Abstract. Background. Whilst the literature abounds with patient reported outcomes following total knee replacement (TKR) there is a paucity of literature covering objective functional outcomes. Awareness of objective functional outcomes following TKR is key to the consent process and relating it to pre-operative function enables a tailored approach to consent. Objectives. Identify trends in a range of functional outcomes prior to and following TKR up to one year post-operatively. Methods. We prospectively gathered data from 82 patients undergoing TKR, examining over 20 functional measures preoperatively and postoperatively at 6 weeks, 3, 6 and 12 months. Our functional lab incorporated validated assessments and assessments selected by surgeons & physiotherapists seen to be critical to outcomes following TKR, such as: kneeling ability, 6 minute walking distance, time to ascend/descend stairs, quadricep moment strength, single stance difficulty, ability to walk on an uneven surface, “Time to get up and go”, upslope/downslope speed. Results. Our results demonstrated that if a patient was able to kneel preoperatively they had an 82.5% chance of being able to kneel postoperatively; if they could not kneel preoperatively this dropped to only 50% but overall over two-thirds of patients were able to kneel at 1 year postoperatively. Other selected results include: 49% increase in 6-minute walking distance, 45% reduction in time to ascend then descend stairs, over 50% increase in quadriceps moment strength, over 40% increase in both upslope/downslope speed and over 70% reduction in difficulty walking on an uneven surface. Conclusions. With these results we can not only discuss specific functional outcomes following TKR but also relate these to preoperative functional level, enabling a more tailored, detailed and robust consent process. 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

Introduction. Guidelines from the North American Spine Society (2009 and 2013) are the best evidence-based instructions on venous thromboembolism (VTE) and antibiotic prophylaxis in spinal surgery. NICE guidelines exist for VTE prophylaxis but do not specifically address spinal surgery. In addition, the ruling of the UK Supreme Court in 2015 resulted in new guidance on consent being published by the Royal College of Surgeons of England (RCSEng). This study assesses our compliance in antibiotic, VTE prophylaxis and consent in spinal surgery against both US and UK standards. Methods. Retrospective review of spinal operations performed between August and December 2016. Case notes, consent forms and operation notes were analysed for consent, peri-operative antibiotic prescribing and post-operative VTE instructions. Results. Four Spinal surgeons performed 45 operations during this period. 31 patients (69%) received a copy of the signed consent with this process being formally documented in 22 (71%) of those cases. All patients were consented by a competent surgeon. 82% of cases consented prior to the date of procedure were countersigned on the day of operation. There was a mean time of 25.3 days between initial consent and operation (Range: 0–170). 37 (82%) cases had clear instructions for VTE and antibiotic prophylaxis. All prescribed post-operative antibiotics were administered. Discussion. The North American Guidelines state that prophylactic antibiotic is appropriate in all spinal surgery with prolonged cases requiring intraoperative re-dosing and only complex cases needing a postoperative regimen. Eight patients underwent a complex procedure and 7 appropriately received postoperative antibiotics. Of the 29 patients that underwent a simple procedure, 12 did not receive post-operative regimen, in line with the guidelines. However, the remainder 17 were over treated. The US Guidelines recommend mechanical VTE prophylaxis only in elective spinal surgery except in high risk patients. All our patients received VTE mechanical prophylaxis. RCSEng guidelines require consent being taken prior to procedure by a competent surgeon and confirmed on day of procedure. All patients in our cohort were consented prior to the date of operation allowing time for considering options and independent research. 82% of patients had consent confirmed on day of operation. Conclusion. This study demonstrates that we met guideline advice for all patients with regards VTE prophylaxis. We have a tendency to over treat with post-operative antibiotics and not all patients had their consent confirmed on day of procedure but was consented well before day of operation. North America still lead the way with guidelines on spinal surgery to which we should adhere, with NICE guidelines providing limited instructions. New consenting guidelines from RCSEng may not be currently widely known and thus should be a source of education for all surgeons

