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Bone & Joint Research
Vol. 3, Issue 4 | Pages 108 - 116
1 Apr 2014
Cheng K Giebaly D Campbell A Rumley A Lowe G

Objective

Mortality rates reported by the National Joint Registry for England and Wales (NJR) were higher following cemented total knee replacement (TKR) compared with uncemented procedures. The aim of this study is to examine and compare the effects of cemented and uncemented TKR on the activation of selected markers of inflammation, endothelium, and coagulation, and on the activation of selected cytokines involved in the various aspects of the systemic response following surgery.

Methods

This was a single centre, prospective, case-control study. Following enrolment, blood samples were taken pre-operatively, and further samples were collected at day one and day seven post-operatively. One patient in the cemented group developed a deep-vein thrombosis confirmed on ultrasonography and was excluded, leaving 19 patients in this cohort (mean age 67.4, (sd 10.62)), and one patient in the uncemented group developed a post-operative wound infection and was excluded, leaving 19 patients (mean age 66.5, (sd 7.82)).


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 8 - 8
1 Mar 2006
Verettas D
Full Access

Joint replacement implants, especially in their modular forms, are subjected to wear and corrosion at various sites in their articulation, such as the bearing surfaces, the undersurface of the insert, the femoral head-neck junction and the implant or polymethylmethacrylate-bone interface. Movement of the bearing surfaces is not the only cause, as faulty implant positioning can initiate wear through impingement between two parts of the articulation.

These wear products of polyethelene or metal, in particulate form, are influential to the ultimate fate of the prostheses through the initiation of local and systemic immune reactions.

These debris are phagocytised by macrophages and phagocytised proteins are partly degraded in intracellular vesicles, where they become associated with the major histocompatability complex molecule HLA-DR. This molecule when transported to the cell membrane, interacts with CD4+ lymphocytes to activate an immune response and initiate the production of interleukin1b, interleukin 6 and tumor necrosing factor a. These cytokines mediate the inflammatory response and activate osteoclasts causing periprosthetic osteolysis.

Polyethelene and metal wear particles, in addition to their local effects, can be disseminated beyond the periprosthetic tissues and reach distant organs and regional lymphnodes. The concentrations of certain elements of metallic implants, such as iron, cobalt, chromium or titanium have been detected in lymphnodes, the liver and the spleen in levels a lot higher than normal, especially in patients with loose prostheses and, less so, in patients with stable prostheses.

The reported values of metal ions in published series vary. Thus certain investigators (Brodner et al) have reported continuous systemic cobalt release during a five year follow-up period and in levels slightly above detection values, while others (Clarke et al, Lohtka et al) have reported consistently high levels of cobalt and chromium ions in metal on metal articulations. The diameter of the femoral head appears to be a significant factor. In surface hip replacements with large diameter heads the amount of detected metal ions was significantly higher compared with total hip replacements with use of 28mm diameter femoral heads. In that type of replacement the levels of cobalt was 50 times higher than normal and of chromium 100 times higher.

Polyethelene particles, similarily have been detected in paraaortic lymphnodes in percentages similar to metal ions. However the detection of PE particles in the liver or the spleen was less, compared to metal ions, possibly due to the difficulty of modern methods to detect PE particles of submicrometre size. The relevance of the dissemination of metal ions and of PE wear debris in organs distal to the operated joint need to be carefully evaluated since certain of these elements are known carcinogens. Two studies have reported slight increase of haemopoeitic cancers in patients with cobalt alloy implants and in patients with metal on metal devices, while others have documented the development of malignant tumours in the vicinity of total hip replacements.

Since prostheses with metal on metal bearing surfaces are used more and more frequently in younger patients, these patients require careful monitoring for longer periods.


The Bone & Joint Journal
Vol. 104-B, Issue 3 | Pages 359 - 367
1 Mar 2022
Deere K Matharu GS Ben-Shlomo Y Wilkinson JM Blom AW Sayers A Whitehouse MR

