Prosthetic joint infection (PJI) is a complex disease that causes significant damage to the peri-implant tissue. Developing an animal model that is clinically relevant in depicting this disease process is an important step towards developing novel successful therapies. In this study, we have performed a thorough histologic analysis of peri-implant tissue harvested post Staphylococcus aureus (S. aureus) infection of a cemented 3D-printed titanium hip implant in rats. Sprague-Dawley rats underwent left hip cemented 3D-printed titanium hemiarthroplasty via posterior approach under general anesthesia. Four surgeries were performed for the control group and another four for the infected group. The hip joint was inoculated with 5×10. 9. CFU/mL of S. aureus Xen36 prior to capsule closure. The animals were scarified 3 weeks after infection. The femur was harvested and underwent micro-CT and histologic analysis. Hematoxylin and eosin (H&E), as well as Masson's trichrome (MT) stains were performed. Immunohistochemistry (IHC) using rabbit antibody for S. aureus was also used to localize bacterial presence within femur and acetabulum tissue . The histologic analysis revealed strong resemblance to tissue changes in the clinical setting of chronic PJI. IHC demonstrated the extent of bacterial spread within the peri-implant tissue away from the site of infection. The H&E and MT stains showed 5 main features in infected bone: 1) increased PMNs, 2) fibrovascular inflammation, 3) bone necrosis, and 4) increased osteoclasts 5)
Aim. To describe the histopathology of the first and last debrided bone tissue in chronic osteomyelitis and answer the following research question; is the last debrided bone tissue viable and without signs of inflammation?. Method. In total, 15 patients with chronic osteomyelitis were allocated to surgical treatment using a one stage protocol including extensive debridement. Suspected infected bone tissue eradicated early in the debridement procedure was collected as a clearly infected sample (S1). Likewise, the last eradicated bone tissue was collected as a suspected non-infected sample (S2), representing the status of the bone void. In all cases, the surgeon debrided the bone until visual confirmation of healthy bleeding bone. The samples were processed for histology, i.e. decalcification and paraffin embedding, followed by cutting and staining with Haematoxylin and Eosin. Immunohistochemistry with MAC-387 antibodies towards the calprotectin of neutrophil granulocytes (NGs) was also performed and used for estimation of a neutrophil granulocyte (NG) score (0, 1, 2 or 3), by the method described for fracture related infections (1). Results. For the S1 samples the median NG score was 3 which is considered confirmatory for infection. However, following debridement the median NG score was significantly (p = 0.032) reduced to 2. Often NGs were seen as single cells, but in seven S1 samples and in one S2 sample massive NG accumulations were observed. The S1 samples showed a mix of granulation tissue,
Stiffness after total knee arthroplasty (TKA) is a common problem occurring between 5% and 30% of patients. Stiffness is defined as limited range of motion (ROM) that affects activities of daily living. A recent International Consensus on definition of stiffness of the knee graded stiffness as mild, moderate or severe (90–100, 70–89, <70, respectively) or an extension deficit (5–10, 11–20, >20). Stiffness can be secondary to an osseous, soft tissue, or prosthetic block to motion. Heterotopic bone or retained posterior osteophytes, abundant fibrotic tissue, oversized components with tight flexion or extension gaps or component malrotation can all limit knee motion. Infection should always be considered in the knee that gradually loses motion. Alternative causes include complex regional pain syndrome and Kinesiophobia that can limit motion without an underlying mechanical cause. The evaluation of knee stiffness radiographs of the knee and cross-section imaging should be performed if component malrotation is considered. A metal suppression MRI assists in quantifying the extent of
Aberrant infrapatellar fat metabolism is a notable feature provoking inflammation and
Tungsten has been increasing in demand for use in manufacturing and recently, medical devices, as it imparts flexibility, strength, and conductance of metal alloys. Given the surge in tungsten use, our population may be subjected to elevated exposures. For instance, embolism coils made of tungsten have been shown to degrade in some patients. In a cohort of breast cancer patients who received tungsten-based shielding for intraoperative radiotherapy, urinary tungsten levels remained over tenfold higher 20 months post-surgery. In vivo models have demonstrated that tungsten exposure increases tumor metastasis and enhances the adipogenesis of bone marrow-derived mesenchymal stem cells while inhibiting osteogenesis. We recently determined that when mice are exposed to tungsten [15 ppm] in their drinking water, it bioaccumulates in the intervertebral disc tissue and vertebrae. This study was performed to determine the toxicity of tungsten on intervertebral disc. Bovine nucleus pulposus (bNP) and annulus fibrosus (bAF) cells were isolated from bovine caudal tails. Cells were expanded in flasks then prepared for 3D culturing in alginate beads at a density of 1×10. ∧. 