Development and prospects of dedicated tracers for the molecular imaging of bacterial infections

Bacterial infections have always been, and still are, a major global healthcare problem. For accurate treatment it is of utmost importance that the location(s), severity, type of bacteria, and therapeutic response can be accurately staged. Similar to the recent successes in oncology, tracers specific for molecular imaging of the disease may help advance the patient management. Chemical design and bacterial targeting mechanisms are the basis for the specificity of such tracers. The aim of this review is to provide a comprehensive overview of the molecular imaging tracers developed for optical and nuclear identification of bacteria and bacterial infections. Hereby we envision that such tracers can be used to diagnose infections and aid their clinical management. From these compounds we have set-out to identify promising targeting mechanisms and select the most promising candidates for further development.The Netherlands Organisation for Scientific Research (NWO; STW BGT 11272).http://pubs.acs.org/bchb201

FDG-PET/CT for differentiating between aseptic and septic delayed union in the lower extremity

Background: 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) has proven to have a high diagnostic accuracy for the detection of bone infections. In patients with delayed union it may be clinically important to differentiate between aseptic and septic delayed union. The aim of this study was to evaluate the efficacy and to assess the optimal diagnostic accuracy of FDG-PET/CT in differentiating between aseptic and septic delayed union in the lower extremity. Methods: This is a retrospective study of consecutive patients who underwent FDG-PET/CT scanning for suspicion of septic delayed union of the lower extremity. Diagnosis of aseptic delayed union or septic delayed union was made based on surgical deep cultures following PET/CT scanning and information on clinical follow-up. FDG-uptake values were measured at the fractured site by use of the maximum standardized uptake value (SUVmax). Sensitivity, specificity and diagnostic accuracy of FDG-PET/CT were calculated at various SUVmax cut-off points. Results: A total of 30 patients were included; 13 patients with aseptic delayed unions and 17 patients with septic delayed unions. Mean SUVmax in aseptic delayed union patients was 3.23 (SD ± 1.21). Mean SUVmax in septic delayed union patients was 4.77 (SD ± 1.87). A cut-off SUVmax set at 4.0 showed sensitivity, specificity and diagnostic accuracy of FDG-PET/CT were 65, 77 and 70% to differentiate between aseptic and septic delayed union, respectively. Conclusion: Using a semi-quantitative measure (SUVmax) for interpretation of FDG-PET/CT imaging seems to be a promising tool for the discrimination between aseptic and septic delayed union

Preventing acute infection in total hip prostheses implanted after external fixation of the femur: is there a need for a staged procedure?

We report two cases of acute infection of an uncemented femoral component in a hip prosthesis implanted after external fixation of a femoral fracture. In both cases, the surgical access did not cross over the pin scars. When the prosthesis was implanted the stem crossed one or more pin tracts. The preoperative clinical examination, laboratory tests and bone scintigraphy with marked granulocytosis did not show signs of local infection in either case. We suggest that every patient destined to receive a prosthesis after external fixation should be treated with a staged procedure, the first step being excision of the soft tissues around the pin tracts and curettage or drilling of the bony holes, followed by prosthesis implant

High prevalence of secondary factors for bone fragility in patients with a recent fracture independently of BMD

In this study, we demonstrate a high prevalence of secondary factors in patients with a recent fracture independently of bone mineral density (BMD). Our results suggest that patients with a recent fracture should be screened for secondary factors for bone fragility regardless of BMD values.INTRODUCTION: Secondary factors for bone fragility are common in patients with osteoporosis who have sustained a fracture. The majority of fragility fractures occurs, however, in patients with osteopenia, and it is not known whether secondary factors may contribute to fracture risk in these patients or in those with normal BMD.METHODS: Prospective cohort study evaluating the prevalence of secondary factors for bone fragility in consecutive patients referred to our fracture liaison service from June 2012 to June 2014 after a recent fracture.RESULTS: Seven hundred nine patients were included, 201 (28 %) with osteoporosis, 391 (55 %) with osteopenia and 117 (17 %) with normal BMD. Mean age was 66.0 ± 9.8 years, 504 (73 %) were women and 390 (57 %) had one or more underlying secondary factor. Evaluation of clinical risk factors using fracture risk assessment tool (FRAX) identified 38 % of patients with ≥1 secondary factor including smoking (18 %), excessive alcohol use (12 %), glucocorticoid use (12 %) and rheumatoid arthritis (3 %). Laboratory investigations revealed chronic kidney disease in 13 %, monoclonal gammopathy also in 13 % and primary or secondary hyperparathyroidism in 1 and 6 %, respectively. Secondary factors for bone fragility were equally prevalent in patients with osteoporosis, osteopenia or normal BMD.CONCLUSIONS: Our findings demonstrate a high prevalence of secondary factors for bone fragility in patients who have sustained a recent fracture, independently of BMD. The significant number of documented factors, which were treatable, suggest that patients who sustained a fracture should be screened for secondary factors for bone fragility regardless of BMD values to optimise secondary fracture prevention.Trauma Surger

Technological shocks mechanism on Macroeconomic Variables: A Dynamic Stochastic General Equilibrium (DSGE) approach.

