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Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_2 | Pages 7 - 7
10 Feb 2023
Brennan A Doran C Cashman J
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As Total Hip Replacement (THR) rates increase healthcare providers have sought to reduce costs, while at the same time improving patient safety and satisfaction. Up to 50% of patients may be appropriate for Day Case THR, and in appropriately selected patients’ studies show no increase in complication rate while affording a significant cost saving and maintaining a high rate of patient satisfaction. Despite the potential benefits, levels of adoption of Day Case THR vary. A common cause for this is the perception that doing so would require the adoption of new surgical techniques, implants, or theatre equipment. We report on a Day-Case THR pathway in centres with an established and well-functioning Enhanced Recovery pathway, utilising the posterior approach and standard implants and positioning. We prospectively collected the data on consecutive THRs performed by a single surgeon between June 2018 and July 2021. A standardised anaesthetic regimen using short acting spinal was used. Surgical data included approach, implants, operative time, and estimated blood loss. Outcome data included time of discharge from hospital, post operative complications, readmissions, and unscheduled health service attendance. Data was gathered on 120 consecutive DCTHRs in 114 patients. 93% of patients were successfully discharged on the day of surgery. Four patients required re-admission: one infection treated with DAIR, one dislocation, one wound ooze admitted for a day of monitoring, one gastric ulcer. One patient had a short ED attendance for hypertension. Our incidence of infection, dislocation and wound problems were similar to those seen in inpatient THR. Out data show that the widely used posterior approach using standard positioning and implants can be used effectively in a Day Case THR pathway, with no increase in failure of same-day discharge or re-admission to hospital


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_3 | Pages 112 - 112
23 Feb 2023
Deng Y Zhang D Smith P Li R
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Hip and knee arthroplasty (HKA) are two of the most successful orthopaedic procedures. However, one major complication necessitating revision surgery is osteolysis causing aseptic loosening of the prosthesis. JAK-STAT has been demonstrated to influence bone metabolism and can be regulated by microRNA (miRNA). Adult patients with osteolysis or aseptic loosening undergoing revision HKA were recruited. Age and gender matched patients undergoing primary hip or knee arthroplasty were our controls. Samples of bone, tissue and blood were collected and RNA isolation was performed. The best quality samples were used for RNA-sequencing. Data analysis was performed using RStudio and Galaxy to identify differentially expressed genes. Western blotting of IL6 was used to confirm protein expression. Five circulating miRNA were identified which had 10 differentially expressed genes in bone and 11 differentially expressed genes in tissue related to the JAK-STAT pathway. IL6 in bone and EpoR in bone were highly significant and IL6 in tissue, MPL in bone, SOCS3 in tissue, JAK3 in bone and SPRED1 in bone were borderline significant. Western blot results demonstrated up-expression of IL6 in bone tissue of revision patients. Periprosthetic osteolysis and aseptic loosening can be attributed to miRNA regulation of the JAK-STAT pathway in osteoblasts and osteoclasts, leading to increased bone resorption. These findings can be used for further experiments to determine utility in the clinical setting for identifying diagnostic markers or therapeutic targets


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_3 | Pages 30 - 30
23 Feb 2023
Abdul NM Raymond A Finsterwald M Malik S Aujla R Wilson H Dalgleish S Truter P Giwenewer U Simpson A Mattin A Gohil S Ricciardo B Lam L D'Alessandro P
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Traditionally, sports Injuries have been sub-optimally managed through Emergency Departments (ED) in the public health system due to a lack of adequate referral processes. Fractures are ruled out through plain radiographs followed by a reactive process involving patient initiated further follow up and investigation. Consequently, significant soft tissue and chondral injuries can go undiagnosed during periods in which early intervention can significantly affect natural progression. The purpose of this quality improvement project was to assess the efficacy of an innovative Sports Injury Pathway introduced to detect and treat significant soft tissue injuries. A Sports Injury Pathway was introduced at Fiona Stanley Hospital (WA, Australia) in April 2019 as a collaboration between the ED, Physiotherapy and Orthopaedic Departments. ED practitioners were advised to have a low threshold for referral, especially in the presence of a history of a twisting knee injury, shoulder dislocation or any suggestion of a hip tendon injury. All referrals were triaged by the Perth Sports Surgery Fellow with early follow-up in our Sports Trauma Clinics with additional investigations if required. A detailed database of all referrals was maintained, and relevant data was extracted for analysis over the first 3 years of this pathway. 570 patients were included in the final analysis. 54% of injuries occurred while playing sport, with AFL injuries constituting the most common contact-sports injury (13%). Advanced Scope Physiotherapists were the largest source of referrals (60%). A total of 460 MRI scans were eventually ordered comprising 81% of total referrals. Regarding Knee MRIs, 86% identified a significant structural injury with ACL injuries being the most common (33%) followed by isolated meniscal tears (16%) and multi-ligament knee injuries (11%). 95% of Shoulder MRI scans showed significant pathology. 39% of patients required surgical management, and of these 50% were performed within 3 months from injury. The Fiona Stanley Hospital Sports Injury Pathway has demonstrated its clear value in successfully diagnosing and treating an important cohort of patients who present to our Emergency Department. This low threshold/streamlined referral pathway has found that the vast majority of these patients suffer significant structural injuries that may have been otherwise missed, while providing referring practitioners and patients access to prompt imaging and high-quality Orthopaedic sports trauma services. We recommend the implementation of a similar Sports Injury Pathway at all secondary and tertiary Orthopaedic Centres


