Periprosthetic joint infection (PJI) demonstrates the most feared complication after total joint replacement (TJR). The current work analyzes the demographic, comorbidity, and complication profiles of all patients who had in-hospital treatment due to PJI. Furthermore, it aims to evaluate the in-hospital mortality of patients with PJI and analyze possible risk factors in terms of secondary diagnosis, diagnostic procedures, and complications. In a retrospective, cross-sectional study design, we gathered all patients with PJI (International Classification of Diseases (ICD)-10 code: T84.5) and resulting in-hospital treatment in Germany between 1 January 2019 and 31 December 2022. Data were provided by the Institute for the Hospital Remuneration System in Germany. Demographic data, in-hospital deaths, need for intensive care therapy, secondary diagnosis, complications, and use of diagnostic instruments were assessed. Odds ratios (ORs) with 95% confidence intervals (CIs) for in-hospital mortality were calculated.Aims
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This study aimed to evaluate the clinical application of the PJI-TNM classification for periprosthetic joint infection (PJI) by determining intraobserver and interobserver reliability. To facilitate its use in clinical practice, an educational app was subsequently developed and evaluated. A total of ten orthopaedic surgeons classified 20 cases of PJI based on the PJI-TNM classification. Subsequently, the classification was re-evaluated using the PJI-TNM app. Classification accuracy was calculated separately for each subcategory (reinfection, tissue and implant condition, non-human cells, and morbidity of the patient). Fleiss’ kappa and Cohen’s kappa were calculated for interobserver and intraobserver reliability, respectively.Aims
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The number of periprosthetic joint infections (PJI) is increasing due to ageing population and increasing numbers of arthroplasty procedures and treatment is costly. Aim of the study was to analyze the direct healthcare costs of PJI in Europe for total hip arthroplasties (THA) and total knee arthroplasties (TKA). A systematic review in PubMed with search of direct costs of PJI in European countries was performed. Thereby the term Aim
Method
Sepsis is a life-threatening complication of periprosthetic joint infections (PJI) that requires early and effective therapy. This study aims to investigate the epidemiology, associated risk factors, and outcome of sepsis in the context of periprosthetic joint infections (PJI). This single-center retrospective cohort study included patients treated for PJI from 2017 to 2020. Patients were classified based on the criteria of the European Bone and Joint Infection Society. The presence of sepsis was determined using the SOFA score and SIRS criteria. The cohort with PJI and sepsis (sepsis) was compared to patients with PJI without sepsis (non-sepsis). Risk factors considered were patient characteristics, affected joints, surgical therapy, microbiological findings, preexisting medical conditions, clinical symptoms, and symptom duration. Outcome parameters were mortality, length of hospital stay, and length of stay in the intensive care unit.Aim
Method
To classify Fracture-related Infection (FRI) allowing comparison of clinical studies and to guide decision-making around the main surgical treatment concepts. An international group of FRI experts met in Lisbon, June 2022 and proposed a new FRI classification. A core group met during the EBJIS Meeting in Graz, 2022 and on-line, to determine the preconditions, purpose, primary factors for inclusion, format and the detailed description of the elements of an FRI Classification.Aim
Method
The aim of this investigation was to compare risk of infection in both cemented and cementless hemiarthroplasty (HA) as well as total hip arthroplasty (THA) following femoral neck fracture. Data collection was performed using the German Arthroplasty Registry (EPRD) In HA and THA following femoral neck fracture fixation method was divided into cemented and cementless protheses and paired according to age, sex, body mass index (BMI), and the Elixhauser score using Mahalanobis distance matching.Aim
