Introduction and Objective. The effectiveness of anti-embolic graduated compression stockings (GCSs) has recently been questioned. The aim of this study is to systematically review all the relevant randomised controlled trials published to date. Materials and Methods. We systematically reviewed all the randomised controlled trials comparing anti-embolism stockings with no stockings. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and CINAHL, Cochrane Musculoskeletal Injuries Group specialized register and the reference lists of articles as well as hand search results. Trials were independently assessed and data for the main outcome measures; deep vein thrombosis (DVT), pulmonary embolism and skin ulceration, were extracted by two reviewers. Results. A total of 26 relevant RCTs involving 8279 participants were systematically reviewed. The occurrence of deep vein thrombosis was 306/4159 (7.3%) with the stocking to 492/4120 (11.9%) without the stockings (RR 0.49, 95% CI 0.39–0.62). The occurrence of pulmonary embolism was also reduced from 1.2% to 0.7% (95% 0.33–0.92). This initial finding was unsound due to the potential underreporting of negative studies and the subsequent changes to clinical practice. For the three large contemporary studies involving 5171 participants, these failed to show any statistically significant reduction in thrombosis, with DVT confirmed in 158 (6.1%) participants in those allocated to stocking, as opposed to 171 (6.6%) in the control group. Conclusions. The current recommendations regarding the use of thrombo-embolic stockings need to be reconsidered, as their effectiveness at reducing the occurrence of post-operative deep vein thrombosis is minimal at best, based on the current evidence and clinical practices

Abstract. BACKGROUND. The effectiveness of anti-embolic graduated compression stockings (GCSs) has recently been questioned. The aim of this study is to systematically review all the relevant randomised controlled trials published to date. PATIENTS AND METHODS. We systematically reviewed all the randomised controlled trials comparing anti-embolism stockings with no stockings. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and CINAHL, Cochrane Musculoskeletal Injuries Group specialized register and the reference lists of articles as well as hand search results. Trials were independently assessed and data for the main outcome measures; deep vein thrombosis (DVT), pulmonary embolism and skin ulceration, were extracted by two reviewers. RESULTS. A total of 26 relevant RCTs involving 8279 participants were systematically reviewed. Theoccurrence of deep vein thrombosis was 306/4159(7.3%) with the stocking to 492/4120(11.9%) without the stockings (RR 0.49, 95% CI 0.39–0.62). The occurrence of pulmonary embolism was also reduced from 1.2% go 0.7% (95% 0.33–0.92). This initial finding was unsound due to the potential underreporting of negative studies and the subsequent changes to clinical practice. For the three large contemporary studies involving 5171 participants, these failed to show any statistically significant reduction in thrombosis, with DVT confirmed in 158(6.1%) participants in those allocated to stocking, as opposed to 171(6.6%) in the control group. CONCLUSION. The current recommendations regarding the use of GCSs need to be reconsidered, as their effectiveness at reducing the occurrence of post-operative DVT is minimal at best, based on the current evidence and clinical practices

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

An increased number of neutrophils (NEUs) has long been associated with infections in the knee joints; their contribution to knee osteoarthritis (KOA) pathophysiology remains largely unexplored. This study aimed to compare the phenotypic and functional characteristics of synovial fluid (SF)-derived NEUs in KOA and knee infection (INF). Flow cytometric analysis, protein level measurements (ELISA), NEU oxidative burst assays, detection of NEU phagocytosis (pHrodo. TM. Green Zymosan Biparticles. TM. Conjugate for Phagocytosis), morphological analysis of the SF-derived/synovial tissue NEUs, and cultivation of human umbilical vein endothelial cells (HUVECs) using SF supernatant were used to characterise NEUs functionally/morphologically. Results: Compared with INF NEUs, KOA NEUs were characterised by a lower expression of CD11b, CD54 and CD64, a higher expression of CD62L, TLR2 and TLR4, and lower production of inflammatory mediators and proteases, except CCL2. Functionally, KOA NEUs displayed an increased production of radical oxygen species and phagocytic activity compared with INF NEUs. Morphologically, KOA and INF cells displayed different cell sizes and morphology, histological characteristics of the surrounding synovial tissues and influence on endothelial cells. KOA NEUs were further subdivided into two groups: SF containing <10% and SF with 10%–60% of NEUs. Analyses of two KOA NEU subgroups revealed that NEUs with SF <10% were characterised by 1) higher CD54, CD64, TLR2 and TLR4 expression on their surface; 2) higher concentrations of TNF-α, sTREM-1, VILIP-1, IL-1RA and MMP-9 in SFs. Our findings reveal a key role for NEUs in the pathophysiology of KOA, indicating that these cells are morphologically and functionally different from INF NEUs. Further studies should explore the mechanisms that contribute to the increased number of NEUs and their crosstalk with other immune cells in KOA. This study was supported by the Ministry of Health of the Czech Republic (NU20-06-00269; NU21-06-00370)

