Fracture related infections (FRI) are debilitating complications of musculoskeletal trauma surgery that can result in permanent functional loss or amputation. This study aims to determine risk factors associated with FRI treatment failure, allowing clinicians to optimise them prior to treatment and identify patients at higher risk. A major trauma centre database was retrospectively reviewed over a six-year period. Of the 102 patients identified with a FRI (66 male, 36 female), 29.4% (n=30) had acute infections (onset <6 weeks post-injury), 34.3% (n=35) had an open fracture. Open fractures were classified using Gustilo-Anderson (GA) classification (type 2:n=6, type 3A:n=16, type 3B:n=10, type 3C:n=3). Patients with periprosthetic infections of the hip and knee joint, those without prior fracture fixation, soft tissue infections, diabetic foot ulcers, pressure sore infections, patients who died within one month of injury, <12 months follow-up were excluded. FRI treatment failure was defined as either infection recurrence, non-union, or amputation. Lifestyle, clinical, and intra-operative data were documented via retrospective review of medical records. Factors with a P-value of p<0.05 in univariate analysis were included in a stepwise multivariate logistic regression model. FRI treatment failure was encountered in 35.3% (n=36). The most common FRI site was the femoral shaft (16.7%; n=17), and 15.7% (n=16) presented with signs of systemic sepsis. 20.6% (n=21) had recurrent infection, 9.8% (n=10) had non-union, and 4.9% (n=5) required an amputation. The mean age at injury was 49.71 years old. Regarding cardiovascular risk factors, 37 patients were current smokers (36.3%), 31 patients were diabetics (30.4%), and 32 patients (31.4%) were obese (BMI≥30.0). Average follow-up time was 2.37 (range: 1.04-5.14) years. Risk factors for FRI treatment failure were BMI>30, GA type 3c, and implant retention. Given that FRI treatment in 35.3% (36/102) ended up in failure, clinicians need to take into account the predictive variables analysed in this study, and implement a multidisciplinary team approach to optimise these factors. This study could aid clinicians to redirect efforts to improve high risk patient management, and prompt future studies to trial adjuvant technologies for patients at higher risk of failure

Open tibial fractures can be difficult to manage, with a range of factors that could affect treatment and outcome. We present a large cohort of patients, and analyse which factors have significant associations with infection outcome. Elucidation will allow clinicians to strive for treatment optimisation, and patients to be advised on likely complications. Open tibia fractures treated at a major trauma centre between 2015-2021 were included. Mean age at injury was 55.4 (range 13-102). Infection status was categorized into no infection, superficial infection, and osteomyelitis. Age, mode of injury, polytrauma, fibula status, Gustilo-Anderson (GA) classification, wound contamination, time from injury to: first procedure/definitive plastics procedure/definitive fixation, type of definitive fixation, smoking and diabetic status, and BMI, were collected. Multicollinearity was calculated, with highly correlated factors removed. Multinomial logistic regression was performed. Chi Squared testing, with Post Hoc Bonferroni correction was performed for complex categorical factors. Two hundred forty-four patients with open tibial fractures were included. Forty-five developed superficial infection (18.4%), and thirty-nine developed osteomyelitis (16.0%). Polytrauma, fibula status, and type of definitive fixation were excluded from the multivariate model due to strong multicollinearity with other variables. With reference to the non-infected outcome; superficial infection patients had higher BMI (p<0.01), higher GA grade (p<0.01), osteomyelitis patients had longer time to definitive fixation (p=0.049) and time to definitive plastics procedure (p=0.013), higher GA grade (p<0.01), and positive wound contamination(p=0.015). Poc hoc analysis showed “no infection” was positively associated with GA-I (p=0.029) and GA-II (p<0.01), and negatively associated with GA-IIIC (p<0.01). Osteomyelitis was positively associated with GA-IIIc (p<0.01). This study investigated the associations between the injury and presentation factors that may affect infection outcome. The variables highlighted are the factors clinicians should give extra consideration to when treating cases, and take preventative measures to optimize treatment and mitigate infection risk