Aims. A recent report from France suggested an association between the use of cobalt-chrome (CoCr) femoral heads in total hip arthroplasties (THAs) and an increased risk of dilated cardiomyopathy and heart failure. CoCr is a commonly used material in orthopaedic implants. If the reported association is causal, the consequences would be significant given the millions of joint arthroplasties and other orthopaedic procedures in which CoCr is used annually. We examined whether CoCr-containing THAs were associated with an increased risk of all-cause mortality, heart outcomes, cancer, and neurodegenerative disorders in a large national database. Methods. Data from the National Joint Registry was linked to NHS English hospital inpatient episodes for 374,359 primary THAs with up to 14.5 years' follow-up. We excluded any patients with bilateral THAs, knee arthroplasties, indications other than osteoarthritis, aged under 55 years, and diagnosis of one or more outcome of interest before THA. Implants were grouped as either containing CoCr or not containing CoCr. The association between implant construct and the risk of all-cause mortality and incident heart failure, cancer, and neurodegenerative disorders was examined. Results. There were 158,677 individuals (42.4%) with an implant containing CoCr. There were 47,963 deaths, 27,332 heart outcomes, 35,720 cancers, and 22,025 neurodegenerative disorders. There was no evidence of an association between patients with CoCr implants and higher rates of any of the outcomes. Conclusion. CoCr-containing THAs did not have an increased risk of all-cause mortality, or clinically meaningful heart outcomes, cancer, or neurodegenerative disorders into the second decade post-implantation. Our findings will help reassure clinicians and the increasing number of patients receiving primary THA worldwide that the use of CoCr-containing implants is not associated with significant adverse systemic effects. Cite this article: Bone Joint J 2022;104-B(3):359–367


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 10 | Pages 1394 - 1400
1 Oct 2006
Eid K Labler L Ertel W Trentz O Keel M

Systemic factors are believed to be pivotal for the development of heterotopic ossification in severely-injured patients. In this study, cell cultures of putative target cells (human fibroblastic cells, osteoblastic cells (MG-63), and bone-marrow stromal cells (hBM)) were incubated with serum from ten consecutive polytraumatised patients taken from post-traumatic day 1 to day 21 and with serum from 12 healthy control subjects.

The serum from the polytraumatised patients significantly stimulated the proliferation of fibroblasts, MG-63 and of hBM cells. The activity of alkaline phosphatase in MG-63 and hBM cells was significantly decreased when exposed to the serum of the severely-injured patient. After three weeks in 3D cell cultures, matrix production and osteogenic gene expression of hBM cells were equal in the patient and control groups. However, the serum from the polytraumatised patients significantly decreased apoptosis of hBM cells compared with the control serum (4.3% vs 19.1%, p = 0.031).

Increased proliferation of osteoblastic cells and reduced apoptosis of osteoprogenitors may be responsible for increased osteogenesis in severely-injured patients.


Bone & Joint Research
Vol. 10, Issue 6 | Pages 348 - 350
1 Jun 2021
Skinner JA Sabah SA Hart AJ


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_15 | Pages 76 - 76
1 Nov 2018
Guise T
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Breast and other cancers commonly metastasize to bone to cause bone destruction, pain, fractures hypercalcemia and muscle weakness. Recently, we described a specific molecular mechanism by which bone-derived transforming growth factor (TGF)-beta, released as a consequence of tumor-induced bone destruction causes muscle dysfunction, before the loss of muscle mass. Circulating TGF-beta induces oxidation of the ryanodine receptor (RYR1) on the sarcoplasmic reticulum of skeletal muscle to induce calcium leak and muscle weakness. Blocking TGF-beta, or its release from bone (with bisphosphonates), preventing oxidation of or stabilizing RyR1 all prevented muscle weakness in mouse models of breast cancer bone metastases. In addition to these effects on skeletal muscle, circulating TGF-beta may act on beta cells of the pancreas to impair insulin secretion and result in glucose intolerance. These and other potential systemic effects of TGF-beta released from the tumor-bone microenvironment or from cancer treatment-induced bone destruction implicate bone as a major source of systemic effects of cancer and cancer treatment. Therapy to block the systemic effects of the bone microenvironment will improve morbidity associated with bone metastases and cancer treatment


Aim. Bone and implant-associated infections caused by microorganisms that grow in biofilm are difficult to treat because of persistence and recurrence. Systemic administration of antibiotics is often inefficient because the poor vascularization of the site of infection. This issue has led to the development of biomaterials capable to locally deliver high doses of therapeutic agents to the injured bone with minimal systemic effects. In this context, calcium sulphate/hydroxyapatite (CS/HA) bone graft substitutes are widely used being safe, osteoconductive and resorbable biomaterials that can be easily enriched with consistent amounts of antibiotics. In this in vitro study, the capability of the eluted antibiotics to select the tested bacterial strains for antibiotic resistance was evaluated to confirm the safe use of the product. Method. S. aureus, S. epidermidis and P. aeruginosa isolated in our Institute from bone and joint infection with different resistance phenotypes were used. 6 × 2.5 mm CS/HA discs were generated by pouring the antibiotic loaded formulations in a mold and were used as a modified disk diffusion test. The resistance selection was evaluated by subculturing cells growing on the edge of the zone of inhibition (ZOI) for seven days. Minimum inhibitory concentrations (MICs) of gentamicin and vancomycin were determined by broth microdilution method before and after the selection of resistance assay. In addition, MICs were assessed after seven day passage on antibiotic free agar plates to evaluate if eventual decrease of antibiotic susceptibility was stable or only transient. Results. Commonly, no adaptation in presence of both CS/HA formulations was observed by analysing ZOI on agar medium. The kinetic of decrease of the ZOI was similar between the strains, with the exception of gentamicin resistant staphylococci in presence of gentamicin loaded CS/HA, which was faster with respect to the susceptible strains. Conclusions. The present study shows that elution of gentamicin and vancomycin from CS/HA bone graft substitutes did not induce a decrease in susceptibility to these antibiotics in an in vitro setting, suggesting the safe use of the product