The process of gaining informed consent can be a complex and much debated pursuit, especially within a paediatric setting. The role of the trainee surgeon and its explanation to children and their families prior to an operation has not been explored from the resident surgeons' point of view. Ten face-to-face interviews were conducted with orthopaedic surgery trainees at a tertiary level paediatric hospital in Toronto, Canada. These were transcribed and subsequently thematically coded by 3 reviewers. Three main themes were identified from the interviews. 1) Surgical trainees feel their level of participation and autonomy gradually increases dependent on their observed skills and level of training. 2) Trainees feel the consent process is adequate but acknowledge it is often purposely vague with regards to their intra-operative involvement as this is often unpredictable and it avoids patient/family anxiety. 3) Trainees believe families are aware of their participation however most likely underestimate their role during operations. Trainees in surgical specialties believe their level of autonomy is variable dependent on a number of factors and that this impacts on the ability to be more specific when gaining informed consent. This must be balanced with a family's right to an appropriate understanding of their child's operation and who is performing it. It may be that further patient education regarding trainees and their role in operations would help develop a more thorough and patient centred informed consent process

Aim. To investigate the role of websites in enhancing patients' understanding of reason and risk of surgery as a part of informed consent for elective un-instrumented lumbar spine surgery (EULSS). Methodology. This was a National Research Ethical Committee approved RCT study. 63 patients underwent EULSS, out of which 14(29%) declined participation and 14(29%) were excluded. One did not have surgery therefore 34 were randomised to Standard (S) and intervention group (I) using sealed envelope. Standard group were given verbal information & leaflet while the Intervention group were given information on relevant section of . www.eurospine.org. and . www.spinesurgeons.ac.uk. websites. A 13 item Informed Consent Questionnaire (ICQ) was used to collect data. The primary outcomes were patients' perceived understanding of reason and risk of EULSS. Results. Average age was 54 (21–82) years, with similar demographics in both groups. Complete data was available for 20 (13 Standard and 7 Intervention group). No difference (χ. 2. = 0.42, df=1, p= 0.52) was observed on perception of reason and risk of surgery between two groups. Website usage increased from 30% to 50% in intervention group who continued to use the website. Conclusion. Website use appears to be useful to participants. Although support has not been found to accept the experimental hypothesis, valuable information has been gained that will serve to facilitate larger study to further explore the effectiveness of websites in enhancing of EULSS. No Conflict of interest. No funding obtained. This abstract has not been previously published in whole or substantial part nor has it been presented previously at a national meeting

Obtaining informed consent for an operation is a fundamental daily interaction between orthopaedic surgeon and patient. It is based on a patient's capacity to understand and retain information about the proposed procedure, the potential consequences of having it and the alternative options available. We used validated tests of memory on 59 patients undergoing lower limb arthroplasty to assess how well they learned and recalled information about their planned procedure. All patients showed an ability to learn new material, however, younger age and higher educational achievement correlated with better performance. These results have serious implications for orthopaedic surgeons discussing planned procedures. They identify groups of patients who may require enhanced methods of communicating the objectives, risks and alternatives to surgery. Further research is necessary to assess interventions to improve communication prior to surgery

The computational modelling and 3D technology are finding more and more applications in the medical field. Orthopedic surgery is one of the specialties that can benefit the most from this solution. Three case reports drawn from the experience of the authors’ Orthopedic Clinic are illustraded to highlight the benefits of applying this technology. Drawing on the extensive experience gained within the authors’ Operating Unit, three cases regarding different body segments have been selected to prove the importance of 3D technology in preoperative planning and during the surgery. A sternal transplant by allograft from a cryopreserved cadaver, the realization of a custom made implant of the glenoid component in a two-stage revision of a reverse shoulder arthroplasty, and a case of revision on a hip prosthesis with acetabular bone loss (Paprosky 3B) treated with custom system. In all cases the surgery was planned using 3D processing software and models of the affected bone segments, printed by 3D printer, and based on CT scans of the patients. The surgical implant was managed with dedicated instruments. The use of 3D technology can improve the results of orthopedic surgery in many ways: by optimizing the outcomes of the operation as it allows a preliminary study of the bone loss and an evalutation of feasibility of the surgery, it improves the precision of the positioning of the implant, especially in the context of severe deformity and bone loss, and it reduces the operating time; by improving surgeon training; by increasing patient involvement in decision making and informed consent. 3D technology, by offering targeted and customized solutions, is a valid tool to obtain the tailored care that every patient needs and deserves, also providing the surgeon with an important help in cases of great complexity