A hot swollen joint is a commonly encountered condition in clinical practice. With a broad range of differentials, septic arthritis (SA) is perhaps one of the most concerning. Treated by culture-specific antibiotics and arthroscopic lavage, some patients require multiple washouts. We aimed to determine:. (1) What are the risk factors for development of SA?. (2) What are the risk factors for repeat washout in SA patients?. (3) What are the important clinical differences between a periprosthetic joint infection (PJI) and SA cohort?. All patients presenting to the emergency department, orthopaedic, and rheumatology clinics between January 2020 to January 2021 with a hot, swollen joint were retrospectively evaluated. Patients with previous trauma on the ipsilateral joint, with data missing from their medical records in any of the variables required for analysis, <24 months follow-up were excluded. Variables of interest in the three-month period preceding the diagnosis of SA were compared between SA and non-SA patients. Factors with a p-value of p<0.100 in univariate analysis were included in a stepwise multivariate logistic regression model. Similar analyses were performed to compare SA patients with multiple washouts with those needing one washout. Demographical and clinical data for PJI patients were collected to delineate important differences with SA cohort. 211 patients were included (SA:28;PJI:24;pseudogout:32;gout:26;others:101). Multivariate analysis showed rheumatoid arthritis (RA), skin infection, and liver disease were risk factors for SA. Amongst patients with septic arthritis, multivariate analysis showed that WBC levels above normal limits (3.6-10.5×109 cells/L) and RA were risk factors for multiple washouts. Between the SA and PJI cohorts, BMI (p=0.002) was significantly lower in the former, whilst WBC level (p=0.023) and CRP (p<0.0001) was significantly higher in the former. Early diagnosis of septic arthritis requires understanding the risk factors, namely RA, skin infection, and liver disease. Considering PJI and septic arthritis as the same entity can lead to wrong clinical judgement, and clinicians should be aware of important differences. We believe that the models in this study are of prognostic value to clinicians who are presented with the common presenting compliant of a hot swollen joint

Abstract. Objectives. Achilles tendon ruptures are common in the UK, with data demonstrating a significant rise in incidence over the past years. Chronic Achilles ruptures have been less well defined in literature, and repair techniques vary significantly. A surge in publications reporting various management options for chronic Achilles ruptures has necessitated a review that systematically maps and summarises current evidence regarding treatments and identifies areas for future research. This scoping review aims to improve knowledge of various treatment strategies and their associated outcomes, thereby aiding clinicians in optimising treatment protocols. Methods. The Arksey and O'Malley, Levac and Peters frameworks were used. A computer-based search in PubMed, Embase, Emcare, Cinahl, ISI Web of Science and Scopus was performed for articles reporting the treatment of chronic Achilles ruptures. Two reviewers independently performed title/abstract and full text screening according to a pre-defined selection criteria. Results. A total of 747 articles were identified, of which 73 were finally included. Various management strategies were described with flexor hallucis longus tendon transfer being the most common. The American Orthopaedic Foot and Ankle Society (AOFAS) score was the most commonly reported outcome, but 16 other measures were described within the literatures. All studies comparing pre- and post-operative outcomes reported a significant improvement. 50 studies reported complications, with an overall pooled complication rate of 168/1065 (15.8%). Conclusions. Beneficial results were reported following various techniques, but comparison between these was challenging due to the low-level study designs used and confounding factors including treatment delay and tendon gap size. Further research exploring the efficacy of different techniques is required to facilitate the development of evidenced-based treatment protocols. Such a work would allow for clinicians to better understand the suitability of specific techniques, thereby selecting the optimal management strategy for each individual patient

Critical-sized bone defects remain challenging in the clinical setting. Autologous bone grafting remains preferred by clinicians. However, the use of autologous tissue is associated with donor-site morbidity and limited accessibility to the graft tissue. Advances in the development of synthetic bone substitutes focus on improving their osteoinductive properties. Whereas osteoinductivity has been demonstrated with ceramics, it is still a challenge in case of polymeric composites. One of the approaches to improve the regenerative properties of biomaterials, without changing their synthetic character, is the addition of inorganic ions with known osteogenic and angiogenic properties. We have previously reported that the use of a bioactive composite with high ceramic content composed of poly(ethyleneoxide terephthalate)/poly(butylene terephthalate) (1000PEOT70PBT30, PolyActive, PA) and 50% beta-tricalcium phosphate (β-TCP) with the addition of zinc in a form of a coating of the TCP particles can enhance the osteogenic differentiation of human mesenchymal stromal cells (hMSCs) (3). To further support the regenerative properties of these scaffolds, inorganic ions with known angiogenic properties, copper or cobalt, were added to the coating solution. β-TCP particles were immersed in a zinc and copper or zinc and cobalt solution with a concentration of 15 or 45 mM. 3D porous scaffolds composed of 1000PEOT70PBT30 and pure or coated β-TCP were additively manufactured by 3D fibre deposition. The osteogenic and angiogenic properties of the fabricated scaffolds were tested in vitro through culture with hMSCs and human umbilical vein endothelial cells, respectively. The materials were further evaluated through ectopic implantation in an in vivo mini-pig model. The early expression of relevant osteogenic gene markers (collagen-1, osteocalcin) of hMSCs was upregulated in the presence of lower concentration of inorganic ions. Further analysis will focus on the evaluation of ectopic bone formation and vascularisation of these scaffolds after implantation in a mini-pig ectopic intramuscular model