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The identification of novel biomarker which is highly specific and sensitive for periprosthetic joint (PJI) have the potential to improve diagnostic accuracy and ultimately improve patient outcomes. Thus, the aim of this systemic review is to identify and evaluate novel biomarkers for the preoperative diagnostics of PJI. MEDLINE, EMBASE, PubMed and Cochrane Library databases identified from 1st of January 2018 to 30th of September. 2022. We used “periprosthetic joint infection” OR “prosthetic joint infection” OR “periprosthetic infection” as the diagnosis of interest and the target index applied AND “marker”. To focus on novel biomarkers already used biomarkers of the established PJI diagnostic criteria of MSIS, ICM and EBJIS were not included in the analysis. These three criteria were considered the reference standard during quality assessment.Background
Methods
This work aimed at answering the following research questions: 1) What is the rate of mechanical complications, nonunion and infection for head/neck femoral fractures, intertrochanteric fractures, and subtrochanteric fractures in the elderly USA population? and 2) Which factors influence adverse outcomes? Proximal femoral fractures occurred between 1 January 2009 and 31 December 2019 were identified from the Medicare Physician Service Records Data Base. The Kaplan-Meier method with Fine and Gray sub-distribution adaptation was used to determine rates for nonunion, infection, and mechanical complications. Semiparametric Cox regression model was applied incorporating 23 measures as covariates to identify risk factors.Aims
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The aim of this investigation was to compare risk of infection in both cemented and uncemented hemiarthroplasty (HA) as well as in total hip arthroplasty (THA) following femoral neck fracture. Data collection was performed using the German Arthroplasty Registry (EPRD). In HA and THA following femoral neck fracture, fixation method was divided into cemented and uncemented prostheses and paired according to age, sex, BMI, and the Elixhauser Comorbidity Index using Mahalanobis distance matching.Aims
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The goal was to analyze the cellular response, specifically the osteogenic capacity, of titanium (Ti) implants harbouring a novel laserbased-surface-structure with the overall aim: augmented osteointegration. Surface micro-/nanoproperties greatly influence cell behaviour at the tissue-implant-interface and subsequent osteointegration. We investigated Ti-materials subjected to a specially developed shifted-Laser-Surface-Texturing (sLST) technology and compared them to a standard roughening-technique (sand-blasting-acid-etching, SLA). The biological response was evaluated with hMSCs, which are naturally available at the bone-implant-interface. We hypothesized: the novel surface is beneficial for our three different (young/healthy-YH; aged/healthy-AH;aged/osteoporotic-OP) cohorts. The sLST was performed using a SPI-G3-series laser (beam-wavelength=1064nm, pulse-duration=200ns). For the SLA surface, Ti was sandblasted, afterwards acid-etched (HCl/H2SO4). Three different hMSC cohorts were studied: YH: n=6,29±6; AH: n=5,79±5; OP: n=5,76±5 years (osteoporosis confirmed via DEXA-scan). OP hMSCs show e.g. ColI-deficient-matrix and decreased mineralization. Cells were examined for survival, cell proliferation and cytoskeleton arrangement. Osteogenic differentiation was carried out over 21 days, matrix mineralization was validated with Alizarin-Red-S-staining and quantification. Laser-texturing generated precisely the desired microgeometry. On nanostructural level, differently-sized Ti-droplets were formed stochastically by laser-induced-Ti-plasma. Live/dead-/Actin-stainings showed comparable results for all cohorts and surfaces in terms of survival and cell shape. On Ti-materials, cell growth showed no significant difference between the 3 cohorts. Alizarin quantification revealed the highest levels on laser-textured-surfaces; highest value for YH, followed by AH, lastly OP; no significance between AH/YH, but between OP/YH (p<0.0001). However, mineralization of all cohorts cultured on laser-textured-surfaces increased significantly (p<0.0001) compared to respective SLA-group, with >20fold higher value in the OP-cohort (AH:11fold, YH:6fold). The data proves the biocompatibility of the laser-structured-Ti for young+aged cohorts. Osteogenic differentiation was significantly augmented on laser-treated-Ti. Most intriguingly, OP-donors could reach manifold increased mineralization, suggesting the novel laser texturing can counteract the osteoporotic phenotype. As osteogenesis-enhancing capacities may be related to mechanisms controlling cellular shape/fate, further investigations referring to this are currently ongoing. In conclusion, our laser-textured-Ti-materials are safe, can have a demand-oriented designer-surface-topography and represent a great potential for development into next-generation-implants suitable for different patient-cohorts, especially osteoporosis patients.
