Summary. Metastatic spinal disease is a common entity of much debate in terms of ideal surgical treatment. The introduction of MIS can be a game-changer in the treatment of MSD due to less peri-operative morbidity and allowing earlier radiotherapy and/or chemotherapy. Introduction. Less invasive techniques have always been welcome for management of patients with ‘Metastatic Spinal Disorders’. This is because these patients can be poor candidates for extensive / major invasive surgery even though radiologically, there may be an indication for one. The aim of the treatment with Minimal Invasive Fixation (MIS) systems is mainly for ‘pain relief’ than to radically decrease tumour burden or to achieve near total spinal cord decompression, which could be major presentations in these patients. These procedures address the ‘spinal instability’ very well and they can address pain associated with compression fractures resulting from metastatic disease from a solid organ as well as multiple myeloma with minimal complications. These procedures can be combined with radiology and chemotherapy without much concern for wound problems in the way of infection or dehiscence. They also have a great advantage of timing of adjunct therapy closer to the index procedure. The disadvantage, however, are they do not allow thorough decompression of the spinal cord. There could also be problem in addressing patients who have severe vertebral height loss or loss of integrity of the anterior column where anterior column reconstruction may be required. There is a risk of inadequate fixation or implant loosening or failure. We aim to examine the results of MIS surgery in our department and support the rationale for its use. Patients and Methods. We prospectively collected data of patients who underwent MIS posterior instrumentation for MSD. Between June 2011 and December 2012, 10 patients presented with acute motor deficit, instability and/or threatening radiological features. Effectiveness of MIS was assessed in terms of operative parameters and clinical outcomes. Results. No patient suffered intra-operative complications. The median surgical time was 198 minutes (range: 149 – 403), median blood loss was 100 ml (range: 60 – 400). All patients maintained full neurological function and reported effective pain reduction. All patients were discharged with a median hospital stay was 13 days (range: 4 – 45) post-surgery. 9 patients started oncological treatment as planned. The median time in 7 patients who had radiotherapy post-surgery was 23 days (range: 20 – 40). Chemotherapy was initiated in 4 patients at a median of 9 days post-surgery (range: 6 – 23). No patient as yet has required open procedure due to progression of the disease. Discussion/Conclusion. We have shown that satisfactory outcomes are achievable with MIS in a selected group of patients with MSD. While our results are limited by small study size, we have been able to improve patient quality of living through minimally invasive intervention. By reducing surgical morbidity and enabling early implementation of oncological treatment, MIS has the potential to re-evaluate multi-disciplinary decision making for early surgery in MSD

The application of immune regenerative strategies to deal with unsolved pathologies, such as tendinopathies, is getting attention in the field of tissue engineering exploiting the innate immunomodulatory potential of stem cells [1]. In this context, Amniotic Epithelial Cells (AECs) represent an innovative immune regenerative strategy due to their teno-inductive and immunomodulatory properties [2], and because of their high paracrine activity, become a potential stem cell source for a cell-free treatment to overcome the limitations of traditional cell-based therapies. Nevertheless, these immunomodulatory mechanisms on AECs are still not fully known to date. In these studies, we explored standardized protocols [3] to better comprehend the different phenotypic behavior between epithelial AECs (eAECs) and mesenchymal AECs (mAECs), and to further produce an enhanced immunomodulatory AECs-derived secretome by exposing cells to different stimuli. Hence, in order to fulfill these aims, eAECs and mAECs at third passage were silenced for CIITA and Nrf2, respectively, to understand the role of these molecules in an inflammatory response. Furthermore, AECs at first passage were seeded under normal or GO-coated coverslips to study the effect of GO on AECs, and further exposed to LPS and/or IL17 priming to increase the anti-inflammatory paracrine activity. The obtained results demonstrated how CIITA and Nrf2 control the immune response of eAECs and mAECs, respectively, under standard or immune-activated conditions (LPS priming). Additionally, GO exposition led to a faster activation of the Epithelial-Mesenchymal transition (EMT) through the TGFβ/SMAD signaling pathway with a change in the anti-inflammatory properties. Finally, the combinatory inflammatory stimuli of LPS+IL17 enhanced the paracrine activity and immunomodulatory properties of AECs. Therefore, AECs-derived secretome has emerged as a potential treatment option for inflammatory disorders such as tendinopathies.