As Ghana assumes a position of oil producer and middle-income country, it must learn to effectively deal with the related pressures from shocks. We analyze the effects of productivity shocks on Ghana’s total output using the multi-sector dynamic stochastic general equilibrium (DSGE) model. It was actualized that a productivity shock results in a temporary shrinkage in the final goods sectors due to the reallocation of labour from the final and intermediate goods sectors. We demonstrated that technological shock induces an initial fall in marginal cost of production but later rises to reach equilibrium

Reduction of routine use of radiography in patients with ankle fractures leads to lower costs and has no impact on clinical outcome: an economic evaluation

Background: To evaluate the cost-effectiveness of a reduction in the number of routine radiographs in the follow-up of patients with ankle fractures.Methods: We performed an economic evaluation alongside the multicentre, randomised WARRIOR trial. Participants were randomised to a reduced imaging follow-up protocol (i.e. radiographs at week 6 and 12 follow-up obtained on clinical indication) or usual care (i.e. routine radiography at weeks 6 and 12). The Olerud & Molander Ankle Score (OMAS) was used to assess ankle function and the EQ-5D-3L was used to estimate Quality-Adjusted Life Years (QALYs). Costs and resource use were assessed using self-reported questionnaires and medical records, and analysed from a societal perspective. Multiple imputation was used for missing data, and data were analysed using seemingly unrelated regression analysis and bootstrapping.Results: In total, 246 patients had data available for analysis (reduced imaging = 118; usual care = 128). Fewer radiographs were obtained in the reduced imaging group (median = 4) compared with the usual-care group (median = 5). Functional outcome was comparable in both groups. The difference in QALYs was - 0.008 (95% CI:-0.06 to 0.04) and the difference in OMAS was 0.73 (95% CI:-5.29 to 6.76). Imaging costs were lower in the reduced imaging group (-(sic)48; 95% CI:- (sic)72 to -(sic)25). All other cost categories did not statistically differ between the groups. The probability of the reduced imaging protocol being cost-effectiveness was 0.45 at a wiliness-to-pay of (sic)20,000 per QALY.Conclusions: Reducing the number of routine follow-up radiographs has a low probability of being cost-effective compared with usual care. Functional outcome, health-related quality of life and societal costs were comparable in both groups, whereas imaging costs were marginally lower in the reduced imaging group. Given this, adherence to a reduced imaging follow-up protocol for those with routine ankle fractures can be followed without sacrificing quality of care, and may result in reduced costs.Trauma Surger

The accuracy of diagnostic imaging for the assessment of chronic osteomyelitis: a systematic review and meta-analysis.

Background: A variety of diagnostic imaging techniques is available for excluding or confirming chronic osteomyelitis. Until now, an evidence-based algorithmic model for choosing the most suitable imaging technique has been lacking. The objective of this study was to determine the accuracy of current imaging modalities in the diagnosis of chronic osteomyelitis. Methods: A systematic review and meta-analysis of the literature was conducted with a comprehensive search of the MEDLINE, EMBASE, and Current Contents databases to identify clinical studies on chronic osteomyelitis that evaluated diagnostic imaging modalities. The value of each imaging technique was studied by determining its sensitivity and specificity compared with the results of histological analysis, findings on culture, and clinical follow-up of more than six months. Results: A total of twenty-three clinical studies in which the accuracy was described for radiography (two studies), magnetic resonance imaging (five), computed tomography (one), bone scintigraphy (seven), leukocyte scintigraphy (thirteen), gallium scintigraphy (one), combined bone and leukocyte scintigraphy (six), combined bone and gallium scintigraphy (three), and fluorodeoxyglucose positron emission tomography (four) were included in the review. No meta-analysis was performed with respect to computed tomography, gallium scintigraphy, and radiography. Pooled sensitivity demonstrated that fluorodeoxyglucose positron emission tomography was the most sensitive technique, with a sensitivity of 96% (95% confidence interval, 88% to 99%) compared with 82% (95% confidence interval, 70% to 89%) for bone scintigraphy, 61% (95% confidence interval, 43% to 76%) for leukocyte scintigraphy, 78% (95% confidence interval, 72% to 83%) for combined bone and leukocyte scintigraphy, and 84% (95% confidence interval, 69% to 92%) for magnetic resonance imaging. Pooled specificity demonstrated that bone scintigraphy had the lowest specificity, with a specificity of 25% (95% confidence interval, 16% to 36%) compared with 60% (95% confidence interval, 38% to 78%) for magnetic resonance imaging, 77% (95% confidence interval, 63% to 87%) for leukocyte scintigraphy, 84% (95% confidence interval, 75% to 90%) for combined bone and leukocyte scintigraphy, and 91% (95% confidence interval, 81% to 95%) for fluorodeoxyglucose positron emission tomography. The sensitivity of leukocyte scintigraphy in detecting chronic osteomyelitis in the peripheral skeleton was 84% (95% confidence interval, 72% to 91%) compared with 21% (95% confidence interval, 11% to 38%) for its detection of chronic osteomyelitis in the axial skeleton. The specificity of leukocyte scintigraphy in the axial skeleton was 60% (95% confidence interval, 39% to 78%) compared with 80% (95% confidence interval, 61% to 91%) for the peripheral skeleton. Conclusions: Fluorodeoxyglucose positron emission tomography has the highest diagnostic accuracy for confirming or excluding the diagnosis of chronic osteomyelitis. Leukocyte scintigraphy has an appropriate diagnostic accuracy in the peripheral skeleton, but fluorodeoxyglucose positron emission tomography is superior for detecting chronic osteomyelitis in the axial skeleton. Level of Evidence: Diagnostic Level III. Copyright © 2005 by The Journal of Bone and Joint Surgery, Incorporated

FDG-PET/CT for differentiating between aseptic and septic delayed union in the lower extremity

Trauma Surger