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_15 | Pages 86 - 86
7 Nov 2023
Berberich C
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Periprosthetic joint infection (PJI) in geriatric and/or multimorbid patients is an enormous challenge for orthopaedic surgeons. Revision procedures have also been demonstrated to expose patients to higher infection risks. Prior patient stratification according to presumed infection risks, followed by a more potent local antibiotic prophylaxis protocol with selective use of DALBC, is an interesting strategy to decrease the burden of PJI in high risk patients. The PubMed & EMBASE databases were screened for publications pertaining to the utilization of DALBC in cement for infection prophylaxis & prosthesis fixation. 6 preclinical & 7 clinical studies were identified which met the inclusion criteria and were stratified by level of clinical evidence. Only those studies were considered which compared the PJI outcome in the DALBC vs the SALBC group. (1). DALBC have been shown to exert a much stronger and longer lasting inhibition of biofilm formation on many PJI relevant bacteria (gram-positive and gram-negative pathogens) than single gentamicin-only containing cements. (2). DALBC use (COPAL G+C) in the intervention arm of 7 clinical studies has led to a significant reduction of PJI cases in a) cemented hemiarthroplasty procedures (3 studies, evidence level I and III), in b) cemented septic revision surgeries (2 studies, evidence level III), in c) cemented aseptic knee revisions (1 study, evidence level III) and in d) cemented primary arthroplasties in multi-morbid patients (1 study, evidence level III-IV). These benefits were not associated with more systemic side effects or a higher prevalence of broad antimicrobial resistancies. Use of DALBC is likely to be more effective in preventing PJI in high risk patients. The preliminar findings so far may encourage clinicians to consolidate this hypothesis on a wider clinical range


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_3 | Pages 36 - 36
23 Feb 2023
Ma N Gogos S Moaveni A
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Surgical site infections following orthopaedic surgery are a serious complication associated with increased morbidity and mortality. Intra-wound antibiotic powder may be able to provide infection prophylaxis locally with less systemic adverse effects, and promising results have been reported in systematic reviews of its use in spine surgery. This study aims to analyse the efficacy and adverse effect profile of intra-wound antibiotics in reducing surgical site infections in orthopaedic surgery for traumatic pelvic and lower limb fractures. A systematic review was conducted for studies reporting on the incidence of surgical site infections following administration of intra-wound antibiotic powder in pelvic and lower limb trauma surgery. Randomised controlled trials, cohort and case-control studies were included. A meta-analysis was conducted for deep surgical site infections. Seven studies were included in the systematic review including six retrospective case-control studies and one randomised controlled trial. Results of the meta-analysis suggest a potential 23% reduction in the odds of developing a deep surgical site infection in patients treated with intra-operative antibiotic powder compared with those managed with intravenous antibiotics alone (OR 0.77, 95% CI 0.52 – 1.13), although the results did not reach statistical significance. Notable selective bias against intra-wound antibiotics and suboptimal study design were found in the retrospective studies, however the randomised controlled trial reported a significant reduction in deep surgical site infections with intra-wound vancomycin powder. There were no reports of systemic adverse outcomes and minimal risk of wound complications with the use of intra-wound antibiotics. This review suggests the use of intra-wound antibiotic powder in pelvic and lower limb trauma surgery may reduce the incidence of deep surgical site infections. Further powered studies including randomised controlled trials are required to confirm the results highlighted in this study