Traumatic acute or chronic tendon injuries are a wide clinical problem in modern society, resulting in important economic burden to the health system and poor quality of life in patients. Due to the low cellularity and vascularity of tendon tissue the repair process is slow and inefficient, resulting in mechanically, structurally, and functionally inferior tissue. Tissue engineering and regenerative medicine are promising alternatives to the natural healing process for tendon repair, especially in the reconstruction of large damaged tissues. The aim of TRITONE project is to develop a smart, bioactive implantable 3D printed scaffold, able to reproduce the structural and functional properties of human tendon, using FDA approved materials and starting from MSC and their precursor, MPC cell mixtures from human donors. Total cohort selected in the last 12 months was divided in group 1 (N=20) of subjects with tendon injury and group 2 (N=20) of healthy subject. Groups were profiled and age and gender matched. Inclusion criteria were age>18 years and presence of informed consent. Ongoing pregnancy, antihypertensive treatment, cardiovascular diseases, ongoing treatment with anti-aggregants, acetylsalicylic-acid or lithium and age<18 years were exclusion criteria. Firstly, we defined clinical, biological, nutritional life style and genetic profile of the cohort. The deficiency of certain nutrients and sex hormonal differences were correlated with tendon-injured patients. It was established the optimal amount of MPC/MSC human cell (collected from different patients during femoral neck osteotomy). Finally, most suitable biomaterials for tendon regeneration and polymer tendon-like structure were identified. Hyaluronic acid, chemical surface and soft-molecular imprinting (SOFT-MI) was used to functionalize the scaffold. These preliminary results are promising. It will be necessary to enroll many more patients to identify genetic status connected with the onset of tendinopathy. The functional and structural characterization of smart bioactive tendon in dynamic environment will represent the next project step

Autografts containing bone marrow (BM) are current gold standard in the treatment of critical size bone defects, delayed union and bone nonunion defects. Although reaching unprecedented healing rates in bone reconstruction, the mode of action and cell-cell interactions of bone marrow mononuclear cell (BM-MNC) populations have not yet been described. BM-MNCs consist of a heterogeneous mixture of hematopoetic and non-hematopoetic lineage fractions. Cell culture in a 3D environment is necessary to reflect on the complex mix of these adherend and non-adherend cells in a physiologically relevant context. Therefore, the main aim of this approach was to establish conditions for a stable 3D BM-MNC culture to assess cellular responses on fracture healing strategies. BM samples were obtained from residual material after surgery with positive ethical vote and informed consent of the patients. BM-MNCs were isolated by density gradient centrifugation, and cellular composition was determined by flow cytometry to obtain unbiased data sets on contained cell populations. Collagen from rat tail and human fibrin was used to facilitate a 3D culture environment for the BM-MNCs over a period of three days. Effects on cellular composition that could improve the regenerative potential of BM-MNCs within the BM autograft were assessed using flow cytometry. Cell-cell-interactions were visualized using confocal microscopy over a period of 24 hours. Cell localization and interaction partners were characterized using immunofluorescence labeled paraffin sectioning. Main BM-MNC populations like Monocytes, Macrophages, T cells and endothelial progenitor cells were determined and could be conserved in 3D culture over a period of three days. The 3D cultures will be further treated with already clinically available reagents that lead to effects even within a short-term exposure to stimulate angiogenic, osteogenic or immunomodulatory properties. These measures will help to ease the translation from “bench to bedside” into an intraoperative protocol in the end

Cartilage degeneration and loss are key events in the initiation and progression of osteoarthritis (OA). Changes to chondrocyte volume and morphology (in the form of cytoplasmic processes) and thus cell phenotype are implicated, as they lead to the production of a mechanically-weakened extracellular matrix. The chondrocyte cytoskeleton is intimately linked to cell volume and morphology and hence we have investigated alterations to levels and distribution of chondrocyte F-actin that occur during early OA. The femoral heads (FH) from hip joints (N=16) were obtained with ethical permission and patient consent following femoral neck fracture. Cartilage was assessed as grade 0 (non-degenerate) and grade 1 (superficial fibrillation) using OARSI criteria. In situ chondrocyte volume and F-actin distribution were assessed using the fluorescent indicators (5-chloromethyl fluorescein diacetate (CMFDA)) and phalloidin, and imaged and quantified by confocal microscopy, Imaris. TM. and ImageJ software. There were no differences between the volume or total F-actin levels of in situ chondrocytes within the superficial zone of grade 0 (n=164 cells) compared to grade 1 (n=145) cartilage (P>0.05). However, a more detailed analysis of phalloidin labelling was performed, which demonstrated significant increases in both intense punctuate (IP) or intense areas (IA) (P<0.0001; P=0.0175 respectively). A preliminary analysis of IP and IA F-actin labelling suggested that while the former did not appear to be associated with changes to chondrocyte morphology, most of the cytoplasmic processes were associated with the presence of IA at the starting point of the protrusion. These results demonstrate marked changes to F-actin distribution in chondrocytes in the very early stages of cartilage degeneration as occurs in OA. These subtle changes are probably an early indication of a change to the chondrocyte phenotype and thus worthy of further study as they may lead to deleterious alterations to matrix metabolism and ultimately cartilage weakening

