To make an inoculum for induction of Implant-Associated Osteomyelitis (IAO) in pigs based on bacterial aggregates resembling those found on the human skin, i.e. aggregates of 5–15 µm with low metabolic activity. The aggregates were evaluated and compared to a standard planktonic bacterial inoculum. The porcine Aim
Method
The aim of this study was to assess the incidence the microbiological spectrum and clinical outcome of hip and knee revision arthroplasties with unexpected-positive-intraoperative-cultures (UPIC) at a single center with minimum follow up of 2 years. We retrospectively analyzed our prospectively maintained institutional arthroplasty registry. Between 2011 and 2020 we performed presumably aseptic rTHA (n=939) and rTKA (n= 1,058). Clinical outcome, re-revision rates and causes as well as the microbiological spectrum were evaluated.Aims
Methods
Synovial calprotectin point-of-care test (POC) has shown promising clinical value in diagnosing periprosthetic joint infections (PJIs). However, limited data are available in unclear cases. Moreover, cut-off values for calprotectin lateral flow assay (LFA) and enzyme-linked immunosorbent assay (ELISA) need to be adapted. The aim of this study was to evaluate the performance of an upgraded and more sensitive version of a synovial calprotectin LFA along with ELISA immunoassay in patients with septic, aseptic, and unclear cases. Overall, 206 prospectively collected periprosthetic synovial fluid samples from 169 patients (106f/63m; 38 hip/131 knee) who underwent revision surgeries were retrospectively evaluated for calprotectin concentration. The following groups were analyzed: unexpected negative cultures (UNC; 32/206), unexpected positive cultures (UPC; 28/206), and unclear cases (65/206) with conflicting clinical results. In addition, we added a true aseptic (40/206), and true septic (41/206) control groups according to the international consensus meeting (ICM) 2018 PJI classification. Calprotectin concentration was determined by a rapid quantitative LFA (n=206) (Lyfstone®, Norway), and compared to calprotectin ELISA immunoassay (171/206). For the determination of a new calprotectin cut-off value, analysis of the area under the curve (AUC) followed by Youden's J statistic were performed using the calproctectin values from clear septic and aseptic cases. Sensitivity and specificity for calprotectin were calculated. All statistical analyses were performed using IBM-SPSS® version 25 (Armonk, NY, USA).Aim
Methods
Several local antibiotic-eluting drug delivery systems have been developed to treat bacterial bone infections. However, available systems have significant shortcomings, including suboptimal drug-release profiles with a burst followed by subtherapeutic release, which may lead to treatment failure and selection for drug resistance. Here, we present a novel injectable, biocompatible, These studies aimed to determine the therapeutic potential of CarboCell formulations for treatment of implant-associated osteomyelitis by mono- and dual antimicrobial therapy. The solubility and stability of several antibiotics were determined in various CarboCell formulations, and Aim
Methods
Culture-based conventional methods are still the gold standard to identify microorganisms in hip and knee PJIs diagnosis. However, such approach presents some limitations due to prior antimicrobial treatment or the presence of unusual and fastidious organisms. Molecular techniques, in particular specific real-time and broad-range polymerase chain reaction (PCR), are available for diagnostic use in a suspected PJI. However, limited data is available on their sensitivity and specificity. This study aimed to evaluate the performance of a rapid and simple Investigational Use Only (IUO) version of the BioFire® JI multiplex PCR panel when compared to traditional microbiological procedures. Fifty-eight native synovial fluid samples were recovered from 49 patients (female n=26; male =23) who underwent one or multiple septic or aseptic revision arthroplasties of the hip (n=12) and knee (n=46). The JI panel methodology was used either on specimens freshly collected (n=6) or stored at −80°C in our Musculoskeletal Biobank (n=52). The JI panel performance was evaluated by comparison with culture reference methods. Patient's medical records were retrieved from our institutional arthroplasty registry as well as our prospectively maintained PJI infection database.Aim
Method