Acknowledgement: This research is part of the P4FIT project ESR1, funded under the H2020-ITN-EJD-Marie-Skłodowska-Curie grant agreement 955685.

In the context of regenerative medicine for the treatment of musculoskeletal pathologies mesenchymal stromal cells (MSCs) have shown good results thanks to secretion of therapeutic factors, both free and conveyed within the extracellular vesicles (EV), which in their totality constitute the “secretome”. The portfolio and biological activity of these molecules can be modulated by both in vitro and in vivo conditions, thus making the analysis of these activities very complex. A deep knowledge of the targets regulated by the secretome has become a matter of fundamental importance and a homogeneous and complete molecular characterization is still lacking in the field of applications for the musculoskeletal system. Therefore, the aim of this work was to characterize the secretome obtained from adipose-derived MSCs (ASCs), and its modulation after pre-conditioning of the ASCs. Pre-conditioning was done by culturing cells in the presence of i) high levels of IFNγ, as proposed for the production of clinical grade secretome with enhanced regenerative potential, ii) low levels of inflammatory stimuli, mimicking conditions found in the osteoarthritis (OA) synovial fluid. Furthermore, EVs ability to migrate within cartilage, chondrocyte and synoviocytes obtained from OA patients was evaluated.

The data showed that more than 50 cytokines / chemokines and more than 200 EV-microRNAs are detectable at various intensity levels in ASCs secretomes. The majority of the most abundantly present molecules are involved in the remodelling of the extracellular matrix and in the homeostasis and chemotaxis of inflammatory cells including macrophages, which in OA are often characterized by an M1 inflammatory polarization, promoting their transition to an M2 anti-inflammatory phenotype. Inflammatory priming with IFNγ and synovial fluid-like conditions were able to further increase the ability of the secretome to interact with inflammatory cells and modulate their migration. Finally, the penetration of the EVs in the cartilage explants resulted a rapid process, which begins a few minutes after administration of the EVs that are able to reach a depth of 30-40 μm in 5 hours. The same capacity for interaction was also verified in chondrocytes and synoviocytes isolated from the cartilage and synovial membrane of OA patients.

Thanks to the soluble factors and EV-microRNAs, the ASCs secretome has shown a strong propensity to modulate the inflammatory and degenerative processes that characterize OA. The inflammatory pre-conditioning through high concentrations of inflammatory molecules or in conditions similar to the synovial fluid of OA patients was able to increase this capacity by increasing their chemotactic power. The microscopy data also support the hypothesis of the ability of MSC-EVs to influence the chondrocytes residing in the ECM of the cartilage and the synovial cells of the synovial membrane through active interaction and the release of their therapeutic content.

Introduction and Objective

Dislocation of a hip hemiarthroplasty is a significant complication with a high mortality rate in elderly patients. Previous studies have shown a higher risk of dislocation in patients with neuromuscular conditions. In this study, we reviewed our larger cohort of patients to identify if there is a link between neuromuscular disorders and dislocation of hip hemiarthroplasty in patients with neuromuscular conditions.

Abstract

Introduction and Objective

The use of microfragmented adipose tissue (mFAT) for the treatment of musculoskeletal disorders, especially osteoarthritis, is gaining popularity following the positive results reported in recent case series and clinical trials. The purpose of this study is to characterize mFAT in terms of structure, cell content and secretome (i.e. protein and microvescicles released as paracrine mediators), and to compare it with unprocessed lipoaspirate tissue, in order to understand the possible mechanisms of action and the benefit derived from tissue processing.

