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Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_16 | Pages 18 - 18
17 Nov 2023
Gallagher H Naeem H Wood N Daou HN Pereira MG Giannoudis PV Roberts LD Howard A Bowen TS
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Abstract. Introduction. Skeletal muscle wasting is an important clinical issue following acute traumatic injury, and can delay recovery and cause permanent functional disability particularly in the elderly. However, the fundamental mechanisms involved in trauma-induced muscle wasting remain poorly defined and therapeutic interventions are limited. Objectives. To characterise local and systemic mediators of skeletal muscle wasting in elderly patients following acute trauma. Methods. Experiments were approved by a local NHS Research Ethics Committee and all participants provided written informed consent. Vastus lateralis biopsies and serum samples were taken from human male and female patients shortly after acute trauma injury in lower limbs (n=6; mean age 78.7±4.4 y) and compared to age-matched controls (n=6; mean age 72.6±6.3 y). Atrogenes and upstream regulators (MuRF1; MAFbx; IL6, TNFα, PGC-1α) mRNA expression was assessed in muscle samples via RT-qPCR. Serum profiling of inflammatory markers (e.g. IL6, TNFα, IL1β) was further performed via multiplex assays. To determine whether systemic factors induced by trauma directly affect muscle phenotype, differentiated primary human myotubes were treated in vitro with serum from controls or trauma patients (pooled; n=3 each) in the final 24 hours of differentiation. Cells were then fixed, stained for myogenin and imaged to determine minimum ferret diameter. Statistical significance was determined at P<0.05. Results. There was an increase in skeletal muscle mRNA expression for E3 ligase MAFbx and inflammatory cytokine IL-6 (4.6 and 21.5-fold respectively; P<0.05) in trauma patients compared to controls. Expression of myogenic determination factor MyoD and regulator of mitochondrial biogenesis PGC-1α was lower in muscle of trauma patients vs controls (0.5 and 0.39-fold respectively; P<0.05). In serum, trauma patients showed increased concentrations of circulating pro-inflammatory cytokines IL-6 (14.5 vs. 0.3 pg/ml; P<0.05) and IL-16 (182.7 vs. 85.2 pg/ml; P<0.05) compared to controls. Primary myotube experiments revealed serum from trauma patients induced atrophy (32% decrease in diameter) compared to control serum-treated cells (P<0.001). Conclusion. Skeletal muscle from patients following acute trauma injury showed greater expression of atrophy and inflammatory markers. Trauma patient serum exhibited higher circulating pro-inflammatory cytokine concentrations. Primary human myotubes treated with serum from trauma patients showed significant atrophy compared to healthy serum-treated controls. We speculate a mechanism(s) acting via circulating factors may contribute to skeletal muscle pathology following acute trauma. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_2 | Pages 110 - 110
2 Jan 2024
Barbosa F Silva J Garrudo F Cabral J Morgado J Ferreira F
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Bone defects can result from different incidents such as acute trauma, infection or tumor resection. While in most instances bone healing can be achieved given the tissue's innate ability of self-repair, for critical-sized defects spontaneous regeneration is less likely to occur, therefore requiring surgical intervention. Current clinical procedures have failed to adequately address this issue. For this reason, bone tissue engineering (BTE) strategies involving the use of synthetic grafts for replacing damaged bone and promoting the tissue's regeneration are being investigated. The electrical stimulation (ES) of bone defects using direct current has yielded very promising results, with neo tissue formation being achieved in the target sites in vivo. Electroactive implantable scaffolds comprised by conductive biomaterials could be used to assist this kind of therapy by either directing the ES specifically to the damaged site or promoting the integration of electrodes within the bone tissue as a coating. In this study, we developed novel conductive heat-treated polyacrylonitrile/poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PAN/PEDOT:PSS) nanofibers via electrospinning capable of mimicking key native features of the bone tissue's extracellular matrix (ECM) and providing a platform for the delivery of exogenous ES. The developed scaffolds were doped with sulfuric acid and mineralized in Simulated Body Fluid to mimic the inorganic phase of bone ECM. As expected, the doped PAN/PEDOT:PSS nanofibers exhibited electroconductive properties and were able to preserve their fibrous structure. The addition of PEDOT:PSS was found to improve the bioactivity of the scaffolds, with a more significant in vitro mineralization being obtained. By seeding the scaffolds with MG-63 osteoblasts and human mesenchymal stem/stromal cells, an increased cell proliferation was observed for the mineralized PAN/PEDOT:PSS nanofibers, which also registered an increased expression of key osteogenic markers (e.g Osteopontin). Our findings appear to corroborate the promising potential of the generated nanofibers for future ES-based BTE applications. Acknowledgements: The authors thank FCT for funding through the projects InSilico4OCReg (PTDC/EME-SIS/0838/2021), BioMaterARISES (EXPL/CTM-CTM/0995/2021) and OptiBioScaffold (PTDC/EME-SIS/32554/2017, POCI-01- 0145-FEDER- 32554), the PhD scholarship (2022.10572.BD) and through institutional funding to iBB (UIDB/04565/2020 and UIDP/04565/2020), Associate Laboratory i4HB (LA/P/0140/2020) and IT (UIDB/50008/2020)