Successful application of patient derived cells to engineer vascularized bone grafts is often hampered by low cell numbers and lengthy in vitro expansion. With sound induced morphogenesis (SIM), local cell density enhancement was shown to improve microvasculature formation at lower cell concentration than conventional methods [1]. SIM takes advantage of hydrodynamic forces that act on cells to arrange them within a hydrogel. Following, we are evaluating the potential of cell-hydrogel biografts with high local cell density to improve the therapeutic efficacy in clinical scenarios such as anastomosis or bone formation within non-union fractures. To assess anastomosis, human umbilical vein endothelial cells (HUVEC) and human mesenchymal stromal cells (MSC) were mixed at a 1:1 ratio in PEG-based or Dextran-based hydrogels at a final concentration of 2×10. 6. cells×mL. -1. For ectopic bone formation, MSC were resuspended in PEG-based hydrogels at 2×10. 6. or 5×10. 6. cells×mL. -1. , with or without BMP-2. Cells were assembled into distinct patterns at a frequency of 60 Hz. Four biografts of 4 × 9 mm. 2. were implanted at the back of nude mice (total of 7 animals) and harvested after 2 or 8 weeks. Explants were fixed and imaged as whole constructs or embedded in paraffin for histological analysis. Upon explantation, microscopic evaluation indicated that HUVEC were retained within the PEG-hydrogel after 2 weeks and formed a pre-vascular network. In the second study, ectopic bone formation was more pronounced in areas of higher local cell density based on visual inspection. Ongoing experiments are further characterizing bone formation by micro-CT and histological evaluation. Our results indicate that local cell density enhancement by sound requires a lower initial cell concentration than conventional, static seeding methods to achieve comparable microvasculature structures or local osteogenesis

Introduction. Endochondral ossification (EO) is the process of bone development via a cartilage template. It involves multiple stages, including chondrogenesis, mineralisation and angiogenesis. Importantly, how cartilage mineralisation affects angiogenesis during EO is not fully understood. Here we aimed to develop a new in vitro co-culture model to recapitulate and study the interaction between mineralised cartilage generated from human mesenchymal stromal cells (hMSCs) and microvascular networks. Method. Chondrogenic hMSC pellets were generated by culture with transforming growth factor (TGF)-β3. For mineralised pellets, β-glycerophosphate (BGP) was added from day 7 and TGF-β3 was withdrawn on day 14. Conditioned medium (CM) from the pellets was used to evaluate the effect on human umbilical vein endothelial cells (HUVECs) in migration, proliferation and tube formation assays. To perform direct co-cultures, pellets were embedded in fibrin hydrogels containing vessel-forming cells (HUVECs, adipose stromal cells) for 10 days with BGP to induce mineralisation. The pellets and hydrogels were characterised by immunohistochemistry and confocal imaging. Result. The CM from d14 chondrogenic or mineralised pellets significantly stimulated HUVEC migration and proliferation, as well as in vitro vascular network formation. When CM from pellets subjected to prolonged mineralisation (d28) was used, these effects were strongly reduced. When chondrogenic and mineralised pellets were directly co-cultured with vessel-forming cells in fibrin hydrogels, the cartilage matrix (collagen type II/X stainings) and the mineral deposition (von Kossa staining) were well preserved. Confocal imaging analyses demonstrated the formation of microvascular networks with well-formed lumina. Importantly, more microvascular structures were formed in the proximity of chondrogenic pellets than mineralized pellets. Conclusion. The angiogenic properties of tissue engineered cartilage are significantly reduced upon prolonged mineralisation. We developed a 3D co-culture model to study the role of angiogenesis in endochondral bone formation, which can have applications in disease modelling studies

