The loss of full muscle activation contributes to weakness of the quadriceps muscle in patients with deficiency of the anterior cruciate ligament (ACL). We examined whether a deficit of voluntary activation (VA) of the quadriceps muscle can be reversed by reconstruction of the ACL and assessed its influence on muscle strength and clinical parameters. We evaluated 12 male subjects with an isolated tear of the ACL and 12 matched control subjects before operation and two years after reconstruction of the ACL. Assessment included measurements of isometric knee-extension torque at maximal voluntary contraction (MVC force), knee stability tests, the International Knee Ligament Standard Evaluation Form and the Tegner activity score. A sensitive method of twitch interpolation was used to quantify the VA and to calculate true muscle force. Before operation we found a deficit of VA on both the injured (mean ±SEM 74.9 ± 3.5%) and the uninjured side (74.6 ± 3.0%) in comparison with the control group (91 ± 0.9%). Two years after reconstruction of the ACL the VA improved significantly on both sides but remained less than that of the controls. Correlation analysis revealed an improvement of the VA in patients who returned to a higher level of activity. The deficit of true muscle force, however, persisted regardless of the clinical outcome and ligament stability

Aims. Bacterial infection activates neutrophils to release neutrophil extracellular traps (NETs) in bacterial biofilms of periprosthetic joint infections (PJIs). The aim of this study was to evaluate the increase in NET activation and release (NETosis) and haemostasis markers in the plasma of patients with PJI, to evaluate whether such plasma induces the activation of neutrophils, to ascertain whether increased NETosis is also mediated by reduced DNaseI activity, to explore novel therapeutic interventions for NETosis in PJI in vitro, and to evaluate the potential diagnostic use of these markers. Methods. We prospectively recruited 107 patients in the preoperative period of prosthetic surgery, 71 with a suspicion of PJI and 36 who underwent arthroplasty for non-septic indications as controls, and obtained citrated plasma. PJI was confirmed in 50 patients. We measured NET markers, inflammation markers, DNaseI activity, haemostatic markers, and the thrombin generation test (TGT). We analyzed the ability of plasma from confirmed PJI and controls to induce NETosis and to degrade in vitro-generated NETs, and explored the therapeutic restoration of the impairment to degrade NETs of PJI plasma with recombinant human DNaseI. Finally, we assessed the contribution of these markers to the diagnosis of PJI. Results. Patients with confirmed PJI had significantly increased levels of NET markers (cfDNA (p < 0.001), calprotectin (p < 0.001), and neutrophil elastase (p = 0.022)) and inflammation markers (IL-6; p < 0.001) in plasma. Moreover, the plasma of patients with PJI induced significantly more neutrophil activation than the plasma of the controls (p < 0.001) independently of tumour necrosis factor alpha. Patients with PJI also had a reduced DNaseI activity in plasma (p < 0.001), leading to a significantly impaired degradation of NETs (p < 0.001). This could be therapeutically restored with recombinant human DNaseI to the level in the controls. We developed a model to improve the diagnosis of PJI with cfDNA, calprotectin, and the start tail of TGT as predictors, though cfDNA alone achieved a good prediction and is simpler to measure. Conclusion. We confirmed that patients with PJI have an increased level of NETosis in plasma. Their plasma both induced NET release and had an impaired ability to degrade NETs mediated by a reduced DNaseI activity. This can be therapeutically restored in vitro with the approved Dornase alfa, Pulmozyme, which may allow novel methods of treatment. A combination of NETs and haemostatic biomarkers could improve the diagnosis of PJI, especially those patients in whom this diagnosis is uncertain. Cite this article: Bone Joint J 2024;106-B(9):1021–1030

Aims. The aim of this study was to determine whether closed suction drain (CSD) use influences recovery of quadriceps strength and to examine the effects of drain use on secondary outcomes: quadriceps activation, intra-articular effusion, bioelectrical measure of swelling, range of movement (ROM), pain, and wound healing complications. Patients and Methods. A total of 29 patients undergoing simultaneous bilateral total knee arthroplasty (TKA) were enrolled in a prospective, randomized blinded study. Patients were randomized to receive a CSD in one limb while the contralateral limb had the use of a subcutaneous drain (SCDRN) without the use of suction (‘sham drain’). Isometric quadriceps strength was collected as the primary outcome. Secondary outcomes consisted of quadriceps activation, intra-articular effusion measured via ultrasound, lower limb swelling measured with bioelectrical impendence and limb girth, knee ROM, and pain. Outcomes were assessed preoperatively and postoperatively at day two, two and six weeks, and three months. Differences between limbs were determined using paired Student’s t-tests or Wilcoxon’s signed-rank tests. Results. No significant differences were identified between limbs prior to surgery for the primary or secondary outcomes. No significant differences in quadriceps strength were seen between CSD and SCDRN limbs at postoperative day two (p = 0.09), two weeks (primary endpoint) (p = 0.7), six weeks (p = 0.3), or three months (p = 0.5). The secondary outcome of knee extension ROM was significantly greater in the CSD limb compared with the SCDRN (p = 0.01) at two weeks following surgery, but this difference was absent at all other intervals. Secondary outcomes of quadriceps activation, intra-articular effusion, lower limb swelling, and pain were not found to differ significantly at any timepoint following surgery. Conclusion. The use of CSD during TKA did not influence quadriceps strength, quadriceps activation, intra-articular effusion, lower limb swelling, ROM, or pain. These results have limited drain use by the authors in primary uncomplicated TKA. Cite this article: Bone Joint J 2019;101-B (7 Supple C):84–90

Aims. This study aimed to determine if macrophages can attach and directly affect the oxide layers of 316L stainless steel, titanium alloy (Ti6Al4V), and cobalt-chromium-molybdenum alloy (CoCrMo) by releasing components of these alloys. Methods. Murine peritoneal macrophages were cultured and placed on stainless steel, CoCrMo, and Ti6Al4V discs into a 96-well plate. Cells were activated with interferon gamma and lipopolysaccharide. Macrophages on stainless steel discs produced significantly more nitric oxide (NO) compared to their control counterparts after eight to ten days and remained elevated for the duration of the experiment. Results. On stainless steel, both nonactivated and activated cell groups were shown to have a significant increase in metal ion release for Cr, Fe, and Ni (p < 0.001, p = 0.002, and p = 0.020 respectively) compared with medium only and showed macrophage-sized corrosive pits on the stainless steel surface. On titanium alloy discs there was a significant increase in aluminum (p < 0.001) among all groups compared with medium only. Conclusion. These results indicated that macrophages were able to attach to and affect the oxide surface of stainless steel and titanium alloy discs. Cite this article: Bone Joint J 2020;102-B(7 Supple B):116–121

Evaluating musculoskeletal conditions of the lower limb and understanding the pathophysiology of complex bone kinematics is challenging. Static images do not take into account the dynamic component of relative bone motion and muscle activation. Fluoroscopy and dynamic MRI have important limitations. Dynamic CT (4D-CT) is an emerging alternative that combines high spatial and temporal resolution, with an increased availability in clinical practice. 4D-CT allows simultaneous visualization of bone morphology and joint kinematics. This unique combination makes it an ideal tool to evaluate functional disorders of the musculoskeletal system. In the lower limb, 4D-CT has been used to diagnose femoroacetabular impingement, patellofemoral, ankle and subtalar joint instability, or reduced range of motion. 4D-CT has also been used to demonstrate the effect of surgery, mainly on patellar instability. 4D-CT will need further research and validation before it can be widely used in clinical practice. We believe, however, it is here to stay, and will become a reference in the diagnosis of lower limb conditions and the evaluation of treatment options. Cite this article: Bone Joint J 2021;103-B(5):822–827

Abnormal wear of cobalt-containing metal-on-metal joints is associated with inflammatory pseudotumours. Cobalt ions activate human toll-like receptor 4 (TLR4), which normally responds to bacterial lipopolysaccharide (LPS) in sepsis. Activation of TLR4 by LPS increases the expression of chemokines IL-8 and CXCL10, which recruit leukocytes and activated T-cells, respectively. This study was designed to determine whether cobalt induces a similar inflammatory response to LPS by promoting the expression of IL-8 and CXCL10. A human monocytic cell line, derived from acute monocytic leukaemia, was treated with cobalt ions and expression of IL-8 and CXCL10 measured at mRNA and protein levels. Cobalt-treated macrophages showed a 60-fold increase in IL-8 mRNA, and an eightfold increase in production of the mature chemokine (both p < 0.001); expression of the CXCL10 gene and protein was also significantly increased by cobalt (both p < 0.001). Experiments were also performed in the presence of CLI-095, a TLR4-specific antagonist which abrogated the cobalt-mediated increase in IL-8 and CXCL10 expression. . These findings suggest that cobalt ions induce inflammation similar to that observed during sepsis by the simultaneous activation of two TLR4-mediated signalling pathways. These pathways result in increased production of IL-8 and CXCL10, and may be implicated in pseudotumour formation following metal-on-metal replacement. Cite this article: Bone Joint J 2014; 96-B:1172–7

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The aim of this study was to report the long-term prognosis of patients with multiple Langerhans cell histiocytosis (LCH) involving the spine, and to analyze the risk factors for progression-free survival (PFS).

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To determine whether platelet-rich plasma (PRP) injection improves outcomes two years after acute Achilles tendon rupture.