Symptomatic articular cartilage defects are one of the most common knee injuries, arising from acute trauma, overuse, ligamentous instability, malalignment, meniscectomy, osteochondritis dissecans. Surgical treatment options include bone marrow–stimulating techniques such as abrasion arthroplasty and microfracture, osteochondral mosaicplasty, corrective osteotomy, cartilage resurfacing techniques and tissue engineering techniques using combinations of autologous cells (chondrocytes and mesenchymal stem cells), bioscaffolds, and growth factors. Matrix induced autologous chondrocyte implantation (MACI) is considered the most surgically simple form of autologous chondrocyte implantation. Our group has involved in the development of MACI since 2000 and has led to the FDA approval of MACI as the first tissue engineering product for cartilage repair in 2016. In this article, we have documented the characterisation of autologous chondrocytes, the surgical procedure of MACI and the long term clinical assessment (15 years) of patients with treatment of MACI. We have also reported the retrospective survey in patients with MACI in Australia. Our results suggest that MACI has gained good to excellent long term clinical outcome and probably can delay total knee replacement. However, restoration of hyaline-like cartilage by MACI may be interrupted by the osteoarthritic condition of the joint in patients with progressed osteoarthritis. In addition, because articular cartilage and subchondral bone are considered a single functional unit that is essential for joint function, many cartilage repair technologies including MACI and microfractures have failed short to address the functional barrier structure of osteochondral unit. Further studies are required to develop tissue engineering osteochondral construct that is able to fulfil the function of articular cartilage-subchondral bone units