Introduction. As per national guidelines for Ankle fractures in the United Kingdom, fractures considered stable can be treated with analgesia, splinting and allowed to weight bear as tolerated. The guidelines also suggest further follow-up not mandatory. This study was aimed at evaluating the current clinical practice of managing stable ankle fractures at a university hospital against national guidelines. Method. The study was undertaken using retrospectively collected data, the inclusion criteria being all adults with stable ankle fracture pattern treated non-operatively between December 2022 and April 2023. Collected data included age of patient, date of injury, type of immobilization, number of clinical visits and any complications. Results. 41 cases were identified and analyzed. The mean age of the cohort was 49.8 years (Standard deviation 20.01). Twelve percent (n = 5) were reviewed in clinic, treated and discharged as stable Weber B type fracture pattern as per national guidelines after the first visit. About 52% (n = 21) were seen in clinic twice before discharge, first visit between 1-2 weeks and the last clinic visit between 5-7 weeks. About a third of patients (30%, n = 12) were seen in clinic on more than two occasions. At the first clinic visit 87% (n = 36) were given a boot and allowed to weight bear as tolerated. Two patients were diagnosed with deep vein thrombosis/pulmonary embolism during the treatment duration. Three patients had extended duration of follow up for ongoing symptoms. None discharged after first or second visit needed surgery for displaced or malunited fracture. Conclusion. Patients discharged from clinic after first or second visit did not need any further surgery. As per national guidelines, patients deemed stable weber B lateral malleolus fracture pattern after weight bearing radiograph can be treated safely with a weight bearing walking boot with no further follow up

Abstract. Objective. Meta-analysis of clinical trials highlights that non-operative management of degenerative knee meniscal tears is as effective as surgical management. Surgical guidelines though support arthroscopic partial meniscectomy which remains common in NHS practice. Physiotherapists are playing an increasing role in triage of such patients though it is unclear how this influences clinical management and patient outcomes. Methods. A 1-year cohort (July 2019–June 2020) of patients presenting with MRI confirmed degenerative meniscal tears to a regional orthopaedic referral centre (3× ESP physiotherapists) was identified. Initial clinical management was obtained from medical records alongside subsequent secondary care management and routinely collected outcome scores in the following 2-years. Management options included referral for surgery, conservative (steroid injection and rehabilitation), and no active treatment. Outcome scores collected at 1- and 2-years included the Forgotten Joint Score-12 (FJS-12) questionnaire and 0–10 numerical rating scales for worst and average pain. Treatment allocation is presented as absolute and proportional figures. Change in outcomes across the cohort was evaluated with repeated measures ANOVA, with Bonferroni correction for multiple testing, and post-hoc Tukey pair-wise comparisons. As treatment decision is discrete, no direct contrast is made between outcomes of differing interventions but additional explorative outcome change over time evaluated by group. Significance was accepted at p=0.05 and effect size as per Cohen's values. Results. 81 patients, 50 (61.7%) male, mean age 46.5 years (SD13.13) presented in the study timeframe. 32 (40.3%) received conservative management and 49 (59.7%) were listed for surgery. Six (18.8%) of the 32 underwent subsequent surgery and nine of the 49 (18.4%) patients switched from planned surgery to receiving non-operative care. Two post-operative complications were noted, one cerebrovascular accident and one deep vein thrombosis. The cohort improved over the course of 2-years in all outcome measures with improved mean FJS-12 (34.36 points), mean worst pain (3.74 points) average pain (2.42 points) scores. Overall change (all patients) was statistically significant for all outcomes (p<0.001), with sequential year-on-year change also significant (p<0.001). Effect size of these changes were large with all Cohen-d values over 1. Controlling for age and BMI, males reported superior change in FJS-12 (p=0.04) but worse pain outcomes (p<0.03). Further explorative analysis highlighted positive outcomes across all surgical, conservative and no active treatment groups (p<0.05). The 15 (18%) patients that switched between surgical and non-surgical management also reported positive outcome scores (p<0.05). Conclusion(s). In a regional specialist physiotherapy-led soft tissue knee clinic around 60% of degenerative meniscal tears assessed were referred for surgery. Over 2-years, surgical, non-operative and no treatment management approaches in this cohort all resulted in clinical improvement suggesting that no single strategy is effective in directly treating the meniscal pathology, and that perhaps none do. Clinical intervention rather is directed at individual symptom management based on clinical preferences. 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