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Postoperative complication rates remain relatively high after adult spinal deformity (ASD) surgery. The extent to which modifiable patient-related factors influence complication rates in patients with ASD has not been effectively evaluated. The aim of this retrospective cohort study was to evaluate the association between modifiable patient-related factors and complications after corrective surgery for ASD.

Adolescent idiopathic scoliosis (AIS), defined by an age at presentation of 11 to 18 years, has a prevalence of 0.47% and accounts for approximately 90% of all cases of idiopathic scoliosis. Despite decades of research, the exact aetiology of AIS remains unknown. It is becoming evident that it is the result of a complex interplay of genetic, internal, and environmental factors. It has been hypothesized that genetic variants act as the initial trigger that allow epigenetic factors to propagate AIS, which could also explain the wide phenotypic variation in the presentation of the disorder. A better understanding of the underlying aetiological mechanisms could help to establish the diagnosis earlier and allow a more accurate prediction of deformity progression. This, in turn, would prompt imaging and therapeutic intervention at the appropriate time, thereby achieving the best clinical outcome for this group of patients.

Cite this article: Bone Joint J 2022;104-B(8):915–921.

Recent reports have suggested an association between Perthes’ disease and an underlying thrombophilic or hypofibrinolytic tendency. In Northern Ireland there is a high incidence of Perthes’ disease (11.7 per 100 000 or 1 in 607 children) in a stable paediatric population. We reviewed 139 children with Perthes’ disease and compared them with a control group of 220 aged- and gender-matched healthy primary schoolchildren with similar racial and ethnic backgrounds. There were no significant deficiencies of antithrombotic factors protein C, protein S, antithrombin III or resistance to activated protein C. A total of 53 (38.1%) of the children with Perthes’ disease had a prolonged activated partial thromboplastin time (> 38) compared with 13 (5.9%) of the control group (p < 0.001). Our findings have shown that using standard assays, thrombophilia secondary to antithrombotic factor deficiency or resistance to activated protein does not appear to be an aetiological factor for Perthes’ disease. The cause of the prolonged activated partial thromboplastin time, usually associated with a clotting factor deficiency, is under further investigation

Desmoid tumours are a rare fibroblastic proliferation of monoclonal origin, arising in deep soft-tissues. Histologically, they are characterized by locally aggressive behaviour and an inability to metastasize, and clinically by a heterogeneous and unpredictable course. Desmoid tumours can occur in any anatomical site, but commonly arise in the limbs. Despite their benign nature, they can be extremely disabling and sometimes life-threatening, causing severe pain and functional limitations. Their surgical management is complex and challenging, due to uncertainties surrounding the biological and clinical behaviour, rarity, and limited available literature. Resection has been the first-line approach for patients with a desmoid tumour but, during the last few decades, a shift towards a more conservative approach has occurred, with an initial ‘wait and see’ policy. Many medical and regional forms of treatment are also available for the management of this condition, and others have recently emerged with promising results. However, many areas of controversy remain, and further studies and global collaboration are needed to obtain prospective and randomized data, in order to develop an appropriate shared stepwise approach.

Cite this article: Bone Joint J 2023;105-B(7):729–734.

Paediatric bone sarcomas are a dual challenge for orthopaedic surgeons in terms of tumour resection and reconstruction, as it is important to minimize functional and growth problems without compromising survival rates. Cañadell’s technique consists of a Type I epiphysiolysis performed using continuous distraction by an external fixator prior to resection. It was designed to achieve a safe margin due to the ability of the physeal cartilage to be a barrier to tumour spread in some situations, avoiding the need for articular reconstruction, and preserving the growth capacity most of the times. Despite initial doubts raised in the scientific community, this technique is now widely used in many countries for the treatment of metaphyseal paediatric bone sarcomas. This annotation highlights the importance of Cañadell’s work and reviews the experience of applying it to bone sarcoma patients over the last 40 years.

Cite this article: Bone Joint J 2023;105-B(1):11–16.

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Historically, patients undergoing surgery for adolescent idiopathic scoliosis (AIS) have been nursed postoperatively in a critical care (CC) setting because of the challenges posed by prone positioning, extensive exposures, prolonged operating times, significant blood loss, major intraoperative fluid shifts, cardiopulmonary complications, and difficulty in postoperative pain management. The primary aim of this paper was to determine whether a scoring system, which uses Cobb angle, forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and number of levels to be fused, is a valid method of predicting the need for postoperative critical care in AIS patients who are to undergo scoliosis correction with posterior spinal fusion (PSF).

Rotator cuff tears are common in middle-aged and elderly patients. Despite advances in the surgical repair of rotator cuff tears, the rates of recurrent tear remain high. This may be due to the complexity of the tendons of the rotator cuff, which contributes to an inherently hostile healing environment. During the past 20 years, there has been an increased interest in the use of biologics to complement the healing environment in the shoulder, in order to improve rotator cuff healing and reduce the rate of recurrent tears. The aim of this review is to provide a summary of the current evidence for the use of forms of biological augmentation when repairing rotator cuff tears.

Cite this article: Bone Joint J 2024;106-B(9):978–985.

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The aim of this study was to evaluate the reliability and validity of a patient-specific algorithm which we developed for predicting changes in sagittal pelvic tilt after total hip arthroplasty (THA).

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To investigate the impact of consecutive perioperative care transitions on in-hospital recovery of patients who had primary total knee arthroplasty (TKA) over an 11-year period.

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Metal and ceramic humeral head bearing surfaces are available choices in anatomical shoulder arthroplasties. Wear studies have shown superior performance of ceramic heads, however comparison of clinical outcomes according to bearing surface in total shoulder arthroplasty (TSA) and hemiarthroplasty (HA) is limited. This study aimed to compare the rates of revision and reoperation following metal and ceramic humeral head TSA and HA using data from the National Joint Registry (NJR), which collects data from England, Wales, Northern Ireland, Isle of Man and the States of Guernsey.

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Multiple secondary surgical procedures of the shoulder, such as soft-tissue releases, tendon transfers, and osteotomies, are described in brachial plexus birth palsy (BPBP) patients. The long-term functional outcomes of these procedures described in the literature are inconclusive. We aimed to analyze the literature looking for a consensus on treatment options.

Cytological analysis of material aspirated from the effusion which occasionally develops around a polyglycolic acid (PGA) osteosynthesis implant showed a predominance of inflammatory monocytes and in particular lymphocytes. In order to discover whether PGA implants are immunologically inert, density gradient-isolated peripheral blood mononuclear cells were cultured in 0.2 ml of 10% delta FCS-RPMI 1640 culture medium supplemented with 10 mg PGA. Phytohaemagglutinin (PHA) lectin, a purified protein derivate of tuberculin (PPD) antigen and culture medium alone were used as positive and negative controls. We studied lymphocyte activation kinetics on days 0, 1, 3 and 5. Major histocompatibility complex locus II antigen (MHC locus II antigen) and interleukin-2 receptor (IL-2R) expression were analysed using the avidin-biotin-peroxidase complex (ABC) method and lymphocyte DNA synthesis by using 3H-thymidine incorporation and beta-scintillation counting. Especially on culture days 0 and 1, lymphocytes and monocytes were seen by light microscopy to be attached to PGA particles. However, our results show no PGA-induced lymphocyte DNA synthesis, but PGA-induced MHC locus II antigen and IL-2R activation marker expression was seen, greater than in negative controls, but less than that seen in PPD antigen driven lymphocyte response. This suggests that PGA is an immunologically inert implant material, but it does seem to induce inflammatory mononuclear cell migration and adhesion, leading to a slight non-specific lymphocyte activation. This activation is lower than that seen in mitogen and antigen-driven lymphocyte responses

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Heterotopic ossification (HO) is a common complication after elbow trauma and can cause severe upper limb disability. Although multiple prognostic factors have been reported to be associated with the development of post-traumatic HO, no model has yet been able to combine these predictors more succinctly to convey prognostic information and medical measures to patients. Therefore, this study aimed to identify prognostic factors leading to the formation of HO after surgery for elbow trauma, and to establish and validate a nomogram to predict the probability of HO formation in such particular injuries.

We have assessed the effect of a variety of implants commonly used in fracture fixation and joint replacement on the activation of metal detectors at airport security gates. A volunteer with metal implants strapped on and patients with implants in situ walked through the device. Implants used in fixation do not activate it, except for Richards cannulated screws. An Austin-Moore prosthesis does set off the detector, but a single joint replacement does not. Three or four joint replacements activate the alarm and patients with these implants should be warned of this possibility

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Hip fracture commonly affects the frailest patients, of whom many are care-dependent, with a disproportionate risk of contracting COVID-19. We examined the impact of COVID-19 infection on hip fracture mortality in England.