Complex acetabular reconstruction for oncology and bone loss are challenging for surgeons due to their often hostile biological and mechanical environments. Titrating concentrations of silver ions on implants and alternative modes of delivery allow surgeons to exploit anti-infective properties without compromising bone on growth and thus providing a long-term stable fixation. We present a case series of 12 custom acetabular tri-flange and custom hemipelvis reconstructions (Ossis, Christchurch, New Zealand), with an ultrathin plasma coating of silver particles embedded between layers of siloxane (BioGate HyProtect™, Nuremberg, Germany). At the time of reporting no implant has been revised and no patient has required a hospital admission or debridement for a deep surgical site infection. Routine follow up x-rays were reviewed and found 2 cases with loosening, both at their respective anterior fixation. Radiographs of both cases show remodelling at the ilium indicative of stable fixation posteriorly. Both patients remain asymptomatic. 3 patients were readmitted for dislocations, 1 of whom had 5 dislocations within 3 weeks post-operatively and was immobilised in an abduction brace to address a lack of muscle tone and has not had a revision of their components. Utilising navigation with meticulous implant design and construction; augmented with an ultrathin plasma coating of silver particles embedded between layers of siloxane with controlled and long-term generation of silver ion diffusion has led to outstanding outcomes in this series of 12 custom acetabular and hemipelvis reconstructions. No patients were revised for infection and no patients show signs of failure of bone on growth and incorporation. Hip instability remains a problem in these challenging mechanical environments and we continue to reassess our approach to this multifaceted problem.
The optimal choice of management for proximal humerus fractures (PHFs) has been increasingly discussed in the literature, and this work aimed to answer the following questions: 1) what are the incidence rates of PHF in the geriatric population in the USA; 2) what is the mortality rate after PHF in the elderly population, specifically for distinct treatment procedures; and 3) what factors influence the mortality rate? PHFs occurring between 1 January 2009 and 31 December 2019 were identified from the Medicare physician service records. Incidence rates were determined, mortality rates were calculated, and semiparametric Cox regression was applied, incorporating 23 demographic, clinical, and socioeconomic covariates, to compare the mortality risk between treatments.Aims
Methods
The aim of the present work was (i) to survey the situation of healthcare regarding the use of antibiotics in orthopaedics and trauma surgery in Germany, (ii) to determine which empiric antibiotic regimens are preferred in the treatment of periprosthethic joint infections (PJI) and (iii) to evaluate the hypothetical antibiotic adequacy of the applied empirical antibiotic therapy regimens based on a patient collective of a German university hospital. A survey on empirical and prophylactic antibiotic therapy was conducted at German university and occupational health clinics (BG clinics), each in the specialties of orthopedics and trauma surgery. A total of 71 clinics were contacted by email. The questionnaire sent included open-ended questions on systemic antibiotic prophylaxis in primary hip arthroplasty; a distinction was made between hip arthroplasty due to femoral fractures and elective hip arthroplasty. In addition, the empirical antibiotic therapy used in PJIs was surveyed. To determine the success rate of prophylaxis and therapy according to sensitivity to the antibiotics applied, the survey results were compared with previously published data on antimicrobial treatment in n=81 PJI patients treated in our department between 2017 and 2020.Aim
Method
Osteomyelitis is a difficult-to-treat disease with high chronification rates. The surgical amputation of the afflicted limb sometimes remains as the patients’ last resort. Several studies suggest an increase in mitochondrial fission as a possible contributor to the accumulation of intracellular reactive oxygen species and thereby to cell death of infectious bone cells. The aim of this study is to analyze the ultrastructural impact of bacterial infection and its accompanying microenvironmental tissue hypoxia on osteocytic and osteoblastic mitochondria. 19 Human bone tissue samples from patients with osteomyelitis were visualized via light microscopy and transmission electron microscopy. Osteoblasts, osteocytes and their respective mitochondria were histomorphometrically analyzed. The results were compared to the control group of 5 non-infectious human bone tissue samples.Aim