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_4 | Pages 50 - 50
1 Apr 2018
Hafez M Cameron R Rice R
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Background. Surgical wound closure is not the surgeon”s favorite part of the total knee arthroplasty (TKA) surgery however it has vital rule in the success of surgery. Knee arthoplasty wounds are known to be more prone to infection, breakdown or delayed healing compared to hip arthroplasty wounds, and this might be explained by the increased tensile force applied on the wound with knee movement. This effect is magnified by the enhanced recovery protocols which aim to obtain high early range of movement. Most of the literature concluded that there is no difference between different closure methods. Objectives. We conducted an independent study comparing the complication rate associated with using barbed suture (Quill-Ethicon), Vicryl Rapide (polyglactins910-Ethicon) and skin staples for wound closure following TKA. Study Design & Methods. Retrospective study where the study group included all the patients admitted to our unit for elective primary knee arthroplasty in 2015, we excluded patients admitted for partial knee arthroplasty, revision knee arthroplasty or arthroplasty for treatment of acute trauma due to the relatively higher complication rates. All the patients notes were reviewed to identify wound related problems such as wound dehiscence, wound infection and delayed healing (defined as delayed wound healing more than 6 weeks). Results. 327 patients were included in this study; 151 in Quill group, 99 in staples group and 77 in the last group where the wound closed with Rapide. We identified 9 (5.9%) cases of wound dehiscence in the Quill group, 3 cases of wound dehiscence in each of other two groups (3.8%) with Rapide and (3%) with staples. On the other hand superficial wound infection was higher with staples with 6 (6%) cases of wound infection compared to the other groups, wound infection occurred in 2 patients (2.5%) with Rapide and 5 patients (3.3%) in the Quill”s group. Most of the delayed wound healing happened after using Quill where it is reported in 5 patients (3.3%) and the lowest was in staples group with 1 patient (1%) and slightly higher percentage in Rapide group 2 patients (2.5%). The total figure of wound related problems was the highest in Quill”s group with 19 reported cases (12.5%), lower in staples” group with 10 cases (1.1%) and the lowest in Rapide”s group with 7 cases (9%). Conclusions. Our study showed different results to the reported literature suggesting that each closure method has its own advantages and disadvantages. Quill is quick, knotless and absorbable but on the other side it is significantly more expensive than other alternatives and it is associated with the highest complication rates. On the other hand Rapide is cheap absorbable alternative with the lowest percentage of wound problems but on the negative side it is time consuming. Finally staples method is the quickest, relatively cheap and rarely associated with wound dehiscence but it is not absorbable which might cause inconvenience to patients


Bone & Joint 360
Vol. 12, Issue 6 | Pages 49 - 51
1 Dec 2023
Burden EG Whitehouse MR Evans JT


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_31 | Pages 26 - 26
1 Aug 2013
Welsh F Martin D
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The aim is to report a rare technique for correction of intramedullary nail acute angular deformity. Intramedullary tibial nail fixation of diaphyseal tibial fractures is the gold standard treatment allowing early mobilisation whilst preserving the soft tissues around the fracture site. Most commonly, intramedullary nails fail by metal fatigue secondary to non union, without significant deformity of the metalwork. Plastic deformity of the nail can result following new acute trauma, particularly before bone union has occurred. This is a clinical challenge as a reamed intramedullary nail is designed to achieve three point fixation with close anatomical fit, such that removal of a bent nail is technically difficult and also risks further damage to bone and soft tissues. We report a case of a 20 year old patient treated with intramedullary nail fixation of a diaphyseal right tibial fracture who was subsequently assaulted 4 weeks post operatively. This produced an unacceptable deformation of the nail into 25 degrees valgus and procurvatum. To remove the nail, the authors used a previously reported but rare technique of partial (up to 50%) nail division on the convex surface of the apex using Midas Rex High Speed Drill to weaken the nail then manipulation to correct deformity with minimal stress. The technique produced minimal metal debris and allowed simple exchange nail replacement without further complication. The authors believe this is the first reported use of the technique from the United Kingdom