Partial meniscectomy patients have a greater likelihood for the development of early osteoarthritis (OA). To prevent the onset of early OA, patient-specific treatment algorithms need to be created that predict patient risk to early OA after meniscectomy. The aim of this work was to identify patient-specific risk factors in partial meniscectomy patients that could potentially lead to early OA. Partial meniscectomy patients operated between 01/2017 and 12/2019 were evaluated in the study (n=317). Exclusion criteria were other pathologies or surgeries for the evaluated knee and meniscus (n = 114). Following informed consent, an online questionnaire containing demographics and the “Knee Injury and Osteoarthritis Outcome Score” (KOOS) questionnaire was sent to the patient. Based on the KOOS pain score, patients were classified into “low” (> 75) and “high” (< 75) risk patients, indicating risk to symptomatic OA. The “high risk” patients also underwent a follow-up including an MRI scan to understand whether they have developed early OA. From 203 participants, 96 patients responded to the questionnaire (116 did not respond) with 61 patients considered “low-risk” and 35 “high-risk” patients. Groups that showed a significant increased risk for OA were patients aged > 40 years, females, overweight (BMI >25 kg/m2 ≤ 30 kg/m2), and smokers (*p < 0.05). The “high-risk”-follow-up revealed a progression of early osteoarthritic cartilage changes in seven patients, with the remaining nineteen patients showing no changes in cartilage status or pain since time of operation. Additionally, eighteen patients in the high-risk group showed a varus or valgus axis deviation. Patient-specific factors for worse postoperative outcomes after partial meniscectomy and indicators for an “early OA” development were identified, providing the basis for a patient-specific treatment approach. Further analysis in a multicentre study and computational analysis of MRI scans is ongoing to develop a patient-specific treatment algorithm for meniscectomy patients

The development of cytoplasmic processes from in situ chondrocytes is a characteristic feature of early osteoarthritis in human cartilage. The processes involve cytoskeletal elements and are distinct from the short primary cilia described in human chondrocytes. Vimentin is an intermediate filament playing an essential structural and signal-transduction role. We determined cellular levels and distribution of vimentin in chondrocytes of different morphologies in non-degenerate and mildly osteoarthritic cartilage. Femoral heads were obtained after consent from patients undergoing hip arthroplasty following femoral neck fracture. Cartilage explants were graded as non-degenerate (grade 0;G0) or mildly osteoarthritic (grade 1;G1) and labelled with the cytoplasmic dye CMFDA (5-chloromethylfluorescein-diacetate) for cell shape. Explants were cryosectioned and labelled for vimentin by fluorescence immunohistochemistry. In situ chondrocyte morphology was identified by confocal microscopy as either normal (rounded/elliptical) or abnormal (with one or more cytoplasmic process of ≥2µm) and vimentin levels and distribution determined semi-quantitatively and related to chondrocyte morphology. When all cells in G0 and G1 cartilage were compared, there was no difference between average levels of vimentin per cell (P=0.144)[6(261)];femoral heads:cells). When cells were separated on the basis of morphology, there was no difference between vimentin levels in cells with one or more cytoplasmic process compared to those of normal morphology (P>0.05;[6(261)]). However vimentin levels were much greater at the base of cytoplasmic processes compared to distant areas of the same cells (P=0.021)[5(29)]). Although overall levels of chondrocyte vimentin do not change in these early stages of osteoarthritis, the formation and structure of these substantial chondrocyte cytoplasmic processes involves changes to its distribution. These morphological changes are similar to those occurring during chondrocyte de-differentiation to fibroblasts reported in osteoarthritis which results in the formation of mechanically-inferior fibro-cartilage. Alterations to chondrocyte vimentin distribution either directly or indirectly may play a role in cartilage degeneration