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_1 | Pages 15 - 15
1 Jan 2022
Tamboowalla KB Gandbhir V Nagai H Wynn-Jones H Talwalker S Kay P
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Abstract. Background. The COVID-19 pandemic has strongly impacted elective orthopaedic surgery. At our trust, a geographically discrete elective site deals with planned orthopaedic surgery. There was a need to define a green pathway to deliver surgical care safely and efficiently, and tackle mounting waiting lists. Methods. Records of patients operated at our elective site, between 1. st. July 2020 and 14. th. January 2021, under a green pathway, including pre-operative self-isolation, COVID screening and segregating perioperative patients, were reviewed, and analysed retrospectively. Patients who did not attend (DNA) their post-operative follow-up appointments were identified. Finally, regional COVID incidence was compared with that in our centre. Results. During this period, 2466 patients were admitted for elective orthopaedic surgery, of which sixteen (0.6%) tested COVID-positive. Among these, two tested positive during asymptomatic in-patient screening, five tested positive within two weeks of discharge, while six tested positive beyond two weeks. One patient tested positive on the day of surgery, which was then postponed. Fourteen (87.5%) patients who tested positive recovered, with two COVID-related mortalities. We identified 34 (1.4%) DNA patients. The COVID incidence in our centre closely paralleled the regional incidence. There were no major COVID outbreaks and no definite evidence of in-hospital transmission. Conclusion. This green pathway has helped streamline patient flow for continuing elective surgery safely through the pandemic, under cautionary monitoring. Modulating elective activity in response to regional COVID rates is vital for addressing waiting lists. Given the encouraging results, this pathway is an effective measure for maintaining elective activity through the pandemic


Bone & Joint Open
Vol. 1, Issue 9 | Pages 562 - 567
14 Sep 2020
Chang JS Wignadasan W Pradhan R Kontoghiorghe C Kayani B Haddad FS

Aims. The safe resumption of elective orthopaedic surgery following the peak of the COVID-19 pandemic remains a significant challenge. A number of institutions have developed a COVID-free pathway for elective surgery patients in order to minimize the risk of viral transmission. The aim of this study is to identify the perioperative viral transmission rate in elective orthopaedic patients following the restart of elective surgery. Methods. This is a prospective study of 121 patients who underwent elective orthopaedic procedures through a COVID-free pathway. All patients underwent a 14-day period of self-isolation, had a negative COVID-19 test within 72 hours of surgery, and underwent surgery at a COVID-free site. Baseline patient characteristics were recorded including age, American Society of Anaesthesiologists (ASA) grade, body mass index (BMI), procedure, and admission type. Patients were contacted 14 days following discharge to determine if they had had a positive COVID-19 test (COVID-confirmed) or developed symptoms consistent with COVID-19 (COVID-19-presumed). Results. The study included 74 females (61.2%) and 47 males (38.8%) with a mean age of 52.3 years ± 17.6 years (18 to 83 years). The ASA grade was grade I in 26 patients (21.5%), grade II in 70 patients (57.9%), grade III in 24 patients (19.8%), and grade IV in one patient (0.8%). A total of 18 patients (14.9%) had underlying cardiovascular disease, 17 (14.0%) had pulmonary disease, and eight (6.6%) had diabetes mellitus. No patients (0%) had a positive COVID-19 test in the postoperative period. One patient (0.8%) developed anosmia postoperatively without respiratory symptoms or a fever. The patient did not undergo a COVID-19 test and self-isolated for seven days. Her symptoms resolved within a few days. Conclusion. The development of a COVID-free pathway for elective orthopaedic patients results in very low viral transmission rates. While both surgeons and patients should remain vigilant, elective surgery can be safely restarted using dedicated pathways and procedures. Cite this article: Bone Joint Open 2020;1-9:562–567


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_11 | Pages 35 - 35
1 Nov 2022
Bommireddy L Daoud H Morris D Espag M Tambe A Clark D
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Abstract. Introduction. In our quality improvement project we implemented a novel pathway, performing acute fixation in mid-third clavicle fractures with >15% shortening. Patients with <15% shortening reviewed at 6 weeks, non-union risk identified as per Edinburgh protocol and decision to operate made accordingly. Methods. Retrospective pre-pathway analysis of patients presenting 04/2017–04/2019. Prospective post-pathway analysis of patients presenting 10/2020–10/2021. Fracture shortening measured using Matsumura technique. QuickDASH and recovery questionnaires posted to >15% shortening patients and done post-pathway at 3 months. Results. Pre-pathway retrospective cohort included 141 patients; 69 <15%, 72 >15% shortening. Acute ORIF performed in 15(22%) <15% and 34(47%) >15%. In those conservatively managed, non-union occurred in 2 patients with <15% shortening, and 5 with >15% shortening. Union time was significantly longer in >15% treated non-operatively compared to those requiring ORIF and <15% (18.4 vs 13.4 vs 12.0 weeks; p<0.05). QuickDASH significantly worse in >15% managed conservatively than operatively (17.6 vs 2.8; p<0.05). >15% ORIF had significantly fewer number of weeks until undisturbed sleep than those treated non-operatively (2.3 vs 10.1; p<0.05). Post-pathway prospective cohort included 37 patients; 17 <15% (of which 1 underwent delayed ORIF), 20 >15% shortening (of which 15 underwent acute ORIF). No significant increase in proportion ORIF performed (43% vs 38%). No non-unions occurred. Conclusion. Acute fixation in >15% shortening was associated with better QuickDash scores and reduced union times than those treated non-operatively. Implementation of our pathway resulted in no nonunions compared to 5% pre-implementation and thus identifies patients benefitting from acute fixation