In the differentiation of osteoclasts the differentiation factor (RANKL) interacts with the receptor activator of NF-κB (RANK) in a direct cell-to-cell contact between osteoblast and (pre)osteoclast. This is inhibited by soluble osteoprotegerin (OPG). The mRNA levels of both RANKL (p < 0.01) and RANK (p < 0.05) were high in peri-implant tissue and RANKL+ and RANK+ cells were found in such tissue. Double labelling also disclosed soluble RANKL bound to RANK+ cells. We were unable to stimulate fibroblasts to express RANKL in vitro, but monocyte activation with LPS gave a fivefold increase in RANK mRNA levels. In contrast to RANKL and RANK expression in peri-implant tissue, expression of OPG was restricted to vascular endothelium. Endothelial cell OPG mRNA levels were regulated by TNF-α and VEGF, but not by hypoxia. It is concluded that activated cells in the interface tissue overproduce both RANKL and RANK and they can interact without interference by OPG

Aims . Recently, several synovial biomarkers have been introduced into the algorithm for the diagnosis of a prosthetic joint infection (PJI). Alpha defensin is a promising biomarker, with a high sensitivity and specificity, but it is expensive. Calprotectin is a protein that is present in the cytoplasm of neutrophils, is released upon neutrophil activation and exhibits anti-microbial activity. Our aim, in this study, was to determine the diagnostic potential of synovial calprotectin in the diagnosis of a PJI. Patients and Methods. In this pilot study, we prospectively collected synovial fluid from the hip, knee, shoulder and elbow of 19 patients with a proven PJI and from a control group of 42 patients who underwent revision surgery without a PJI. PJI was diagnosed according to the current diagnostic criteria of the Musculoskeletal Infection Society. Synovial fluid was centrifuged and the supernatant was used to measure the level of calprotectin after applying a lateral flow immunoassay. . Results. The median synovial calprotectin level was 991 mg/L (interquartile range (IQR) 154 to 1787) in those with a PJI and 11 mg/L (IQR 3 to 29) in the control group (p < 0.0001). Using a cut-off value of 50 mg/L, this level showed an excellent diagnostic accuracy, with an area under the curve of 0.94. The overall sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) was 89%, 90%, 81% and 95% respectively. The NPV was 97% in the nine patients with a chronic PJI. . Conclusion . Synovial calprotectin may be a valuable biomarker in the diagnosis of a PJI, especially in the exclusion of an infection. With a lateral flow immunoassay, a relatively rapid quantitative diagnosis can be made. The measurement is cheap and is easy to use. . Cite this article: Bone Joint J 2017;99-B:660–5

We investigated in vitro a mechanism by which particulate debris may induce bone resorption and cause implant loosening. We first studied two standard particles: latex, which is considered to be inert, and zymosan, which is inflammatory. Macrophages that phagocytosed either particle became activated, and stimulated 15 times as much bone resorption as did control macrophages. For activation to occur, 100 times more latex than zymosan had to be phagocytosed. We also found that bone cement and polyethylene particles activated macrophages in a similar manner, and that the necessary amounts of these were intermediate between those of latex and zymosan. None of the particles were toxic. It was concluded that implant loosening may result from bone resorption stimulated by mediators released by macrophages that have phagocytosed particles of bone cement or polyethylene

The most frequent cause of failure after total hip replacement in all reported arthroplasty registries is peri-prosthetic osteolysis. Osteolysis is an active biological process initiated in response to wear debris. The eventual response to this process is the activation of macrophages and loss of bone. Activation of macrophages initiates a complex biological cascade resulting in the final common pathway of an increase in osteolytic activity. The biological initiators, mechanisms for and regulation of this process are beginning to be understood. This article explores current concepts in the causes of, and underlying biological mechanism resulting in peri-prosthetic osteolysis, reviewing the current basic science and clinical literature surrounding the topic

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Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are common orthopaedic procedures requiring postoperative radiographs to confirm implant positioning and identify complications. Artificial intelligence (AI)-based image analysis has the potential to automate this postoperative surveillance. The aim of this study was to prepare a scoping review to investigate how AI is being used in the analysis of radiographs following THA and TKA, and how accurate these tools are.

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Both the femoral and tibial component are usually cemented at revision total knee arthroplasty (rTKA), while stems can be added with either cemented or press-fit (hybrid) fixation. The aim of this study was to compare the long-term stability of rTKA with cemented and press-fitted stems, using radiostereometric analysis (RSA).

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Platelet-rich plasma (PRP) intra-articular injections may provide a simple and minimally invasive treatment for early-stage knee osteoarthritis (OA). This has led to an increase in its adoption as a treatment for knee OA, although there is uncertainty about its efficacy and benefit. We hypothesized that patients with early-stage symptomatic knee OA who receive multiple PRP injections will have better clinical outcomes than those receiving single PRP or placebo injections.

Periprosthetic joint infection (PJI) is a difficult complication requiring a comprehensive eradication protocol. Cure rates have essentially stalled in the last two decades, using methods of antimicrobial cement joint spacers and parenteral antimicrobial agents. Functional spacers with higher-dose antimicrobial-loaded cement and antimicrobial-loaded calcium sulphate beads have emphasized local antimicrobial delivery on the premise that high-dose local antimicrobial delivery will enhance eradication. However, with increasing antimicrobial pressures, microbiota have responded with adaptive mechanisms beyond traditional antimicrobial resistance genes. In this review we describe adaptive resistance mechanisms that are relevant to the treatment of PJI. Some mechanisms are well known, but others are new. The objective of this review is to inform clinicians of the known adaptive resistance mechanisms of microbes relevant to PJI. We also discuss the implications of these adaptive mechanisms in the future treatment of PJI.

Cite this article: Bone Joint J 2022;104-B(5):575–580.

Previous studies support the important role of vascular endothelial growth factor (VEGF) and syndecan-4 in the pathogenesis of osteoarthritis (OA). Both VEGF and syndecan-4 are expressed by chondrocytes and both are involved in the regulation of matrix metalloproteinase-3, resulting in the activation of aggrecanase II (ADAMTS-5), which is essential in the pathogenesis of OA. However, the relationship between VEGF and syndecan-4 has not been established. As a pilot study, we assayed the expression of VEGF and syndecan-4 in cartilage samples and cultured chondrocytes from osteoarthritic knee joints and analysed the relationship between these two factors. Specimens were collected from 21 female patients (29 knees) who underwent total knee replacement due to severe medial OA of the knee (Kellgren–Lawrence grade 4). Articular cartilage samples, obtained from bone and cartilage excised during surgery, were analysed and used for chondrocyte culture. We found that the levels of expression of VEGF and syndecan-4 mRNA did not differ significantly between medial femoral cartilage with severe degenerative changes and lateral femoral cartilage that appeared grossly normal (p = 0.443 and 0.622, respectively). Likewise, the levels of expression of VEGF and syndecan-4 mRNA were similar in cultured chondrocytes from medial and lateral femoral cartilage. The levels of expression of VEGF and syndecan-4 mRNAs were significantly and positively correlated in cartilage explant (r = 0.601, p = 0.003) but not in cultured chondrocytes. These results suggest that there is a close relationship between VEGF and syndecan-4 in the cartilage of patients with OA. Further studies are needed to determine the exact pathway by which these two factors interact in the pathogenesis of OA. Cite this article: Bone Joint J 2014;96-B:1319–24

We evaluated the possible induction of a systemic immune response to increase anti-tumour activity by the re-implantation of destructive tumour tissue treated by liquid nitrogen in a murine osteosarcoma (LM8) model. The tumours were randomised to treatment by excision alone or by cryotreatment after excision. Tissue from the tumour was frozen in liquid nitrogen, thawed in distilled water and then re-implanted in the same animal. In addition, some mice received an immunological response modifier of OK-432 after treatment. We measured the levels of interferon-gamma and interleukin-12 cytokines and the cytotoxicity activity of splenocytes against murine LM8 osteosarcoma cells. The number of lung and the size of abdominal metastases were also measured. Re-implantation of tumour tissue after cryotreatment activated immune responses and inhibited metastatic tumour growth. OK-432 synergistically enhanced the anti-tumour effect. Our results suggest that the treatment of malignant bone tumours by reconstruction using autografts containing tumours which have been treated by liquid nitrogen may be of clinical value

The stress response to trauma is the summation of the physiological response to the injury (the ‘first hit’) and by the response to any on-going physiological disturbance or subsequent trauma surgery (the ‘second hit’). Our animal model was developed in order to allow the study of each of these components of the stress response to major trauma. High-energy, comminuted fracture of the long bones and severe soft-tissue injuries in this model resulted in a significant tropotropic (depressor) cardiovascular response, transcardiac embolism of medullary contents and activation of the coagulation system. Subsequent stabilisation of the fractures using intramedullary nails did not significantly exacerbate any of these responses

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The preoperative diagnosis of periprosthetic joint infection (PJI) remains a challenge due to a lack of biomarkers that are both sensitive and specific. We investigated the performance characteristics of polymerase chain reaction (PCR), interleukin-6 (IL6), and calprotectin of synovial fluid in the diagnosis of PJI.