The future of work brings several challenges and opportunities for occupational health and safety on three major drivers: the rapid progress of technological innovation; demographic changes, in particular ageing of the workforce and migration; and changes in the labour market, especially owing to new ways of per-forming jobs. Innovation technologies are leading to an overall transformation of industrial processes that offer huge developmental perspectives in the world of work and opportunities for society. In the field of prevention of musculoskeletal disorders, relevant progresses have been made in the clinical setting and in the context of care, also in relation to the ageing society. In the near future, the adaptation of workstations and the implementation of sensors and enabling technologies (collaborative robots and exoskeletons) will offer, together with the innovations in the clinic and orthopaedic surgery, a significant contribution to the reduction of risks from biomechanical overload, as well as support interventions to increase work ability and reduce the impact of disability. However, the potential risk scenarios for health and safety in the workplace, along with the progress in occupational health research, lead to the need for creating an inte-grated system of skills and approaches to adopt a Prevention through Design perspective. This requires designing and conceiving processes taking into consideration occupational risk prevention and guarantee-ing the return to work in a multidisciplinary and integrated perspective.

Background/Purpose of study

The increasing aging of the population will see a growing number of patients presenting for spine surgery with appropriate indications but numerous medical comorbidities. This complicates decision-making, requiring that the likely benefit of surgery (outcome) be carefully weighed up against the potential risk (complications). We assessed the influence of comorbidity on the risks and benefits of spine surgery.

Objectives. This study reports on a secondary exploratory analysis of the early clinical outcomes of a randomised clinical trial comparing robotic arm-assisted unicompartmental knee arthroplasty (UKA) for medial compartment osteoarthritis of the knee with manual UKA performed using traditional surgical jigs. This follows reporting of the primary outcomes of implant accuracy and gait analysis that showed significant advantages in the robotic arm-assisted group. Methods. A total of 139 patients were recruited from a single centre. Patients were randomised to receive either a manual UKA implanted with the aid of traditional surgical jigs, or a UKA implanted with the aid of a tactile guided robotic arm-assisted system. Outcome measures included the American Knee Society Score (AKSS), Oxford Knee Score (OKS), Forgotten Joint Score, Hospital Anxiety Depression Scale, University of California at Los Angeles (UCLA) activity scale, Short Form-12, Pain Catastrophising Scale, somatic disease (Primary Care Evaluation of Mental Disorders Score), Pain visual analogue scale, analgesic use, patient satisfaction, complications relating to surgery, 90-day pain diaries and the requirement for revision surgery. Results. From the first post-operative day through to week 8 post-operatively, the median pain scores for the robotic arm-assisted group were 55.4% lower than those observed in the manual surgery group (p = 0.040). At three months post-operatively, the robotic arm-assisted group had better AKSS (robotic median 164, interquartile range (IQR) 131 to 178, manual median 143, IQR 132 to 166), although no difference was noted with the OKS. At one year post-operatively, the observed differences with the AKSS had narrowed from a median of 21 points to a median of seven points (p = 0.106) (robotic median 171, IQR 153 to 179; manual median 164, IQR 144 to 182). No difference was observed with the OKS, and almost half of each group reached the ceiling limit of the score (OKS > 43). A greater proportion of patients receiving robotic arm-assisted surgery improved their UCLA activity score. Binary logistic regression modelling for dichotomised outcome scores predicted the key factors associated with achieving excellent outcome on the AKSS: a pre-operative activity level > 5 on the UCLA activity score and use of robotic-arm surgery. For the same regression modelling, factors associated with a poor outcome were manual surgery and pre-operative depression. Conclusion. Robotic arm-assisted surgery results in improved early pain scores and early function scores in some patient-reported outcomes measures, but no difference was observed at one year post-operatively. Although improved results favoured the robotic arm-assisted group in active patients (i.e. UCLA ⩾ 5), these do not withstand adjustment for multiple comparisons. Cite this article: M. J. G. Blyth, I. Anthony, P. Rowe, M. S. Banger, A. MacLean, B. Jones. Robotic arm-assisted versus conventional unicompartmental knee arthroplasty: Exploratory secondary analysis of a randomised controlled trial. Bone Joint Res 2017;6:631–639. DOI: 10.1302/2046-3758.611.BJR-2017-0060.R1