Early changes within articular cartilage during human idiopathic osteoarthritis are poorly understood. However alterations to chondrocyte morphology occur with the development of fine cytoplasmic processes and cell clusters, potentially playing a role in cartilage degeneration. The aggrecanase ADAMTS-4 (A disintegrin and metalloproteinase with thrombospondin motifs-4) has been implicated as an important factor in cartilage degradation, so we investigated the relationship between chondrocyte morphology and levels of ADAMTS-4 in both non-degenerate and mildly osteoarthritic human cartilage. Human femoral heads were obtained following consent from patients undergoing hip arthroplasty following femoral neck fracture. Cartilage explants of normal (grade 0; G0) and mildly osteoarthritic (grade 1; G1) cartilage were labelled with the cytoplasmic dye CMFDA (5-chloromethylfluorescein-diacetate). Explants were cryosectioned (30μm sections), and labelled for ADAMTS-4 by fluorescence immunohistochemistry. Sections were imaged with confocal microscopy, allowing the semi-quantitative analysis of ADAMTS-4 and 3D visualisation of in situ cell morphology. With cartilage degeneration from G0 to G1, there was a decrease in the proportion of chondrocytes with normal rounded morphology (P<0.001) but an increase in the proportion of cells with processes (P<0.01) and those in clusters (P<0.001;[4(1653)]; femoral heads:cells). Although average levels of ADAMTS-4 for all cells was the same between G0 and G1 (P>0.05), a change was evident in the distribution curves for cell-specific ADAMTS-4 labelling. Cell-by-cell analysis showed that ADAMTS-4 levels were higher in chondrocytes with cytoplasmic processes compared to normal cells (P=0.044) however cells in clusters had lower levels than normal cells (P=0.003;[3(436)]). Preliminary data suggested that ADAMTS-4 levels increased with larger chondrocyte clusters. These results suggest complex heterogeneous changes to levels of cell-associated ADAMTS-4 with early cartilage degeneration – increasing in cells with processes and initially decreasing in clusters. Increased levels of ADAMTS-4 are likely to produce focal areas of matrix weakness potentially leading to early cartilage degeneration

Introduction. Approximately 20-25% of patients having joint replacement in the UK have moderate-severe frailty. Frailty is associated with poorer outcomes after joint replacement. Targeting frailty pre-operatively with exercise and protein supplementation could improve post-operative outcomes. Prior to conducting a randomised controlled trial (RCT), a feasibility study was necessary to inform trial design and delivery. Method. We conducted a randomised feasibility study with embedded qualitative work. Patients aged ≥65 years, frail and undergoing THR or TKR were recruited from three UK hospitals. Participants were randomly allocated on a 1:1 ratio to the intervention or usual care group. The intervention group had a 1:1 appointment with a physiotherapist and were provided with a home-based, tailored daily exercise programme and a daily protein supplement for 12 weeks before their operation, supported by six telephone calls from a physiotherapist. Questionnaires were administered at baseline and 12 weeks after randomisation. Interviews were conducted with 19 patients. Feasibility outcomes were eligibility and recruitment rates, intervention adherence, and acceptability of the trial and the intervention. Result. 411 patients were sent a screening pack. Of the 168 patients who returned a screening questionnaire, 79 were eligible and consented to participate, and 64 were randomised. Of the 33 participants randomised to the intervention, 26 attended the intervention appointment. Eighteen participants (69%) received all six intervention follow-up telephone calls. Nineteen participants completed an intervention adherence log; 13 (68%) adhered to the exercise programme and 11 (58%) adhered to the protein supplementation. The overall retention rate was 86% at 12 weeks. The 12-week follow-up questionnaire was returned by 84% of participants who were sent a questionnaire. Interviews found that the trial and intervention were generally acceptable, but areas of potential improvements were identified. Conclusion. This study demonstrated that a larger study is possible and has identified improvements to optimise the design of a RCT