Primary malignant bone and soft tissue tumours often occur in the lower extremities of active individuals including children, teenagers and young adults. Survivors routinely face long-term physical disability. Participation in sports is particularly important for active young people but the impact of sarcoma treatment is not widely recognised and clinicians may be unable to provide objective advice about returning to sports. We aimed to identify and summarise the current evidence for involvement in sports following treatment of lower limb primary malignant bone and soft tissue tumours. A comprehensive search strategy was used to identify relevant studies combining the main concepts of interest: (1) Bone/Soft Tissue Tumour, (2) Lower Limb, (3) Surgical Interventions and (4) Sports. Studies were selected according to eligibility criteria with the consensus of three authors. Customised data extraction and quality assessment tools were used. 22 studies were selected, published between 1985 – 2020, and comprising 1005 patients. Fifteen studies with data on return to sports including 705 participants of which 412 (58.4%) returned to some form of sport at a mean follow-up period of 7.6 years. Four studies directly compared limb sparing and amputation; none of these were able to identify a difference in sports participation or ability. Return to sports is important for patients treated for musculoskeletal tumours, however, there is insufficient published research to provide good information and support for patients. Future prospective studies are needed to collect better pre and post-treatment data at multiple time intervals and validated clinical and patient sports participation outcomes such as type of sports participation, level and frequency and a validated sports specific outcome score, such as UCLA assessment. In particular, more comparison between limb sparing and amputation would be welcome

3D accurate measurements of the skeletal structures of the foot, in physiological and impaired subjects, are now possible using Cone-Beam CT (CBCT) under real-world loading conditions. In detail, this feature allows a more realistic representation of the relative bone-bone interactions of the foot as they occur under patient-specific body weight conditions. In this context, varus/valgus of the hindfoot under altered conditions or the thinning of plantar tissues that occurs with advancing age are among the most complex and interesting to represent, and numerous measurement proposals have been proposed. This study aims to analyze and compare these measurements from CBCT in weight-bearing scans in a clinical population. Sixteen feet of diabetic patients and ten feet with severe adult flatfoot acquired before/after corrective surgery underwent CBCT scans (Carestream, USA) while standing on the leg of interest. Corresponding 3D shapes of each bone of the shank and hindfoot were reconstructed (Materialise, Belgium). Six different techniques found in the literature were used to calculate the varus/valgus deformity, i.e., the inclination of the hindfoot in the frontal plane of the shank, and the distance between the ground and the metatarsal heads was calculated along with different solutions for the identification of possible calcifications. Starting with an accurate 3D reconstruction of the skeletal structures of the foot, a wide range of measurements representing the same angle of hindfoot alignment were found, some of them very different from each other. Interesting correlations were found between metatarsal height and subject age, significant in diabetic feet for the fourth and fifth metatarsal bones. Finally, CBCT allows 3D assessment of foot deformities under loaded conditions. The observed traditional measurement differences and new measurement solutions suggest that clinicians should consider carefully the anatomical and functional concepts underlying measurement techniques when drawing clinical and surgical conclusions

Introduction. The current methods for measuring femoral torsion have limitations, including variability and inaccuracies. Existing 3D methods are not reliable for abnormal femoral anteversion measurement. A new 3D method is needed for accurate measurement and planning of proximal femoral osteotomies. Currently available software for viewing and modelling CT data lacks measurement capabilities. The MSK Hip planner aims to address these limitations by combining measurement, planning, and analysis functionalities into one tool. We aim to answer 5 key questions: Is there a difference between 2D measurement methods? Is there a difference between 3D measurement methods? Is there a difference between 2D and 3D measurement methods? Are any of the measurement methods affected by the presence of osteoarthritis or a CAM deformity?. Method. After segmentation was carried out on 42 femoral CT scans using Osirix, 3D bone models were landmarked in the MSK lab hip planning software. Murphy's, Reikeras’, McBryde, and the novel MSK lab method were used to measure femoral anteversion. Result. Murphy's method had the lowest mean femoral neck anteversion (FNA) at 24.98°, while the MSK method had the highest at 28.55°. Bland-Altman plots showed systematic errors between 2D (1.201°) and 3D (1.074°) methods. All methods demonstrated good intra- and inter-user reliability. Significant differences were found between measurement methods and between patient groups. Conclusion. The MSK Hip Planner software proved useful and convenient to measure FNA. Statistically significant differences in FNA were observed between the measurement methods, as well as between patient groups when split by presence of osteoarthritis and cam deformity. Complex joint pathology and altered femoral morphology should be considered by clinicians when deciding which method to use when measuring FNA

