Aim. Arthroscopic interventions have revolutionized the treatment of joint pathologies. The appropriate diagnostics and treatment are required for infections after ligament reconstructions using non-resorbable material such as tendon grafts, anchors, and sutures, prone to biofilm formation. The infection rate is around 1% for knee and shoulder, while up to 4% for Achilles tendon reconstructions. Despite high number of these procedures worldwide, there is limited evidence about the best treatment protocol. Our study aimed to provide a general protocol for the treatment of small implants for soft tissue reconstruction. Method. Between 2019 and 2023, we treated 48 infections of ligament, meniscus, and tendon reconstructions out of 7291 related procedures performed in the same time period. Early infection (<30 days) were treated with an arthroscopic debridement and implant retention (DAIR), except Achilles tendons had open DAIR, while those with delayed or chronic infection (>30 days) were treated with extensive debridement and lavage combined with one-stage exchange (OSE) or implant removal. During surgery, at least 5 microbiological s and samples for histopathology were obtained. The removed material was sonicated. After surgery, all patients were one week on iv. antibiotics, followed by oral antibiofilm antibiotics for 6 weeks including rifampicin and/or a quinolone. All patients were followed for at least 1 year. Failure was defined as the need for additional revision surgery after finished iv. antibiotic treatment. Results. Among 48 patients, 38 were early and 10 were late acute or chronic infections. The incidence of infection for our cohort was 0.7%. We observed 27 infections after ligament reconstruction of the knee, 15 of the shoulder, 5 of the ankle, and 1 infection of the elbow joint. 40 patients were treated with DAIR, 5 with OSE, and 3 with implant removal. We had 11 C. acnes, 10 S. aureus, 6 S. epidermidis, 2 P. aeruginosa, 2 S. lugdunensis, 10 mixed flora, and 3 culture-negative infections. 12 patients received antibiotics before surgery, and all culture-negative infections were related to this subgroup. We observed 2 failures, both in a combination of proximal tibial osteotomy and ligament reconstruction of the knee joint. The success rate of our protocol was 96%. Conclusions. Prompt surgical treatment followed by 6 weeks of antibiotic treatment cured 96% of infections of small implants after reconstruction procedures of knee, shoulder, and ankle joints. Our study is the first to provide a treatment protocol for infections of small implants after ligament reconstruction procedures

Aim. This study aims to evaluate the effectiveness of a pre-formulated irrigation solution. 1. (containing ethanol, acetic acid, sodium acetate, benzalkonium chloride, and sterile water) compared to saline solution in managing acute periprosthetic joint infections (A-PJI) during Debridement, Antibiotic, and Implant Retention (DAIR) surgeries. The primary objective is to assess the healing rate using this solution. 1. versus saline in A-PJI patients, with “cure” defined by a set of criteria including no recurrence, wound issues, or need for ongoing suppressive antibiotics after 1 year. Principio del formularioFinal del formulario. Method. This single-center, randomized controlled trial will involve patients with acute periprosthetic infections undergoing standard DAIR surgery, divided into two groups: one receiving saline solution and the other receiving pre-formulated solution. 1. The study is single-blinded, with patients unaware of their group assignment. The study is registered at ISRCTN: https://doi.org/10.1186/ISRCTN10873696. Inclusion criteria include patients over 18 with hip or knee prostheses suffering from acute or hematogenous periprosthetic infections, while exclusion criteria include a history of prior debridement or multiple infected implants, among others. Principio del formularioFinal del formulario A total of 50 subjects are needed for statistical significance, with a 5% dropout rate anticipated. An interim safety analysis will assess early effectiveness and adverse effects, and the results are presented in this study. Data will be managed in online databases and analyzed using SPSS software, with a significance level of p<0.05. Results. Twenty-four patients were eligible for analysis, twelve in each group. The overall average age was 75 years, and the gender distribution was predominantly female (9 F and 3 M in each group). No significant differences were found at the baseline characteristics level between the two groups (p>0.05). The minimum follow-up of 1 year was achieved in all cases except three due to deaths not related to periprosthetic infection. Regarding efficacy, a non-statistically significant difference was observed (p>0.05), with 58% in the serum group and 42% in the pre-formulated irrigation solution. 1. group (X. 2. = 0.17, p=0.683). The average hospital stay was 38.42 days (SD 26.32) in the pre-formulated irrigation solution group. 1. and 24.42 days (SD 18.72) in the serum group, with this difference being not significant (t=1.5, p=0.148). Conclusions. While the current analysis indicates no significant differences between both groups in terms of efficacy, the study's ongoing progress and the inclusion of a larger sample size could potentially yield more definitive results