Following the discovery of a powerful venous pump in the foot that is activated by weight-bearing independently of muscular action, a pneumatic impulse device was developed to actuate this pump artificially. In a multicentre international trial the device was shown to reduce post-traumatic and postoperative swelling; pain also was alleviated. Evidence is also presented that dangerously high compartment pressures may be reduced to acceptable levels and fasciotomy avoided. We present an explanation of the clinical effects of activation of the venous footpump, based on recent improved understanding of the physiology of the microcirculation. The hyperaemic response that follows the liberation of endothelial-derived relaxing factor (EDRF) by sudden changes of pressure after weight-bearing or impulse compression is particularly important

The membranes surrounding seven loose cementless acetabular implants were shown to contain polyethylene particles, birefringent in polarised light. Three of these implants were made of titanium alloy and the membranes around these contained titanium particles as well. There was no metallosis around the four implants made of chromium-cobalt-steel alloy. Both titanium and polyethylene particles caused migration, adherence and phagocytosis of CD11b-positive, peroxidase-negative macrophages. There were no histological signs of activation of the specific immune response; neither interleukin-2 receptor-positive activated T cells nor PCA-1 plasmablasts/plasma cells were present in the tissues. In cases of simple loosening, resident mesenchymal fibroblast-like cells were active. In aggressive granulomatosis, there were many macrophages and multinucleated giant cells but little fibroblast reaction. The clinical relevance of the findings is that the use of cementless prostheses is not a guarantee against adverse tissue reactions

Aseptic loosening and osteolysis around prosthetic joints are the principal causes of failure and consequent revision. During this process activated macrophages produce cytokines which are thought to promote osteolysis by osteoclasts. Changes in pressure within the space around implants have been proposed as a cause of loosening and osteolysis. We therefore studied the effect of two different regimes of cyclic pressure on the production of interleukin-1β (IL-1β), IL-6 and tumour necrosis factor-α (TNF-α) by cultured human monocyte-derived (M-D) macrophages. There was a wide variation in the expression of cytokines in non-stimulated M-D macrophages from different donors and therefore cells from the same donor were compared under control and pressurised conditions. Both regimes of cyclic pressure were found to increase expression of IL-6 and TNF-α. Expression of IL-1β was increased by a higher-frequency regime only. Our findings suggest that M-D macrophages are activated by cyclic pressure. Further work will be required to understand the relative roles of frequency, amplitude and duration of applied pressure in the cellular effects of cyclic pressure in this system

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The modified Glasgow Prognostic Score (mGPS) uses preoperative CRP and albumin to calculate a score from 0 to 2 (2 being associated with poor outcomes). mGPS is validated in multiple carcinomas. To date, its use in soft-tissue sarcoma (STS) is limited, with only small cohorts reporting that increased mGPS scores correlates with decreased survival in STS patients.

We investigated the effect of progesterone on the nerve during lengthening of the limb in rats. The sciatic nerves of rats were elongated by leg lengthening for ten days at 3 mm per day. On alternate days between the day after the operation and nerve dissection, the progesterone-treated group received subcutaneous injections of 1 mg progesterone in sesame oil and the control group received oil only. On the fifth, tenth and 17th day, the sciatic nerves were excised at the midpoint of the femur and the mRNA expression level of myelin protein P0 was analysed by quantitative real time polymerase chain reaction. On day 52 nodal length was examined by electron microscopy, followed by an examination of the compound muscle action potential (C-MAP) amplitude and the motor conduction velocity (MCV) of the tibial nerve on days 17 and 52. The P0 (a major myelin glycoprotein) mRNA expression level in the progesterone-treated group increased by 46.6% and 38.7% on days five and ten, respectively. On day 52, the nodal length in the progesterone-treated group was smaller than that in the control group, and the MCV of the progesterone-treated group had been restored to normal. Progesterone might accelerate the restoration of demyelination caused by nerve elongation by activating myelin synthesis

The interactions between the different cell types in periprosthetic tissue are still unclear. We used a non-contact coculture model to investigate the effects of polymethylmethacrylate (PMMA) particles and human macrophage-derived soluble mediators on fibroblast activation. Macrophages were either exposed or not exposed to phagocytosable PMMA particles, but fibroblasts were not. Increasing numbers of macrophages were tested in cocultures in which the fibroblast cell number was held constant and cultures of macrophages alone were used for comparison of cytokine release. We used the release of interleukin-1 beta (IL-1β), interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-α), lysosomal enzyme and metalloproteinase activity to assess the cultivation of macrophages and fibroblasts. In cocultures, IL-6 release was increased 100-fold for both unchallenged and particle-challenged cultures when compared with macrophage cultures alone. Furthermore, particle-challenged cocultures had threefold higher IL-6 levels than unchallenged cocultures. Release of TNF-α was similar in cocultures and in macrophage cultures. IL-1β release in cocultures was independent of the macrophage-fibroblast ratio. Lysosomal enzyme activity and metalloproteinase activity were increased in cocultures. Our data show that macrophages and fibroblasts in coculture significantly increase the release of IL-6 and to a less degree other inflammatory mediators; particle exposure accentuates this effect. This suggests that macrophage accumulation in fibrous tissue may lead to elevated IL-6 levels that are much higher than those caused by particle activation of macrophages alone. This macrophage-fibroblast interaction represents a novel concept for the initiation and maintenance of the inflammatory process in periprosthetic membranes

1. The response of the first regional lymph node to a homograft of fresh iliac cancellous bone inserted subcutaneously into the rabbit's ear three weeks after the introduction of a similar graft from the same donor into the same ear has been investigated in thirty rabbits. Fifteen rabbits which received second-set autografts of cancellous bone have also been studied. 2. The insertion of second-set homografts of fresh marrow-containing cancellous bone evokes an immune secondary response in the lymph nodes draining the grafts. 3. The increase in weight of the first regional lymph nodes on the side receiving second-set homografts is more rapid and of greater magnitude than that of nodes draining first-set homografts of cancellous bone. Second-set autografts evoke weight changes in the draining nodes similar to those in nodes draining first-set autografts of cancellous bone. 4. The histological changes which occur in the lymph nodes draining the second-set homografts (secondary response) are described and compared with those occurring in lymph nodes draining first-set homografts of cancellous bone (primary response). 5. In the primary response the distribution of large and medium lymphoid cells is throughout an activated sector of the cortex of the lymph node (Burwell and Gowland 1961), but in the secondary response these cells are found peripherally within the activated sector of the node. In both the primary and the secondary responses large and medium lymphoid cells are found in the medullary trabeculae of the lymph nodes. 6. The differences between the primary response of lymph nodes draining a tissue homograft (cancellous bone) and the primary response of lymph nodes draining classical antigens, and reported by other workers, are described. 7. Knowledge concerning the inflammatory response in the tissues of the host surrounding homografts of fresh cortical and cancellous bone implanted into animals previously sensitised to tissue from the respective donor is reviewed. 8. The late phase of new bone formation by homografts of fresh cancellous bone is discussed in the light of immunological studies

We measured the changes during operation in seven markers of coagulation in a prospective series of 84 patients with fractures of the tibia or femur who were undergoing reamed intramedullary nailing. All patients were also continually monitored using transoesophageal echocardiography to assess marrow embolism. In a subset of 40 patients, intraoperative cardiopulmonary function was monitored, using pulmonary and systemic arterial catheterisation. The procedure produced a significant increase in prothrombin time, activated partial thromboplastin time, the level of prothrombin fragments F. 1+2. and D-dimers, and a decrease in the fibrinogen level, suggesting activation of both the coagulation and fibrinolytic pathways. There was evidence of both platelet hyper-reactivity and depletion, as estimated by an increase in β-thromboglobulin levels and a decrease in the platelet count. In the patients who had invasive monitoring there was an incremental increase in mean pulmonary arterial pressure, with the changes being greatest during insertion of the guide-wire and reaming. The change in markers of coagulation, pulmonary artery pressure and arterial oxygen partial pressures correlated with the intraoperative embolic response. Greater changes in these parameters were observed during stabilisation of pathological fractures and in those patients in whom surgery had been delayed for more than 48 hours. Seven patients with pathological fractures developed more severe hypoxic episodes during reaming, which were associated with significantly greater arterial hypoxaemia, a fall in the right ventricular ejection fraction and an increase in the mean pulmonary artery pressure, pulmonary capillary wedge pressure, central venous pressure and the pulmonary vascular resistance index. These changes suggested that the patients had transient intraoperative right heart strain. Eight patients developed significant postoperative respiratory compromise. They all had severe intraoperative embolic responses and, in the three who had invasive monitoring, there was a significantly greater increase in pulmonary artery pressure and alveolar-arterial oxygen gradient, and a fall in the ratio of arterial partial pressure of oxygen to the inspired oxygen concentration. Operative delay, intraoperative paradoxical embolisation and the scores for the severity of the coagulative and embolic responses were predictive of the development of postoperative respiratory complications on univariate logistic regression analysis. On multivariate analysis, however, only the embolic and coagulative scores were significant independent predictors of respiratory complications

Wear of polyethylene is associated with aseptic loosening of orthopaedic implants and has been observed in hip and knee prostheses and anatomical implants for the shoulder. The reversed shoulder prostheses have not been assessed as yet. We investigated the volumetric polyethylene wear of the reversed and anatomical Aequalis shoulder prostheses using a mathematical musculoskeletal model. Movement and joint stability were achieved by EMG-controlled activation of the muscles. A non-constant wear factor was considered. Simulated activities of daily living were estimated from in vivo recorded data. After one year of use, the volumetric wear was 8.4 mm. 3. for the anatomical prosthesis, but 44.6 mm. 3. for the reversed version. For the anatomical prosthesis the predictions for contact pressure and wear were consistent with biomechanical and clinical data. The abrasive wear of the polyethylene in reversed prostheses should not be underestimated, and further analysis, both experimental and clinical, is required

Aims

This study used an artificial neural network (ANN) model to determine the most important pre- and perioperative variables to predict same-day discharge in patients undergoing total knee arthroplasty (TKA).