Introduction. The non-union of long bones poses a substantial challenge to clinicians and patients alike. The Ilizarov fixation system and Limb Reconstruction System (LRS), renowned for their versatility in managing complex non-unions. The purpose of this retrospective study was to assess the outcomes of acute docking with the bone peg-in-bone technique for the management of non-unions of long bones. The study seeks to evaluate its effectiveness in achieving complete bony union, preserving limb length and alignment, correcting existing deformities, and preventing the onset of new ones. Method. A retrospective analysis of 42 patients was done with infected and non-infected non-unions of long bones who received treatment at a tertiary care hospital between April 2016 to April 2022. We utilized the Association for the Study and Application of Methods of the Ilizarov (ASAMI) scoring system to assess both bone and functional outcomes and measured mechanical lateral distal femoral angle (mLDFA) for the femur and the medial proximal tibial angle (MPTA) for the tibia. Result. In our retrospective study involving 42 patients, a total of 30 patients had post debridement gap of >2 cm and average gap of 4.54 cm (range 1 – 13 cm) and therefore underwent corticotomy and lengthening. The average external fixation time was 6.52 (range 4 – 11 months) and average external fixation index of 2.08 (range 0.4 – 4.5 months/cm). The ASAMI scoring system showed bone result of 38 excellent, 3 good and 1 fair. Functional result of 40 excellent and 2 good outcomes. The post op mLDFA and MPTA were in normal range except in 3 patients which not statistically significant. Conclusion. In conclusion, the use of acute docking provides several advantages such as promoting early fracture healing, increasing stability, shortening treatment time, reducing the number of surgical procedures and reduced number of complications

Unicompartmental knee arthroplasty (UKA) is associated with a higher risk of revision compared with total knee arthroplasty (TKA). The outcomes of knee arthroplasty are typically presented as implant survival or incidence of revision after a set number of years, which can be difficult for patients and clinicians to conceptualise. We aimed to calculate the ‘lifetime risk’ of revision for UKA as a more relatable estimate of risk projection over a patient's remaining lifetime, and make comparisons to TKA. All primary UKAS performed from 1999 to 2019 (n=13,481) captured by the New Zealand Joint Registry (NZJR) were included. The lifetime risk of revision was calculated and stratified by age, gender and American Society of Anesthesiologists (ASA) status. The lifetime risk of revision for UKA was highest in the youngest patients (46-50 years; 40.4%) and lowest in the oldest patients (86-90 years; 3.7%). Lifetime risk of revision was higher for females (range 4.3%-43.4% cf. males 2.9%-37.4%) and patients with higher ASA status (ASA 3-4 range 8.8%-41.2% cf. ASA 1 1.8%-29.8%), regardless of age. The lifetime risk of UKA was two-fold higher than TKA (ranging from 3.7%-40.4% UKA, 1.6%-22.4% TKA) across all age groups. Increased risk of revision in the younger patients was associated with aseptic loosening in both males and females, and pain in females. Periprosthetic joint infections (PJI) accounted for 4% of all UKA revisions, in contrast to 27% for TKA; risk of PJI was higher for males than females for both procedures. The lifetime risk of revision is a more meaningful measure of arthroplasty outcomes and can aid with patient counselling prior to UKA. Findings from this study show the increased lifetime risk of UKA revision for younger patients, females and those with higher ASA status

Introduction. Achieving an appropriate primary stability after implantation is a prerequisite for the long-term viability of a dental implant. Virtual testing of the bone-implant construct can be performed with finite element (FE) simulation to predict primary stability prior to implantation. In order to be translated to clinical practice, such FE modeling must be based on clinically available imaging methods. The aim of this study was to validate an FE model of dental implant primary stability using cone beam computed tomography (CBCT) with ex vivo mechanical testing. Method. Three cadaveric mandibles (male donors, 87-97 years old) were scanned by CBCT. Twenty-three bone samples were extracted from the bones and conventional dental implants (Ø4.0mm, 9.5mm length) were inserted in each. The implanted specimens were tested under quasi-static bending-compression load (cf. ISO 14801). Sample-specific homogenized FE (hFE) models were created from the CBCT images and meshed with hexahedral elements. A non-linear constitutive model with element-wise density-based material properties was used to simulate bone and the implant was considered rigid. The experimental loading conditions were replicated in the FE model and the ultimate force was evaluated. Result. The experimental ultimate force ranged between 67 N and 789 N. The simulated ultimate force correlated better with the experimental ultimate force (R. 2. =0.71) than the peri-implant bone density (R. 2. =0.30). Conclusion. The developed hFE model was demonstrated to provide stronger prediction of primary stability than peri-implant bone density. Therefore, hFE Simulations based on this clinically available low-radiation imaging modality, is a promising technology that could be used in future as a surgery planning tool to assist the clinician in evaluating the load-bearing capacity of an implantation site. Acknowledgements. Funding: EU's Horizon 2020 grant No: 953128 (I-SMarD). Dental implants: THOMMEN Medical AG

