MACI - a new era?

Full thickness articular cartilage defects have limited regenerative potential and are a significant source of pain and loss of knee function. Numerous treatment options exist, each with their own advantages and drawbacks. The goal of this review is to provide an overview of the problem of cartilage injury, a brief description of current treatment options and outcomes, and a discussion of the current principles and technique of Matrix-induced Autologous Chondrocyte Implantation (MACI). While early results of MACI have been promising, there is currently insufficient comparative and long-term outcome data to demonstrate superiority of this technique over other methods for cartilage repair

New live mycobacterial vaccines: the Geneva consensus on essential steps towards clinical development

As the disease caused by Mycobacterium tuberculosis continues to be a burden, which the world continues to suffer, there is a concerted effort to find new vaccines to combat this problem. Of the various vaccines strategies, one viable option is the development of live mycobacterial vaccines. A meeting with researchers, regulatory bodies, vaccines developers and manufactures was held to consider the challenges and progress, which has been achieved with live mycobacterial vaccines (either modified BCG or attenuated M. tuberculosis). Discussion led to the production of a consensus document of the proposed entry criteria for Phase I clinical trials of candidate live mycobacterial vaccines. The vaccine must be characterised thoroughly to prove identity and consistency, as clinical trial lots are prepared. In pre-clinical studies, greater protective efficacy as well as improved safety potential relative to BCG should be considered when assessing potential vaccine candidates. A standard way to measure the protective efficacy to facilitate comparison between vaccine candidates was suggested. Additional safety criteria and verification of attenuation must be considered for attenuated M. tuberculosis. Two non-reverting independent mutations are recommended for such vaccines. When entering Phase I trials, enrolment should be based upon an acceptable characterisation of the study population regarding mycobacterium status and exclude HIV+ individuals. BCG could be used as a comparator for blinding during the trials and to properly assess vaccine-specific adverse reactions, while assays are being developed to assess immunogenicity of vaccines. The proposed criteria suggested in this consensus document may facilitate the movement of the most promising vaccine candidates to the clinic and towards control of tuberculosi

Comparison of Pathogen DNA Isolation Methods from Large Volumes of Whole Blood to Improve Molecular Diagnosis of Bloodstream Infections

For patients suffering from bloodstream infections (BSI) molecular diagnostics from whole blood holds promise to provide fast and adequate treatment. However, this approach is hampered by the need of large blood volumes. Three methods for pathogen DNA isolation from whole blood were compared, i.e. an enzymatic method (MolYsis, 1-5 ml), the novel nonenzymatic procedure (Polaris, 1-5 ml), and a method that does not entail removal of human DNA (Triton-Tris-EDTA EasyMAG, 200 mu l). These methods were evaluated by processing blood spiked with 0-1000 CFU/ml of Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. Downstream detection was performed with real-time PCR assays. Polaris and MolYsis processing followed by real-time PCRs enabled pathogen detection at clinically relevant concentrations of 1-10 CFU/ml blood. By increasing sample volumes, concurrent lower cycle threshold (Ct) values were obtained at clinically relevant pathogen concentrations, demonstrating the benefit of using larger blood volumes. A 100% detection rate at a concentration of 10 CFU/ml for all tested pathogens was obtained with the Polaris enrichment, whereas comparatively lower detection rates were measured for MolYsis (50-67%) and EasyMAG (58-79%). For the samples with a concentration of 1 CFU/ml Polaris resulted in most optimal detection rates of 70-75% (MolYsis 17-50% and TTE-EasyMAG 20-36%). The Polaris method was more reproducible, less labour intensive, and faster (45 minutes (including Qiagen DNA extraction) vs. 2 hours (MolYsis)). In conclusion, Polaris and MolYsis enrichment followed by DNA isolation and real-time PCR enables reliable and sensitive detection of bacteria and fungi from 5 ml blood. With Polaris results are available within 3 hours, showing potential for improved BSI diagnostics

Development of a clinically appilicable tool for bone density assessment

Objectives To assess the accuracy and reliability of new software for radiodensitometric evaluations. Methods A densitometric tool developed by MevisLab® was used in conjunction with intraoral radiographs of the premolar region in both in vivo and laboratory settings. An aluminum step wedge was utilized for comparison of grey values. After computer-aided segmentation, the interproximal bone between the premolars was assessed in order to determine the mean grey value intensity of this region and convert it to a thickness in aluminum. Evaluation of the tool was determined using bone mineral density (BMD) values derived from decalcified human bone specimens as a reference standard. In vivo BMD data was collected from 35 patients as determined with dual X-ray absorptiometry (DXA). The intra and interobserver reliability of this method was assessed by Bland and Altman Plots to determine the precision of this tool. Results In the laboratory study, the threshold value for detection of bone loss was 6.5%. The densitometric data (mm Al eq.) was highly correlated with the jaw bone BMD, as determined using dual X-ray absorptiometry (r = 0.96). For the in vivo study, the correlations between the mm Al equivalent of the average upper and lower jaw with the lumbar spine BMD, total hip BMD and femoral neck BMD were 0.489, 0.537 and 0.467, respectively (P < 0.05). For the intraobserver reliability, a Bland and Altman plot showed that the mean difference ± 1.96 SD were within ±0.15 mm Al eq. with the mean difference value small than 0.003 mm Al eq. For the interobserver reliability, the mean difference ±1.96 SD were within ±0.11 mm Al eq. with the mean difference of 0.008 mm Al eq. Conclusions A densitometric software tool has been developed, that is reliable for bone density assessment. It now requires further investigation to evaluate its accuracy and clinical applicability in large scale studies