6 cells/mL. Beads were cultured in medium supplemented with increasing tungsten concentrations in the form of sodium tungstate [0, 0.5, 5, 15 ug/mL] for 12 days. A modified GAG assay was performed on the beads to determine proteoglycan content and Western blotting for type II collagen (Col II) synthesis. Cell viability was determined by counting live and dead cells in the beads following incubation with the Live/Dead Viability Assay kit (Thermo Fisher Scientific). Cell numbers in beads at the end of the incubation period was determined using Quant-iT dsDNA Assay Kit (Thermo Fisher Scientific). Tungsten dose-dependently decreased the synthesis of proteoglycan in IVD cells, however, the effect was significant at the highest dose of 15 ug/mL. (n=3). Furthermore, although tungsten decreased the synthesis of Col II in IVD cells, it significantly increased the synthesis of Col I. Upregulation of catabolic enzymes ADAMTS4 and −5 were also observed in IVD cells treated with tungsten (n=3). Upon histological examination of spines from mice treated with tungsten [15 ug/mL] in their drinking water for 30 days, disc heights were diminished and Col I upregulation was observed (n=4). Cell viability was not markedly affected by tungsten in both bNP and bAF cells, but proliferation of bNP cells decreased at higher concentration. Surprisingly, histological examination of IVDs and gene expression analysis demonstrated upregulation of NGF expression in both NP and AF cells. In addition, endplate capillaries showed increases in CGRP and PGP9.5 expression as determined on histological sections of mouse IVDs, suggesting the development of sensory neuron invasion of the disc. We provide evidence that prolonged tungsten exposure can induce disc
Aim. To study the antimicrobial effect of a gentamicin loaded bio-composite bone void filler in relation to a limited or extensive debridement of osteomyelitis lesions, respectively. Methods. Nine pigs were inoculated into the right proximal tibial bone with a high virulent gentamicin sensitive strain of Staphylococcus aureus (10. 4. CFU). Seven days after inoculation, Group A pigs (n=3) were exposed to a limited debridement of the bone lesion, whereas Group B pigs (n=3) were exposed to an extensive debridement. The bone defects of Groups A and B were filled with (2–5 ml) of an absorbable gentamicin (175 mg/10 mL) loaded bio-composite. The animals of Group A and B were euthanized 12 days after revision surgery. Group C animals did not undergo revision surgery and were euthanized seven (n=1) or nineteen (n=2) days post inoculation in order to follow the development of the untreated infection. None of the animals were treated with systemic antimicrobials. All bones were exposed to a post mortem CT scan and rigours pathological examinations. The surrounding bone tissue and the bio-composite were sampled for microbiology. Results. All animals developed a substantial purulent bone infection in the inoculated leg prior to revision surgery. In the cases of limited debridement, the bone lesions surrounding the bio-composite bone void filler had clearly expanded since revision surgery, and contained extensive amounts of pus, necrotic bone tissue and oedematous fibrotic tissue. In the cases of extensive debridement, the bio-composite bone void filler was surrounded by only a few mm of
Modifiable factors contributing to stiffness include alignment, implant size, implant position and rotation, and soft tissue tightness or laxity. Less modifiable factors include genetics as in predisposition to inflammation and
This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms. We analyzed microarray data from the Gene Expression Omnibus (GEO) database using weighted gene co-expression network analysis (WGCNA), machine learning, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify common genetic factors between POMP and sarcopenia. Further validation was done via differential gene expression in a new cohort. Single-cell analysis identified high expression cell subsets, with mononuclear macrophages in osteoporosis and muscle stem cells in sarcopenia, among others. A competitive endogenous RNA network suggested regulatory elements for these genes.Aims
Methods
Bacterial infection activates neutrophils to release neutrophil extracellular traps (NETs) in bacterial biofilms of periprosthetic joint infections (PJIs). The aim of this study was to evaluate the increase in NET activation and release (NETosis) and haemostasis markers in the plasma of patients with PJI, to evaluate whether such plasma induces the activation of neutrophils, to ascertain whether increased NETosis is also mediated by reduced DNaseI activity, to explore novel therapeutic interventions for NETosis in PJI in vitro, and to evaluate the potential diagnostic use of these markers. We prospectively recruited 107 patients in the preoperative period of prosthetic surgery, 71 with a suspicion of PJI and 36 who underwent arthroplasty for non-septic indications as controls, and obtained citrated plasma. PJI was confirmed in 50 patients. We measured NET markers, inflammation markers, DNaseI activity, haemostatic markers, and the thrombin generation test (TGT). We analyzed the ability of plasma from confirmed PJI and controls to induce NETosis and to degrade in vitro-generated NETs, and explored the therapeutic restoration of the impairment to degrade NETs of PJI plasma with recombinant human DNaseI. Finally, we assessed the contribution of these markers to the diagnosis of PJI.Aims
Methods