Introduction. Patients (2.7M in EU) with positive cancer prognosis frequently develop metastases (≈1M) in their remaining lifetime. In 30-70% cases, metastases affect the spine, reducing the strength of the affected vertebrae. Fractures occur in ≈30% patients. Clinicians must choose between leaving the patient exposed to a high fracture risk (with dramatic consequences) and operating to stabilise the spine (exposing patients to unnecessary surgeries). Currently, surgeons rely on their sole experience. This often results in to under- or over-treatment. The standard-of-care are scoring systems (e.g. Spine Instability Neoplastic Score) based on medical images, with little consideration of the spine biomechanics, and of the structure of the vertebrae involved. Such scoring systems fail to provide clear indications in ≈60% patients. Method. The HEU-funded METASTRA project is implemented by biomechanicians, modellers, clinicians, experts in verification, validation, uncertainty quantification and certification from 15 partners across Europe. METASTRA aims to improve the stratification of patients with vertebral metastases evaluating their risk of fracture by developing dedicated reliable computational models based on Explainable Artificial Intelligence (AI) and on personalised Physiology-based biomechanical (VPH) models. Result. The METASTRA-AI model is expected to be able to stratify most patients with limited effort end cost, based on parameters extracted semi-automatically from the medical files and images. The cases which are not reliably stratified through the AI model, are examined through a more detailed and personalised biomechanical VPH model. These METASTRA numerical tools are trained through an unprecedentedly large multicentric retrospective study (2000 cases) and validated against biomechanical ex vivo experiments (120 specimens). Conclusion. The METASTRA decision support system is tested in a multicentric prospective observational study (200 patients). The METASTRA approach is expected to cut down the indeterminate diagnoses from the current 60% down to 20% of cases. METASTRA project funded by the European Union, HEU topic HLTH-2022-12-01, grant 101080135

Precision health aims to develop personalised and proactive strategies for predicting, preventing, and treating complex diseases such as osteoarthritis (OA). Due to OA heterogeneity, which makes developing effective treatments challenging, identifying patients at risk for accelerated disease progression is essential for efficient clinical trial design and new treatment target discovery and development. To create a reliable and interpretable precision health tool that predicts rapid knee OA progression over a 2-year period from baseline patient characteristics using an advanced automated machine learning (autoML) framework, “Autoprognosis 2.0”. All available 2-year follow-up periods of 600 patients from the FNIH OA Biomarker Consortium were analysed using “Autoprognosis 2.0” in two separate approaches, with distinct definitions of clinical outcomes: multi-class predictions (categorising disease progression into pain and/or radiographic progression) and binary predictions. Models were developed using a training set of 1352 instances and all available variables (including clinical, X-ray, MRI, and biochemical features), and validated through both stratified 10-fold cross-validation and hold-out validation on a testing set of 339 instances. Model performance was assessed using multiple evaluation metrics. Interpretability analyses were carried out to identify important predictors of progression. Our final models yielded higher accuracy scores for multi-class predictions (AUC-ROC: 0.858, 95% CI: 0.856-0.860) compared to binary predictions (AUC-ROC: 0.717, 95% CI: 0.712-0.722). Important predictors of rapid disease progression included WOMAC scores and MRI features. Additionally, accurate ML models were developed for predicting OA progression in a subgroup of patients aged 65 or younger. This study presents a reliable and interpretable precision health tool for predicting rapid knee OA progression. Our models provide accurate predictions and, importantly, allow specific predictors of rapid disease progression to be identified. Furthermore, the transparency and explainability of our methods may facilitate their acceptance by clinicians and patients, enabling effective translation to clinical practice

During the COVID-19 pandemic, video/phone consultations (VPC) were increasingly utilised as an alternative to face-to-face (F2F) consultations, to minimise nosocomial viral exposure. We previously demonstrated that VPCs were highly rated by both patients and clinicians. This study compared satisfaction between both clinic modalities in contemporaneously delivered outpatient surveys. We also assessed the feasibility and effects of converting F2F orthopaedic consultations to VPC. Surveys were posted to patients who attended VPCs and F2F consultations at a large tertiary centre from August to October 2020 inclusive, across 51 specialties. F2F and VPC patients ranked their overall satisfaction with their consultation on a 10-point numerical scale (10=highest satisfaction). Simultaneously, a pilot study was undertaken of outpatient fracture clinics to identify patients suitable for VPCs, with X-rays (if needed) taken and transferred from satellite sites to reduce tertiary centre footfall. For F2F consultations, 1419 of 4465 surveys (31.8%) were returned with similar rates for VPCs (1332 of 4572, 29.1%). While mean satisfaction ratings were high for both clinic modalities, they were significantly higher for F2F: 9.13 (95% CI 9.05-9.22) for F2F clinics, compared to 8.23 (95% CI 8.11-8.35) for VPCs (p<0.001, t-test). F2F patients were almost four times more likely to state a preference for future F2F appointments compared to VPCs, whereas patients who attended VPCs showed an equal preference for either option (p< 0.001, chi2 test). 53% of 111 fracture clinic patients sampled were identified as suitable for VPCs. 1 patient (1.7%) requested their VPC to be converted to F2F due to poor symptom control. Our study showed patients reported high satisfaction ratings for both F2F clinics and VPCs, with prior experience of VPCs affecting patients’ future preferences. Only 1.7% of F2F patients converted to VPCs declined their virtual appointment. Our results support future use of VPCs