Aims

Highly cross-linked polyethylene (HXLPE) has greatly improved the durability of total hip arthroplasty (THA) in young patients because of its improved wear characteristics. Few studies have followed this population into the second decade, and therefore the purpose of this investigation was to evaluate the clinical outcome for THA patients 50 years of age and younger at a minimum of 15 years postoperatively. The second purpose was to evaluate the radiological findings secondary to wear or mechanical failure of the implant.

Platelet-rich plasma is a new inductive therapy which is being increasingly used for the treatment of the complications of bone healing, such as infection and nonunion. The activator for platelet-rich plasma is a mixture of thrombin and calcium chloride which produces a platelet-rich gel. We analysed the antibacterial effect of platelet-rich gel in vitro by using the platelet-rich plasma samples of 20 volunteers. In vitro laboratory susceptibility to platelet-rich gel was determined by the Kirby-Bauer disc-diffusion method. Baseline antimicrobial activity was assessed by measuring the zones of inhibition on agar plates coated with selected bacterial strains. Zones of inhibition produced by platelet-rich gel ranged between 6 mm and 24 mm (mean 9.83 mm) in diameter. Platelet-rich gel inhibited the growth of Staphylococcus aureus and was also active against Escherichia coli. There was no activity against Klebsiella pneumoniae, Enterococcus faecalis, and Pseudomonas aeruginosa. Moreover, platelet-rich gel seemed to induce the in vitro growth of Ps. aeruginosa, suggesting that it may cause an exacerbation of infections with this organism. We believe that a combination of the inductive and antimicrobial properties of platelet-rich gel can improve the treatment of infected delayed healing and nonunion

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Local recurrence remains a challenging and common problem following curettage and joint-sparing surgery for giant cell tumour of bone (GCTB). We previously reported a 15% local recurrence rate at a median follow-up of 30 months in 20 patients with high-risk GCTB treated with neoadjuvant Denosumab. The aim of this study was to determine if this initial favourable outcome following the use of Denosumab was maintained with longer follow-up.

Between October 2001 and February 2002, 324 healthcare workers were screened for methicillin-resistant Staphylococcus aureus (MRSA) by nose and throat swabs. A positive finding led to activation of a standardised control programme for the affected person who was immediately excluded from work. Family members of those who were MRSA-positive were offered screening free of charge. An eradication programme was carried out in the permanent carriers. MRSA was found in 17 (5.3%) healthcare workers, 11 of whom proved to be permanent carriers, and six temporarily colonised. Three children of a positive healthcare worker showed nasopharyngeal MRSA, the acquisition of which occurred within the hospital. The standardised eradication programme for carriers was successful in most cases but failed in two individuals, whereupon systemic antibiotics were used successfully. The decolonised carriers, observed for more than one year, remained MRSA negative. Isolation precautions in hospitals do not always prevent hospital staff and their families from acquiring MRSA. The identification of affected employees is difficult because in most cases only asymptomatic colonisation occurs. Screening and eradication can be complicated and costly, and for the affected employees the occupational consequences can be far-reaching as they have no guaranteed legal protection

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We aimed to address the question on whether there is a place for shoulder stabilization surgery in patients who had voluntary posterior instability starting in childhood and adolescence, and later becoming involuntary and uncontrollable.

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Despite recent advances in arthroscopic rotator cuff repair, re-tear rates remain high. New methods to improve healing rates following rotator cuff repair must be sought. Our primary objective was to determine if adjunctive bone marrow stimulation with channelling five to seven days prior to arthroscopic cuff repair would lead to higher Western Ontario Rotator Cuff (WORC) scores at 24 months postoperatively compared with no channelling.

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The aim of this study was to identify the minimal clinically important difference (MCID), minimal important change (MIC), minimal detectable change (MDC), and patient-acceptable symptom state (PASS) threshold in the Forgotten Joint Score (FJS) according to patient satisfaction six months following total knee arthroplasty (TKA).

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The primary aim of this study was to compare the postoperative systemic inflammatory response in conventional jig-based total knee arthroplasty (conventional TKA) versus robotic-arm assisted total knee arthroplasty (robotic TKA). Secondary aims were to compare the macroscopic soft tissue injury, femoral and tibial bone trauma, localized thermal response, and the accuracy of component positioning between the two treatment groups.

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To assess the safety of tranexamic acid (TXA) in a large cohort of patients aged over 65 years who have sustained a hip fracture, with a focus on transfusion rates, mortality, and thromboembolic events.

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The aim of this study was to investigate the hypothesis that a single dose of tranexamic acid (TXA) would reduce blood loss and transfusion rates in elderly patients undergoing surgery for a subcapital or intertrochanteric (IT) fracture of the hip.

Antibiotic resistance represents a threat to human health. It has been suggested that by 2050, antibiotic-resistant infections could cause ten million deaths each year. In orthopaedics, many patients undergoing surgery suffer from complications resulting from implant-associated infection. In these circumstances secondary surgery is usually required and chronic and/or relapsing disease may ensue. The development of effective treatments for antibiotic-resistant infections is needed. Recent evidence shows that bacteriophage (phages; viruses that infect bacteria) therapy may represent a viable and successful solution. In this review, a brief description of bone and joint infection and the nature of bacteriophages is presented, as well as a summary of our current knowledge on the use of bacteriophages in the treatment of bacterial infections. We present contemporary published in vitro and in vivo data as well as data from clinical trials, as they relate to bone and joint infections. We discuss the potential use of bacteriophage therapy in orthopaedic infections. This area of research is beginning to reveal successful results, but mostly in nonorthopaedic fields. We believe that bacteriophage therapy has potential therapeutic value for implant-associated infections in orthopaedics.

Cite this article: Bone Joint J 2021;103-B(2):234–244.

Aims

Calprotectin (CLP) is produced in neutrophils and monocytes and released into body fluids as a result of inflammation or infection. The aim of this study was to evaluate the utility of blood and synovial CLP in the diagnosis of chronic periprosthetic joint infection (PJI).

Between October 2001 and September 2009 we lengthened 242 lower-limb segments in 180 patients using the Intramedullary Skeletal Kinetic Distractor (ISKD). Mechanical failure was defined either as breakage of the ISKD or failure of the internal mechanism to activate. Retrieved nails which failed mechanically were examined by the manufacturer for defects. In all, 15 ISKDs in 12 patients (13 limbs) failed mechanically representing an overall failure rate of 6.2%, with fracture of the device occurring in ten of the 15 failures. Two nails in one patient failed to lengthen and had to be replaced. The manufacturer detected an error in the assembly of the nail, which prompted a wide recall. One nail jammed after being forcefully inserted, and two nails failed to lengthen fully. Lengthening was achieved in all 12 patients, although three required a second operation to exchange a defective nail for a new, functioning device. The ISKD is a complex mechanical device which lengthens by the oscillation of two telescopic sections connected by a threaded rod. The junction between these sections is surrounded by a keyring collar. This keyring collar is the weakest part of the device

Aims

Malignancy and surgery are risk factors for venous thromboembolism (VTE). We undertook a systematic review of the literature concerning the prophylactic management of VTE in orthopaedic oncology patients.

There is good scientific rationale to support the use of growth factors to promote musculoskeletal tissue regeneration. However, the clinical effectiveness of platelet-rich plasma (PRP) and other blood-derived products has yet to be proven. Characterization and reporting of PRP preparation protocols utilized in clinical trials for the treatment of musculoskeletal disease is highly inconsistent, and the majority of studies do not provide sufficient information to allow the protocols to be reproduced. Furthermore, the reporting of blood-derived products in orthopaedics is limited by the multiple PRP classification systems available, which makes comparison of results between studies challenging. Several attempts have been made to characterize and classify PRP; however, no consensus has been reached, and there is lack of a comprehensive and validated classification. In this annotation, we outline existing systems used to classify preparations of PRP, highlighting their advantages and limitations. There remains a need for standardized universal nomenclature to describe biological therapies, as well as a comprehensive and reproducible classification system for autologous blood-derived products.

Cite this article: Bone Joint J 2019;101-B:891–896.

Aims

Reverse shoulder arthroplasty (RSA) reliably improves shoulder pain and function for a variety of indications. However, the safety and efficacy of RSA in elderly patients is largely unknown. The purpose of this study was to report the mortality, morbidity, complications, reoperations, and outcomes of primary RSA in patients aged > 80 years.

Aims

To investigate metallosis in patients with magnetically controlled growing rods (MCGRs) and characterize the metal particle profile of the tissues surrounding the rod.

This paper describes a procedure of activating osteogenesis by the use of the "petal" technique. The osteogenetic effect of these "petals" has been established in experimentally produced fractures and pseudarthroses in rats by radiographical, biomechanical, mechanical and histological examinations. The conventional concept of the osteogenetic activity of bone transplants is discussed. The authors feel that this method will find its clinical application in the operative treatment of pseudarthroses and, in selected cases, of fractures that are known for their tendency to unite slowly

Aims

Patient engagement in adaptive health behaviours and interactions with their healthcare ecosystem can be measured using self-reported instruments, such as the Patient Activation Measure (PAM-13) and the Effective Consumer Scale (ECS-17). Few studies have investigated the influence of patient engagement on limitations (patient-reported outcome measures (PROMs)) and patient-reported experience measures (PREMs). First, we assessed whether patient engagement (PAM-13, ECS-17) within two to four weeks of an upper limb fracture was associated with limitations (the Quick Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH), and Patient-Reported Outcome Measurement Information System Upper Extremity Physical Function computer adaptive test (PROMIS UE PF) scores) measured six to nine months after fracture, accounting for demographic, clinical, and psychosocial factors. Secondly, we assessed the association between patient engagement and experience (numerical rating scale for satisfaction with care (NRS-C) and satisfaction with services (NRS-S) six to nine months after fracture.