Disorders of bone integrity carry a high global disease burden, frequently requiring intervention, but there is a paucity of methods capable of noninvasive real-time assessment. Here we show that miniaturized handheld near-infrared spectroscopy (NIRS) scans, operated via a smartphone, can assess structural human bone properties in under three seconds. A hand-held NIR spectrometer was used to scan bone samples from 20 patients and predict: bone volume fraction (BV/TV); and trabecular (Tb) and cortical (Ct) thickness (Th), porosity (Po), and spacing (Sp).Aims
Methods
Treatment of recurrent dislocation: approximately: 1/3 of failures (probably higher in the absence of a clear curable cause). In the US: most popular treatment option: constrained liners with high redislocation and loosening rates in most reports. Several interfaces leading to various modes of failures. In Europe: dual mobility cups (or tripolar unconstrained): first design Gilles Bousquet 1976 (Saint Etienne, France), consisting of a metal shell with a highly polished inner surface articulating with a mobile polyethylene insert (large articulation). The femoral head is captured into the polyethylene (small articulation) using a snap fit type mechanism leading to a large effective unconstrained head inside the metal cup. With dual mobility, most of the movements occur in the small articulation therefore limiting wear from the large polyethylene on metal articulation. Contemporary designs include: CoCr metal cup for improved friction, outer shell coated with titanium and hydroxyapatite, possible use of screws to enhance primary stability (revision), cemented version in case of major bone defect requiring bone reconstruction. Increased stability obtained through an ultra-large diameter effective femoral head increasing the jumping distance. Dual mobility in revision for recurrent dislocation provided hip stability in more than 94% of the cases with less than 3% presenting redislocation up to 13-year follow-up. A series from the UK concerning 115 revisions including 29 revisions for recurrent dislocation reported 2% dislocation in the global series and 7% re-dislocation in patients revised for instability. A recent report of the Swedish hip arthroplasty register including 228 patients revised for recurrent dislocation showed 99% survival with revision for dislocation as the endpoint and 93% with revision for any reason as the endpoint. One specific complication of dual mobility sockets: intra-prosthetic dislocation (ie: dislocation at the small articulation): often asymptomatic or slight discomfort, eccentration of the neck on AP radiograph, related to wear and fatigue of the polyethylene rim at the capturing are through aggressive stem neck to mobile polyethylene insert contact (3rd articulation). Risk factors include: large and aggressive femoral neck design implants, small head/neck ratio, skirted heads, major
Although there is strong evidence that bisphosphonates prevent certain types of osteoporotic fractures, there are concerns that they may be associated with rare atypical femoral fractures. 1480 patients of proximal femur and shaft fractures over a period of 2 years from Jan 2014 to Jan 2016 were retrospectively reviewed in Gloucestershire Hospitals NHS trust. Hospital trauma database was used.195 patients had fractures in subtrochancteric and femoral shaft area. 11 patients had atypical femur fractures as defined by American society for bone and mineral research (ASBMR) task force 2013, revised criteria. Ten were female, one was male. Patients were aged from 68 to 97. In 6 patients, fractures were in the shaft, 5 in subtrochancteric area and 4 patients out of these had bilateral fractures. 10 out of 11 patients were on bisphosphonates. 4 patients had delayed diagnosis. 5 out of 11 patients did not have contralateral femoral x-rays. Treatment, 9 patients had intramedullary nail, one blade plate, and one treated conservatively. One patient in the IM group, had bilateral nailing. Average follow up was 7.6 months (range 1 to 16 months). At the end of the study, only 4 had united, 6 had not united and one not followed up. 4 out of 7 had low Vitamin D levels, 3 out of 7 had their bisphosphonate treatment stopped and 2 had histology which showed necrotic bone with trabeculae surrounded by
Introduction. We have previously demonstrated that peroxide crosslinked vitamin E-blended UHMWPE maintains its clinically-required wear and mechanical properties [1]. This material can potentially be used as an irradiation-free bearing surface for TJA. However, using organic peroxides in medical devices requires a thorough examination of tissues in contact with the implant. For this study we crosslinked polyethylene using five times the needed concentration of peroxide (2,5-Dimethyl-2,5-di(t-butylperoxy)-hexyne-3 or P130), followed by implantation to determine implant biocompatibility, and pre and post implant peroxide residual contents. Methods. The study was performed after institutional approval following ISO standard 10993–6. Study groups: not crosslinked (0.2 (1050) VE), crosslinked (0.2 VE (1050)/5% P130) and crosslinked-high temperature melted (HTM) (0.2 VE (1050)/5% P130). Materials were blended and consolidated, machined (2.5 diameter × 2.5 cm height), sterilized and implanted in the dorsum New Zealand white rabbits. Pre and post implantation FTIR was performed. Two samples were implanted in each rabbit; n=6 samples were included for each group. After 4 weeks, samples were explanted, analyzed using FTIR, and