Method
The poly methyl methacrylate (PMMA) with and without gentamicin and liquid methyl methacrylate (MMA) were kindly provided by Heraeus Medical GmbH, Wehrheim. To make the bone cement implants as cubes, Teflon plate (Karl Lettenbauer, Erlangen) with specified well size was used. The Radiopaque polymer and monomer were mixed well in a bowl, applied over on to the Teflon plate and pressed with spatula to form fine and uniform cubes. After polymerization, the bone cement implants were taken out of the Teflon well plate with the help of pin. For the infection process, bone cement cubes were pre-incubated with Aim
Method
Fungal periprosthetic joint infections are difficult to treat and often associated with a limited outcome for patients. Candida species account for approximately 90% of all fungal infections. Titanium and Stainless steel K-wires were cut into small pieces with size of 4mm. For the infection process, implants were pre-incubated in specified fungal growth culture Aim
Method
This observational cross-sectional study aimed to answer the following questions: 1) how has nonunion incidence developed from 2009 to 2019 in a nationwide cohort; 2) what is the age and sex distribution of nonunions for distinct anatomical nonunion localizations; and 3) how high were the costs for surgical nonunion treatment in a level 1 trauma centre in Germany? Data consisting of annual International Classification of Diseases (ICD)-10 diagnosis codes from German medical institutions from 2009 to 2019, provided by the Federal Statistical Office of Germany (Destatis), were analyzed. Nonunion incidence was calculated for anatomical localization, sex, and age groups. Incidence rate ratios (IRRs) were determined and compared with a two-sample z-test. Diagnosis-related group (DRG)-reimbursement and length of hospital stay were retrospectively retrieved for each anatomical localization, considering 210 patients.Aims
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Bone regeneration during treatment of staphylococcal bone infection is challenging due to the ability of The human osteoblast-like Saos-2 cells infected with Aims
Methods
Bone regeneration following the treatment of Here, we investigated the influence of Using our Aim
Method
Staphylococcus aureus is the leading pathogen in fracture-related infection (FRI). Virulence factors vary between different strains, which may have a decisive influence on the course of infection. Previous in vitro experiments, in vivo testing in wax moth larvae, and genomic analysis of S. aureus isolates from FRI identified a low- and high-virulent strain. These findings correlated with the acute course of FRI induced by the high-virulent pathogen, whereas the low-virulent strain caused a chronic FRI in its human host. However, the role of bacterial virulence in FRI is not completely understood. Therefore, the present study aimed to compare the identified high- and low-virulent S. aureus isolates in a murine FRI model. Skeletally mature C57Bl/6N mice received a femoral osteotomy stabilized by titanium locking plates. FRI was established by inoculation of either high-virulent S. aureus EDCC 5458 or low-virulent S. aureus EDCC 5464 in the fracture gap. Mice were euthanized 4 and 14 days after surgery, respectively. Severity and progression of infection were assessed in terms of clinical presentation, quantitative bacteriology, semiquantitative histopathologic evaluation, and serum cytokine profile.Aim
Method
Fracture-related infection (FRI) is a challenging complication. This study aims to investigate Patients treated for FRI from 2013 to 2020 were grouped into early (< 2 weeks), delayed (2– 10 weeks) and late (> 10 weeks) onset of infection. Pathogens detected during treatment were evaluated for pathogens. Antibiotic susceptibility profiles were examined with respect to broadly used antibiotics and antibiotic combinations.Aim
Method
Adequate debridement of necrotic bone is of paramount importance for eradication of infection in chronic osteomyelitis. Currently, no tools are available to detect the exact amount of necrotic bone in order to optimize surgical resection. The aim of the present study was to evaluate the feasibility of an intraoperative illumination method (VELscope®) and the correlation between intraoperative and pathohistological findings in surgically treated chronic fracture related infection patients. Ten consecutive patients with chronic fracture related infections of the lower extremity were included into this prospectively performed case series. All patients had to be treated surgically for fracture related infections requiring bony debridement. An intraoperative illumination method (VELscope®) was used to intraoperatively differentiate between viable and necrotic bone. Tissue samples from the identified viable and necrotic bone areas were histopathologically examined and compared to intraoperative findings.Aim