Subtotal synovectomy was performed in the knee joints of New Zealand white rabbits. The changes noted in the articular cartilage as manifest by decreased metachromatic staining of the matrix were considered to indicate matrix degradation caused by the altered joint environment. The documentation of the enzyme changes suggests that the histological alteration in the articular cartilage noted after synovectomy may be mediated through the activation of endogenous chondrocyte lysozomal enzymes, particularly cathepsin and acid hydrolases

Plasmin, a proteolytic enzyme derived from the blood, may be activated in synovial fluid both by trauma to synovial tissue and cartilage, and by kinases produced by streptococci and staphylococci. Plasmin normally removes fibrin, but, when in excess, attacks the protein of cartilage matrix. Conversely, excess inhibitor favours the persistence of fibrin and subsequent fibrosis. The relationship of excess protease to the chondrolysis of suppurative arthritis and of excess inhibitor to pannus formation and fibrous ankylosis in tuberculous and rheumatoid arthritis are discussed

The changes in a number of haemostatic factors after fractures of the tibia or femur were compared with those observed in patients with fat embolism complicating such fractures. After fractures uncomplicated by fat embolism there was a rise in the fibrinogen, α. 1. -antitrypsin and serum activation inhibitor. The plasminogen level and platelet count initially fell, but later increased to above the initial levels. Patients whose fractures were complicated by fat embolism had the same pattern of changes but quantitatively greater

Aims

Tranexamic acid (TXA) has been shown to reduce blood loss and transfusion requirements in patients undergoing orthopaedic surgery. There remains a lack of prospective evidence for the use of TXA in patients undergoing periacetabular osteotomy (PAO). The purpose of this study was to determine if intravenous (IV) TXA is effective in reducing calculated blood loss and transfusions after PAO.

Skeletal muscle grafts, when thawed after freezing, can be used to repair peripheral nerves. This method was used after transection of the median nerve in the upper arm in marmosets. Examination at 28 days showed total denervation of flexor carpi radialis; at 150 days electrophysiological evidence of recovery of nerve conduction across the graft and of muscle activation was seen. Sections at this time showed nerve fibres and new functional neuromuscular junctions in the muscle. It is concluded that effective reinnervation of target muscles is possible after peripheral nerve repair using skeletal muscle autografts

Chronic ankle instability after ligamentous injuries has been attributed to loss of proprioception, but there has been no previous study of the mechanoreceptors in human ligaments at this joint. We have examined the ligaments from five cadaver ankles for mechanoreceptors and classified them into the four types described by Wyke and Freeman in their study of feline ligaments. Type-II receptors, thought to provide the sensation of the beginning of joint motion, and type-III receptors, thought to be activated at the extremes of movement, were the most common. Our findings provide some neuroanatomical data to validate further research into the use of proprioceptive training after ligamentous injuries about the ankle

Aims

The primary aim was to assess the independent influence of coronavirus disease (COVID-19) on 30-day mortality for patients with a hip fracture. The secondary aims were to determine whether: 1) there were clinical predictors of COVID-19 status; and 2) whether social lockdown influenced the incidence and epidemiology of hip fractures.

1. Severe osteolathyrism has been induced in chicks of different ages by a diet containing 50 per cent seeds of Lathyrus odoratus. 2. In these chicks, most of which became paraplegic after seven days, a meningeal tumour, articular and bony deformities, spontaneous fractures and osteoporosis have been observed. 3. In cartilage the lesion involves depletion of both neutral and acidic polysaccharides. 4. The primary effect on bone consists of changes in the osteoblasts and in the osteocytes involving cytoplasmic granulation and vacuolation, "mineralisation" and eventual disintegration of the cells. 5. These events are followed by osteoporosis. abnormal mineral deposits in the marrow spaces and reactive callus-like activation of the periosteum. 6. The role of the osteoblast and of the osteocyte in mineral transit and deposition is reconsidered

We examined ten femoral veins with duplex ultrasound during total hip replacement to demonstrate the operative manoeuvres which cause venous obstruction and to assess prophylactic measures which may overcome it. Exposure of the acetabulum by distraction of the femur with a hook was less likely to occlude flow than retraction with bone levers. Adequate exposure of the femoral shaft by adduction, flexion and either internal or external rotation caused cessation of flow in all cases. In four cases an A-V Impulse System foot pump was activated during periods of stasis. In each case it overcame the obstruction and produced peak velocities which were twice that of the resting state. In five cases, towards the end of the procedure, debris was seen travelling proximally through the femoral vein

Compartment syndrome is a unique form of ischaemia of skeletal muscle which occurs despite patency of the large vessels. Decompression allows the influx of activated leucocytes which cause further injury. Vitamin C is a powerful antioxidant which concentrates preferentially in leucocytes and attenuates reperfusion-induced muscle injury. We have evaluated the use of pretreatment with oral vitamin C in the prevention of injury caused by compartment syndrome in a rat cremasteric muscle model. Acute and delayed effects of pretreatment with vitamin C were assessed at one and 24 hours after decompression of compartment syndrome. Muscle function was assessed electrophysiologically. Vascular, cellular and tissue inflammation was assessed by staining of intercellular adhesion molecule-1 (ICAM-1) and by determination of the activity of myeloperoxidase (MPO) in neutrophils and tissue oedema. Compartment syndrome impaired skeletal muscle function and increased the expression of ICAM-1, activity of MPO and muscle weight increased significantly. Pretreatment with vitamin C preserved muscle function and reduced the expression of ICAM-1, infiltration of the neutrophils and oedema

Aims

It has been generally accepted that open fractures require early skeletal stabilization and soft-tissue reconstruction. Traditionally, a standard gauze dressing was applied to open wounds. There has been a recent shift in this paradigm towards negative pressure wound therapy (NPWT). The aim of this study was to compare the clinical outcomes in patients with open tibial fractures receiving standard dressing versus NPWT.

Aims

We studied the safety and efficacy of multimodal thromboprophylaxis in patients with a history of venous thromboembolism (VTE) who undergo total hip arthroplasty (THA) within the first 120 postoperative days, and the mortality during the first year. Multimodal prophylaxis includes discontinuation of procoagulant medications, VTE risk stratification, regional anaesthesia, an intravenous bolus of unfractionated heparin prior to femoral preparation, rapid mobilization, the use of pneumatic compression devices, and chemoprophylaxis tailored to the patient’s risk of VTE.

Aims

The current pandemic caused by COVID-19 is the biggest challenge for national health systems for a century. While most medical resources are allocated to treat COVID-19 patients, several non-COVID-19 medical emergencies still need to be treated, including vertebral fractures and spinal cord compression. The aim of this paper is to report the early experience and an organizational protocol for emergency spinal surgery currently being used in a large metropolitan area by an integrated team of orthopaedic surgeons and neurosurgeons.

Bone loss around replacement prostheses may be related to the activation of mononuclear phagocytes (MNP) by prosthetic wear particles. We investigated how osteoblast-like cells were regulated by human MNP stimulated by particles of prosthetic material. Particles of titanium-6-aluminium-4-vanadium (TiAlV) stimulated MNP to release interleukin (IL)-1β, tumour necrosis factor (TNF)α, IL-6 and prostaglandin E. 2. (PGE. 2. ). All these mediators are implicated in regulating bone metabolism. Particle-activated MNP inhibited bone cell proliferation and stimulated release of IL-6 and PGE. 2. The number of cells expressing alkaline phosphatase, a marker associated with mature osteo-blastic cells, was reduced. Experiments with blocking antibodies showed that TNFα was responsible for the reduction in proliferation and the numbers of cells expressing alkaline phosphatase. By contrast, IL-1β stimulated cell proliferation and differentiation. Both IL-1β and TNFα stimulated IL-6 and PGE. 2. release from the osteoblast-like cells. Our results suggest that particle-activated mono-nuclear phagocytes can induce a change in the balance between bone formation and resorption by a number of mechanisms

Seven subjects with normal joints were tested for active and passive position sense of ankle inversion, peroneal reflex reaction time to sudden ankle inversion, and postural stability during single-leg stance. The tests were performed before and after regional block of the ankle and foot with local anaesthetic. Passive position sense, assessed with the muscles relaxed, was greatly impaired by anaesthesia but active position sense, with the calf muscles activated, was preserved, and the peroneal reaction time to sudden ankle inversion was not altered. The magnitude of postural sway during single-leg stance was also unchanged by anaesthesia of the ankle and foot. The results suggest that the afferent input from intact lateral ankle ligaments is important in sensing correct placement of the foot at heel-strike, but that this input can be replaced by afferent information from active calf muscles. Afferent input from these muscles seems also to be responsible for dynamic ankle protection against sudden ankle inversion and is adequate to allow stable single-leg stance

Aims

The purpose of this study was to use pharmacogenetics to determine the frequency of genetic variants in our total knee arthroplasty (TKA) patients that could affect postoperative pain medications. Pharmacogenetic testing evaluates patient DNA to determine if a drug is expected to have a normal clinical effect, heightened effect, or no effect at all on the patient. It also predicts whether patients are likely to experience side effects from medicine. We further sought to determine if changing the multimodal programme based on these results would improve pain control or reduce side effects.