Analysis of microbiological spectrum and resistance patterns as well as the clinical outcome of patients who underwent a Debridement, antibiotics and implant retention (DAIR) procedure in the early phase following failed two-stage exchange arthroplasty of the knee and hip. Of 312 patients treated with two-stage exchange arthroplasty between January 2011 and December 2019, 16 (5.1%) patients (9 knee, 7 hip) underwent a DAIR procedure within 6 months following second stage. We retrospectively analyzed the microbiological results as well as changes in the microbiological spectrum and antibiotic resistance patterns between stages of two-stage exchange arthroplasties and DAIR procedures. Patient's re-revision rates after a minimum follow-up of 12 months following DAIR procedure were evaluated. Moreover, differences between knee and hip and between infected primary total joint replacement (TJRs) and infected revision TJRs as well as patient's host factors and microbiological results regarding the outcome of DAIR were analyzed.Aim
Method
Unexpected-positive-intraoperative-cultures (UPIC) in presumed aseptic revision-total-knee-arthroplasties (rTKA) are common, and the clinical significance is not entirely clear. In contrast, in some presumably septic rTKA, an identification of an underlying pathogen was not possible, so called unexpected-negative-intraoperative-cultures (UNIC). The purpose of this study was to evaluate alpha defensin (AD) levels in these patient populations. In this retrospective analysis of our prospectively maintained biobank, we evaluated synovial AD levels from 143 rTKAs. The 2018-Musculoskeletal Infection Society score (MSIS) was used to define our study groups. Overall, 20 rTKA with UPIC with a minimum of one positive intraoperative culture with MSIS 2-≥6 and 14 UNIC samples with MSIS≥6 were compared to 34 septic culture-positive samples (MSIS ≥6) and 75 aseptic culture-negative (MSIS 0–1) rTKAs. Moreover, we compared the performance of both AD-lateral-flow-assay (ADLF) and an enzyme-linked-immunosorbent-assay (ELISA) to test the presence of AD in native and centrifuged synovial fluid. Concentration of AD determined by ELISA and ADLF methods, as well as microbiological, and histopathological results, serum and synovial parameters along with demographic factors were considered.Purpose
Methods
In severe cases of postoperative spinal implant infections (PSII) multiple revision surgeries may be needed. Little is known if changes of the microbiological spectrum and antibiotic resistance pattern occur between revision surgeries. Therefore, the aim of this study was to analyze the microbiological spectrum and antibiotic resistance pattern in patients with multiple revision surgeries for the treatment of PSII. Furthermore, changes of the microbiological spectrum, distribution of mono vs. polymicrobial infections, and changes of the antimicrobial resistance profile in persistent microorganisms were evaluated. A retrospective analysis of a prospectively maintained single center spine infection database was performed with a minimum follow-up of 3 years. Between 01/2011 and 12/2018, 103 patients underwent 248 revision surgeries for the treatment of PSII. Overall, 20 patients (6 male/14 female) underwent 82 revisions for PSII (median 3; range 2–12). There were 55/82 (67.1%) procedures with a positive microbiological result. Microbiological analysis was performed on tissue and implant sonication fluid. Changes in microbial spectrum and antibiotic resistance pattern between surgeries were evaluated using Chi-Square and Fisher's exact test.Aim
Method
Head-taper corrosion is a cause of failure in total hip arthroplasty (THA). Recent reports have described an increasing number of V40 taper failures with adverse local tissue reaction (ALTR). However, the real incidence of V40 taper damage and its cause remain unknown. The aim of this study was to evaluate the long-term incidence of ALTR in a consecutive series of THAs using a V40 taper and identify potentially related factors. Between January 2006 and June 2007, a total of 121 patients underwent THA using either an uncemented (Accolade I, made of Ti12Mo6Zr2Fe; Stryker, USA) or a cemented (ABG II, made of cobalt-chrome-molybdenum (CoCrMo); Stryker) femoral component, both with a V40 taper (Stryker). Uncemented acetabular components (Trident; Stryker) with crosslinked polyethylene liners and CoCr femoral heads of 36 mm diameter were used in all patients. At a mean folllow-up of 10.8 years (SD 1.1), 94 patients (79%) were eligible for follow-up (six patients had already undergone a revision, 15 had died, and six were lost to follow-up). A total of 85 THAs in 80 patients (mean age 61 years (24 to 75); 47 (56%) were female) underwent clinical and radiological evaluation, including the measurement of whole blood levels of cobalt and chrome. Metal artifact reduction sequence MRI scans of the hip were performed in 71 patients.Aims
