CT-only surgical planning with combined CT- and MRI-based planning to evaluate whether MRI integration improves positioning accuracy. Methods: Two cohorts of non‑dysplastic cadaveric hips were studied. In cohort 1 (five hips), implant design was based solely on CT imaging. In cohort 2 (four hips), both CT and MRI datasets were used, incorporating capsular soft‑tissue anatomy. Postoperative implant positioning was compared with preoperative plans using point-cloud analyses, clockface coverage graphs, and Dice coefficients. Acceptable placement was defined as: median Euclidean distance < 5 mm, median angular deviation < 5°, and Dice > 0.75 respectively. Results: In the CT‑only cohort, three of five implants failed one or more accuracy thresholds, with Euclidean distances up to 8.5 mm, coverage deviations up to 6°, and Dice coefficients as low as 0.37. CT‑only designed implants consistently tilted away from the acetabular rim, reflecting underestimation of hip capsule thickness and insertion height. In the CT+MRI cohort, all four implants met the <5 mm and <5° deviation thresholds, and three achieved Dice ≥0.75. No consistent deviation patterns were observed. Conclusion: Combined CT and MRI planning improved implant positioning accuracy by better accounting for variations in hip capsule morphology. MRI integration demonstrated superior performance over CT‑only planning for patient‑specific shelf implant placement.

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.

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 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.

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.

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.

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.

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: 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.

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.

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.

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.

Background: Lumbar interbody fusion (IF) is a common procedure to fuse the anterior spine. However, a lack of consensus on image-based fusion assessment limits the validity and comparison of IF studies. This systematic review aims to (1) report on IF assessment strategies and definitions and (2) summarize available literature on the diagnostic reliability and accuracy of these assessments. Methods: Two searches were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Search 1 identified studies on adult lumbar IF that provided a detailed description of image-based fusion assessment. Search 2 analyzed studies on the reliability of specific fusion criteria/classifications and the accuracy assessed with surgical exploration. Results: A total of 442 studies were included for search 1 and 8 studies for search 2. Fusion assessment throughout the literature was highly variable. Eighteen definitions and more than 250 unique fusion assessment methods were identified. The criteria that showed most consistent use were continuity of bony bridging, radiolucency around the cage, and angular motion <5°. However, reliability and accuracy studies were scarce. Conclusion: This review highlights the challenges in reaching consensus on IF assessment. The variability in IF assessment is very high, which limits the translatability of studies. Accuracy studies are needed to guide innovations of assessment. Future IF assessment strategies should focus on the standardization of computed tomography-based continuity of bony bridging. Knowledge from preclinical and imaging studies can add valuable information to this ongoing discussion.