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_6 | Pages 1 - 1
1 May 2021
Rossiter D Roberts J Heylen J Harb Z Elliott D
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Introduction. Ashford and St Peter's Hospital (ASPH) is a district general hospital in Chertsey, Surrey. It is a tertiary referral unit offering a circular frame service to manage complex trauma patients in the South East of England. This study analyses the patient pathway in 66 consecutive tertiary referrals from 2015–2020. All patients were managed with an Ilizarov frame for either a tibial plateau fracture or pilon fracture. Materials and Methods. The patient journey of 66 consecutive tertiary referrals for tibial plateau and pilon fractures were analysed. The following data was captured: patient demographics; type of injury; referring centre; date of injury; date of referral; date of arrival at ASPH; date of surgery and date of discharge. Using this data we aimed to identify areas of the pathway that can be improved. In addition, the 66 patients were split into two groups of 33 patients. 33 patients were referred via an electronic referral platform and 33 patients were referred verbally prior to the implementation of the electronic referral platform. The groups were compared to see the impact of an electronic referral platform on the patient's journey. Results. Average age 45 (range 17–88 years), Male percentage 54.55%, 45 tibial plateau patients, 21 pilon patients. Injury to Admission at ASPH- 6 days (median), Injury to Surgery 8 days (median), Surgery to Discharge 4 days (median), Total stay in ASPH 6 days (median). Conclusions. The biggest delay in our tertiary referral pathway is from referral to arrival at ASPH. The implementation of an electronic referral pathway has not improved times from referral to arrival at ASPH. Ring fenced beds for tertiary referrals would be the greatest way to improve flow through the pathway and reduce the complications related to delayed surgery


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_6 | Pages 73 - 73
1 Jul 2020
Albiero A Piombo V Diamanti L Birch M McCaskie A
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Osteoarthritis is a global problem and the treatment of early disease is a clear area of unmet clinical need. Treatment strategies include cell therapies utilising chondrocytes e.g. autologous chondrocyte implantation and mesenchymal stem/stromal cells (MSCs) e.g. microfracture. The result of repair is often considered suboptimal as the goal of treatment is a more accurate regeneration of the tissue, hyaline cartilage, which requires a more detailed understanding of relevant biological signalling pathways. In this study, we describe a modulator of regulatory pathways common to both chondrocytes and MSCs. The chondrocytes thought to be cartilage progenitors are reported to reside in the superficial zone of articular cartilage and are considered to have the same developmental origin as MSCs present in the synovium. They are relevant to cartilage homeostasis and, like MSCs, are increasingly identified as candidates for joint repair and regenerative cell therapy. Both chondrocytes and MSCs can be regulated by the Wnt and TGFβ pathways. Dishevelled Binding Antagonist of Beta-Catenin (Dact) family of proteins is an important modulator of Wnt and TGFβ pathways. These pathways are key to MSC and chondrocyte function but, to our knowledge, the role of DACT protein has not been studied in these cells. DACT1 and DACT2 were localised by immunohistochemistry in the developing joints of mouse embryos and in adult human cartilage obtained from knee replacement. RNAi of DACT1 and DACT2 was performed on isolated chondrocytes and MSCs from human bone marrow. Knockdown efficiency and cell morphology was confirmed by qPCR and immunofluorescence. To understand which pathways are affected by DACT1, we performed next-generation sequencing gene expression analysis (RNAseq) on cells where DACT1 had been reduced by RNAi. Top statistically significant (p < 0 .05) 200 up and downregulated genes were analysed with Ingenuity® Pathway Analysis software. We observed DACT1 and DACT2 in chondrocytes throughout the osteoarthritic tissue, including in chondrocytes forming cell clusters. On the non-weight bearing and visually undamaged cartilage, DACT1 and DACT2 was localised to the articular surface. Furthermore, in mouse embryos (E.15.5), we observed DACT2 at the interzones, sites of developing synovial joints, suggesting that DACT2 has a role in cartilage progenitor cells. We subsequently analysed the expression of DACT1 and DACT2 in MSCs and found that both are expressed in synovial and bone marrow-derived MSCs. We then performed an RNAi knockdown experiment. DACT1 knockdown in both chondrocyte and MSCs caused the cells to undergo apoptosis within 24 hours. The RNA-seq study of DACT1 silenced bone marrow-derived MSCs, from 4 different human subjects, showed that loss of DACT1 has an effect on the expression of genes involved in both TGFβ and Wnt pathways and putative link to relevant cell regulatory pathways. In summary, we describe for the first time, the presence and biological relevance of DACT1 and DACT2 in chondrocytes and MSCs. Loss of DACT1 induced cell death in both chondrocytes and MSCs, with RNA-seq analysis revealing a direct impact on transcript levels of genes involved in the Wnt and TFGβ signalling, key regulatory pathways in skeletal development and repair


Objective. Guidelines published by the British Association of Spine Surgeons (BASS) and Society of British Neurological Surgeons (SBNS) recommend urgent MRI imaging and intervention in individuals suspected of having CES. The need for an evidence based protocol is driven by a lack of 24/7 MRI services and centralisation of neurosurgery to tertiary centres, compounded by CES's significant medico-legal implications. We conducted an audit to evaluate the pathway for suspected CES in BCUHB West between 2018 and 2021. Methods. A retrospective audit of patients managed for suspected CES between 01/11/2018 and 01/05/2021 was performed, using the SBNS/BASS guidelines as the standard. Results. A total of 252 patients received an emergency MRI for suspected CES between 2018 and 2021. 99% of patients were scanned in compliance with SBNS/BASS standards. Radiological evidence of CES was found in 18% of patients. 33% of emergency scans were performed by out-of-hours services. 4% of patients had repeated scans within the same 6-month period. The majority of referrals originated from Orthopaedics surgeons (78%), or staff in the Emergency Department (8%). 92% of ambulatory patients were not admitted to hospital. During the peak of the COVID-19 pandemic, referrals increased from 2.5 to 3.5 per week. Conclusion. SBNS/BASS standards were largely met, avoiding life changing disability and medico-legal consequences. The department should continue to follow SBNS/BASS guidance on the management of individuals with suspected CES. Challenges regarding the use of repeated scans should be addressed to avoid unnecessary costs. Introduction of new early recognition guidelines and Same Day Emergency Care (SDEC) has likely driven an increase in suspected CES referrals, and subsequent MRI demand. This audit should be utilised as an ongoing tool to ensure best practice continues, and to implement simple measures which may improve compliance with the pathway