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 268 - 268
1 Jul 2014
Doornberg J Bosse T Cohen M Jupiter J Ring D Kloen P
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Summary. In contrast to the current literature, myofibroblasts are not present in chronic posttraumatic elbow contractures. However, myofibroblasts are present in the acute phase after an elbow fracture and/or dislocation. This suggests a physiological role in normal capsule healing and a potential role in the early phase of posttraumatic contracture formation. Introduction. Elbow stiffness is a common complication after elbow trauma. The elbow capsule is often thickened, fibrotic and contracted upon surgical release. The limited studies available suggest that the capsule is contracted because of fibroblast to myofibroblast differentiation. However, the timeline is controversial and data on human capsules are scarce. We hypothesise that myofibroblasts are absent in normal capsules and early after acute trauma and elevated in patients with posttraumatic elbow contracture. Patients & Methods. We obtained twenty-one human elbow joint capsules within fourteen days after an elbow fracture and/or dislocation and thirty-four capsules from thirty-four patients who had operative release of posttraumatic contractures greater than five months after injury. Myofibroblasts in the joint capsules were quantified using immunohistochemistry. Alpha-smooth muscle actin (α-SMA) was used as a marker for myofibroblasts. Samples were characterised and scored by an independent pathologist blinded for clinical data. Results. Eleven capsules were associated with the acute phase after trauma (hours to 7 days), and staining for α-SMA was negative in all eleven specimens. Ten specimens were associated with a later phase post trauma with myofibroblasts staining positive for α-SMA in all but two. All, but two, thirty-four long standing contractures showed a histological pattern consistent with chronic stages of fibrosis, characterised by increased fibroblast-like cell proliferation and higher cellular density of fibroblast-like cells with highly unstructured collagen. There was no staining of α-SMA in fibroblast-like cells in, all but two of these longstanding contractures suggesting absence of myofibroblasts. Conclusions. This study present ‘negative results’ on the hypothesis that myofibroblast numbers are elevated in longstanding (> 5 months) human posttraumatic elbow capsules. This is in contrast to all studies on human tissue in the literature to date. One recent animal study is in agreement withy our data. We did find some myofibroblasts in elbow capsules in the late-phase posttrauma (between 7 and 14 days) suggesting a potential role in early phase of posttraumatic contracture formation


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XI | Pages 9 - 9
1 Apr 2012
Holt G Smith R Duncan K McKeown DW
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Delay to theatre after hip fracture is common in order to medically optimise the patient prior to surgery. The association between delay to surgery and mortality after hip fracture remains a contentious issue. We aimed to investigate how medical postponement, time to surgery and correction of medical abnormalities prior to surgery affect peri-operative mortality after hip fracture. From February to December 2007 prospective data was collected from all acute trauma units in Scotland relating to hip fracture patients' fitness for theatre, reasons for postponement of surgery and subsequent plans of action. The data-set recorded whether medical abnormalities were identified following criteria reported by McLaughlin et al. Survival at 30-days post-operation was used as primary outcome measure. Multivariable logistic regression models were used to control for differences in case-mix between patients. Data were available for 4284 patients. Patients postponed for medical reasons were less likely to survive to 30 days compared to patients who were not postponed (87% (122/947) versus 93% (3098/3337)). Survival also decreased as time to theatre increased - 92% of patients operated on during the same/next day vs. 89% of those operated on admission day four. However, after controlling for differences in case-mix variables and co-morbidities, neither variable significantly affected survival. We then analysed whether delaying surgery to resolve medical problems improved survival. Adjusted survival was not significantly different between those patients who had their medical problem resolved prior to surgery compared to those patients who were not postponed. Individuals who were postponed but did not have their clinical abnormality resolved prior to surgery had significantly lower adjusted 30 day survival. The possible benefits of postponement need to be weighed against prolonged discomfort and the possibility of developing other complications. Postponing patients who cannot be medically improved should be avoided


Bone & Joint Research
Vol. 6, Issue 5 | Pages 259 - 269
1 May 2017
McKirdy A Imbuldeniya AM

Objectives

To assess the clinical and cost-effectiveness of a virtual fracture clinic (VFC) model, and supplement the literature regarding this service as recommended by The National Institute for Health and Care Excellence (NICE) and the British Orthopaedic Association (BOA).

Methods

This was a retrospective study including all patients (17 116) referred to fracture clinics in a London District General Hospital from May 2013 to April 2016, using hospital-level data. We used interrupted time series analysis with segmented regression, and direct before-and-after comparison, to study the impact of VFCs introduced in December 2014 on six clinical parameters and on local Clinical Commissioning Group (CCG) spend. Student’s t-tests were used for direct comparison, whilst segmented regression was employed for projection analysis.