Aims

A retrospective longitudinal study was conducted to compare directly volumetric wear of retrieved polyethylene inserts to predicted volumetric wear modelled from individual gait mechanics of total knee arthroplasty (TKA) patients.

We performed transoesophageal echocardiography in 111 operations (110 patients) which included medullary reaming for fresh fractures of the femur and tibia, pathological lesions of the femur, and hemiarthroplasty of the hip. Embolic events of varying intensity were seen in 97 procedures and measured pulmonary responses correlated with the severity of embolic phenomena. Twenty-four out of the 25 severe embolic responses occurred while reaming pathological lesions or during cemented hemiarthroplasty of the hip and, overall, pathological lesions produced the most severe responses. Paradoxical embolisation occurred in four patients, all with pathological lesions of the femur (21%); two died. In 12 patients large coagulative masses became trapped in the heart. Extensive pulmonary thromboembolism with reamed bone and immature clot was found at post-mortem in two patients; there was severe systemic embolisation of fat and marrow in one who had a patent foramen ovale and widespread mild systemic fat embolisation in the other without associated foraminal defect. Sequential analysis of blood from the right atrium in five patients showed considerable activation of clotting cascades during reaming

We investigated the lymphocyte-mediated immune response to polymethylmethacrylate bone cement in 26 patients who had revision surgery for aseptic loosening of cemented total hip arthroplasties, at a mean time of seven years after the first replacement. We studied eight patients with cemented total hip arthroplasties which were not loose as controls. Patch tests to polymethylmethacrylate bone cement were positive in 13 patients with loosening, and these patients had higher lymphoblast transformation values against polymethylmethacrylate bone cement patients with a negative skin reaction (p < 0.01) or those in the control group (p < 0.001). Specific monoclonal antibodies were used to assess the percentage of certain cells of the immune system according to their cluster of differentiation (CD). There was a higher number of total T and B lymphocytes (CD2 and CD22) and interleukin-2 receptor-positive lymphocytes (activated cells, CD25) in patients with loose prostheses. More CD25 lymphocytes were found in patients with positive patch tests. The activation of the lymphocyte-mediated immune response was not related to the presence or absence of aggressive granulomatous lesions at the cement-bone interface

Particulate wear debris is associated with periprosthetic inflammation and loosening in total joint arthroplasty. We tested the effects of titanium alloy (Ti-alloy) and PMMA particles on monocyte/macrophage expression of the C-C chemokines, monocyte chemoattractant protein-1 (MCP-1), monocyte inflammatory protein-1 alpha (MIP-1α), and regulated upon activation normal T expressed and secreted protein (RANTES). Periprosthetic granulomatous tissue was analysed for expression of macrophage chemokines by immunohistochemistry. Chemokine expression in human monocytes/macrophages exposed to Ti-alloy and PMMA particles in vitro was determined by RT-PCR, ELISA and monocyte migration. We observed MCP-1 and MIP-1α expression in all tissue samples from failed arthroplasties. Ti-alloy and PMMA particles increased expression of MCP-1 and MIP-1α in macrophages in vitro in a dose- and time-dependent manner whereas RANTES was not detected. mRNA signal levels for MCP-1 and MIP-1α were also observed in cells after exposure to particles. Monocyte migration was stimulated by culture medium collected from macrophages exposed to Ti-alloy and PMMA particles. Antibodies to MCP-1 and MIP-1α inhibited chemotactic activity of the culture medium samples. Release of C-C chemokines by macrophages in response to wear particles may contribute to chronic inflammation at the bone-implant interface in total joint arthroplasty

Wear products of metal implants are known to induce biological events which may have profound consequences for the microcirculation of skeletal muscle. Using the skinfold chamber model and intravital microscopy we assessed microcirculatory parameters in skeletal muscle after confrontation with titanium and stainless-steel wear debris, comparing the results with those of bulk materials. Implantation of stainless-steel bulk and debris led to a distinct activation of leukocytes combined with a disruption of the microvascular endothelial integrity and massive leukocyte extravasation. While animals with bulk stainless steel showed a tendency to recuperation, stainless-steel wear debris induced such severe inflammation and massive oedema that the microcirculation broke down within 24 hours after implantation. Titanium bulk caused only a transient increase in leukocyte-endothelial cell interaction within the first 120 minutes and no significant change in macromolecular leakage, leukocyte extravasation or venular diameter. Titanium wear debris produced a markedly lower inflammatory reaction than stainless-steel bulk, indicating that a general benefit of bulk versus debris could not be claimed. Depending on its constituents, wear debris is capable of eliciting acute inflammation which may result in endothelial damage and subsequent failure of microperfusion. Our results indicate that not only the bulk properties of orthopaedic implants but also the microcirculatory implications of inevitable wear debris play a pivotal role in determining the biocompatibility of an implant

Aims

The use of frozen tumour-bearing autograft combined with a vascularized fibular graft (VFG) represents a new technique for biological reconstruction of massive bone defect. We have compared the clinical outcomes between this technique and Capanna reconstruction.

The long-term effect of stainless steel and titanium alloy plates on structural remodelling and bone mass of osteotomised canine femora was studied and the effects of early and late removal of plates were compared in 27 adult Beagles. Radiological, histological, histomorphometric and tetracycline fluorescence studies led to three conclusions. First, the continuous (60 weeks) presence of plates, irrespective of their composition, delays remodelling and leads to a reduction of bone mass. This loss is significantly greater under stainless steel plates. Secondly, the removal of plates at eight weeks leads during the 52 ensuing weeks to a marked and widespread structural remodelling and to a return to normal bone mass, irrespective of the type of plate used. However, remodelling is more intense after titanium alloy plates have been used; it is not complete 60 weeks after osteotomy. Thirdly, removal of plates at 40 weeks activates remodelling during the ensuing 20 weeks to a lesser degree and to a more limited extent than early plate removal. The clinical significance of this study is that less rigid but stable internal fixation permits the radiological assessment of healing and thus the determination of the optimal moment for removal of the plates. It also reduces the degree of bone loss should the plate be left in situ for any reason

Mononuclear osteoclast precursors are present in the wear-particle-associated macrophage infiltrate found in the membrane surrounding loose implants. These cells are capable of differentiating into osteoclastic bone-resorbing cells when co-cultured with the rat osteoblast-like cell line, UMR 106, in the presence of 1,25(OH). 2. vitamin D. 3. In order to develop an in vitro model of osteoclast differentiation which more closely parallels the cellular microenvironment at the bone-implant interface in situ, we determined whether osteoblast-like human bone-derived cells were capable of supporting the differentiation of osteoclasts from arthroplasty-derived cells and analysed the humoral conditions required for this to occur. Long-term co-culture of arthroplasty-derived cells and human trabecular-bone-derived cells (HBDCs) resulted in the formation of numerous tartrate-resistant-acid-phosphatase (TRAP) and vitronectin-receptor (VNR)-positive multinucleated cells capable of extensive resorption of lacunar bone. The addition of 1,25(OH). 2. vitamin D. 3. was not required for the formation of osteoclasts and bone resorption. During the formation there was release of substantial levels of M-CSF and PGE. 2. Exogenous PGE. 2. (10. −8. to 10. −6. M) was found to stimulate strongly the resorption of osteoclastic bone. Our study has shown that HBDCs are capable of supporting the formation of osteoclasts from mononuclear phagocyte precursors present in the periprosthetic tissues surrounding a loose implant. The release of M-CSF and PGE. 2. by activated cells at the bone-implant interface may be important for the formation of osteoclasts at sites of pathological bone resorption associated with aseptic loosening

It has been suggested that reamed intramedullary nailing of the femur should be avoided in some patients with multiple injuries. We have studied prospectively the effect of femoral reaming on the inflammatory process as implicated in the pathogenesis of acute respiratory distress syndrome (ARDS) and multiple-organ failure (MOF). We studied changes in the levels of serum interleukin-6 (IL-6) (proinflammatory cytokine), neutrophil CD11b (C3) receptor expression (activated neutrophil adhesion molecule), serum soluble intracellular adhesion molecule (s-ICAM-1), serum soluble E-selectin (the soluble products of endothelial adhesion molecules) and plasma elastase (neutrophil protease) in a series of patients with femoral fractures treated by nailing. We have also compared reamed nailing with unreamed nailing. We found that the levels of serum IL-6 and elastase rose significantly during the nailing procedure indicating a measurable ‘second hit’. There was no clear response in leukocyte activation and no difference in the release of endothelial adhesion molecule markers. There was no significant difference between groups treated by reamed and unreamed nailing. Although clinically unremarkable, the one patient who died from ARDS was shown to be hyperstimulated after injury and again after nailing, suggesting the importance of an excessive inflammatory reaction in the pathogenesis of these serious problems. Our findings have shown that there is a second hit associated with femoral nailing and suggest that the degree of the inflammatory reaction may be important in the pathogenesis of ARDS and MOF

Aims

The aim of this study was to determine and compare the congruency of the articular surface contact area of the patellofemoral joint (PFJ) during both active and passive movement of the knee with the use of an MRI mapping technique in both the stable and unstable PFJ.