Osteomyelitis is an inflammatory condition accompanied by the destruction of bone and caused by an infecting microorganism. Open contaminated fractures can lead to the development of osteomyelitis of the fractured bone in 3-25% of cases, depending on fracture type, degree of soft-tissue injury, degree of microbial contamination, and whether systemic and/or local antimicrobial therapies have been administered. Untreated, infection will ultimately lead to non-union, chronic osteomyelitis, or amputation. We report a case series of 10 patients that presented with post-operative infected non-union of the distal femur with or without prior surgery. The cases were performed at Padmashree Dr. D. Y. Patil Hospital, Nerul, Navi Mumbai, India. All the patients’ consents were taken for the study which was carried out in accordance with the Helsinki Declaration. The methodology involved patients undergoing a two-stage procedure in case of no prior implant or a three-stage procedure in case of a previous implant. Firstly, debridement and implant removal were done. The second was a definitive procedure in form of knee arthrodesis with ring fixator and finally followed by limb lengthening surgery. Arthrodesis was planned in view of infection, non-union, severe arthritic, subluxated knee, stiff knee, non-salvage knee joint, and financial constraints. After all the patients demonstrated wound healing in 3 months along with good radiographic osteogenesis at the knee arthrodesis site, limb lengthening surgeries by tibial osteotomy were done to overcome the limb length discrepancy. Distraction was started and followed up for 5 months. All 10 patients showed results with sound knee arthrodesis and good osteogenesis at the osteotomy site followed by achieving the limb length just 1-inch short from the normal side to achieve ground clearance while walking. Our case series is unique and distinctive as it shows that when patients with infected nonunion of distal femur come with the stiff and non-salvage knee with severe arthritic changes and financial constraints, we should consider knee arthrodesis with Ilizarov ring fixator followed by limb lengthening surgery

Articular cartilage has poor repair potential and the tissue formed is mechanically incompetent. Mesenchymal stromal cells (MSCs) show chondrogenic properties and the ability to re-grow cartilage, however a viable human model for testing cartilage regeneration and repair is lacking. Here, we describe an ex vivo pre-clinical femoral head model for studying human cartilage repair using MSCs. Human femoral heads (FHs) were obtained following femoral neck fracture with ethical permission/patient consent and full-depth cartilage wells made using a 3mm biopsy punch. Pancreas-derived mesenchymal stromal cells (P-MSC) were prepared in culture media at ~5000 cells/20µl and added to each well and leakage prevented with fibrin sealant. After 24hrs, the sealant was removed and medium replaced with StemPro. TM. chondrogenesis differentiation medium. The FHs were incubated (37. o. C;5% CO. 2. ) for 3wks, followed by a further 3wks in standard medium with 10% human serum with regular medium changes throughout. Compared to wells with medium only, A-MSCs produced a thin film across the wells which was excised en-block, fixed with 4% paraformaldehyde and frozen for cryo-sectioning. The cell/tissue films varied in thickness ranging over 20-440µm (82±21µm; mean±SEM; N=3 FHs). The thickness of MSC films abutting the cartilage wells was variable but generally greater (15-1880µm) than across the wells, suggesting an attachment to native articular cartilage. Staining of the films using safranin O (for glycosaminoglycans; quantified using ImageJ) was variable (3±8%; mean±SEM; N=3) but in one experiment reached 20% of the adjacent cartilage. A preliminary assessment of the repair tissue gave an O'Driscoll score of 10/24 (24 is best). These preliminary results suggest the ex vivo femoral head model has promise for studying the capacity of MSCs to repair cartilage directly in human tissue, although optimising MSCs to produce hyaline-like tissue is essential. Supported by the CSO (TCS/17/32)