Aim. Periprosthetic joint infection (PJI) is one of the most serious and frequent complications in prosthetic surgery. Despite significant improvements in the criteria for diagnosis of PJI, the diagnostic workflow remains complex and, sometimes, inconclusive. Host immune factors hold great potential as diagnostic biomarkers in bone and joint infections. We have recently reported that the synovial concentration of the humoral pattern recognition molecule long pentraxin 3 (PTX3) is a sensitive and specific marker of PJI in total hip and knee arthroplasty patients (THA and TKA) undergoing revision surgery [1]. However, the contribution to risk and diagnosis of PJI of the genetic variation in PTX3 and inflammatory genes that are known to affect its expression (IL-1b, IL-6, IL-10, and IL-17A) has not been addressed. Therefore, we assessed these relationships in a cohort of THA and TKA patients who underwent prosthesis revision by focusing on a panel of single nucleotide polymorphisms (SNPs) in the PTX3, IL-1β, IL-6, IL-10 and IL-17A genes. Method. A case-control retrospective study was conducted on an historic cohort of patients that received THA or TKA revision and were diagnosed with PJI (cases) or aseptic complications (controls) [1]. Samples of saliva were collected from 93 subjects and used for extraction of genomic DNA to perform genotyping of the PTX3, IL-1β, IL-6, IL-10 and IL-17A polymorphisms. Moreover, whenever available, samples of synovial fluid and plasma [1] were used to measure the concentration of the IL-1β, IL-10, and IL-6 proteins by immunoassay. Uni-and multivariate analyses were performed to evaluate the relationships between genetic, biochemical, and clinical variables. Results. The rs3024491 (IL-10) and rs2853550 (IL-1b) SNPs were found to be strongly associated with the risk of PJI. The synovial levels of PTX3, IL-1β, IL-10, and IL-6 were higher in cases than in controls, and a clear correlation emerged between the synovial concentration of PTX3 and IL-1b in cases only. Also, we identified a causal relationship between rs2853550, synovial concentration of IL-1b and that of PTX3 (that is induced by IL-1b). Conclusions. Our findings suggest that SNPs in the IL-10 and IL-1b genes could be used for early identification of THA and TKA patients with high risk of PJI. It is therefore conceivable that integrating genetic data into current diagnostic criteria would improve diagnosis of PJI

Aim. Predicting success of a Debridement, Antibiotics and Implant Retention (DAIR) procedure for Periprosthetic Joint Infection (PJI) remains a challenge. A failed DAIR might adversely affect the outcome of any future revision surgery for PJI. Hence, the ability to identify and optimise factors predictive of DAIR success would help target the procedure to the appropriate patient cohort and avoid unnecessary surgery for patients where a DAIR is unlikely to eradicate infection. Method. A retrospective review of our prospective Bone Infection Group database was performed to identify all patients who underwent a DAIR of their hip or knee arthroplasty. Diagnosis of PJI was confirmed using the Musculoskeletal Infection Society (MSIS) 2013 and the European Bone and Joint Infection Society (EBJIS) 2021 classification systems. DAIR surgery was grouped into “successful” or “unsuccessful” outcomes as per the MSIS working group outcome-reporting tool. Results. Sixty-Four consecutive patients with an acute PJI underwent a DAIR procedure between 2009 and 2020. Treatment was successful in 44 (69%). The chance of a successful DAIR was significantly greater if performed within one week of symptom onset compared to greater than one week duration (adjusted odds ratio (OR 0.11; p=0.027; 95% CI [0.02- 0.78]). The chances of a successful DAIR was not influenced by whether the surgeon was an arthroplasty or non-arthroplasty surgeon (OR 0.28; p=0.13; 95% CI [0.05- 1.48]). Isolated Streptococcus infection had a success rate of 100%; followed by Coagulasenegative Staphylococci 71% and Methicillin-susceptible Staphylococcus Aureus 65%. Polymicrobial infection had the worst outcome with a success rate of 47%. Conclusions. In our experience DAIR surgery performed within one week of symptom onset, significantly increased chances of successful infection eradication. Collaborative work is required to ensure arthroplasty patients access prompt appropriate surgical decision-making, remove barriers to early assessment and minimise delays to surgery