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Aim
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Vertebral osteomyelitis (VO) is an infection of the spine mostly caused by bacterial pathogens. The pathogenesis leading to destruction of intervertebral discs (IVD) and adjacent vertebral bodies (VB) is poorly described. We aimed to investigate the connection between infection, bone- and disc-metabolism in VO patients. Fourteen patients with VO (infection group) and 14 patients with incomplete burst fractures of the spine (fracture group as controls) were included prospectively. Demographic data, treatment details, laboratory infection markers, and patient-reported outcome were assessed. Tissue biopsies from affected IVDs and adjacent VBs were analyzed for mRNA-expression levels of 18 target genes including chemokines, adipokines and genes involved in bone-metabolism by RT-qPCR.Aim
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We aimed to evaluate the impact of knee periprosthetic joint infection (PJI) by assessing the patients’ long-term quality of life and explicitly their psychological wellbeing after successful treatment. Thirty-six patients with achieved eradication of infection after knee PJI were included. Quality of life was evaluated with the EQ-5D and SF-36 outcome instruments as well as with an ICD-10 based symptom rating (ISR) and compared to normative data.Aim
Method
Here, we are aimed to evaluate bacteriophage (191219) to treat The bacteriophages (191219) were provided from D&D Pharma GmbH. These bacteriophages were tested against Aim
Method
Empiric antibiotic therapy for suspected pyogenic spondylodiscitis (SD) should be initiated immediately with severely ill patients and may also be necessary for culture-negative SD. The aim of this study was to infer an appropriate empiric antibiotic regimen by analyzing the antimicrobial susceptibility of isolated pathogens from microbiologically proven pyogenic spondylodiscitis. We performed a retrospective review of adult patients with clinically proven SD treated at our level 1 trauma center between 2013 and 2020. Demographic data, radiologic findings, and treatment modalities were evaluated. The appropriateness of empiric antibiotic regimens was assessed based on the antibiograms of the isolated pathogens. Anamneses were used to distinguish between community-acquired (CA) and healthcare-associated (HA) pathogens, which included cases that had a hospital stay or invasive intervention in the past 6 months.Aim
Method
We aimed to evaluate the long-term impact of fracture-related infection (FRI) on patients’ physical health and psychological wellbeing. For this purpose, quality of life after successful surgical treatment of FRIs of long bones was assessed. A total of 37 patients treated between November 2009 and March 2019, with achieved eradication of infection and stable bone consolidation after long bone FRI, were included. Quality of life was evaluated with the EuroQol five-dimension questionnaire (EQ-5D) and German Short-Form 36 (SF-36) outcome instruments as well as with an International Classification of Diseases of the World Health Organization (ICD)-10 based symptom rating (ISR) and compared to normative data.Aims
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Cell-based tendon engineering is an attractive alternative therapeutic approach to established treatments of tendon injuries. Numerous cell types are promising source of tendon engineering; however, there are certain disadvantages for each cell type. Interestingly, dermal fibroblasts (DFs) are able to transdifferentiate into other cell types, they are widely distributed in dermis and easy to harvest and isolate. Furthermore, pilot clinical studies suggested a promising therapeutic potential of autologous DFs for discorded tendons (Connell et al., 2009&2011), but the underlining repair mechanisms remain unclarified. To investigate tenogenic differentiation process in great detail, we have previously established a three-dimensional (3D) cell sheet model, comprising of three consecutive step (expansion, stimulation and maturation) leading to the formation of 3D tendon-like tube (Hsieh et al., 2018; Yan et al., 2020). Hence, the aim of this study was to carry out pilot examination of the