Methods
Due to well-known complications of metal-on-metal hip resurfacing arthroplasty the indication for this procedure has significantly decreased over the past years. As a high number of patients is currently living with resurfacing implants, however, there is a clear need for information about the longterm results and especially about the rate of local as well as systemic adverse effects. We retrospectively reviewed our first 95 patients who had 100 consecutive BHR hip resurfacings performed from 1998–2001. Median age at surgery was 52 years (range, 28–69 years); 49% were men. After a mean follow-up period of 16.1 years (range 15.2 – 17.6 years) we assessed survival rate (revision for any reason as endpoint), radiographic changes and patient-related outcome in patients who had not undergone revision. In addition we measured whole blood concentrations of cobalt at follow-up. 17% of our patients in the original cohort were lost to follow-up. In the remaining patients the 16-year survivorship was 80.1%. The overall survival rate was slightly higher in males (80.6%) than in females (77.1%). The WOMAC overall score showed a median value of 91.7 points (range 35.4 – 100). Median whole blood ion levels were 1.9 µg/L for cobalt (0.6 – 140.2 µg/L), 14.9% of patients showed elevated levels. The number of patients with relevant radiographic signs of local adverse reactions to metal debris was relatively low. In contrast to earlier reports and very few other longterm studies our results show an unsatisfactory performance of resurfacing. In particular the outcome of male patients deteriorated between 10 and 16 years of follow-up. Although only a small number of patients shows relevant elevation of metal-ion levels, the clinical relevance has still to be determined.
To review the natural history of upper limb osteochondromas and assess their functional effect. We performed a retrospective casenote review of a consecutive patient cohort presenting between 1997–2012 with upper limb osteochondromas. Indications for surgical intervention were noted and considered to be cosmetic, functional (including pain relief) and ‘prophylactic’ in terms of deformity prevention. All patients were invited to complete questionnaires for the PODCI, DASH, OSS and MHS scores.Aim
Materials
Soft tissue sarcomas (STS) include a spectrum of his-tologically and clinically different tumors. Patients are typically relatively young and the course of disease is characterized by early metastasis as well as limited response to chemotherapy. However, a few subtypes such as small round cell tumors (SRCTs) and rhabdomyosarcoma (except from pleomorphic), are considered chemotherapy-sensitive. In addition, reflecting successful translational research of recent years, gastrointestinal stromal tumor (GIST) and dermatofibrosarcoma protuberans have become model diseases for targeted oncological therapy. With a very limited number of active compounds at hand, treatment choices in metastatic STS with inkonsistent genomic alterations were easy to overview until only a few years ago. However, with novel therapeutic strategies such as the antiangiogenic approach and a multitude of novel compounds available both outside and within clinical studies, it may have become more difficult to keep track of currently available treatment options and their clinical safety and efficacy. Anthracyclines with or without ifosfamide are still considered standard of care in most STS-subtypes, especially in high-grade tumors. There is no evidence-based recommendation as to second-line treatment options. However, a number of established compounds, including dacarbazine/temozolomide, gemcitabine, taxanes, trofosfamide, DNA topoisomerase I inhibitors, DNA minor groove binders, and bendamustine, have shown activity. Recently, trabectedin, a DNA minor groove binder initially isolated from a sea sponge, has proven effective and received European approval for use in treatment-refractory STS. In addition, novel compounds such as bevacizumab, multityrosine kinase inhibitors, mTOR inhibitors, imatinib mesylate, and the thrombospondin agonist ABT 510 represent attractive partners for the above-mentioned cytostatic agents or may even be effective single agents in the clinically advanced setting. Novel combinations are being evaluated in clinical studies. In order to be successful, we may have to combine not only different compounds but also different targets beyond the proliferation machinery of sarcoma cells such as tumor angiogenesis, the tumor stromal compartment or tumor cell oncogene products.