Aim. To report outcomes of soft tissue reconstruction using free tissue transfer for the treatment of tibial osteomyelitis as part of a single-stage, ortho-plastic procedure. Method. Patients who underwent ortho-plastic reconstructive surgery to excise tibial osteomyelitis in combination with free tissue transfer in one stage were included. Patients underwent surgery between 2015 and 2024 in a single specialist centre within the UK. Baseline patient information, demographics, and infection information was recorded. Adverse outcomes were defined as (i) flap salvage required, (ii) flap failure and (iii) recurrence of infection. Patient reported quality of life was measured using the EuroQol EQ-5D-5L index score. Pre-operative QoL was compared to QoL at 1 year with a control group of 53 similar patients who underwent surgical treatment for tibial osteomyelitis without a free flap (local flap or primary closure). Results. Ninety-three patients were eligible for inclusion, with a mean age of 52 years (range 18–90). 77/93 (82.8%) had a free muscle flap with the remainder (17.2%) receiving a fasciocutaneous flap. The donor tissue was defined as 57 gracilis, 6 latissimus dorsi, 14 hemi-latissimus dorsi, and 16 anterolateral thigh. The recipient area of the tibia was distal 1/3 in 52 cases, middle 1/3 in 27 cases and proximal 1/3 in 12 cases. The average flap ischaemic time was 70 minutes (range 28 to 125). Seven patients (7.5%) required urgent flap salvage at a median time of 1.0 day (range 0.5 – 4.0). Of these, 4 (4.3%) went on to have total flap failure, of which 2 patients underwent below knee amputation subsequently. Flap failure was due to either arterial (n=2) or venous (n=2) anastomotic thrombus. There were 3 (3.2%) episodes of confirmed infection recurrence within the first year after the index procedure. EQ-index scores at 1-year post-operatively were significantly improved when compared to pre-operative scores (p=0.008). At 1-year post-operatively, EQ-index scores in patients who underwent free flap was similar compared to local flaps (p=0.410) and in those who underwent primary closure for tibial osteomyelitis (p=0.070). Conclusions. Microsurgical single stage surgery can achieve high flap survival rate (95.7%). Free flaps fail early due to anastomotic thrombus with no late failures seen. Free tissue transfer does not appear to give inferior QoL compared to matched patients with local flaps or direct closure in tibial osteomyelitis

Aim. This study seeks to outline the clinical, laboratory, and imaging features of patients with pyogenic spondylitis. It aims to define a novel imaging sign that could indicate the severity of suppurative spondylitis, aiding in its early diagnosis and treatment. Method. This retrospective study included 137 patients from 2013 to 2023. Through the analysis and summary of imaging characteristics among all patients, we identified a distinct MRI sign known as ‘the Disc Penetration sign’ (DP). This sign is defined as an image finding on sagittal MRI depicting the anterior and posterior penetration of an abscess through the intervertebral disc space, affecting both the anterior margin of the vertebrae and the structures within the spinal canal. Observational parameters included WBC, ESR, CRP, hemoglobin, and albumin levels. Documentation of the study included location and segment of the lesion, presence or absence of spinal cord compression, and paravertebral abscesses. Results. 56 patients presented with the Disc Penetration sign(DP) and 81 did not. In both groups, there were no significant differences in gender ratio or age (P > 0.05). However, significant differences were observed in the presence of comorbid diabetes and chronic kidney disease (p < 0.05). The DP group had a significantly greater ESR level (74.30±33.79 mm/h vs. 51.46±30.46 mm/h, P < 0.001) and CRP level (47.28 mg/L vs. 26.18 mg/L, P = 0.003). Additionally, the DP group had a significantly lower Hb (100.66±19.82 g/L vs. 116.99±19.99g/L,P < 0.001) and the serum albumin level (28.81±6.59 g/L vs. 34.09±6.17 g/L,P < 0.001). Imaging results showed no significant differences in affected spinal segments or parts (p>0.05). Patients in the DP group showed a higher likelihood of developing paravertebral abscesses compared to those in the non-DP group (n = 54 [96.4%] vs. n = 33 [40.7%], P < 0.001), and also exhibited a higher incidence of spinal cord compression(n = 32 [57.1%] vs. n = 17 [21.0%], P < 0.001). Conclusions. The study suggests that the Disc Penetration sign in pyogenic spondylitis patients correlates with more severe inflammation and higher incidence of paraspinal abscess, pointing to worse stability of the spine, longer bone restructuring time, and potentially poorer prognosis. These findings enable clinicians to rapidly assess the severity of the disease and prognosticate outcomes more effectively We emphasize the need for early, pathogen-specific diagnosis and treatment, particularly considering surgical intervention for patients demonstrating substantial paraspinal abscesses or spinal instability