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_6 | Pages 101 - 101
1 Jul 2020
Comeau-Gauthier M Tarchala M Ramirez-GarciaLuna J Harvey E Merle G
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Bone regeneration includes a well-orchestrated series of biological events of bone induction and conduction. Among them, the Wnt/β-catenin signaling pathway is critical for bone regeneration. Being involved in several developmental processes, Wnt/β-catenin signaling must be safely targeted. There are currently only few specific therapeutic agents which are FDA-approved and already entered clinical trials. A published work has shown that Tideglusib, a selective and irreversible small molecule non-ATP-competitive glycogen synthase kinase 3-β(GSK-3β) inhibitor currently in trial for Alzheimer's patients, can promote tooth growth and repair cavities. [1]Despite some differences, they are some similarities between bone and tooth formation and we hypothesise that this new drug could represent a new avenue to stimulate bone healing. In this work, we locally delivered Tideglusib (GSK3β inhibitor) in the repair of femoral cortical window defects and investigated bone regeneration. A biodegradable FDA-approved collagen sponge was soaked in GSK-3βinhibitor solution or vehicle only (DMSO) and was implanted in 1 × 2 mm unicortical defects created in femora of 35 adult wild-type male mice. Bone defect repair on control and experimental (GSK-3βinhibitor) groups was assessed after 1 week (n=22), 2 weeks (n=24) and 4 weeks (n=24) with microCT and histological analysis foralkaline phosphatase (ALP, osteoblast activity), tartrate resistant acid phosphatase (TRAP, osteoclasts), and immunohistochemistry to confirm the activation of the Wnt/β-catenin pathway. Our results showed that Tideglusib significantly enhanced cortical bone bridging (20.6 ±2.3) when compared with the control (12.7 ±1.9, p=0.001). Activity of GSK-3β was effectively downregulated at day 7 and 14 resulting in a higher accumulation of active β-catenin at day 14 in experimental group (2.5±0.3) compared to the control (1.1±0.2, p=0.03). Furthermore, the onset of ALP activity appears earlier in the experimental group (day 14, 1.79±0.28), a level of activity never reached at any end-point by the control defects. At 4 weeks treatment, we observed a significant drop in ALP in the experimental group (0.47±0.05) compared to the control (1.01±0.19, p=0.02) and a decrease in osteoclast (experimental=1.32±0.36, control=2.23±0.67, p=0.04). Local downregulation of GSK-3β by tideglusib during bone defect repair resulted in significant increase in amount of new bone formation. The early upregulation of osteoblast activity is one explanation of bone healing augmentation. This is likely the effect of upregulation of β-catenin following pharmaceutical inhibition of GSK-3β since β-catenin activation is known to positively regulate osteoblasts, once committed to the osteoblast lineage. As a GSK-3β inhibitor, Tideglusib demonstrates a different mechanism of action compared with other GSK-3β antagonists as treatment was started immediately upon injury and did not interfere with precursor cells recruitment and commitment. This indicates that tideglusib could be used at the fracture site during the initial intraoperative internal fixation without the need for further surgery. This safe and FDA-approved drug could be used in prevention of non-union in patients presenting with high risk for fracture-healing complications


Rapid discharge pathways (RDP) have been implemented throughout most areas of orthopaedics. The primary goal of these pathways is to standardize the post-surgical hospital course for patients in order to decrease hospital length-of-stay (LOS). Surgical treatment of adolescent idiopathic scoliosis (AIS) remains one of the most invasive pediatric orthopaedic procedure and is routinely associated with a prolonged hospital stay. The implementation of RDPs following surgery for AIS has shown to be successful; however, all of these studies have been conducted within the United States and it has been shown previously that there exists major differences in hospital LOS and in post-operative complications between Canada and the United States. Therefore, the objective of this study was to determine if the implementation of a RDP at a single children's tertiary-referral centre in Canada could decrease hospital LOS without increasing post-operative complications. A retrospective chart review was completed for all patients who underwent posterior spinal instrumentation and fusion (PSIF) between March 1st, 2010 and February 28th, 2019, with date of implementation being March 1st, 2015. Patient pre-operative, operative, and post-operative information was collected from the charts along with the primary outcome variables: LOS, wound complication, 30-day return to the OR, 30-day emergency department admission, and 30-day hospital readmission. An interrupted time series analysis with a robust linear regression model was utilized to assess for any differences in outcomes following implementation of the RDP. Ninety days before and after the implementation of the RDP was not included in this analysis due to variances in practice that were occurring at this time. A total of 244 participants were identified, with 113 patients in the conventional pathway and 131 patients in the RDP cohort. No significant differences in pre-operative or operative characteristics existed between the groups, except for the RDP group having approximately a 50 larger pre-operative curve and the conventional pathway having on average 200mL greater intra-operative blood loss (p<0.05). Hospital LOS was found to be significantly shorter in the RDP group, with the median LOS being 5.2 [95% IQR 4.3–6.1] days in the conventional group and 3.4 [95% IQR 3.3–3.5] days in the RDP group (p<0.05). Patients in the RDP group were also found to stand 0.9 days earlier, walk 1.1 days earlier, their Foley catheter was discontinued 0.5 days earlier and their personal controlled analgesia was discontinued 12 hours sooner (p<0.05). There were no differences in post-operative complications between the two groups (p>0.05). This study demonstrates that implementing a RDP following PSIF for AIS can successfully decrease hospital LOS without increasing post-operative complications in a single payer universal healthcare system. The associated decrease in LOS could correlate with decreasing costs for both the healthcare system and for the patient's family