Arthritis is a common and debilitating disease and is associated with an increased fall risk. The purpose of this study was to examine the effect of impacted joint and limb on fall risk as measured by the margin of stability (MOS). There were 110 participants, including healthy controls (HC; n=30), ankle arthritis (AA; n=30), knee arthritis (KA; n=20) and hip arthritis (HA; n=30) patients. All protocols were Institutional Review Board approved and all participants signed informed consent. Participants walked approximately 6 meters at a self-selected pace. MOS was calculated in the foot coordinate system in the anterior/posterior (AP) and medial/lateral (ML) directions at heel strike. A one-way ANOVA was used to examine group effects (HC, AA, KA, HA) on gait speed. A two-way repeated measures ANOVA was used to examine the effects of limb (Non-Surgical, Surgical) and group on AP and ML MOS. HC had the fastest gait speed (1.40±0.24 m/s; p<0.001) when compared to AA (0.85±0.24 m/s), KA (0.94±0.22 m/s) and HA (1.05±0.22 m/s). HA participants had a greater gait speed compared to AA (p=0.004). AP MOS was greater in the surgical limb compared to the non-surgical limb for AA (p<0.001) and HA (p<0.001). AP MOS was smaller in HC compared to AA, KA, and HA, regardless of limb (p<0.030). AP MOS was similar between AA, KA, and HA for the non-surgical limb (p>0.194) and the surgical limb (p>0.096). ML MOS was greater in the surgical compared to non-surgical limb (p=0.003). ML MOS was smaller in KA participants compared to all other groups (p<0.001). Our results demonstrate stability during gait varies between limbs in arthritis patients, with a more conservative pattern for the surgical limb and suggest KA may be at an increased risk of falls with a smaller ML MOS

Vacuum orthoses are being applied in the care of patients with foot and lower leg conditions, as ankle fractures or sprains. The lower leg is protected and immobilized, which increases mobility. Due to the design, the orthoses lead to a difference in leg length, i.e. the side with the orthosis becomes longer, which changes the gait kinematics. To prevent or mitigate the unfavourable effects of altered gait kinematics, leg length-evening devices (shoe lifts) are offered that are worn under the shoe on the healthy side. Our aim was to evaluate the effect of such a device on the normality of gait kinematics. Gait analysis was conducted with 63 adult, healthy volunteers having signed an informed consent form that were asked to walk on a treadmill at a speed of 4.5km/h in three different conditions:. barefoot - as reference for establishing the normality score baseline. with a vacuum orthosis (VACOPed, OPED GmbH, Germany) and a sport shoe. with a vacuum orthosis and a shoe lift (EVENup, OPED GmbH, Germany). Data was sampled using the gait analysis system MCU 200 (LaiTronic GmbH, Austria). The positions of the joint markers were exported from the software and evaluated for the joint angles during the gait cycle using custom software (implemented in DIAdem 2017, National Instruments). A normality score using a modification of the Gait Profile Score (GPS) was calculated in every 1%-interval of the gait cycle and evaluated with a Wilcoxon signed rank test. The GPS value was reduced by 0.33° (0.66°) (median and IQR) while wearing the shoe lift. The effect was statistically significant, and very large (W = 1535.00, p < .001; r (rank biserial) = 0.52, 95% CI [0.29, 0.70]). The significant reduction of the GPS value indicates a more normal gait kinematics while using the leg length-evening device on the contralateral shoe. This rather simple and inexpensive device thus might improve patient comfort and balance while using the vacuum orthoses

The effects of dexamethasone (dex), during in vitro human osteogenesis, are contrasting. Indeed, dex downregulates SOX9 during osteogenic differentiation of human bone marrow mesenchymal stromal cells (HBMSCs). However, dex also promotes PPARG expression, resulting in the formation of adipocyte-like cells within the osteogenic monolayers. The regulation of both SOX9 and PPARG seems to be downstream the transactivation activity of the glucocorticoid receptor (GR), thus the effect of dex on SOX9 downregulation is indirect. This study aims at determining whether PPAR-γ regulates SOX9 expression levels, as suggested by several studies. HBMSCs were isolated from bone marrow of patients with written informed consent. HBMSCs were cultured in different osteogenic induction media containing 10 or 100 nM dex. Undifferentiated cells were used as controls. Cells were treated either with a pharmacological PPAR-γ inhibitor T0070907 (donors n=4) or with a PPARG-targeting siRNA (donors n=2). Differentiation markers or PPAR-γ target genes were analysed by RT-qPCR. Mineral deposition was assessed by ARS staining. Two-way ANOVA followed by a Tukey's multiple comparison test compared the effects of treatments. At day 7, T0070907 downregulated ADIPOQ and upregulated CXCL8, respectively targets of PPAR-γ-mediated transactivation and transrepression. RUNX2 and SOX9 were also significantly downregulated in absence of dex. PPARG was successfully downregulated by siRNA. ADIPOQ expression was also inhibited, while CXCL8 did not show any significant difference between siRNA treatment groups. RUNX2 was downregulated by the PPARG-siRNA treatment in presence of 100 nM dexamethasone, while SOX9 levels were not affected. ARS showed no change in the mineralization levels when PPARG expression or activity was inhibited. Understanding how dex regulates HBMSC differentiation is of pivotal importance to refine current in vitro models. These results suggest that PPARG does not mediate SOX9 downregulation. Unexpectedly, RUNX2 expression was also unaltered or even downregulated after PPAR-γ inhibition. Acknowledgements: AO Foundation, AO Research Institute (CH) and PRIN 2017 MUR (IT) for financial support