Aim. Periprosthetic joint infection (PJI) is a complication of total joint arthroplasty that typically requires revision surgery for treatment. Systemic antibiotics are usually held prior to surgery to improve yield of intraoperative cultures. However, recent studies suggest that preoperative aspirations have a high concordance with intraoperative cultures, which may allow surgeons to initiate antibiotic treatment earlier. The purpose of the study was to investigate the effect of Pre-surgical systemic antibiotic therapy on the bacterial burden within the periprosthetic space and systemic immune reaction. Method. PJI was induced with MSSA (Xen36) S. aureus in the right knee of 16-week old, female, C57BL6 mice using a previously validated murine model. Mice were randomized to three groups (n=8, each): control; Vanc, receiving systemic vancomycin (110mg/kg, SQ, twice daily); or VancRif receiving vancomycin same as in Vanc group, plus rifampin (12mg/kg dose, IV, once daily). Following 2 weeks of treatment, mice were euthanized and periprosthetic bone, soft tissue and the implant were harvested. Bacterial burden, colony forming units (CFUs), was quantified in soft tissue, tibial bone, and on the implant. Specifically, tissues were homogenized and serially plated for CFUs, while the implant was sonicated and then plated for CFUs. The host immune response was analysed through weighing inguinal and iliac lymph nodes and through measuring serum amyloid A (SAA). Non-parametric pairwise group comparisons of the three outcome measures were performed using a Mann-Whitney U test. Results. VancRif, the combined treatment significantly reduced bacterial burden in the periprosthetic soft tissue, bone, and implant compared to control (p<0.001) and Vanc alone (p<0.001). While not significant, Vanc alone did reduce bacterial load as compared to control. The ipsilateral weight of the iliac lymph nodes was significantly reduced in Vanc and VancRif mice compared to controls (p<0.001), was well as in VancRif versus Vanc alone (p<0.001). Interestingly, SAA levels did not significantly differ among all groups. During tissue harvesting, minimal purulence was observed in antibiotic treatment groups, unlike controls. Conclusions. Treating active PJI with vancomycin alone decreases periprosthetic bacterial loads and reduces the local immunological response. This effect is significantly enhanced with the combined rifampin use. These findings could suggest that when culture positive PJI is diagnosed, pre-surgical treatment with antibiotics may decrease immunosuppression and soft tissue infiltration, leading to a better chance of infection cure with subsequent surgical debridement. Histological investigations and repeat experiments involving subsequent surgical treatment are underway. Acknowledgements. Funding comes from internal institutional grants

Aim. To date, no ultimate diagnostic gold standard for prosthetic joint infections (PJI) has been established. In recent years, next generation sequencing (NGS) has emerged as a promising new tool, especially in culture-negative samples. In this prospective study, we performed metagenomic analysis using 16S rRNA V3-V4 amplicon NGS in samples from patients with suspected PJI. Methods. A total of 257 (187 culture-negative (CN) and 70 culture-positive (CP)) prospectively collected tissues and sonication fluid from 32 patients (56 revisions) were included. 16S rRNA V3-V4 amplicons were sequenced using Illumina's MiSeq (California, USA) followed by bioinformatic analysis using nf-core/ampliseq pipeline. Results. We successfully sequenced 255 samples and detected a total of 105 microorganisms. These were mainly environmental microorganisms present in a small number of reads (≤100), indicating possible contamination. Pseudomonas spp. (non-aeruginosa species) was detected most frequently in 73% (187/255) of samples. The test showed limitations in species classification and identified microorganisms mainly at genus level. Significant differences in the number of reads were observed when comparing CN (≤100) and CP (≥1000) samples. In two CP, no bacteria were identified with sequencing, which is probably due to low bacterial load (1 CFU. Haemophilus spp. was detected with a significant number of reads (≥10000) in five samples from a single patient, in whom infection was considered likely according to EBJIS criteria, changing it to confirmed infection. Staphylococcus spp. was identified with ≥10000 reads in two CNs from an individual who was receiving antibiotic treatment at the time, had clinical signs of infection, and had a confirmed infection with S. lugdunensis one month earlier. Cutibacterium spp. with 36% (93/257) and Staphylococcus spp. with 34% (87/257) were detected with a minimal number of reads (≤100) in several CN, indicating possible contamination with normal skin microbiota. In one patient, Facklamia spp., an opportunistic pathogen, was detected in two samples by sequencing, but not by culture. Conclusions. We consider 16S rRNA V3-V4 amplicon sequencing to be a promising tool; however, further studies are needed to clarify uncertainties regarding the interpretation of the results in combination with other criteria. Using this method, we were able to successfully confirm infection in two patients whose microbiological results were initially negative, leading to a change from likely to confirmed infection in one case. The thresholds and interpretation of the results are currently unclear, therefore the method is being used experimentally rather than diagnostically at the time of writing