The Spine Surgery Unit of IRCCS Istituto Ortopedico Rizzoli is dedicated to the diagnosis and the treatment of vertebral pathologies of oncologic, degenerative, and post-traumatic origin. To achieve increasingly challenging goals, research has represented a further strength for Spinal Surgery Unit for several years. Thanks to the close synergy with the Complex Structure Surgical Sciences and Technologies, IRCCS Istituto Ortopedico Rizzoli, extensive research was carried out. The addition of the research activities intensifies a complementary focus and provides a unique opportunity of innovation. The overall goal of spine research for the Spine Surgery Unit and for the Complex Structure Surgical Sciences and Technologies is and has been to:. - investigate the factors that influence normal spine function;. - engineer and validate new and advanced strategies for improving segmental spinal instrumentation, fusion augmentation and grafting;. - develop and characterize advanced and alternative preclinical models of vertebral bone metastasis to test drugs and innovative strategies, taking into account patient individual characteristics and specific tumour subtypes so predicting patient specific responses;. - evaluate the clinical characteristics, treatment modalities, and potential contributing and prognostic factors in patients with vertebral bone metastases;. - realize customized prosthesis to replace vertebral bodies affected by tumours or major traumatic events, specifically engineered to reduce infections, and increase patients’ surgical options. These efforts have made possible to obtain important results that favour the translation of basic research to application at the patient's bedside, and from here to routine clinical practice (without excluding the opposite pathway, in which the evidence generated by clinical practice helps to guide research). Although translational research can provide patients with valuable therapeutic resources, it is not risk-free. Thus, it is therefore necessary an always close collaboration between researchers and clinicians in order to guarantee the ethicality of translational research, by promoting the good of individuals and minimising the risks

Fracture nonunion is a severe clinical problem for the patient, as well as for the clinician. About 5-20% of fractures does not heal properly after more than six months, with a 19% nonunion rate for tibia, 12% for femur and 13% for humerus, leading to patient morbidity, prolonged hospitalization, and high costs. The standard treatment with iliac crest-derived autologous bone filling the nonunion site may cause pain or hematoma to the patient, as well as major complications such as infection. The application of mesenchymal autologous cells (MSC) to improve bone formation calls for randomized, open, two-arm clinical studies to verify safety and efficacy. The ORTHOUNION * project (ORTHOpedic randomized clinical trial with expanded bone marrow MSC and bioceramics versus autograft in long bone nonUNIONs) is a multicentric, open, randomized, comparative phase II clinical trial, approved in the framework of the H2020 funding programme, under the coordination of Enrique Gòmez Barrena of the Hospital La Paz (Madrid, Spain). Starting from January 2017, patients with nonunion of femur, tibia or humerus have been actively enrolled in Spain, France, Germany, and Italy. The study protocol encompasses two experimental arms, i.e., autologous bone marrow-derived mesenchymal cells after expansion (‘high dose’ or ‘low dose’ MSC) combined to ceramic granules (MBCP™, Biomatlante), and iliac crest-derived autologous trabecular bone (ICAG) as active comparator arm, with a 2-year follow-up after surgery. Despite the COVID 19 pandemic with several lockdown periods in the four countries, the trial was continued, leading to 42 patients treated out of 51 included, with 11 receiving the bone graft (G1 arm), 15 the ‘high dose’ MSC (200x10. 6. , G2a arm) and 16 the ‘low dose’ MSC (100x10. 6. , G2b arm). The Rizzoli Orthopaedic Institute has functioned as coordinator of the Italian clinical centres (Bologna, Milano, Brescia) and the Biomedical Science and Technologies and Nanobiotechnology Lab of the RIT Dept. has enrolled six patients with the collaboration of the Rizzoli’ 3rd Orthopaedic and Traumatological Clinic prevalently Oncologic. Moreover, the IOR Lab has collected and analysed the blood samples from all the patients treated to monitor the changes of the bone turnover markers following the surgical treatment with G1, G2a or G2b protocols. The clinical and biochemical results of the study, still under evaluation, are presented. * ORTHOUNION Horizon 2020 GA 733288