Introduction. Polyacrylamide hydrogel (iPAAG. 1. ), is CE marked for treating symptomatic knee osteoarthritis (OA), meeting the need for an effective, long-lasting, and safe non-surgical option. This study evaluates the efficacy and safety of a single 6 ml intra-articular injection of iPAAG in participants with moderate to severe knee OA over a 5-year post-treatment period, presenting data from the 4-year follow up. Method. This prospective multicentre study (3 sites in Denmark) involved 49 participants (31 females) with an average age of 70 (range 44 – 86 years). They received a single 6 mL iPAAG injection. All participants provided informed consent and re-consented to continue after 1 year. The study followed GCP principles and was approved by Danish health authorities and local Health Research Ethics committees. Twenty-seven participants completed the 4-year follow-up. The study evaluated WOMAC pain, stiffness, function, and Patient Global Assessment (PGA) of disease impact. Changes from baseline were analysed using a mixed model for repeated measurement (MMRM). Sensitivity analyses were applied on the extension data, where the MMRM analysis was repeated only including patients in the extension phase and an ANCOVA model was used, replacing missing values at 4-years with baseline values (BOCF). Results. The planned MMRM analysis (n=49) revealed a statistically significant decrease in WOMAC pain subscale scores (-22.0; 95%CI: -29.5; -14.4) from baseline to 4-years. Analysis of the extension phase (n=27) showed similar results (-21.8; 95%CI: -29.0; -14.6) compared to the initial analysis. Furthermore, BOCF analysis indicated a statistically significant reduction in WOMAC pain subscale scores from baseline (-13.0 units). Four new adverse events were reported between the 3-year and 4-year visits; none were related to treatment. Conclusions. This study shows that single injections of 6 ml intra-articular iPAAG were well tolerated and continued to provide clinically important effectiveness at 4-years after treatment. Acknowledgements. The study was sponsored by Contura International A/S

The purpose of this study is to report the clinical and radiological outcomes of patients undergoing primary or revision reverse total shoulder arthroplasty using custom 3D printed components to manage severe glenoid bone loss with a minimum of 2-year follow-up. After ethical approval (reference: 17/YH/0318), patients were identified and invited to participate in this observational study. Inclusion criteria included: 1) severe glenoid bone loss necessitating the need for custom implants; 2) patients with definitive glenoid and humeral components implanted more than 2 years prior; 3) ability to comply with patient reported outcome questionnaires. After seeking consent, included patients underwent clinical assessment utilising the Oxford Shoulder Score (OSS), Constant-Murley score, American Shoulder and Elbow Society Score (ASES), and quick Disabilities of the Arm, Shoulder, and Hand Score (quickDASH). Radiographic assessment included AP and axial projections. Patients were invited to attend a CT scan to confirm osseointegration. Statistical analysis utilised included descriptive statistics (mean and standard deviation) and paired t test for parametric data. 3 patients had revision surgery prior to the 2-year follow-up. Of these, 2/3 retained their custom glenoid components. 4 patients declined to participate. 5 patients were deceased at the time of commencement of the study. 21 patients were included in this analysis. The mean follow-up was 36.1 months from surgery (range 22–60.2 months). OSS improved from a mean 16 (SD 9.1) to 36 (SD 11.5) (p < 0.001). Constant-Murley score improved from mean 9 (SD 9.2) to 50 (SD 16.4) (p < 0.001). QuickDASH improved from mean 67 (SD 24) to 26 (SD 27.2) (p = 0.004). ASES improved from mean 28 (SD 24.8) to 70 (SD 23.9) (p = 0.007). Radiographic evaluation demonstrated good osseointegration in all 21 included patients. The utility of custom 3D-printed components for managing severe glenoid bone loss in primary and revision reverse total shoulder arthroplasty yields significant clinical improvements in this complex patient cohort