Aim. Candida species are uncommon pathogens causing prosthetic joint infection (PJI). This study evaluated the surgical management and outcome of Candida PJI. Methods. Patients with EBJIS Definition confirmed PJI, due to Candida species, from 19 medical centres were assessed. Demographic, diagnostic, medical and surgical treatment and outcome data were collected. Results. 269 patients were recruited with follow-up for at least one year. Mean age was 70.2 years (+/- 12.4) with 10.8% being immunocompromised. The most common fungal species were C. albicans (55.8%), C. parapsilosis (29.4%), C. glabrata (7.8%) and C. tropicalis (5.6%). Co-infection with bacteria occurred in 138 (51.3%) cases. DAIR was performed in 96 (36.2%) cases, with 169 (63.8%) having implant exchange or removal (76 one-stage, 78 two-stage, 11 removal/Girdlestone arthroplasty, 2 amputation). Patient demographics and antifungal therapy were similar in all surgical groups. Overall, treatment was successful in 156 (58%) cases. Failure was more likely in older patients (>70 years; p=0.008) and those who had DAIR (OR 1.945; 1.156-3.279; p=0.004). Failure was less likely with C. parapsilosis infection compared to C. albicans (31.6% vs 48%; p=0.037). DAIR patients had more co-infection with bacteria (63.5% vs 47.4%; p=0.013) and more previous surgeries (median 4 vs 3; p=0.007), but multivariate analysis showed that these were not independent risk factors for failure. There was no difference in mortality between DAIR patients and those with other surgery (13.5% vs 17.7%; p=0.372). DAIR was successful in 45/96 (46.9%) cases compared to 110/169 (65.1%) cases with other surgery (p<0.004). Early DAIR (surgery performed <I month from implantation/infection onset) was not more effective than late DAIR (surgery performed after 1 month)(early DAIR 44.4% cure vs 63.9% cure in late DAIR; p=0.004). Two-stage revision was successful in 54/78 (69.2%), which was significantly better than DAIR (p=0.003). One-stage revision was successful in 51/76 (67.1%) patients; also significantly better than DAIR (p=0.002), but equivalent to two-stage revision (p=0.777). Conclusion. DAIR was successful in less than half of patients with Candida PJI. We could not identify any subgroup which might have better outcomes with this surgical option. Interestingly, almost 90% of our patients with Candida PJI had no immunocompromise. One or two-stage revision offer a better option, if possible, and do not increase mortality

Introduction. In recent years, many studies demonstrated the efficacy of an early switch to oral antibiotics after surgical treatment in orthopaedic related infections. However, large analyses on periprosthetic joint infections (PJIs) are lacking. Material and Methods. We conducted a retrospective observational multicenter study in patients diagnosed with an early postoperative PJI (i.e less than 3 months after the index arthroplasty) treated with debridement, antibiotics and implant retention (DAIR). Patients from Europe and the USA were included. These two cohorts served as a quasi-randomised trial since an early oral antibiotic switch is routine practice in Europe versus a long duration of intravenous (IV) antibiotic treatment in the USA. Failure was defined as the clinical need for: i) a second DAIR, ii) implant removal, iii) suppressive antibiotic treatment or iv) infection related death. Results. A total of 668 patients were included. 277 received IV antibiotics for <14 days, 232 were given IV antibiotics between 14 - 27 days and 159 received IV antibiotics for >27 days. The overall 1-year failure rate within the 3 groups was 41.5%, 44.4% and 42.1%, respectively (P 0.80), and mainly comprised the need for a second DAIR. The results did not change when analyzing patients with or without obesity, the causative microorganism or the type of oral antibiotics. Conclusion. In early postoperative PJIs, a longer duration of IV antibiotic treatment is not associated with a lower failure rate of a DAIR procedure