Periprosthetic osteolysis is a major cause of aseptic loosening in artificial joint replacement. It is assumed to occur in conjunction with the activation of macrophages. We have shown in vitro that human osteoblast-like cells, isolated from bone specimens obtained from patients undergoing hip replacement, phagocytose fine particles of titanium alloy (TiAlV). The human osteoblast-like cells were identified immunocytochemically by the presence of bone-specific alkaline phosphatase (BAP). With increasing duration of culture, a variable number of the osteoblastic cells became positive for the macrophage marker CD68, independent of the phagocytosis of particles, with a fine granular cytoplasmic staining which was coexpressed with BAP as revealed by immunodoublestaining. The metal particles were not toxic to the osteoblastic cells since even in culture for up to four weeks massively laden cells were vital and had a characteristic morphology. Cells of the human osteosarcoma cell line (HOS 58) were also able to phagocytose metal particles but had only a low expression of the CD68 antigen. Fluorescence-activated cell scanning confirmed our immunocytochemical results. Additionally, the cells were found to be negative for the major histocompatibility complex-II (MHC-II) which is a marker for macrophages and other antigen-presenting cells. Negative results of histochemical tests for tartrate-resistant acid phosphatase excluded the contamination by osteoclasts or macrophages in culture. Our observations suggest that the osteoblast can either change to a phagocytosing cell or that the phagocytosis is an underestimated property of the osteoblast. The detection of the CD68 antigen is insufficient to prove the monocytic lineage. In order to discriminate between macrophages and osteoblasts additional markers should be used. To our knowledge, this is the first demonstration of cells of an osteoblastic origin which have acquired a mixed phenotype of both osteoblasts and macrophages

Aims

Infected and deformed neuropathic feet and ankles are serious challenges for surgical management. In this study we present our experience in performing ankle arthrodesis in a closed manner, without surgical preparation of the joint surfaces by cartilaginous debridement, but instead using an Ilizarov ring fixator (IRF) for deformity correction and facilitating fusion, in arthritic neuropathic ankles with associated osteomyelitis.

Frozen shoulder is a chronic fibrosing condition of the capsule of the joint. The predominant cells involved are fibroblasts and myofibroblasts which lay down a dense matrix of type-I and type-III collagen within the capsule. This subsequently contracts leading to the typical features of pain and stiffness. Cytokines and growth factors regulate the growth and function of the fibroblasts of connective tissue and remodelling of the matrix is controlled by the matrix metalloproteinases (MMPs) and their inhibitors. Our aim was to determine whether there was an abnormal expression or secretion of cytokines, growth factors and MMPs in tissue samples from 14 patients with frozen shoulder using the reverse transcription/polymerase chain reaction (RT/PCR) technique and to compare the findings with those in tissue from four normal control shoulders and from five patients with Dupuytren’s contracture. Tissue from frozen shoulders demonstrated the presence of mRNA for a large number of cytokines and growth factors although the frequency was only slightly higher than in the control tissue. The frequency for a positive signal for the proinflammatory cytokines Il-1β and TNF-α and TNF-β, was not as great as in the Dupuytren’s tissue. The presence of mRNA for fibrogenic growth factors was, however, more similar to that obtained in the control and Dupuytren’s tissue. This correlated with the histological findings which in most specimens showed a dense fibrous tissue response with few cells other than mature fibroblasts and with very little evidence of any active inflammatory cell process. Positive expressions of the mRNA for the MMPs were also increased, together with their natural inhibitor TIMP. The notable exception compared with control and Dupuytren’s tissue was the absence of MMP-14, which is known to be a membrane-type MMP required for the activation of MMP-2 (gelatinase A). Understanding the control mechanisms which play a part in the pathogenesis of frozen shoulder may lead to the development of new regimes of treatment for this common, protracted and painful chronic fibrosing condition

Aims

The aim of this study was to evaluate blood metal ion levels, leucocyte profiles, and serum cytokines in patients with a total hip arthroplasty (THA) involving modular dual-mobility components.

Aseptic loosening is a major cause of failure of total hip arthroplasty. The adverse tissue response to prosthetic wear particles, with activation of cytokine and prostanoid production, contributes to bone loss around the implants. We have investigated the possibility that inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) are expressed in macrophages in the pseudomembrane at the bone-implant interface, thereby contributing to the periprosthetic bone resorption. We also assessed whether peroxynitrite, a nitric oxide (NO)-derived oxidant associated with cellular injury, is generated in the membrane. Enzymatic activity of iNOS was measured using the arginine-citrulline assay technique and prostaglandin E. 2. (PGE. 2. ), as an indicator of COX-2 activity, was measured using an enzyme immunoassay. Cellular immunoreactivity for iNOS, nitrotyrosine (a marker of peroxynitrite-induced cellular injury) and COX-2 was assessed by quantitative peroxidase immunocytochemistry while immunofluorescence methods were used for subsequent co-localisation studies with CD68. +. macrophages. The presence of calcium-independent iNOS activity and PGE. 2. production was confirmed in the homogenized interface membrane. Immunocytochemistry showed that periprosthetic CD68. +. wear-debris-laden macrophages were the most prominent cell type immunoreactive for iNOS, nitrotyrosine and COX-2. Other periprosthetic inflammatory and resident cell types were also found to immunolocalise nitrotyrosine thereby suggesting peroxynitrite-induced protein nitrosylation and cellular damage not only in NO-producing CD68. +. macrophages, but also in their neighbouring cells. These data indicate that both iNOS and COX-2 are expressed by CD68. +. macrophages in the interface membrane and peroxynitrite-induced cellular damage is evident in such tissue. If high-output NO and peroxynitrite generation were to cause macrophage cell death, this would result in the release of phagocytosed wear debris into the extracellular matrix. A detrimental cycle of events would then be established with further phagocytosis by newly-recruited inflammatory cells and subsequent NO, peroxynitrite and prostanoid synthesis. Since both NO and have been implicated in the induction and PGE. 2. maintenance of chronic inflammation with resulting loss of bone, and peroxynitrite in the pathogenesis of disease states, they may be central to the pathogenesis of aseptic loosening

Aims

To investigate the benefits of denosumab in combination with nerve-sparing surgery for treatment of sacral giant cell tumours (GCTs).

We performed a crossover study to evaluate the haemodynamic effect of active dorsal to plantar flexion and seven pneumatic compression devices in ten patients who had a total knee arthroplasty. Using the Acuson 128XP/10 duplex ultrasound unit with a 5MHz linear array probe, we assessed the augmentation of peak venous velocity and venous volume above and below the junction of the greater saphenous and common femoral veins in order to study both the deep and superficial venous systems. The pneumatic compression devices evaluated included two foot pumps (A-V Impulse System and PlexiPulse Foot), a foot-calf pump (PlexiPulse Foot-Calf), a calf pump (VenaFlow System) and three calf-thigh pumps (SCD System, Flowtron DVT and Jobst Athrombic Pump). The devices differed in a number of ways, including the length and location of the sleeve and bladder, the frequency and duration of activation, the rate of pressure rise, and the maximum pressure achieved. A randomisation table was used to determine the order of the test conditions for each patient. The enhancement of peak venous velocity occurred primarily in the deep venous system below the level of the saphenofemoral junction. The increases in peak venous velocity were as follows: active dorsal to plantar flexion 175%; foot pumps, A-V Impulse System 29% and PlexiPulse 65%; foot-calf pump, PlexiPulse, 221%; calf pump, VenaFlow, 302% and calf-thigh pumps, Flowtron DVT 87%, SCD System 116% and Jobst Athrombic Pump 263%. All the devices augmented venous volume, the greatest effect being seen with those incorporating calf compression. The increases in ml/min were found in the deep venous system as follows: foot pumps, A-V Impulse System 9.6 and PlexiPulse Foot 16.7; foot-calf pump, PlexiPulse, 38.1; calf pump, VenaFlow, 26.2; calf-thigh pumps, Flowtron DVT 61.5, SCD System 34.7 and Jobst Athrombic Pump 82.3. Active dorsal to plantar flexion generated 8.5 ml for a single calf contraction

Aims

Improvements in the evaluation of outcomes following peripheral nerve injury are needed. Recent studies have identified muscle fatigue as an inevitable consequence of muscle reinnervation. This study aimed to quantify and characterize muscle fatigue within a standardized surgical model of muscle reinnervation.

Aims

The aim of this study was to investigate the effects of preoperative bisphosphonate treatment on the intra- and postoperative outcomes of arthroplasty of the shoulder. The hypothesis was that previous bisphosphonate treatment would adversely affect both intra- and postoperative outcomes.

Aims

Antifibrinolytic agents, including tranexamic acid (TXA) and epsilon-aminocaproic acid (EACA), have been shown to be safe and effective for decreasing perioperative blood loss and transfusion following total hip arthroplasty (THA) and total knee arthroplasty (TKA). However, there are few prospective studies that directly compare these agents. The purpose of this study was to compare the benefits of intraoperative intravenous TXA with EACA.