Abstract. Objectives. to evaluate the efficacy and safety of topically applied tranexamic acid (TXA) in thoracolumbar spinal tuberculosis surgery, posterior approach. Methods. Thoracolumbar spine tuberculosis patients who requiring debridement, pedicle screw fixation and fusion surgery were divided into two groups. In the TXA group (n=50), the wound surface was soaked with TXA (1 g in 100 mL saline solution) for 3 minutes after exposure, after decompression, and before wound closure, and in the control group (n=116) using only saline. Intraoperative blood loss, drain volume 48 hours after surgery, amount of blood transfusion, transfusion rate, the haemoglobin, haematocrit after the surgery, the difference between them before and after the surgery, incision infection and the incidence of deep vein thrombosis between the two groups. Results. EBL for the control group was 783.33±332.71 mL and for intervention group 410.57±189.72 mL (p<0.001). The operative time for control group was 3.24±0.38 hours and for intervention group 2.99±0.79 hours (p<0.695). Hemovac drainage on days1 and 2 for control group was 167.10±53.83mL and 99.33±37.5 mL, respectively, and for intervention group 107.03±44.37mL and 53.38±21.99mL, respectively (p<0.001). The length of stay was significantly shorter in the intervention group (4.8±1.1 days) compared to control group (7.0±2.3 days). There was bo different in incision side infection and DVT. Conclusions. Topical TXA is a viable, cost-effective method of decreasing perioperative blood loss in major spine surgery with fewer overall complications than other methods. Further studies are required to find the ideal dosage and timing

Abstract. Purpose. It is becoming apparent that mesenchymal stem cells (MSCs) do not directly contribute to mesenchymal tissue regeneration. Pre-clinical attempts to repair large bone defects in big animal models have been hampered by poor MSCs survival after implantation which impedes their direct or indirect effects. Based on previous work, we hypothesized that a venous axial vascularization of the scaffold supporting MSCs or their combination with fresh bone marrow (BM) aspirate would improve their in vivo survival. Methods. Cross-shape profile tubular microporous monetite implants (12mm long, 5mm large) as two longitudinal halves were produced by 3D powder printing. They were implanted around the femoral veins of Wistar rats and loaded with 1mL of BM aspirate either alone or supplemented by 10. 7. MSCs. This was compared with BM-free scaffolds loaded only with 10. 7. MSCs. After 8 weeks bone formation were investigated by micro-CT, scanning electron microscopy, histology and immunohistochemistry. Results. Little bone formation was observed within the scaffold when it was only loaded with MSCs surprisingly. Coupling MSCs, autologous BM and venous perfusion of the scaffold led to a higher volume of new bone than BM alone suggesting that MSCs augmented the bone formation capacity of BM aspirate or enhanced its survival post implantation. Conclusion. Subcutaneous bone formation within 3D-printed implant that mixed of BM with or without MSCs was successfully achieved for the first time by venous perfusion. The inability of MSCs to form differentiated tissues by their own was confirmed in this study; however, contact between MSCs and BM cells and MSCs paracrine secretome (e.g., cytokines, chemokines, extracellular vesicles) may have induced immunomodulatory effects (e.g., macrophages polarization, Treg cells) that triggered bone formation. This approach, if translatable to large animal models, offers immediate clinical value as well as an insight into the role of immune system in tissue regeneration. 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

Background. Charcot neuropathic osteoarthropathy is a rare, destructive process affecting the bones and joints of feet in patients with diabetic peripheral neuropathy. The aetiology of Charcot remains unknown, although it has been suggested that it is triggered by the occurrence of inflammation in the foot of a susceptible individual, and that the inflammation results in increased osteoclastic activity. Hypothesis. The increased bone turnover in acute Charcot is associated with increased concentrations of pro-inflammatory cytokines, related signalling peptides and bone turnover markers. Methods. 17 patients newly presenting with acute Charcot in diabetes and 16 non-diabetic patients without neuropathy undergoing elective forefoot surgery provided informed consented to participate. Samples of bone were taken by needle biopsy, and were stained with H&E to determine bone architecture and bone remodelling. Serum ALP, CTX, OPG and sRANKL TNF, IL1-beta, IL6 and CRP were measured by immunoassay. Blood was taken from the dorsal foot vein of both the affected and the unaffected foot, as well as an antecubital vein. Results. Classic histopathology features of fracture and bone remodelling were evident in Charcot bone biopsies. Systemic circulating concentrations in the Charcot group antecubital vein for both IL6 and OPG were significantly greater than in controls (p<0.05). There were no significant differences between the dorsal vein concentrations of any analyte when the affected and unaffected feet were compared. However, in patients with an acute Charcot foot the concentration of OPG, ALP and CTX was higher in sera from the dorsal vein of affected foot when compared to controls (p<0.05), this difference was highly significant for IL6 (p<0.001). Conclusion. The elevation in CTX observed in the affected foot in patients with an acute Charcot foot reflects the bone breakdown and remodelling which is present. The higher circulating concentration of IL-6 in the Charcot patient group, reflects the inflammation which is present and which is thought to be central to the development of the condition. Although OPG values were significantly greater in Charcot than control group, circulating concentrations of OPG are known to be higher in diabetes