Aim. Periprosthetic joint infection (PJI) is a devastating complication that develops after total joint arthroplasty (TJA) whose incidence is expected to increase over the years. Traditionally, surgical treatment of PJI has been based on algorithms, where early infections are preferably treated with debridement, antibiotics, and implant retention (DAIR), while late infections with two-stage revision surgery. Two-stage revision is considered the “gold standard” for treatment of chronic PJI. In this observational retrospective study, we investigated the potential role of inflammatory blood markers (neutrophil-to- lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic inflammatory index (SII)], systemic inflammatory response index (SIRI), and aggregate index of systemic inflammation (AISI)) as prognostic factors in two-stage exchange arthroplasty for PJI. Method. A single-center retrospective analysis was conducted, collecting clinical data and laboratory parameters from patients submitted to prosthetic explantation for chronic PJI. Laboratory parameters (PCR, NLR, MLR, PLR, SIRI, SII and AISI) were evaluated at the explantation time, at 4, 6, 8 weeks after surgery and at reimplantation time. Correlation between laboratory parameters and surgery success was evaluated, defined as infection absence/resolution at the last follow up. Results. 57 patients with PJI were evaluated (62% males; average age 70 years, SD 12.14). Fifty-three patients with chronic PJI were included. Nineteen patients completed the two-stage revision process. Among them, none showed signs of re-infection or persistence of infection at the last available follow up. The other twenty-three patients did not replant due to persistent infection: among them, some (the most) underwent spacer retention; others were submitted to Girdlestone technique or chronic suppressive antibiotic therapy. Of the patients who concluded the two-stage revision, the ones with high SIRI values (mean 3.08 SD 1.7, p-value 0.04) and MLR values (mean 0.4 SD 0.2, p-value 0.02) at the explantation time were associated with a higher probability of infection resolution. Moreover, higher variation of SIRI and PCR, also defined respectively delta-SIRI (mean −2.3 SD 1.8, p-value 0.03) and delta-PCR (mean −46 SD 35.7, p-value 0.03), were associated with favorable outcomes. Conclusions. The results of our study suggest that, in patients with PJI undergoing two-stage, SIRI and MLR values and delta-SIRI and delta-PCR values could be predictive of favorable outcome. The evaluation of these laboratory indices, especially their determination at 4 weeks after removal, could therefore help to determine which patients could be successfully replanted and to identify the best time to replant

Aims

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

Aims

The Bankart and Latarjet procedures are two of the most common surgical techniques to treat anterior shoulder instability with satisfactory clinical and functional outcomes. However, the outcomes in the adolescent population remain unclear, and there is no information regarding the arthroscopic Latarjet in this population. The purpose of this study was to evaluate the outcomes of the arthroscopic Bankart and arthroscopic Latarjet procedures in the management of anterior shoulder instability in adolescents.

Introduction. Osteoarthritis (OA) causes pain, stiffness, and loss of function due to degenerative changes in joint cartilage and bone. In some forms of OA, exercise can alleviate symptoms by improving joint mobility and stability. However, excessive training after joint injury may have negative consequences for OA development. Sensory nerve fibers in joints release neuropeptides like alpha-calcitonin gene-related peptide (alpha-CGRP), potentially affecting OA progression. This study investigates the role of alpha-CGRP in OA pathogenesis under different exercise regimen in mice. Method. OA was induced in C57Bl/6J WT mice and alpha-CGRP KO mice via surgical destabilization of the medial meniscus (DMM) at 12 weeks of age (N=6). Treadmill exercise began 2 weeks post-surgery and was performed for 30 minutes, 5 days a week, for 2 or 6 weeks at intense (16 m/min, 15° incline) or moderate (10 m/min, 5° incline) levels. Histomorphometric assessment of cartilage degradation (OARSI scoring), serum cytokine analysis, immunohistochemistry, and nanoCT analysis were conducted. Result. OARSI scoring confirmed OA induction 4 weeks post-DMM surgery, with forced exercise exacerbating cartilage degradation regardless of intensity. No significant genotype-dependent differences were observed. Serum analysis revealed elevated cytokine levels associated with OA and inflammation in KO mice compared to WT mice 4 and 8 weeks post-surgery (VEGF-A, MCP-1, CXCL10, RANTES, MIP1-alpha, MIP1-beta, and RANKL). The observed effects were often exacerbated by intense exercise but rarely by DMM surgery. NanoCT analysis demonstrated increased sclerotic bone changes after 6 weeks of forced exercise in KO mice compared to WT mice. Conclusion. Our results suggest an OA promoting effect of exercise in early disease stages of posttraumatic OA. Intense exercise induced inflammatory processes correlated to increased cytokine levels in the serum that might exacerbate OA pathogenesis in later stages. The neuropeptide alpha-CGRP might play a role in protecting against these adverse effects