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_15 | Pages 20 - 20
7 Aug 2024
Snuggs J Ciccione C Vernengo A Tryfonidou M Grad S Vadala G Maitre CL
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Background. Chronic low back pain is strongly linked to degeneration of the intervertebral disc (IVD), which currently lacks any targeted treatments. This study explores NPgel, a biomaterial combined with notochordal cells (NC), developmental precursor cells, as a potential solution. NCs, known for anti-catabolic effects on IVD cells, present a promising avenue for regenerating damaged IVD tissue. Methods. Bovine IVDs underwent enzymatic degeneration before NPgel (+/- NC) injection. Degenerated bovine IVDs were cultured under biomechanical loading for 21 days. Histology and immunohistochemistry assessed NC survival, phenotype, and matrix production. Within an in vivo sheep pilot study, NPgel (+/- NC) was injected into degenerated IVDs, blood was taken, and immune cell activation was monitored via flow cytometry over three months post-injection. Results. Within the ex vivo model, IVDs injected with NPgel (+/- NC) exhibited increased matrix expression and deposition. Viable NCs were detected post-culture, indicating survival and matrix production. In the in vivo model, NPgel injection into sheep IVDs did not significantly increase activation of immune cells compared to controls, suggesting no systemic inflammatory effects. Conclusion. NPgel, combined with NCs, shows promise for IVD regeneration. Ex vivo findings indicate NPgel supports NC survival and matrix production. Moreover, in vivo results demonstrate the absence of systemic immunogenic responses post-NPgel injection. This suggests NPgel's potential as a carrier for NCs in IVD regeneration therapy. These findings underscore NPgel's candidacy for further investigation in addressing chronic low back pain associated with IVD degeneration. Subsequent research, including long-term efficacy and safety evaluations, is imperative for clinical translation. Conflicts of interest. There are no conflicts of interest. Sources of funding. iPSpine, grant # 825925, Horizon 2020


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 66 - 66
11 Apr 2023
Sebastian S Collin M Liu Y Raina D Tägil M Lidgren L
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There is a lack of carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotic for Staphylococcus aureus deep bone infections (DBIs). RIF is also associated with systemic side effects, and known for causing rapid development of antibiotic resistance when given as monotherapy. We evaluated a clinically usedbi-phasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN). It was hypothesized that this combined approach could provide improved biofilm eradication and prevent the development of RIF resistance. Methods: 1) Biofilm eradication: Using a modified crystal violet staining biofilm quantification method, the antibiotics released at different time points (Day 1, 3, 7, 14, 21, 28 and 35) from the hemispherical pellets of CaS/HA(500 mg)-VAN (24.57 mg) / GEN (10.35 mg) composites with or without RIF (8.11 mg) were tested for their ability to disrupt the preformed 48-h old biofilms of S. aureus ATCC 25923, and S. aureus clinical strain P-3 in 96-well microtitre plate. For each tested group of antibiotic fractions, five separate wells were used (n=5). 2) Testing for resistance development: Similar to the method mentioned above the 48-h biofilm embeded bacteria exposed to antibiotic fractions from different time points continuously for 7 days. The biofilms remained were then tested for RIF resistant strains of bacteria. Overall, there was clear antibiofilm biofilm activity observed with CaS/HA-VAN/GEN+RIF combinations compared with CaS/HA-VAN/GEN alone. The S. aureus strains developed resistance to RIF when biofilms were subjected to CaS/HA-RIF alone but not with combinations of CaS/HA-VAN/GEN+RIF. Enhanced antibiofilm effects without development of RIF resistance indicates that biphasic CaS/HA loaded with VAN or GEN could be used as a carrier for RIF for additional local delivery in clinically demanding DBIs. Acknowledgement: We deeply acknowledge the Royal Fysiographic Society of Lund, Landshövding Per Westlings Minnesfond and the Stina and Gunnar Wiberg fond for financial support