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_20 | Pages 13 - 13
1 Nov 2016
Nam D Wang Y Whetstone H Alman B
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The T-lymphocyte secreted pro-inflammatory cytokine, interleukin-17F (IL-17F), was found to be a key mediator in the cellular response of the immune system in the early phase of fracture repair but its intracellular signaling processes are currently not known in osteoblasts. The objective of this study was to identify the signaling proteins and crucial gene targets involved in osteoblast activation via IL-17F. It was hypothesised that IL-17F stimulated osteoblast maturation through a novel GSK3beta / beta-catenin independent pathway. Mouse pre-osteoblast cell line (MC3T3-E1) was used for IL-17F or Wnt3a treatment. Desired proteins were detected using western blot analysis (antibodies: Phospho-GSK-3beta (Tyr 216), Phospho-GSK-3beta (Ser9), Runx2/cbfa1, TRAF6, Act1, p-ERK2, p-JNK and p-MAPK, C/EBP-beta and & delta). Gene-specific siRNAs of mouse IL-17Ra, IL-17Rc and a non-targeting siRNA (control) were utilised. MC3T3-E1 were transfected with IL-17Ra, IL-17Rc or Negative Control and treated with IL-17F. Chromatin Immunoprecipitation (ChIP-qPCR) was used to evaluate the mouse Runx2 P1 promoter region. IL-17F increased expression of Col1, BSP, Runx2/cbfa1 and osteocalcin in MC3T3-E1 cells. Western blot analysis confirmed expression of known Wnt signaling proteins TRAF6, Act1, p-ERK2, p-JNK and p-MAPK in both IL-17F and Wnt3a treated cultures, including up-regulation of Runx2/cbfa1, a key transcription factor associated with osteoblast differentiation. IL-17F up-regulation of Runx2/cbfa1 appears independent of the Wnt/beta-catenin pathway as phosphorylated GSK-3beta at the Ser9 site was not detected with IL-17F treatment. Despite this, IL-17F treatment still increased expression of Runx2/cbfa1 downstream, lending evidence for a GSK3beta/beta-catenin independent manner of IL-17F stimulated osteogenesis. While IL-17F and Wnt3a both induced expression of C/EBP-delta, only IL-17F treatment induced expression of C/EBP-beta, an upstream transcription factor of Runx2/cbfa1. Further, siRNA knock down of the IL-17 receptors directly decreased Act1, C/EBP-beta and Runx2/cfba1 expression. By ChIP analysis, IL-17F was shown to upregulate C/EBP-beta expression and stimulated its binding to the P1 Promoter of the Runx2/cbfa1 gene. The C/EBP-beta transcription factor was shown to be a key regulator of early osteogenesis. C/EBP-beta up-regulates Runx2/cbfa1 expression by directly binding to the Runx2/cbfa1 P1 promoter in osteoblasts. C/EBP-beta was activated in the osteoblast by IL-17F but not by Wnt3a adding further support to a novel GSK3beta/beta-catenin independent pathway. Our data shows that IL-17F, a cytokine secreted by T-lymphocytes, stimulates osteoblast maturation through a novel GSK3beta/beta-catenin independent pathway and reveals a crucial interaction between C/EBP-beta and the Runx2/cbfa1 P1 promoter not previously been shown in osteogenesis signaling further


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_7 | Pages 77 - 77
1 May 2016
Chimento G Duplantier N Sumarriva G Meyer M Thomas L Dias D Schubert A
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Background. The Perioperative Surgical Home (PSH) is a multi-disciplinary rapid recovery pathway aimed at transforming surgical care by delivering value and improving outcomes and patient satisfaction. Our institution developed a PSH pathway for total hip arthroplasty (THA) patients in March 2014. The Orthopaedic and Anesthesia Services co-managed the patients throughout the entire surgical process. Weekly meetings were held to discuss medical and social requirements for upcoming patients including disposition planning. All patients received day of surgery physical therapy, and anesthesia post-surgical pain control and medical co-management. We hypothesized that the PSH would provide enhanced care for THA patients. To our knowledge this is the first report on the PSH in a total joint population. Methods. We prospectively followed 180 THA patients from the PSH group (SH) and compared them to a group matched for age, body mass index (BMI), American society of anesthesiologist score (ASA), and Charleson comorbidity index score (CCI) that were not involved in the PSH (NSH). We used Wilcoxon, Chi square, and multivariate analysis to compare the groups for length of stay (LOS), total direct cost (TDC), complications, readmissions at 30 days, and discharge disposition location. Results. No significant difference was found between the two cohorts with respect to age, BMI, ASA, or CCI. The average age, BMI, ASA and CCI were 64, 30, 2.5, and 3.6. The average LOS of the SH cohort was 2.1 days which was significantly lower than the NSH cohort at 3.6 days (P<0.001). Significantly more patients were discharged to home in the SH group, 83% versus 71% in the NSH group (P=0.006) regardless of age (P=0.003) and ASA (P=0.048). No significant difference was found between the two groups with regard to complications (P=0.346), TDC (P=0.883), or readmissions at 30 days (P=0.637). Discussion. The implementation of the PSH led to decreased length of stay and allowed more patients to be discharged to home, without an increase in complications or readmissions. We were able to accomplish this in patients with higher ASA and CCI scores which has not been the case in other rapid recovery programs. Effective care pathways require contribution and cooperation by multiple healthcare personnel throughout the phases of patient care. We feel that key factors contributing to the success of the PSH include post-surgical co-management by anesthesia, early physical therapy, and weekly meetings to discuss patients’ individual needs for disposition