subcutaneous tissues processed for histological analysis. Results. FTIR absorbances at 914cm. −1. , 1169cm. −1. , and the OH absorbance at 3450cm. −1. showed differences between materials (Fig 1A). There was a significant increase in the absorbance at 914 for the non-crosslinked and crosslinked samples after explantation (p = 2.77E–17, p = 4.22E–23, Fig 1B). There was a significant decrease in all peroxide related absorbances after explantation for the crosslinked and HTM samples (p < 0.05, Fig 1B). Before implantation, these absorbances were significantly higher in the crosslinked and crosslinked/HTM samples than those in the non crosslinked sample (p<0.05, Fig 2A). Peroxide related absorbances of the crosslinked sample were also significantly higher than those of the crosslinked/HTM sample (p<0.05, Fig 2A). After explantation, the crosslinked samples had significantly higher absorbances than both the non crosslinked and crosslinked/HTM samples (p < 0.05, Fig 2A). All peroxide related absorbances of the crosslinked/HTM samples were significantly higher than those of the non crosslinked sample (p < 0.05, Fig 2A). The non crosslinked sample showed no significant differential between these absorbances at implantation and after retrieval. The crosslinked sample had the largest differential between the total peak absorbances before implantation and retrieval at 914cm. −1. The crosslinked/HTM samples had the largest differential between the total peak absorbances before and after implantation for both 1169cm. −1. and the OH absorbances (Fig 2B). All explants were recovered after four weeks in vivo (Fig 3A). No difference was found in the histological analysis of the tissue characterized by a synovial-like lining with signs of
A key component to the success of total knee replacement is the health and integrity of the extensor mechanism. While there are issues related to the patella, such as fracture, dislocation, subluxation, clunk due to peripatellar
A key component to the success of total knee replacement is the health and integrity of the extensor mechanism. While there are issues related to the patella, such as fracture, dislocation, subluxation, clunk due to peripatellar
Optimising post-operative joint function is challenging when treating periarticular soft tissue sarcoma (STS). Radiotherapy reduces local recurrence rates but periarticular
Arthrodesis. Today, knee arthrodesis is most commonly performed for cases of chronic sepsis after total knee arthroplasty in patients who are not candidates for reimplantation. This is typically a host in whom the risk of recurrent infection is high, especially when extensor mechanism problems such as patellar tendon rupture is present. Local and systemic host factors place the patient at this high risk for failure of reimplantation. Local factors include chronic lymphedema, major vessel disease, venous stasis, extensive scarring and radiation
Extracorporeal irradiation of resected bone segments has been used for pelvic reconstruction for 12 years in our unit. The technique allows for a perfect fit, preservation of muscle attachments, and thus, facilitating reconstruction, more rapid osteotomy of autograft bone, low cost, and a low infection rate. Of particular interest is its use in children; revascularisation appears more complete with irradiated autograft, as compared to allograft. There is sparing of adjacent growth plates if the irradiation is given outside the body, whereas external beam radiation would destroy the proximal femoral growth plate—leading to significant leg length discrepancy. Avoiding external beam irradiation also removes any risk of late radiation induced sarcoma and removes the late effects of soft tissue
Melorheostosis is a very rare mesenchymal dysplasia of bone, characterized by sclerosing hyper-pigmentation appearances on the bone, may involve the adjacent soft tissues and lead to joint pain, limitation of joint motion and stiffness as a result of abnormal ossifications and soft tissue contractures, due to periarticular
A randomised controlled pre-clinical trial utilising an existing extremity war wound model compared the efficacy of saline soaked gauze to commercial dressings. The Flexor Carpi Ulnaris of anaesthetised New Zealand rabbits was exposed to high-energy trauma using computer-controlled jig and inoculated with 10. 6. Staphylococcus aureus 3 hours prior to application of dressing. After 7 days the animals were culled. Quantitative microbiological assessment of post-mortem specimens demonstrated statistically significantly reduced S aureus counts in groups treated with iodine or silver based dressings (2-way ANOVA p< 0.05). Clinical observations and haematology were performed during the study. Histopathological assessment of post-mortem muscle specimens included image analysis of digitally scanned haematoxylin and eosin stained tissue sections and subjective semi-quantitative assessment of pathology severity using light microscopy to grade muscle injury and lymph node activation. Tissue samples were also examined using scanning electron microscopy to determine the presence of bacteria and biofilm formation within the injured muscle. Non-parametric data were compared using Kruskal-Wallis. There were no bacteraemias, significantly raised white cell counts, abscesses, purulent discharge or evidence of contralateral axillary lymph node activation. All injured muscle specimens showed evidence of haemorrhage, inflammatory cell infiltration and