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 124 - 124
1 Mar 2021
Jelsma J Schotanus M Kleinveld H Grimm B Heyligers I
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An increase in metal ion levels is seen after implantation of all MoM hip prosthesis due to release from the surface directly, more so during articulation and corrosion of the bearing surfaces. The bearing surfaces in MoM prosthesis consist of cobalt, chromium and molybdenum. Several case-reports of cobalt toxicity due to a MoM prosthesis have been published in the last decade. Cobalt intoxication may lead to a variety of symptoms: neuro-ocular toxicity (tinnitus, vertigo, deafness, blindness, convulsions, headaches and peripheral neuropathy), cardiotoxicity and thyroid toxicity. Nausea, anorexia and unexplained weight loss have been described. Systemic effects from metal ions even with well functioning implants or with ion concentrations lower than those associated with known adverse effects may exist and warrant investigation. The aim of this study is to investigate self-reported systemic complaints in association with cobalt ion concentrations in patients with any type of MoM hip prosthesis. A cohort study was conducted. Patients with both unilateral and bilateral, resurfacing and large head metal on metal total hip arthroplasties were included for the current study. Blood metal ion concentrations (cobalt and chromium) were measured by inductively coupled plasma mass spectrometry (ICP-MS). Based on the known cobalt toxicity symptoms of case-reports and toxicology reports a new non-validated questionnaire was developed. questions were subdivided in general questions/symptoms, vestibular symptoms, neurological symptoms, emotional health and cardio- and thyroid toxicity symptoms. Independent samples T test, Fishers Exact Test and Pearsons (R) correlation were used. Analysis was performed on two groups; a low cobalt ion concentration group and a high cobalt ion concentration group A total of 62 patients, 36 (58%) men and 26 (42%) women, were included with a mean age at surgery of 60.8 ± 9.3 years (41.6 – 78.1) and a mean follow up of 6.3 ± 1.4years (3.7 – 9.6). In these patients a total of 71 prosthesis were implanted: 53 unilateral and 9 bilateral. Of these, 44 were resurfacing and 27 large head metal on metal (LHMoM) total hip arthroplasties. Mean cobalt and chromium ion concentrations were 104 ± 141 nmol/L (9 – 833) and 95 ± 130nmol/L (6 – 592), respectively. Based on the different thresholds (120 – 170 or 220 nmol/L) the low cobalt ion concentration group consisted of 44 (71%), 51 (82%) or 55 (89%) subjects respectively. No differences were found in general characteristics, independently of the threshold. The composite score of vestibular symptoms (vision, hearing, tinnitus, dizziness) was significantly higher (p < .050) in all high cobalt ion concentrations groups, independent of the threshold value This study aimed to detect a trend in self-reported systemic complaints in patients with metal-on-metal hip arthroplasty due to raised cobalt ion concentrations. Vestibular symptoms were more common in high cobalt ion concentration groups independent of the three threshold levels tested. The upper limit of acceptable cobalt ion concentrations remains uncertain. With regards to proactively inquired, self-reported symptoms the threshold where effects may be present could be lower than values currently applied in clinical follow-up. It is unknown what exposure to elevated metal ion concentrations for a longer period of time causes with aging subjects. Further research with a larger cohort and a more standardized questionnaire is necessary to detect previously undiscovered or under-reported effects


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXI | Pages 22 - 22
1 May 2012
J.A. M J.A.H. M J. Q
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Trauma, including major Orthopaedic Surgery, results in an immuno-inflammatory response which is variable in systemic effects.This response is patient specific. The systemic effects may be exaggerated and cause distal organ damage. This study assesses the effects of elective hip and knee arthroplasty on liver function tests. A prospective study of liver function in 316 patients (168 males and 148 females) undergoing elective total hip and knee joint replacement was undertaken by one surgeon using standardised anaesthetic, surgical and post-operative protocols. Alanine aminotransferase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (ALP) and Gammaglutamyl transpeptidase (GGT) were assessed pre-operatively and at one day, one week and six weeks following surgery. There were 166 hip and 150 knee replacement patients. Of the hip replacements, 35% were cemented, 35% hybrid and 30% cementless. All knee replacements were cemented:. ALT levels (IU) pre-operatively were 20, one day 17, one week 45.5 and at six weeks 17. AST levels (IU) pre-operatively were 21, one day 22, one week 38 and at six weeks 19. ALP levels (IU) pre-operatively were 77, one day 57, one week 88.5 and at six weeks 90. GGT levels (IU) pre-operatively were 24, one day18, one week 68 and at six weeks 29. For all enzymes there was a highly significant (p < 0.001) increase in values at one week. ALT and AST levels had returned to normal and GGT nearly normal at six weeks. ALP, also a bone enzyme, remained elevated at six weeks. There was no significant difference for age or gender. There was no significant difference for cemented, hybrid or cementless hips. Liver function tests become elevated one week following elective joint replacement. This is not related to cement. The cause is probably multifactorial and major likely contributory factors are patients' immuno-inflammatory response and drug effects. Surgeons should be aware of this phenomenon and undertake pre-operative LFT screening routinely