The aim of the study is to determine the histological, biochemical, and biomechanical efficacy of fibrin clot and vitamin C in the healing of Achilles tendon ruptures (ATR) in a rat model.52 adult Wistar Albino rats (300–450 g) were used in the study. 12 groups were divided into four groups as Monitor (Group I), Control (Group II), Fibrin Clot (Group III), Fibrin Clot with vitamin C (Group IV). Four rats were used to obtain fibrin clots. Fibroblast Growth Factor (FGF) and Vascular Endothelial Growth Factor (VEGF) were measured in the blood of tail vein (1 cc) on the 3rd, 7th, 14th, and 21st day. Four rats were sacrificed on the 21st day from each group for histological evaluation. The rest of the rats were sacrificed at 42nd day, half for biomechanical and a half for histological evaluation. The 42nd-day HSS scores in group III and group IV were significantly lower than those of group I and group II (p =0.036 and 0.019; respectively). The 42nd-day HSS score of group IV was significantly lower than group III (p =0.036). The Maximum force N value of group III and group IV was significantly higher than those of group I and group II (p <0.05). Group IV showed a significantly higher Maximum force N value than group III (p =0.025). The blood FGF and VEGF levels of group III and group IV on the 3rd, 7th, 14th, and 21st days were higher than those of group I and group II (p <0.05). In the experimentally formed ATR model, fibrin clot and vitamin C produced a stronger tendon structure in terms of biomechanics while providing histological and biochemically better quality tendon healing in the surgical treatment of ATR. We believe that this model can be used to accelerate high-quality tendon healing after ATR

Venous Thromboembolism (VTE) prophylaxis is an essential part of orthopaedic surgeries in preventing life-threatening thromboembolic events such as Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE). Orthopaedic surgery has the highest incidence rate of thromboembolic events as compared to any other surgical specialities, making it an essential component in managing any orthopaedic case. At Queen's Medical Centre (QMC), a major trauma centre in the United Kingdom (UK), sees up to 750 NOF fracture cases annually, making it one of the busiest trauma and orthopaedic centres in the UK. Our study aims to evaluate how VTE Prophylaxis is conducted in a UK Major Trauma Centre for NOF and pelvic fragility fractures and how human factors can improve its efficacy. The Nottingham University Hospitals (NUH) Trust has implemented new guidelines from August 2019 that patients with fragility fractures such as NOF and pelvic fractures are prescribed with 28 days VTE prophylaxis with Enoxaparin, or their own anti-coagulants if risk of thrombosis exceed the risk of bleeding. This is an adaptation from the trust to align their guidelines closer to the NICE 2018 guidelines. We will be evaluating the initial compliance of VTE Prophylaxis, identify and utilise human factors, then re-analyse the department after implementing interventions on the same batch of junior doctors working in the department. Data of 100 patients with fragility fractures were collected, 50 consecutive patients in the pre-intervention window during August 2019 and 50 in the post-intervention window during November 2019. The pre-intervention data had 43 NOF and 7 Pelvic fractures. Our study showed that 93% of NOF fracture and 100% of pelvic fracture received the correct course of VTE prophylaxis. The data was presented at the local department junior doctor academic session. Three simple human factor interventions were implemented over the course of September and October: Education to the trauma and orthopaedic department on the new guideline, extended VTE labels on drug charts for patients with fragility fractures, VTE reminder labels at doctors' stations. Another 50 consecutive patients' data were collected during November 2019. Data shows that 97.8% of NOF (p>0.05) and 60% of pelvic fracture (p>0.05) received the correct course of VTE prophylaxis. Our data has shown an increase in correct VTE prescription for NOF fracture patients, which is the main bulk of our fragility fracture patients whilst we see a drop in pelvic fracture patients. Due to the limited time frame of four months where junior doctors in the UK rotate between specialities, we are only able to collect data during the first month, implement interventions between datasets and collect data on the final month of the four-month rotation. A future bigger study might provide a more significant result on the department. We believe that the key to achieving 100% VTE prophylaxis in the T&O department is optimising human factors, educating junior doctors, who are not orthopaedic trained, with sufficient information of the guidelines, and evidence of the risk and benefits of providing prolonged VTE prophylaxis for orthopaedic patients. In conclusion, we found that QMC, a major trauma centre with high patient volume and turnover, has a high level of compliance with VTE prophylaxis for fragility fractures and it is imperative that utilising human factors will inch the department closer to its goal of 100% VTE compliance