tenogenic potential of human DFs (hDFs) by implementing the 3D cell sheet model. hDFs (company purchased, n=2), hBMSCs (human bone marrow mesenchymal stem cells, n=1) and hTSPCs (human tendon stem/progenitor cells, n=1) were used and subjected to the 3D model. In 2D culture, semi-qPCR was performed to validate the expression of DF markers in hDFs, namely NTN1, PDPN and CD26 for papillary dermis layer, and PPARG, ACTA2 and CD36 for reticular dermis layer). FACS analysis and immunofluorescence were employed to validate expression of CD73, CD90, CD105 and vimentin (mesenchyme marker), respectively. After harvesting the 3D cell sheets, wet weigh measurements, H&E and collagen type I stainings, and semi-qPCR for Scleraxis and tenomodulin were executed.Introduction
Methods
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Polymicrobial infections are expected to complicate the treatment of bone and joint infections. Septic nonunions often occur after initial open fractures, which prophylactically receive broad-spectrum antibiotics. However, no data that describes frequencies of polymicrobial infections and pathogens evident in course of the treatment of septic nonunions is published. Therefore, this study aims at investigating the frequency and pathogen types in polymicrobial infections. Surgically treated Patients with long bone septic nonunion admitted between January 2010 and March 2018 were included in the study. Following parameters were examined: age, gender, American Society of Anesthesiologists (ASA) score, body mass index (BMI), and anatomical location of the infected nonunion. Microbiological culture data, polymerase-chain-reaction results of tissue samples, sonication, and joint fluid of the initial and follow-up revision surgeries were assessed. No exclusion criteria were determined.Introduction
Methods
Silver is known for its excellent antimicrobial activity, including activity against multiresistant strains. The aim of the current study was to analyze the biocompatibility and potential influence on the fracture healing process a silver-coating technology for locking plates compared to silver-free locking plates in a rabbit model. The implants used in this study were 7-hole titanium locking plates, and plasma electrolytic oxidation (PEO) silver coated equivalents. A total of 24 rabbits were used in this study (12 coated, 12 non-coated). An osteotomy of the midshaft of the humerus was created with an oscillating saw and the humerus stabilized with the 7 hole locking plates with a total of 6 screws. X-rays were taken on day 0, week 2, 4, 6, 8, and 10 for continuous radiographical evaluation of the fracture healing. All animals were euthanized after 10 weeks and further assessment was performed using X-rays, micro-CT, non-destructive four-point bending biomechanical testing and histology. Furthermore, silver concentration was measured in the kidney, liver, spleen and brain.Aim
Methods
Preclinical data showed poly(methyl methacrylate) (PMMA) loaded with microsilver to be effective against a variety of bacteria. The purpose of this study was to assess patient safety of PMMA spacers with microsilver in prosthetic hip infections in a prospective cohort study. A total of 12 patients with prosthetic hip infections were included for a three-stage revision procedure. All patients received either a gentamicin-PMMA spacer (80 g to 160 g PMMA depending on hip joint dimension) with additional loading of 1% (w/w) of microsilver (0.8 g to 1.6 g per spacer) at surgery 1 followed by a gentamicin-PMMA spacer without microsilver at surgery 2 or vice versa. Implantation of the revision prosthesis was carried out at surgery 3.Objectives
Methods
Osteoporosis and osteomalacia lead to increased fracture risk. Previous studies documented dysregulated osteoblast and osteoclast activity, leading to a high-turnover phenotype, reduced bone mass and low bone mineral content. Osteocytes, the most abundant bone cell type, are involved in bone metabolism by enabling cell to cell interaction. Osteocytes presence and viability are crucial for bone tissue homeostasis and mechanical integrity. Osseo-integration and implant degradation are the main problems in developing biomaterials for systemically diseased bone. This study examines osteocyte localisation, morphology and on the implant surface and at the implant bone interface. Furthermore, the study investigates ECM proteins regulation correlated to osteocytes and mechanical competence in an ovariectomised rat model with a critical size metaphyseal defect. After induction of osteoporosis, 60 female Sprague-Dawley rats were randomised into five groups: SrCPC (n=15), CPC (n=15), ScB30 (n=15), ScB30Sr20 (n=15) and empty defect (n=15). The left femur of all animals underwent a 4mm wedge-shaped metaphyseal osteotomy that was internally fixed with a T-shaped plate. The defect was then either filled with the above mentioned implants or left empty. After six weeks, histomorphometric analysis showed a statistically significant increase in bone formation at the tissue-implant interface in the SrCPC group compared to the other groups (p<0.01). Osteocyte morphology and networks were detected using silver and staining. ECM proteins were investigated through immunohistochemistry. Cellular populations were tested using enzyme histochemistry. Mineralisation was assessed using time of flight secondary ion mass spectrometry (TOF-SIMS). Statistical analysis was performed using Mann Whitney U test with Bonferroni correction.Objectives
Methodology
Multiple Myeloma is a hematological malignancy of terminally differentiated plasma cells associated with increased osteoclast activity and decreased osteoblast functions. Systemic antiproliferative treatment includes proteasome inhibitors such as bortezomib, a clinical potent antimyeloma agent. Local delivery of biological active molecules via biomaterial composite implants to the site of the lesion has been shown to be beneficial for bone and implant-associated infections. In anticancer treatment local delivery of anticancer agents to the neoplasia via biomaterial carriers has never been reported before. The purpose of the current is to present the concepts and the first in vivo results for proteasome inhibitor composite biomaterials for local delivery of bortezomib to proliferative multiple myeloma bone lesions including concentration measurements at different anatomical regions in a rat model. 80 female Sprague-Dawley rats were randomised into five different treatment groups (n=16/group): 1) Empty (2) Xerogel-granulat: XG (3) Xerogel-granulat+100mgbortezomib [b]: XG100b (4) Xerogel-granulat+500mgb:XG500b (5) Xerogel-granulat+2500mgb:XG2500b. A 2.5 mm drill hole was then created in the metaphysis of the left femur. The defect was then either filled with the previously mentioned substitutes or left empty to serve as a control. After 4 weeks femora were harvested followed by histological, histomorphometrical and immunohistochemical (BMP2; bone-morphogenic protein 2, OPG; osteoprotegerin, RANKL; Receptor activator of nuclear factor kappa-B ligand, ASMA; alpha smooth muscle actin, ED1;CD68 antibody). TOF-SIMS was used to assess the distribution of released strontium ions. Statistical analysis was done using SPSS software. Data was not found normally distributed and hence Mann-Whitney U with bonferroni correction was used. To avoid type I errors due to unequal variances and group sizes Games-Howell test was also performed.Background
Methods
The introduction of new treatments needs to be both clinically effective and cost effective. Clinicians tend to be unaware of the importance of the latter, and how health economic assessments are undertaken, especially in a public health system where the inclusion of funded treatments is made on a national basis. The purpose of this study was to determine the cost savings from a societal perspective in the use of recombinant human Bone Morphogenetic Protein -2 (rhBMP-2) in grade III A and B open tibia fractures treated with a locked intramedullary nail and soft-tissue management in the UK, Germany, and France. Healthcare system (direct healthcare costs) and costs for productivity losses (indirect health-care costs) were calculated using the raw data from the Bone Morphogenetic Protein Evaluation Group in Surgery for Tibial Trauma “BESTT study”. Return-to-work time for estimation of productivity losses was assumed to correspond with the time of fracture healing. For calculation of secondary interventions costs and productivity losses the respective 2007/08 national tariffs for surgical procedures and average national wages for the UK, Germany, and France were used. From a societal perspective, overall savings per case of €7911 for the UK, €9270 for Germany, and €9291 were calculated. Those savings largely offset the upfront price of rhBMP-2 of €2266(£1,790) in the UK, €2970 in Germany, and €2950 in France. Total net savings can be estimated to be €9.6 million for the UK, €14.5 million for Germany, and €11.4 million for France. For all three countries reduced productivity losses are the key driver for the overall savings. In summary, despite the apparent high direct cost of rhBMP-2 in grade III A and B open tibia fractures, at a national level there are net cost-savings from a societal perspective for all three countries.