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 24 - 24
1 Jul 2014
Morrey M Lostis E Franklin S Hakimi O Mouthy P Baboldashti NZ Carr A
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Summary Statement. A novel biomimetic polydioxanone tendon patch with woven and electrospun components is biocompatible, recapitulates native tendon architecture and creates a tissue-healing microenvironment directed by a subpopulation of regenerative macrophages. The woven component provides tensile strength while the tendon heals. Introduction. There is great interest in the use of biomimetic devices to augment tendon repairs. Ideally, implants improve healing without causing adverse local or systemic reactions. Biocompatibility remains a critical issue prior to implantation into humans, as some implants elicit a foreign body response (FBR) involving inflammation, poor wound healing and even fistulae formation. Additionally, the effect on articular cartilage locally or systemically with placement of a juxta-articular implant has not been examined. The purpose of this study is to test the in vivo biocompatibility of a novel hybrid woven and electrospun polydioxanone patch in a rat tendon transection model. Patients and Methods. Sixty Lewis rats were divided into 4 groups in which the infraspinatus was surgically transected 3 mm from its insertion. Tendons were repaired with a woven and electrospun polydioxanone patch (PDOe) and 5-0 Prolene sutures. Vicryl and Silk patches or a simple Prolene suture repair served as comparators. Animals were sacrificed at 1, 2, 4, 6 and 12 weeks to examine the biocompatibility of the implants. Immunohistochemistry was used to examine macrophage subpopulations and hematoxylin and eosin staining was used to assess foreign-body giant cells and both analyzed with a one-way ANOVA with significance set at p<.05. Articular cartilage was scrutinised with semi-quantitative analysis. Hind paw inflammatory indices were used to determine the systemic effects and biomechanical testing the tensile strength of the materials over time. Results. The PDOe patch remained grossly quiescent at all time-points. There was a severe inflammatory reaction to Vicryl at one and 2-week time-points with gross exudate. Silk patches were associated with larger fibrous capsules at each time point. There were no adverse systemic effects and articular cartilage remained normal with no differences between materials to controls. Immunohistochemistry showed a significantly higher ratio of regenerative to inflammatory macrophages for the PDOe patch compared to other constructs at each time-point and similar to controls. Silk and Vicryl patches had a greater than 10-fold increase in foreign-body giant cells compared to the PDOe patch and controls (p<.05) suggesting incorporation rather than rejection and walling off of the biomaterial. Tensile strength of the PDOe patch increased in the first 2 weeks to greater than 90 N and gradually declined to a mean of 22 N at 12 weeks. Discussion/Conclusion. The novel PDOe patch appears to be biocompatible and illicit very little FBR in this rat tendon injury model. Importantly, there was no joint reaction to the biomaterial which has not been addressed previously. We believe the electrospun component of the patch recapitulates native tendon architecture creating a tissue healing microenvironment directed by a regenerative macrophage subpopulation. These results corroborate earlier in vitro work that showed incorporation of tenocytes within the electrospun scaffold. The woven component of the scaffold provides tensile strength as the tendon heals and begins to degrade after healing is underway making it less likely to elicit a FBR. Based on these and earlier in vitro data we believe this implant shows excellent biocompatibility and is ready to proceed to human trials


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_10 | Pages 12 - 12
1 Aug 2021
Deere K Matharu G Ben-Shlomo Y Wilkinson J Blom A Sayers A Whitehouse M
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A recent French report suggested that cobalt metal ions released from total hip replacements (THRs) were associated with an increased risk of dilated cardiomyopathy and heart failure. If the association is causal the consequences would be significant given the millions of Orthopaedic procedures in which cobalt-chrome is used annually. We examined whether cobalt-chrome containing THRs were associated with an increased risk of all-cause mortality, heart failure, cancer, and neurodegenerative disorders. Data from the National Joint Registry was linked to NHS English hospital inpatient episodes for 375,067 primary THRs with up to 14·5 years follow-up. Implants were grouped as either containing cobalt-chrome or not containing cobalt-chrome. The association between implant construct and the risk of all-cause mortality and incident heart failure, cancer, and neurodegenerative disorders was examined. There were 132,119 individuals (35·2%) with an implant containing cobalt-chrome. There were 48,106 deaths, 27,406 heart outcomes, 35,823 cancers, and 22,097 neurodegenerative disorders. There was no evidence of an association that patients with cobalt-chrome implants had higher rates of any of the outcomes. For all-cause mortality there was a very small survival advantage for patients having a cobalt-chrome implant (restricted mean survival time 13·8=days, 95% CI=6·8-20·9). Cobalt-chrome containing THRs did not have an increased risk of all-cause mortality, heart failure, cancer, and neurodegenerative disorders into the second decade post-implantation. Our findings will reassure clinicians and patients that primary THR is not associated with systemic implant effects