Introduction:. Most of the published papers on AI based diagnosis have focused on the algorithm's diagnostic performance in a ‘binary’ setting (i.e. disease vs no disease). However, no study evaluated the actual value for the clinicians of an AI based approach in diagnostic. Detection of Traumatic thoracolumbar (TL) fractures is challenging on planar radiographs, resulting in significant rates of missed diagnoses (30-60%), thus constituting a field in which a performance improvement is needed. Aim of this study is therefore to evaluate the value provided by AI generated saliency maps (SM), i.e. the maps that highlight the AI identified region of interests. Methods:. An AI model aimed at identifying TL fractures on plain radiographs was trained and tested on 567 single vertebrae images. Three expert spine surgeons established the Ground Truth (GT) using CT and MRI to confirm the presence of the fracture. From the test set, 12 cases (6 with a GT of fracture and 6 with a GT of no fracture, associated with varying levels of algorithm confidence) were selected and the corresponding SMs were generated and shown to 7 independent evaluators with different grade of experience; the evaluators were requested to: (1) identify the presence or absence of a fracture before and after the saliency map was shown; (2) grade, with a score from 1 (low) to 6 (high) the pertinency (correlation between the map and the human diagnosis), and the utility (the perceived utility in confirming or not the initial diagnosis) of the SM. Furthermore, the usefulness of the SM was evaluated through the rate of correct change in diagnosis after the maps had been shown. Finally, the obtained scores were correlated with the algorithm confidence for the specific case. Results:. Of the selected maps, 8 had an agreement between the AI diagnosis and the GT, while in 4 the diagnosis was discordant (67% accuracy). The pertinency of the map was found higher when the AI diagnosis was the same as the GT and the human diagnosis (respectively p-value = .021 and <.000). A positive and significant correlation between the AI confidence score and the perceived utility (Spearman: 27%, p-value=.0-27) was found. Furthermore, evaluator with experience < 5 year found the maps more useful than the experts (z-score=2.004; p-value=.0455). Among the 84 evaluation we found 12 diagnostic errors in respect to the GT, 6 (50%) of which were reverted after the saliency map evaluation (z statistic = 1.25 and p-value = .21). Discussion:. The perceived utility of AI generated SM correlate with the model confidence in the diagnosis. This highlights the fact that to be considered helpful, the AI must provide not only the diagnosis but also the case specific confidence. Furthermore, the perceived utility was higher among less experienced users, but overall, the SM were useful in improving the human diagnostic accuracy. Therefore, in this setting, the AI enhanced approach provides value in improving the human performance

Hip Osteoarthritis (HOA) is the most common joint disorder and a major cause of disability in the adult population, leading to total hip replacement (THR). Recently, evidence has mounted for a prominent etiologic role of femoroacetabular impingement (FAI) in the development of early OA in the non-dysplastic hip. FAI is a pathological mechanical process, caused by abnormalities of the acetabulum and/or femur leading to damage the soft tissue structures. FAI can determine chondro-labral damage and groin pain in young adults and can accelerate HOA progression in middle-aged adults. The aim of the study was to determine if the presence of calcium crystal in synovial fluid (SF) at the time of FAI surgery affects the clinical outcomes to be used as diagnostic and predictive biomarker. 49 patients with FAI undergoing arthroscopy were enrolled after providing informed consent; 37 SFs were collected by arthrocentesis at the time of surgery and 35 analyzed (66% males), median age 35 years with standard deviation (SD) 9.7 and body mass index (BMI) 23.4 kg/m. 2. ; e SD 3. At the time of surgery, chondral pathology using the Outerbridge score, labral pathology and macroscopic synovial pathology based on direct arthroscopic visualization were evaluated. Physical examination and clinical assessment using the Hip disability & Osteoarthritis Outcome Score (HOOS) were performed at the time of surgery and at 6 months of follow up. As positive controls of OA signs, SF samples were also collected from cohort of 15 patients with HOA undergoing THR and 12 were analysed. 45% FAI patients showed CAM deformity; 88% presented labral lesion or instability and 68% radiographic labral calcification. 4 patients out of 35 showed moderate radiographic signs of OA (Kellegren-Lawrence score = 3). Pre-operative HOOS median value was 61.3% (68.10-40.03) with interquartile range (IQR) of 75-25% and post-operative HOOS median value 90% with IQR 93.8-80.60. In both FAI and OA patients the calcium crystal level in SFs negatively correlated with glycosaminoglycan (component of the extracellular matrix) released, which is a marker of cartilage damage (Spearman rho=-0.601, p<0.001). In FAI patients a worst articular function after surgery, measured with the HOOS questionnaire, was associated with both acetabular and femoral chondropathy and degenerative labral lesion. Moreover, radiographic labral calcification was also significantly associated with pain, worst articular function and labral lesion. Calcium crystal level in SFs was associated with labral lesions and OA signs. We concluded that the levels of calcium crystals in FAI patients are correlated with joint damage, OA signs and worst post-operative outcome. The presence of calcium crystals in SF of FAI patients might be a potential new biomarker that might help clinicians to make an early diagnosis, evaluate disease progression and monitor treatment response