After big loos of substances of peripheral nerves, in order to connect proximal with distal stump, it is possible to use, in alternative to autologous grafting, different kind of conduits. The chitosan conduit and the muscle in vein technique showed very good results in pre clinical and clinical settings. We compared in this study the efficacy of empty chitosan conduit versus chitosan conduit enriched with fresh muscle fibbers (MIT) to improve peripheral nerve regeneration. The median nerve of rat was repaired by means of empty chitosan conduit or MIT (nerve gam 6mm, conduit length 10 mm). As control group we used auto grafting technique. We performed analysis at short term (7,14,28 days) and at long term (12 weeks) in order to register bimolecular modification (quantitative real time PCRand western blot), morphological modification (optic and electronic microscope) and functional changing (grasping test). Bimolecular analysis showed that muscle fibbers produced and released Neuregulin1, needed for regeneration and activity of Schwann cells. Otherwise also the autograft product Neuregulin1, instead no production was observed in empty conduit. So muscle fibbers compensate this fact. Morphological analysis showed that the first myelinc fibbers appear in MIT after 14 days, but not in empty tube. The results of our work are very interesting because can merge the easiness of the implantation of chitosan tube and the efficacy of fresh muscle fibbers, as previously demonstrated by muscle in vein technique. From a clinical point of view this procedure could be an alternative to auto grafting that is nowadays the gold standard for nerve repair, but present soma disadvantages

The Cochrane Collaboration has produced five new reviews relevant to bone and joint surgery since the publication of the last Cochrane Corner These reviews are relevant to a wide range of musculoskeletal specialists, and include reviews in Morton’s neuroma, scoliosis, vertebral fractures, carpal tunnel syndrome, and lower limb arthroplasty.

Objectives. Regenerative medicine is an emerging field aimed at the repair and regeneration of various tissues. To this end, cytokines (CKs), growth factors (GFs), and stem/progenitor cells have been applied in this field. However, obtaining and preparing these candidates requires invasive, costly, and time-consuming procedures. We hypothesised that skeletal muscle could be a favorable candidate tissue for the concept of a point-of-care approach. The purpose of this study was to characterize and confirm the biological potential of skeletal muscle supernatant for use in regenerative medicine. Methods. Semitendinosus muscle was used after harvesting tendon from patients who underwent anterior cruciate ligament reconstructions. A total of 500 milligrams of stripped muscle was minced and mixed with 1 mL of saline. The collected supernatant was analysed by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The biological effects of the supernatant on cell proliferation, osteogenesis, and angiogenesis in vitro were evaluated using human mesenchymal stem cells (hMSCs) and human umbilical cord vein endothelial cells (HUVECs). Results. The supernatant contained several GFs/CKs, with especially high levels of basic fibroblast growth factor, and CD34+ cells as the stem/progenitor cell fraction. With regard to biological potential, we confirmed that cell proliferation, osteoinduction, and angiogenesis in hMSCs and HUVECs were enhanced by the supernatant. Conclusions. The current study demonstrates the potential of a new point-of-care strategy for regenerative medicine using skeletal muscle supernatant. This attractive approach and readily-available material could be a promising option for tissue repair/regeneration in the clinical setting. Cite this article: M. Yoshikawa, T. Nakasa, M. Ishikawa, N. Adachi, M. Ochi. Evaluation of autologous skeletal muscle-derived factors for regenerative medicine applications. Bone Joint Res 2017;6:277–283. DOI: 10.1302/2046-3758.65.BJR-2016-0187.R1