Enhanced recovery pathways (ERPs) utilise multimodal rehabilitation techniques to reduce post-operative pain and accelerate the rehabilitation process following surgery. Originally described following elective colonic surgery enhanced recovery pathways have gained increasing use following elective hip and knee joint replacement in recent years. Early studies have indicated that enhanced recovery pathways can reduce length of hospital stay, reduce complications and improve cost-effectiveness of joint replacement surgery. Despite this growing evidence base uptake has been slow in certain centres and many surgeons are yet to utilise enhanced recovery pathways in their practice. We look at the process and effects of implementing an enhanced recovery pathway following total hip replacement surgery at a district general hospital in the United Kingdom. A retrospective study was initially undertaken over a four-month period to assess patient demographics, length of stay, time to physiotherapy and complication rates including re-admission within 28 days. Based on national recommendations an enhanced recovery pathway protocol was then implemented for an elective total hip replacement list. Inclusion criteria were elective patients undergoing primary total hip replacement (THR) surgery. The pathway included pre-operative nutrition optimisation, 4mg ondansetron, 8mg dexamethasone and 1g tranexamic acid at induction and 150mL ropivacaine HCL 0.2%, 30mg ketorolac and adrenaline (RKA) mix infiltration to joint capsule, external rotators, gluteus tendon, iliotibial band, soft-tissues and skin around the hip joint. The patient was mobilised four-hours after surgery where possible and aimed to be discharged once mobile and pain was under control. Following implementation a prospective study was undertaken to compare patient demographics, length of stay and complication rates including re-admission within 28 days. 34 patients met the inclusion criteria and were included in each group pre and post-enhanced recovery pathway. Following implementation of an enhanced recovery pathway mean length of stay decreased from 5.4 days to 3.5 days (CI 1.94, p < 0.0001). Sub-group analysis based on ASA grade revealed that this reduction in length of stay was most pronounced in ASA 1 patients with mean length of stay reduced from 5.0 days to 3.2 days (CI 1.83, p < 0.0001). There was no significant change in the number of complications or re-admission rates following enhanced recovery pathway. The enhanced recovery pathway was quick and easy to implement with co-ordination between surgeons, anaesthetist, nursing staff and patients. This observational study of consecutive primary total hip replacement patients shows a substantial reduction in length of stay with no change in complication rates after the introduction of a multimodal enhanced recovery protocol. Both of these factors reduce hospital costs for elective THR patients and may improve patient experiences


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_6 | Pages 1 - 1
1 Jul 2020
Xiong L Hu Y Ding F Shao Z Wang W Liu G Cai X
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The purpose of this study was to evaluate whether AGEs induce annulus fibrosus (AF) cell apoptosis and to further explore the mechanism by which this process occurs. AF cells were treated with various concentrations of AGEs for 3 days. Cell proliferation was measured by the Cell Counting Kit-8 (CCK-8) and EdU incorporation assays. Cell apoptosis was examined by the Annexin V/PI apoptosis detection kit and Hoechst 33342. The expression of apoptosis-related proteins, including Bax, Bcl-2, cytochrome c, caspase-3 and caspase-9, was detected by western blotting. In addition, Bax and Bcl-2 mRNA expression levels were detected by RT-PCR. Mitochondrial membrane potential (MMP) and intracellular reactive oxygen species (ROS) production of AF cell were examined by JC-1 staining and DCFH-DA fluorescent probes, respectively. Our results indicated that AGEs had inhibitory effects on AF cell proliferation and induced AF cell apoptosis. The molecular data showed that AGEs significantly up-regulated Bax expression and inhibited Bcl-2 expression. In addition, AGEs increased the release of cytochrome c into the cytosol and enhanced caspase-9 and caspase-3 activation. Moreover, treatment with AGEs resulted in a decrease in MMP and the accumulation of intracellular ROS in AF cells. The antioxidant N-acetyl-L-cysteine significantly reversed AGE-induced MMP decrease and AF cell apoptosis. These results suggest that AGEs induce rabbit AF cell apoptosis and mitochondrial pathways may be involved in AGE-mediated cell apoptosis, which may provide a theoretical basis for diabetic IVD degeneration


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_1 | Pages 191 - 191
1 Jan 2013
Shenouda M Silk Z Radha S Bouanem E Radford W
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Aim. A new multidisciplinary hip fracture pathway, based on national BOA and NICE guidance, was introduced in our institution to facilitate rapid preoperative medical optimisation and early surgery for patients with hip fractures. The aim of this audit was to assess its impact on patient care and outcomes. Method. A prospective audit of 161 patients admitted with a fractured neck of femur was conducted in the six months before (92 patients) and after (69 patients) implementation of the new pathway. Data included: time to orthogeriatric assessment (TtG); time to surgery (TtS); length of hospital stay (LOS); return to original accommodation; and inpatient mortality rate. Significance was tested using Chi Squared, Fisher's exact and unpaired Student t-Tests. Results. The two groups of patients were equivalent in terms of age, male:female ratio, ASA grade and preoperative AMTS. In the six months after the introduction of the pathway, 85% of patients received a pre-operative medical assessment compared to 19% before (p=0.0001). Average TtG dropped from 91 to 19 hours (p=0.0001). LOS dropped from 24.8 days to 19.5 days (p=0.029). Furthermore, a significant reduction in mortality of 10% (14% before, 4% after, p=0.0336) was found, with an increase in the proportion of patients returning to their original place of accommodation (57% before, 80% after, p=0.0069). Whilst limited by theatre scheduling, there was an observed reduction in TtS of 6 hours (37 vs 31, p=0.0663). Conclusions. Rapid medical optimisation and prompt surgery can significantly reduce length of stay and inpatient mortality of patients with hip fractures. This is especially important in light of their often fragile physiological state and complex co-morbidities. Successful implementation of a multidisciplinary hip fracture pathway can increase the return of patients to their preoperative accommodation, thus maintaining their level of pre-morbid independence and potentially leading to significant future cost savings