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_5 | Pages 21 - 21
1 Apr 2019
Fischer A Nair SB Herbig M Raabe D Wimmer M
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Fretting corrosion of taper junctions is long known and of great concern, because of metal ion and particle release and their related adverse local and systemic effects on the human body (1–3). Orthopedic taper junctions are often comprised of CoCr29Mo6/TiAl6V4 pairings. Beside others the imprinting of the TiAlV-machining marks into the CoCrMo-taper is of clinical interest (4, 5). Thus, the multifactorial details and their interdependencies on the macro-, micro, and nanoscale are still a matter of research (6). This contribution presents the mechanisms of imprinting found in an in-vitro fretting corrosion test. The worn surfaces, the lubricant as well as its remains were analyzed after test and the findings brought into relation to the characteristic wear sub-mechanisms. The fretting tests were conducted by means of a cylinder-on-pin set-up. All details about the test and the sequence of analyses can be found in (7, 8). A marked tribofilm of C-rich organic matter and oxidized wear particles of both bodies was generated at the TiAlV/CoCrMo contact area (Figure 1a, c). After removing the tribofilm chemically, extremely fine scratches of sub-µm depth became visible on the CoCrMo body (Figure 1b). The TiAlV body showed shallow shelves leaving troughs filled with grainy debris (Figure 1d) mainly of Ti-oxide wear particles. The shelves stick to the surfaces and, therefore, move relatively to the counterbody. In combination with the grainy debris this brings about “Microploughing” on the CoCrMo surfaces. Microploughing is known for destroying any passive film resulting in “Tribocorrosion”. The question remains how the shelves are formed. From the surface analyses one could conclude that they point towards “Delamination”. But this would also mean that they would not stick rigidly to the surfaces but be ejected from the contact area. Focused Ion Beam (FIB) cuts were done in order to investigate the near- and subsurface structure of the shelves in order to clarify the governing mechanisms (Figure 2). Below the platinum protection layer appears a laminated structure of highly deformed nanocrystalline and amorphous areas. EDS confirmed that the lighter intermediate layers consist mainly of Ti-oxide. This microstructure is supposedly formed by severe plastic deformation and the generation of shear bands, which under fretting pile up on top of each other. This cannot be connected to “Delamination”. We therefore propose to categorize the formation mechanism of these shelves as a specific form of microploughing. Thus, imprinting is neither driven by any galvanic effects (9) nor by hardness differences of TiO. 2. and Cr. 2. O. 3. (10) but by microploughing on the TiAlV-body leading to tribocorrosion at specific sites of CoCrMo what imprints the surface grooves of the softer TiAlV into the harder CoCrMo. For any figures or tables, please contact the authors directly


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_4 | Pages 57 - 57
1 Apr 2019
Van Onsem S Van Damme E Dedecker D Van Der Straeten C Sande I Wefula E
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Introduction. Today, Uganda has the second highest rate of road accidents in Africa and the world after Ethiopia. According to the World Health Organization's Global Status Report on Road Safety 2013, Uganda is named among countries with alarmingly high road accident rates. If such trend of traffic accidents continues to increase, the health losses from traffic injuries may be ranked as the second to HIV/AIDS by 2020. These road traffic accidents often result in terrible open injuries. Open fractures are complex injuries of bone and soft tissue. They are orthopedic emergencies due to risk of infection secondary to contamination and compromised soft tissues and sometimes vascular supply and associated healing problems. Any wound occurring on the same limb should be suspected as result of open fracture until proven otherwise. The principles of management of open fracture are initial evaluation and exclusion of life threatening injuries, prevention of infection, healing of fracture and restoration of function to injured extremity. Because of the poor hygienic circumstances and the high rate of cross-infection due to the crowded patient-wards, the risk of getting a post-operative infection is relatively high. Osteoset-T® (Wright Medical) is a medical grade calcium sulfate bone graft substitute which is enhanced for use in infected sites by incorporating 4% tobramycin sulfate. The tobramycin is released locally, allowing therapeutic antibiotic levels at the graft site, while maintaining low systemic antibiotic levels. This local treatment of infection allows new bone formation in the defect site, while decreasing potential systemic effects. Purpose/aim. Prevention and treatment of postoperative osteomyelitis by introducing alcoholic hand-sanitizers and the use of wound debridement and implantation of a medicated bone graft substitute. Materials and Methods. We treated some existing osteomyelitis cases and some open fractures with the medicated bone graft substitutes, at Kilembe Mines Hospital, Uganda. A proper debridement with sequestrectomy when needed was performed after which the pellets were implanted and the wound was closed. A preoperative X-ray was taken as well as clinical pictures. Post-operative x-rays were obtained at 6 weeks post-operative and 6 months post-operative when possible. The case presented in this abstract is a 25year old nurse with a bilateral open tibia fracture due to a motorcycle accident. A proper debridement and plate and screw osteosynthesis was performed after which the pellets were implanted underneath the plate. After surgery systemic antibiotics were given and the wound-dressings were changed when dirty. Results. The case presented is currently 6 months post-operatively and is able to walk without support. The fracture is fully consolidated and the wounds are healed without any sign of infection. Conclusion. Even though the clinical follow-up is not easy in this developing country setting, we were able to evaluate some patients postoperatively. By introducing better hand hygiene (by use of alcoholic hand sanitizers) and medicated bone graft substitutes, we hope to be able to prevent osteomyelitis after open fractures and also to treat chronic osteomyelitis cases. More people are being treated at the moment and a case-control study will be started soon


The Bone & Joint Journal
Vol. 98-B, Issue 8 | Pages 1132 - 1137
1 Aug 2016
Lawendy A Bihari A Sanders DW Badhwar A Cepinskas G