Gentamicin was described with negative effects on bone formation. Arginin-Glycin-Aspartat (RGD) sequences play a key role in the adhesion of osteoblasts and have proven to improve implant integration. We have already shown a significant reduction in infection rates by a combined gentamicin-hydroxyapatite (HA) and gentamicin-RGD-hydroxyapatite coating in a rabbit infection model for cementless joint prostheses. The purpose of the study was to assess whether the gentamicin-HA coating had a negative effect on the implant integration and new bone formation, compared to pure HA coating, and whether this could be enhanced by additional gentamicin-RGD-HA coating. There were 5 study groups (8 animals per group) with 5 different stainless steel K-wires: uncoated, HA coated, gentamicin-HA, RGD-coated, gentamicin-RGD-HA coated. A 2.0 mm K-wire with one type of coating was introduced into the intramedullary canal of the tibia. The tibiae were harvested after 12 weeks and standardised longitudinal and transverse sections were performed to study new bone formation around the implant and implant bone contact. New bone formation and osseointegration of the implant surface was assessed using histomorphometrical methods by computerised semi-quantitative analysis and histological methods. There were no significant differences between the HA and the gentamicin-HA group although new bone formation and implant bone contact were always higher for the pure HA coating. Additional RGD coating on the gentamicin-RGD-HA coating did not show significant improvement of bone formation and implant integration compared to gentamicin-HA. There was a very similar histological appearance of new bone formation between all groups with very low frequency of giant cells, indicating good biocompatibility. Gentamicin-HA coating did not have significant negative effects on bone formation and bone implant contact, compared to pure HA coating. In combination with the excellent ability to reduce infection rates, gentamicin-HA coating may have a high interest in cement-less arthroplasty.
Infections in total joint arthroplasty, particularly with multiresistant bacteria, are a serious problem. A new nanoparticulate silver cement had previously shown good biocompatibility combined with good in vitro antimicrobial activity against multiresistant bacteria. The purpose of the current study was to evaluate the antibacterial activity of nanoparticulate silver cement against biofilm-building methicillin-resistant S. aureus (MRSA) in a rabbit model and to compare it to that of gentamicin-loaded cement. Gentamicin cement or nanoparticulate silver bone cement was injected into the proximal half of one femur in 10 animals, respectively. Before hardening of the cement 107 or 108 colony forming units of MRSA with high gentamicin resistance were inoculated at the cement bone interface in 5 rabbits of each group. The animals were euthanized after 14 days and both the cement adjacent bone and the cement itself were studied using microbiological and histological methods. Infection was defined as positive culture growth from the bone and/or cement samples. Infections rates were 100% for the gentamicin group (10 of 10 animals had infection) and 30% for the NanoSilver group (3 of 10 animals). Thus, nanoparticulate silver bone cement significantly reduced infection rates by 70%. Nanoparticulate silver cement exhibited good antimicrobial activity in the prophylaxis of cement-related infections with MRSA and is therefore a promising alternative in total joint arthroplasty.