Diagnosing fracture related infections (FRI) based on clinical symptoms alone can be challenging and additional diagnostic tools such as serum inflammatory markers are often utilized. The aims of this study were 1) to determine the individual diagnostic performance of three commonly used serum inflammatory markers: C-Reactive Protein (CRP), Leukocyte Count (LC) and Erythrocyte Sedimentation Rate (ESR), and 2) to determine the diagnostic performance of a combination of these markers and their value additionally to clinical predictors for FRI. This cohort study included patients who presented with a suspected FRI at two level I academic trauma centers between February 1st 2009 and December 31st 2017. The parameters CRP, LC and ESR, were obtained from hospital records when FRI was suspected. The gold standard for diagnosing or ruling out FRI was defined as: positive microbiology results of surgically obtained tissue samples, or absence of FRI at a clinical follow-up of at least six months. Separate markers were analysed using hospital thresholds, to determine current diagnostic performance, and continuously, to determine maximum possible diagnostic performance. Multivariable logistic regression analyses were performed to obtain the discriminative performance (Area Under the Receiver Operating Characteristic, AUROC) of (1) the combined inflammatory markers, and (2) the value of these markers additional to clinical parameters.Aim
Method
Diagnosing Fracture-Related Infections (FRI) is challenging. White blood cell (WBC) scintigraphy is considered the best nuclear imaging technique to diagnose FRI; a recent study by our group found a diagnostic accuracy of 92%. However, many centers use 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) which has several logistic advantages. Whether 18F-FDG-PET/CT has better diagnostic performance than white blood cell (WBC) scintigraphy is uncertain. Therefore, we aimed: 1) to determine the diagnostic performance of 18F-FDG-PET/CT for diagnosing FRI (defined as infection following an open fracture or fracture surgery) and 2) to determine cut-off values of standardized uptake values (SUV) that result in optimal diagnostic performance. This retrospective cohort study included all consecutive patients who received 18F-FDG-PET/CT to diagnose FRI in two level 1 trauma centers. Baseline demographic- and surgical characteristics were retrospectively reviewed. The reference standard consisted of at least 2 representative microbiological culture results or the presence or absence of clinical confirmatory FRI signs in at least 6 months of clinical follow-up. A nuclear medicine specialist, blinded to the reference standard, re-reviewed all scans. Additionally, SUVs were measured using the “European Association of Nuclear Medicine Research Ltd. (EARL)” reconstructed 18F-FDG-PET/CT scans. Volume of interests were drawn around the suspected- and corresponding contralateral area to obtain the absolute values (SUVmax) and the ratio between suspected and contralateral area (SUVratio). Diagnostic accuracy of the re-reviewed scans was calculated (sensitivity and specificity). Additionally, diagnostic characteristics of the SUV measurements were plotted in the area under the receiver operating characteristics curve (AUROC). The sensitivity and specificity at the optimal threshold was deducted from the AUROC with the Q-point method.Aim
Method
White blood cell (WBC) scintigraphy for diagnosing fracture-related infections (FRIs) has only been investigated in small patient series. Aims of this study were (1) to establish the accuracy of WBC scintigraphy for diagnosing FRIs, and (2) to investigate whether the duration of the time interval between surgery and WBC scintigraphy influences its accuracy. 192 consecutive WBC scintigraphies with 99mTc-HMPAO-labelled autologous leucocytes performed for suspected peripheral FRI were included. The goldstandard was based on the outcome of microbiological investigation in case of surgery, or - when these were not available - on clinical follow-up of at least six months. The discriminative ability of the imaging modalities was quantified by several measures of diagnostic accuracy. A multivariable logistic regression analysis was performed to identify predictive variables of a false-positive or false-negative WBC scintigraphy test result.Aim
Method