Aims. Compartment syndrome results from increased intra-compartmental pressure (ICP) causing local tissue ischaemia and cell death, but the systemic effects are not well described. We hypothesised that compartment syndrome would have a profound effect not only on the affected limb, but also on remote organs. Methods. Using a rat model of compartment syndrome, its systemic effects on the viability of hepatocytes and on inflammation and circulation were directly visualised using intravital video microscopy. Results. We found that hepatocellular injury was significantly higher in the compartment syndrome group (192 PI-labelled cells/10. -1 . mm. 3. , standard error of the mean (. sem. ) 51) compared with controls (30 PI-labelled cells/10. -1 . mm. 3. , . sem . 12, p < 0.01). The number of adherent venular white blood cells was significantly higher for the compartment syndrome group (5 leukocytes/30s/10 000 μm. 2. , . sem 1. ) than controls (0.2 leukocytes/30 s/10 000 μm. 2. , . sem . 0.2, p < 0.01). Volumetric blood flow was not significantly different between the two groups, although there was an increase in the heterogeneity of perfusion. Conclusions. Compartment syndrome can be accompanied by severe systemic inflammation and end organ damage. This study provides evidence of the relationship between compartment syndrome in a limb and systemic inflammation and dysfunction in a remote organ. Cite this article: Bone Joint J 2016; 98-B:1132–7


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_21 | Pages 16 - 16
1 Dec 2016
Tjong V Cogan C Knesek M Nair R Kahlenberg C Terry M
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Previous authors have suggested that the analgesic effects of intra-articular morphine may be beneficial. Clonidine has been found to potentiate the analgesic effect of morphine. Following knee arthroscopy, morphine has demonstrated equivocal effect in comparison to bupivicaine for analgesia while circumventing the issue of chondrotoxicity. There have been no studies evaluating the effect of intra-articular morphine following hip arthroscopy. The purpose of this study was to evaluate the efficacy of intra-articular morphine in combination with clonidine on pain and narcotic consumption following hip arthroscopy surgery for femoroacetabular impingement. A retrospective review was performed on 43 patients that underwent hip arthroscopy between September 2014 and May 2015 at our institution for femoroacetabular impingement. All patients received preoperative Celebrex and Tylenol per our anesthesia protocol, and 22 patients received an additional intra-articular injection of 10 mg morphine and 100 mcg of clonidine at the conclusion of the procedure. Narcotic consumption, duration of anesthesia recovery, and perioperative pain scores were compared between the two groups. We found that patients who received intra-articular morphine and clonidine used significantly less opioid analgesic in the PACU, with 23 mEq of morphine equivalents required in the intra-articular morphine and clonidine group compared to 40 mEq of opiod equivalents in the non-injection group (p=0.0259). There were no statistically significant differences in time spent in recovery prior to discharge or in VAS pain scores recorded immediately post-operatively and at one hour following surgery. In conclusion, we found that an intraoperative intra-articular injection of morphine and clonidine significantly reduced the amount of narcotic requirement following hip arthroscopy. We do believe that there may be significant benefits to this, including less systemic effects from overall narcotic usage in the perioperative period. Our study demonstrated a beneficial effect of intra-articular morphine that may help with overall pain improvement, less narcotic consumption, and improved patient satisfaction following outpatient hip arthroscopy. This study provides the foundation for future research currently being conducted in a randomised-control setting


The Bone & Joint Journal
Vol. 97-B, Issue 10 | Pages 1423 - 1427
1 Oct 2015
Rand BCC Penn-Barwell JG Wenke JC

Systemic antibiotics reduce infection in open fractures. Local delivery of antibiotics can provide higher doses to wounds without toxic systemic effects. This study investigated the effect on infection of combining systemic with local antibiotics via polymethylmethacrylate (PMMA) beads or gel delivery. An established Staphylococcus aureus contaminated fracture model in rats was used. Wounds were debrided and irrigated six hours after contamination and animals assigned to one of three groups, all of which received systemic antibiotics. One group had local delivery via antibiotic gel, another PMMA beads and the control group received no local antibiotics. After two weeks, bacterial levels were quantified. . Combined local and systemic antibiotics were superior to systemic antibiotics alone at reducing the quantity of bacteria recoverable from each group (p = 0.002 for gel; p = 0.032 for beads). There was no difference in the bacterial counts between bead and gel delivery (p = 0.62). . These results suggest that local antibiotics augment the antimicrobial effect of systemic antibiotics. Although no significant difference was found between vehicles, gel delivery offers technical advantages with its biodegradable nature, ability to conform to wound shape and to deliver increased doses. Further study is required to see if the gel delivery system has a clinical role. Cite this article: Bone Joint J 2015;97-B:1423–7