Objectives. We have increased the dose of tranexamic acid (TXA) in our enhanced total joint recovery protocol at our institution from 15 mg/kg to 30 mg/kg (maximum 2.5 g) as a single, intravenous (IV) dose. We report the clinical effect of this dosage change. Methods. We retrospectively compared two cohorts of consecutive patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) surgery in our unit between 2008 and 2013. One group received IV TXA 15 mg/kg, maximum 1.2 g, and the other 30 mg/kg, maximum 2.5 g as a single pre-operative dose. The primary outcome for this study was the requirement for blood transfusion within 30 days of surgery. Secondary measures included length of hospital stay, critical care requirements, re-admission rate, medical complications and mortality rates. Results. A total of 1914 THA and 2537 TKA procedures were evaluated. In THA, the higher dose of TXA was associated with a significant reduction in transfusion (p = 0.02, risk ratio (RR) 0.74, 95% confidence interval (CI) 0.58 to 0.96) and rate of re-admission (p < 0.001, RR 0.50, 95% CI 0.35 to 0.71). There were reductions in the requirement for critical care (p = 0.06, RR 0.55, 95% CI 0.31 to 1.00), and in the length of stay from 4.7 to 4.3 days (p = 0.02). In TKA, transfusion requirements (p = 0.049, RR 0.64, 95% CI 0.41 to 0.99), re-admission rate (p = 0.001, RR 0.56, 95% CI 0.39 to 0.80) and critical care requirements (p < 0.003, RR 0.34, 95% CI 0.16 to 0.72) were reduced with the higher dose. Mean length of stay reduced from 4.6 days to 3.6 days (p < 0.01). There was no difference in the incidence of deep vein thrombosis, pulmonary embolism, gastrointestinal bleed, myocardial infarction, stroke or death in THA and TKA between cohorts. Conclusion. We suggest that a single pre-operative dose of TXA, 30 mg/kg, maximum 2.5g, results in a lower transfusion requirement compared with a lower dose in patients undergoing elective primary hip and knee arthroplasty. However, these findings should be interpreted in the context of the retrospective non-randomised study design. Cite this article: R. J. M. Morrison, B. Tsang, W. Fishley, I. Harper, J. C. Joseph, M. R. Reed. Dose optimisation of intravenous tranexamic acid for elective hip and knee arthroplasty: The effectiveness of a single pre-operative dose. Bone Joint Res 2017;6:499–505. DOI: 10.1302/2046-3758.68.BJR-2017-0005.R1

This edition of Cochrane Corner looks at some of the work published by the Cochrane Collaboration, covering pharmacological interventions for the prevention of bleeding in people undergoing definitive fixation or joint replacement for hip, pelvic, and long bone fractures; interventions for reducing red blood cell transfusion in adults undergoing hip fracture surgery: an overview of systematic reviews; and pharmacological treatments for low back pain in adults: an overview of Cochrane Reviews

We examined the roles of methylmethacrylate (MMA) monomer and cementing technique in the formation, and haemodynamic outcome, of pulmonary fat emboli. The preparation of the femoral canal and the cementing technique were studied in four groups of adult dogs as follows: control (no preparation); lavage; cement pressurisation; and cement pressurisation after lavage. We measured the intramedullary pressure, pulmonary artery pressure (PAP), pulmonary capillary wedge pressure and bilateral femoral vein levels of triglyceride, cholesterol and MMA monomer at rest and after reaming, lavage, and cementing. Femoral vein triglyceride and cholesterol levels did not vary significantly from resting levels despite significant elevations in intramedullary pressure with reaming, lavage and cementing (p = 0.001). PAP was seen to rise significantly with reaming (p = 0.0038), lavage (p = 0.0031), cementing (p = 0.0024) and cementing after lavage (p = 0.0028) while the pulmonary capillary wedge pressure remained unchanged. MMA monomer was detected in femoral vein samples when cement pressurisation was used. Intramedullary lavage before cementing had no significant effect on the MMA level. Haemodynamic evidence of pulmonary embolism was noted with reaming and intramedullary canal preparation, irrespective of the presence of MMA monomer. We found no relationship between MMA monomer level and intramedullary pressure, PAP or pulmonary capillary wedge pressure. Our findings suggest that the presence of MMA monomer in femoral venous blood has no effect on the formation of fat emboli or their pulmonary haemodynamic outcome during cemented hip arthroplasty