Abstract. Introduction. Precision health aims to develop personalised and proactive strategies for predicting, preventing, and treating complex diseases such as osteoarthritis (OA), a degenerative joint disease affecting over 300 million people worldwide. Due to OA heterogeneity, which makes developing effective treatments challenging, identifying patients at risk for accelerated disease progression is essential for efficient clinical trial design and new treatment target discovery and development. Objectives. This study aims to create a trustworthy and interpretable precision health tool that predicts rapid knee OA progression based on baseline patient characteristics using an advanced automated machine learning (autoML) framework, “Autoprognosis 2.0”. Methods. All available 2-year follow-up periods of 600 patients from the FNIH OA Biomarker Consortium were analysed using “Autoprognosis 2.0” in two separate approaches, with distinct definitions of clinical outcomes: multi-class predictions (categorising patients into non-progressors, pain-only progressors, radiographic-only progressors, and both pain and radiographic progressors) and binary predictions (categorising patients into non-progressors and progressors). Models were developed using a training set of 1352 instances and all available variables (including clinical, X-ray, MRI, and biochemical features), and validated through both stratified 10-fold cross-validation and hold-out validation on a testing set of 339 instances. Model performance was assessed using multiple evaluation metrics, such as AUC-ROC, AUC-PRC, F1-score, precision, and recall. Additionally, interpretability analyses were carried out to identify important predictors of rapid disease progression. Results. Our final models yielded high accuracy scores for both multi-class predictions (AUC-ROC: 0.858, 95% CI: 0.856–0.860; AUC-PRC: 0.675, 95% CI: 0.671–0.679; F1-score: 0.560, 95% CI: 0.554–0.566) and binary predictions (AUC-ROC: 0.717, 95% CI: 0.712–0.722; AUC-PRC: 0.620, 95% CI: 0.616–0.624; F1-score: 0.676, 95% CI: 0.673–0679). Important predictors of rapid disease progression included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and MRI features. Our models were further successfully validated using a hold-out dataset, which was previously omitted from model development and training (AUC-ROC: 0.877 for multi-class predictions; AUC-ROC: 0.746 for binary predictions). Additionally, accurate ML models were developed for predicting OA progression in a subgroup of patients aged 65 or younger (AUC-ROC: 0.862, 95% CI: 0.861–0.863 for multi-class predictions; AUC-ROC: 0.736, 95% CI: 0.734–0.738 for binary predictions). Conclusions. This study presents a reliable and interpretable precision health tool for predicting rapid knee OA progression using “Autoprognosis 2.0”. Our models provide accurate predictions and offer insights into important predictors of rapid disease progression. Furthermore, the transparency and interpretability of our methods may facilitate their acceptance by clinicians and patients, enabling effective utilisation in clinical practice. Future work should focus on refining these models by increasing the sample size, integrating additional features, and using independent datasets for external validation. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Telemedicine is the delivery of healthcare from a remote location using integrated computer/communication technology. This systematic review aims to explore evidence for telemedicine in orthopaedics to determine its advantages, validity, effectiveness and utilisation particularly during our current pandemic where patient contact is limited. Databases of PubMed, Scopus and CINHAL were systematically searched and articles were included if they involved any form of telephone or video consultation in an orthopaedic population. Findings were synthesised into four themes: patient/clinician satisfaction, accuracy and validity of examination, safety and patient outcomes and cost effectiveness. Quality assessment was undertaken using Cochrane and Joanna Briggs Institute appraisal tools. Twenty studies were included consisting of nine RCTs across numerous orthopaedic subspecialties including fracture care, elective orthopaedics and oncology. Studies revealed high patient satisfaction with telemedicine for convenience, less waiting and travelling time. Telemedicine was cost effective particularly if patients had to travel long distances, required hospital transport or time off work. No clinically significant differences were found in patient examination nor measurement of patient reported outcome measures. Telemedicine was reported to be a safe method of consultation. However, studies were of variable methodological quality with selection bias. In conclusion, evidence suggests that telemedicine in orthopaedics can be safe, cost effective, valid in clinical assessment with high patient/clinician satisfaction. Further work with high quality RCTs is required to elucidate long term outcomes. This systematic review presents up-to-date evidence on the use of telemedicine and provides data for organisations considering its use in the current COVID-19 pandemic and beyond