Introduction. Homogenous and consistent preparations of mesenchymal stem cells (MSCs) can be acquired by selecting them for integrin α10β1 (integrin a10-MSCs). Safety and efficacy of intra-articular injection of allogeneic integrin a10-MSCs were shown in two post-traumatic osteoarthritis horse studies. The current study investigated immunomodulatory capacities of human integrin a10-MSCs in vitro and their cell fait after intra-articular injection in rabbits. Method. The concentration of produced immunomodulatory factors was measured after licensing integrin a10-MSCs with pro-inflammatory cytokines. Suppression of T-cell proliferation was determined in co-cultures with carboxyfluorescein N-succinimidyl ester (CFSE) labelled human peripheral blood mononuclear cells (PBMCs) stimulated with anti-CD3/CD28 and measuring the CFSE intensity of CD4+ cells. Macrophage polarization was assessed in co-cultures with differentiated THP-1 cells stimulated with lipopolysaccharide and analysing the M2 macrophage cell surface markers CD163 and CD206. In vivo homing and regeneration were investigated by injecting superparamagnetic iron oxide nanoparticles conjugated with Rhodamine B-labeled human integrin a10-MSCs in rabbits with experimental osteochondral defects. MSC distribution in the joint was followed by MRI and fluorescence microscopy. Result. The production of the immunomodulatory factors indoleamine 2,3-dioxygenase and prostaglandin E2 was increased after inflammatory licensing integrin a10-MSCs. Co-cultures with integrin a10-MSCs suppressed T-cell proliferation and increased the frequency of M2 macrophages. In vivo injected integrin a10-MSCs homed to osteochondral defects and were detected in the repair tissue of the defects up to 10 days after injection, colocalized with aggrecan and type II collagen. Conclusion. This study showed that human integrin a10-MSCs have immunomodulatory capacities and in vivo can home to the site of osteochondral damage and directly participate in cartilage regeneration. This suggests that human integrin α10β1-selected MSCs may be a promising therapy for osteoarthritis with dual mechanisms of action consisting of immunomodulation and homing to damage followed by early engraftment and differentiation into chondrocyte-like cells that deposit hyaline cartilage matrix molecules

Introduction. Knee arthroplasty (KA), encompassing Total Knee Replacement (TKR) and Unicompartmental Knee Replacement (UKR), is one of the most common orthopedic procedures, aimed at alleviating severe knee arthritis. Postoperative KA management, especially radiographic imaging, remains a substantial financial burden and lacks standardised protocols for its clinical utility during follow-up. Method. In this retrospective multicentre cohort study, data were analysed from January 2014 to March 2020 for adult patients undergoing primary KA at Imperial NHS Trust. Patients were followed over a five-year period. Four machine learning models were developed to evaluate if post-operative X-ray frequency can predict revision surgery. The best-performing model was used to assess the risk of revision surgery associated with different number of X-rays. Result. The study assessed 289 knees with a 2.4% revision rate. The revision group had more X-rays on average than the primary group. The best performing model was Logistic Regression (LR), which indicated that each additional X-ray raised the revision risk by 52% (p<0.001). Notably, having four or more X-rays was linked to a three-fold increase in risk of revision (OR=3.02; p<0.001). Our results align with the literature that immediate post-operative X-rays have limited utility, making the 2nd post-operative X-ray of highest importance in understanding the patient's trajectory. These insights can enhance management by improving risk stratification for patients at higher revision surgery risk. Despite LR being the best-performing model, it is limited by the dataset's significant class imbalance. Conclusion. X-ray frequency can independently predict revision surgery. This study provides insights that can guide surgeons in evidence-based post-operative decision-making. To use those findings and influence post-operative management, future studies should build on this predictive model by incorporating a more robust dataset, surgical indications, and X-ray findings. This will allow early identification of high-risk patients, allowing for personalised post-operative recommendations