Sarcomas are rare malignant tumors of mesenchymal origin and primarily occur in children, adolescents and young adults. With multimodal treatment concepts survival has significantly improved and is now in the range of 60–70 %. Following relapse or metastasis, however, the prognosis still is poor as is also the case for patients presenting with primary disseminated disease. TranSaR-Net aims to develop novel treatment strategies overcoming tumor cell resistance directed against novel targets. To achieve this goal the German pediatric, adolescent and adult sarcoma research groups have formed a collaborative network linking the nationwide and European trial groups with access to over 90 % of all pediatric and adolescent sarcoma patients and a large number of adult sarcoma patients to basic and translational sarcoma research groups. Within TranSaRNet a registry for patients at relapse is established as target cohort for innovative treatment strategies as well as a biomaterial banking network in order to facilitate the availability of tumor and other biomaterial for basic and translational research. A joint bioinformatics platform will integrate existing array data, to standardize laboratory and evaluation procedures and for modeling new theoretical concepts in a joint effort. Within the basic and translational research work packages, the sarcoma research groups in Germany have coordinated their research activities in a joint effort. The basic research work package (WP1) includes projects on genomic (WP1.1) and epigenetic (WP1.2) tumor characterization as well as identification of the tumor initiating cell (WP1.3) and resistance mechanisms (WP1.3 und 1.4), and the identification of new targets in apoptotic pathways (WP1.4, 2.4) and tumor-induced angiogenesis (WP1.5). The translational research work package (WP2) is focused on innovative immunological treatment strategies including sarcoma specific T-cells (WP2.1), dendritic cells (WP2.2), NK- cells (WP2.4) and tumor imaging (WP2.3). A brief overview of the projects will be provided.
A giant cell tumour is a primary lesion of bone of intermediate severity. Its histogenesis is unclear. In a few cases pulmonary metastases have been described. Multiple skeletal metastases in the absence of sarcomatous change have been observed. We present a case report of a 25-year-old woman with a recurrent giant cell tumour of the distal fibula. After a second recurrence and six years after the initial diagnosis, she rapidly developed multiple bony metastases. The outcome was fatal.
Of 41 consecutive patients with newly diagnosed osteogenic sarcoma admitted to the Children's Orthopedic Hospital and Medical Center in Seattle, Washington, between 1952 and 1977, 19 treated before 1973 did not receive adjunctive chemotherapy (histological group) whereas after 1972 22 have been so treated (chemotherapy group). Chemotherapy consisted primarily of high doses of methotrexate and adriamycin for 16 months after surgical treatment. Patients in the historical group have been observed for a minimum of nine years (six patients) or until death (13 patients). The 13 surviving patients in the chemotherapy group have been followed for a minimum of three years (median five years) and all 12 disease-free patients have been off therapy for between one and a half and five and a half years (median three years). Overall, the chemotherapy group has had a significant increase in both survival (p = 0.03) and disease-free survival (P = 0.02) compared to the historical group. In 35 patients with localised disease at diagnosis, the three-year disease-free survival and the three-year survival rates were 18 per cent and 41 per cent respectively in the historical group, and 67 per cent and 78 per cent (life table estimates) respectively in the chemotherapy group. With adjunctive chemotherapy only one of the seven patients developing pulmonary metastases did so later than nine months after diagnosis. The superior results in the chemotherapy group could not be accounted for by differences in age, sex, presence of metastases at diagnosis, histopathology, location of primary tumour, type of initial or subsequent surgical treatment, or the use of standard or computerised lung tomography. Although the use of historical controls in this study does not exclude other changes as contributing to the observed improvement in outcome, our data support the contention that adjunctive chemotherapy improves both the disease-free survival and the overall survival of patients with osteosarcoma and rarely delays the onset of recurrent or metastatic disease.