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XLI | Pages 32 - 32
1 Sep 2012
Yu Y Luk F Yang J Walsh W
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To set up an osteosarcoma mouse model with spontaneous lung metastasis and to identify a marker of osteosarcoma metastasis and to inhibit the marker against the invasive ability of an osteosarcoma cell line. A human osteosarcoma orthotopic mouse model was set up by injecting 143B human osteosarcoma cells into mouse tibia. Type I insulin-like growth factor receptor (IGF-1R) and its downstream signalling factors were measured in samples from the primary tumor and the lung secondaries by immunohistochemistry. Human Alu mRNA expression was tested using in situ hybridization assay. A Matrigel assay was used to assess cell invasion ability under the interference of a MEK/ERK pathway specific inhibitor, U0126. All fifteen mice showed tumour mass at the left tibia and lung metastasis. Human Alu expression in the primary and secondary tumours confirmed human origin of the tumour cells. Total IGF-1R, MEK, Akt, p38 and phosphorylated MEK (p-MEK), but not p-Akt and p-p38, were positive in both local tumours and lung secondaries. Leiomyosarcoma controls expressed p-Akt and p-MEK, but not p-p38. The 143B cells treated with U0126 had significantly lower in vitro invasion ability compared with controls. The IGF-1R-MEK signalling pathway, particularly Ras/Raf/MEK/ERK, may play an important role in osteosarcoma lung metastasis, and the targeting MEK/ERK by its specific inhibitor may have a potential use in the effective treatment of osteosarcoma


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_3 | Pages 68 - 68
1 Feb 2017
Chimento G Duplantier N Sumarriva G Meyer M Thomas L Dias D Schubert A
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Background. The Perioperative Surgical Home (PSH) is a physician-led, patient centered, rapid recovery care delivery model that includes multi-specialty care teams and cost-efficient use of resources developed to deliver patient centered value based care. The purpose of this study was to compare a group of patients undergoing primary total hip arthroplasty (THA) managed in the PSH model to a matched group managed in a more traditional fashion with respect to clinical outcomes, complications, and costs. Methods. We prospectively followed the first 180 THA patients from the PSH group, comparing them to a group matched for age, Body Mass Index (BMI), American Society of Anesthesiologists (ASA) Score, and Charlson Comorbidity Index (CCI) that was treated prior to implementation of the PSH. A combination of regional anesthesia and multi-modal pain control was used to minimize patient narcotic consumption. There was a rapid de-escalation of care post-operatively. Weekly multi disciplinary meetings were held where advanced discharge planning was discussed and we evaluated successes and areas of improvement of the prior week in an effort to continuously improve. We used Wilcoxon, Chi square, and multivariate regression analysis to compare the groups for length of stay (LOS), total direct cost (TDC), complications, 30-day readmissions, and discharge location. Results. The mean age, BMI, ASA Score, and CCI was 64, 30, 3.0, and 3.5 for both groups. The LOS in the PSH group was 2.1 days, which was significantly lower than the Non Surgical Home (NSH) group at 3.6 days (P<0.001). Significantly more patients were discharged home in the PSH group, 83%, versus 71% in the NSH (P=0.006). No significant difference was found between the two groups with regard to complications (P=0.346), TDC (P=0.883), or readmissions at 30 days (P=0.637). Regarding the TDC, room and board cost $1,916 for the NSH group, and $1,375 for the PSH group secondary to the shorter LOS. This was a 28% reduction in room and board cost for the PSH group. This was offset, however, by an unforeseen increase in operating room labor cost during the study period. This cost increased from $1,672 in 2012–2013 (the period from which the NSH cohort was obtained) to $2,265 in the PSH time period. This was over a 26% increase. Multivariate analysis showed the PSH cohort was an independent variable associated with decreased LOS (P<0.001) and discharge to home (P<0.001). Conclusion. We believe the implementation of the Perioperative Surgical Home led to decreased LOS and allowed more patients to be discharged to home, without an increase in complications or readmissions. We believe this model is successful at providing patient centered value based care. The actual clinical pathway continues to be in use and is being further refined as we are regularly evaluating outcomes and finding areas of improvement


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 48 - 48
1 Dec 2022
Yee N Iorio C Shkumat N Rocos B Ertl-Wagner B Green A Lebel D Camp M
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Neuromuscular scoliosis patients face rates of major complications of up to 49%. Along with pre-operative risk reduction strategies (including nutritional and bone health optimization), intra-operative strategies to decrease blood loss and decrease surgical time may help mitigate these risks. A major contributor to blood loss and surgical time is the insertion of instrumentation which is challenging in neuromuscular patient given their abnormal vertebral and pelvic anatomy. Standard pre-operative radiographs provide minimal information regarding pedicle diameter, length, blocks to pedicle entry (e.g. iliac crest overhang), or iliac crest orientation. To minimize blood loss and surgical time, we developed an “ultra-low dose” CT protocol without sedation for neuromuscular patients.