Introduction. The arch of the foot has been described as a truss where the plantar fascia (PF) acts as the tensile element. Its role in maintaining the arch has likely been underestimated because it only rarely torn in patients with progressive collapsing foot deformity (PCFD). We hypothesized that elongation of the plantar fascia would be a necessary and sufficient precursor of arch collapse. Method. We used a validated finite element model of the foot reconstructed from CT scan of a female cadaver. Isolated and combined simulated ligament transection models were created for each combination of the ligaments. A collapsed foot model was created by simulated transection of all the arch supporting ligaments and unloading of the posterior tibial tendon. Foot alignment angles, changes in force and displacement within each of the ligaments were compared between the intact, isolated ligament transection, and complete collapse conditions. Result. Isolated release of the PF did not cause deformity, but lead to increased force in the long (142%) and short plantar (156%), deltoid (45%), and spring ligaments (60%). The PF was the structure most able to prevent arch collapse and played a secondary role in preventing hindfoot valgus and forefoot abduction deformities. Arch collapse was associated with substantial attenuation of the spring (strain= 41%) and interosseous talocalcaneal ligaments (strain= 27%), but only a small amount in the plantar fascia (strain= 10%). Conclusion. Isolated PF release did not cause arch collapse, but arch collapse could not occur without at least 10% elongation of the PF. Simulated transection of the PF led to substantial increase in the force in the other arch supporting ligaments, putting the foot at risk of arch collapse over time. Chronic degeneration of the PF leading to plantar fasciitis may be an early sign of impending PCFD

Introduction. Recent studies suggested that the progression of osteoarthritis (OA), a chronic degenerative joint disease, may be affected by the autonomic nervous system (ANS). Under healthy conditions, the sympathetic (SNS) and parasympathetic (PNS) branches of the ANS are well coordinated to maintain homeostasis. However, pathological conditions are frequently associated with a disturbance of this fine-tuned balance. Therefore, we analyzed whether an autonomic dysfunction occurs in OA patients. Method. 225 participants with early- or late-stage knee OA as well as 40 healthy age-matched probands were included in this study. Autonomic activity was investigated by analyzing heart rate variability (HRV), which decreases under chronic sympathetic overactivity. Time- and frequency-domain HRV indices SDRR, RMSSD, pRR50 and LF were examined. Linear regression analysis was performed to adjust for clinical characteristics, such as age, sex, BMI, or medication. Moreover, perceived chronic stress (PSQ) and pain (WOMAC) were assessed via questionnaires. In addition, the serum stress hormones cortisol, DHEA-S and IL-6 were analyzed via ELISA. Result. SDRR, RMSSD, and pRR50 were slightly reduced in the early stage of OA and showed significant decrease in the later stage of the disease. Also LF decreased significantly with OA progression. HRV was significantly influenced by the grade of OA, but not other patient characteristics. Moreover, late-stage OA patients demonstrated significantly higher PSQ and WOMAC levels compared to healthy controls. In addition, cortisol/DHEA-S ratio and IL-6 serum concentrations were significantly higher in late-stage than in early-stage OA patients and healthy controls. Conclusion. Reduced HRV, increased cortisol/DHEA-S ratio and PSQ level as well as elevated systemic IL-6 concentration indicated an autonomic shift towards a more pronounced SNS activity due to PNS deficiency in OA patients, particularly in the late-stage of the disease. Therefore, modulation of the ANS, for example by vagus nerve stimulation, might be a potential treatment strategy for of knee OA patients

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

Introduction. The human wrist is a highly complex joint, offering extensive motion across various planes. This study investigates scapholunate ligament (SLL) injuries’ impact on wrist stability and arthritis risks using cadaveric experiments and the finite element (FE) method. It aims to validate experimental findings with FE analysis results. Method. The study utilized eight wrist specimens on a custom rig to investigate Scapho-Lunate dissociation. Contact pressure and flexion were measured using sensors. A CT-based 3D geometry reconstruction approach was used to create the geometries needed for the FE analysis. The study used the Friedman test with pairwise comparisons to assess if differences between testing conditions were statistically significant. Result. The study found significant variations in scaphoid and lunate bone movement based on ligament condition. Full tears increased scapholunate distance in the distal-proximal direction and decreased in the medial-lateral direction. Lunate angles shifted from flexion to extension with fully torn ligaments. Conversely, the scaphoid shifted significantly from extension to flexion with full tears. A proximal movement was observed in the distal-proximal direction in all groups, with significant differences in the partial tear group. Lateral deviation of the scaphoid and lunate occurred with ligament damage, being more pronounced in the partial tear group. All groups exhibited statistically significant movement in the volar direction, with the full tear group showing the least movement. Also, radiocarpal joint and finger contact pressure and contact area were studied. Whereas the differences in contact area were not significant, scapholunate ligament tears resulted in significantly decreased finger contact pressures. FEA confirmed these findings, showing notable peak radiocarpal contact pressure differences between intact and fully torn ligaments. Conclusion. Our study found that SLL damage alters wrist stability, potentially leading to early arthritis. The FEA model confirmed these findings, indicating the potential for the clinical use of computer models from CT scans for treatment planning