Fracture related infection (FRI) remains a challenging diagnosis in orthopedic and trauma surgery. In addition to clinical signs and imaging, serum inflammatory markers are often used to estimate the probability of FRI. To what extent serum inflammatory markers can be used to rule out and diagnose FRI remains unclear. The aim of this systematic review was to assess the diagnostic value of the serum inflammatory markers C-reactive protein (CRP), leukocyte count (LC) and erythrocyte sedimentation rate (ESR) in suspected fracture related infection. PubMed, Embase and Cochrane databases were searched for all articles focusing on the diagnostic value of CRP, LC and ESR in FRI. Studies on other inflammatory markers or other types of orthopedic infection, such as periprosthetic and diabetic foot infections, were excluded. For each serum inflammatory marker, all reported sensitivity and specificity combinations were extracted and graphically visualized. Average estimates were obtained using bivariate mixed effects models. This study utilized the QUADAS-2 criteria and was reported following the PRISMA statement.Aim
Method
To assess the diagnostic value of C-reactive protein (CRP), leucocyte count (LC), and erythrocyte sedimentation rate (ESR) in late fracture-related infection (FRI). PubMed, Embase, and Cochrane databases were searched focusing on the diagnostic value of CRP, LC, and ESR in late FRI. Sensitivity and specificity combinations were extracted for each marker. Average estimates were obtained using bivariate mixed effects models.Aims
Materials and Methods
We have examined whether primary human muscle-derived cells can be used in ex vivo gene therapy to deliver BMP-2 and to produce bone in vivo. Two in vitro experiments and one in vivo experiment were used to determine the osteocompetence and BMP-2 secretion capacity of cells isolated from human skeletal muscle. We isolated five different populations of primary muscle cells from human skeletal muscle in three patients. In the first in vitro experiment, production of alkaline phosphatase by the cells in response to stimulation by rhBMP-2 was measured and used as an indicator of cellular osteocompetence. In the second, secretion of BMP-2 was measured after the cell populations had been transduced by an adenovirus encoding for BMP-2. In the in vivo experiment, the cells were cotransduced with a retrovirus encoding for a nuclear localised β-galactosidase gene and an adenovirus encoding for BMP-2. The cotransduced cells were then injected into the hind limbs of severe combined immune-deficient (SCID) mice and analysed radiographically and histologically. The nuclear localised β-galactosidase gene allowed identification of the injected cells in histological specimens. In the first in vitro experiment, the five different cell populations all responded to in vitro stimulation of rhBMP-2 by producing higher levels of alkaline phosphatase when compared with non-stimulated cells. In the second, the five different cell populations were all successfully transduced by an adenovirus to express and secrete BMP-2. The cells secreted between 444 and 2551 ng of BMP-2 over three days. In the in vivo experiment, injection of the transduced cells into the hind-limb musculature of SCID mice resulted in the formation of ectopic bone at 1, 2, 3 and 4 weeks after injection. Retroviral labelling of the cell nuclei showed labelled human muscle-derived cells occupying locations of osteoblasts in the ectopic bone, further supporting their osteocompetence. Cells from human skeletal muscle, because of their availability to orthopaedic surgeons, their osteocompetence, and their ability to express BMP-2 after genetic engineering, are an attractive cell population for use in BMP-2 gene therapy approaches.
Injury to muscles is very common. We have previously observed that basic fibroblast growth factor (b-FGF), insulin growth factor type 1 (IGF-1) and nerve growth factor (NGF) are potent stimulators of the proliferation and fusion of myoblasts in vitro. We therefore injected these growth factors into mice with lacerations of the gastrocnemius muscle. The muscle regeneration was evaluated at one week by histological staining and quantitative histology. Muscle healing was assessed histologically and the contractile properties were measured one month after injury. Our findings showed that b-FGF, IGF and to a less extent NGF enhanced muscle regeneration in vivo compared with control muscle. At one month, muscles treated with IGF-1 and b-FGF showed improved healing and significantly increased fast-twitch and tetanus strengths. Our results suggest that b-FGF and IGF-1 stimulated muscle healing and may have a considerable effect on the treatment of muscle injuries.
Twenty-nine bone defects caused by chronic osteomyelitis have been treated by radical excision of necrotic bone followed by packing the cavities with cancellous homografts held in position by a fibrin sealant. At follow-up three years after operation all except one had healed, though one case had needed a repeat operation. Good incorporation and remodelling of the grafts was observed even when the osseous bed was severely sclerosed.