Our prospective quality improvement study aimed to determine: if ultra-low dose CT without sedation was feasible given the movement disorders in this population; what the radiation exposure was compared to standard pre-operative imaging; whether the images allowed accurate assessment of the anatomy and intra-operative navigation given the ultra-low dose and potential movement during the scan.

Fifteen non-ambulatory surgical patients with neuromuscular scoliosis received the standard spine XR and an ultra-low dose CT scan. Charts were reviewed for etiology of neuromuscular scoliosis and medical co-morbidities. The CT protocol was a high-speed, high-pitch, tube-current modulated acquisition at a fixed tube voltage. Adaptive statistical iterative reconstruction was applied to soft-tissue and bone kernels to mitigate noise. Radiation dose was quantified using reported dose indices (computed tomography dose index (CTDIvol) and dose-length product (DLP)) and effective dose (E), calculated through Monte-Carlo simulation. Statistical analysis was completed using a paired student's T-test (α = 0.05). CT image quality was assessed for its use in preoperative planning and intraoperative navigation using 7D Surgical System Spine Module (7D Surgical, Toronto, Canada).

Eight males and seven females were included in the study. Their average age (14±2 years old), preoperative Cobb angle (95±21 degrees), and kyphosis (60±18 degrees) were recorded. One patient was unable to undergo the ultra-low dose CT protocol without sedation due to a co-diagnosis of severe autism. The average XR radiation dose was 0.5±0.3 mSv. Variability in radiographic dose was due to a wide range in patient size, positioning (supine, sitting), number of views, imaging technique and body habitus. Associated CT radiation metrics were CTDIvol = 0.46±0.14 mGy, DLP = 26.2±8.1 mGy.cm and E = 0.6±0.2 mSv. CT radiation variability was due to body habitus and arm orientation. The radiation dose differences between radiographic and CT imaging were not statistically significant. All CT scans had adequate quality for preoperative assessment of pedicle diameter and orientation, obstacles impeding pedicle entry, S2-Alar screw orientation, and intra-operative navigation.

“Ultra-low dose” CT scans without sedation were feasible in paediatric patients with neuromuscular scoliosis. The effective dose was similar between the standard preoperative spinal XR and “ultra-low dose” CT scans. The “ultra-low dose” CT scan allowed accurate assessment of the anatomy, aided in pre-operative planning, and allowed intra-operative navigation despite the movement disorders in this patient population.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_12 | Pages 68 - 68
1 Dec 2022
Yee N Lorio C Shkumat N Rocos B Ertl-Wagner B Green A Lebel D Camp M
Full Access

Neuromuscular scoliosis patients face rates of major complications of up to 49%. Along with pre-operative risk reduction strategies (including nutritional and bone health optimization), intra-operative strategies to decrease blood loss and decrease surgical time may help mitigate these risks. A major contributor to blood loss and surgical time is the insertion of instrumentation which is challenging in neuromuscular patient given their abnormal vertebral and pelvic anatomy. Standard pre-operative radiographs provide minimal information regarding pedicle diameter, length, blocks to pedicle entry (e.g. iliac crest overhang), or iliac crest orientation. To minimize blood loss and surgical time, we developed an “ultra-low dose” CT protocol without sedation for neuromuscular patients.

Our prospective quality improvement study aimed to determine:

if ultra-low dose CT without sedation was feasible given the movement disorders in this population;

what the radiation exposure was compared to standard pre-operative imaging;

whether the images allowed accurate assessment of the anatomy and intra-operative navigation given the ultra-low dose and potential movement during the scan.

Fifteen non-ambulatory surgical patients with neuromuscular scoliosis received the standard spine XR and an ultra-low dose CT scan. Charts were reviewed for etiology of neuromuscular scoliosis and medical co-morbidities. The CT protocol was a high-speed, high-pitch, tube-current modulated acquisition at a fixed tube voltage. Adaptive statistical iterative reconstruction was applied to soft-tissue and bone kernels to mitigate noise. Radiation dose was quantified using reported dose indices (computed tomography dose index (CTDIvol) and dose-length product (DLP)) and effective dose (E), calculated through Monte-Carlo simulation. Statistical analysis was completed using a paired student's T-test (α= 0.05). CT image quality was assessed for its use in preoperative planning and intraoperative navigation using 7D Surgical System Spine Module (7D Surgical, Toronto, Canada).

Eight males and seven females were included in the study. Their average age (14±2 years old), preoperative Cobb angle (95±21 degrees), and kyphosis (60±18 degrees) were recorded. One patient was unable to undergo the ultra-low dose CT protocol without sedation due to a co-diagnosis of severe autism. The average XR radiation dose was 0.5±0.3 mSv. Variability in radiographic dose was due to a wide range in patient size, positioning (supine, sitting), number of views, imaging technique and body habitus. Associated CT radiation metrics were CTDIvol = 0.46±0.14 mGy, DLP = 26.2±8.1 mGy.cm and E = 0.6±0.2 mSv. CT radiation variability was due to body habitus and arm orientation. The radiation dose differences between radiographic and CT imaging were not statistically significant. All CT scans had adequate quality for preoperative assessment of pedicle diameter and orientation, obstacles impeding pedicle entry, S2-Alar screw orientation, and intra-operative navigation.

“Ultra-low dose” CT scans without sedation were feasible in paediatric patients with neuromuscular scoliosis. The effective dose was similar between the standard preoperative spinal XR and “ultra-low dose” CT scans. The “ultra-low dose” CT scan allowed accurate assessment of the anatomy, aided in pre-operative planning, and allowed intra-operative navigation despite the movement disorders in this patient population.