NAMSA (France)

Risks associated with drugs and treatments are a key concern in clinical investigations of therapeutics. There is a keen attention to side effects and adverse events included in critical safety documentation presented in regulatory submissions for new drugs. Likewise, Companion Diagnostic (CDx) technology is subject to rigorous regulated research and testing because of the risk associated with a false test result that could affect clinical decisions and treatment. The rigor of testing imposed by the regulatory path to clearance or approval is intended to ensure an assay is reliable when performance criteria are defined by a fixed set of these variables so that there is the least risk of false test results. The clinical validation of these assays is especially important when the test result is used to manage therapeutic decisions for patients. The same patients that expect a clinician to use reliable diagnostics to recommend treatment may also be recruited to participate in CDx clinical investigations. This educational review of CDx product development, regulations, and clinical investigations involving human subjects is important to: (1) Clinicians who rely on the test results to manage patient care; (2) Patients who trust these test results are informing the clinician, and (3) Hospital administrators who oversee human subjects safety and data intergrity for clinical investigations in the personalized medicine space.

The paradigm shift brought about by the expansion of tissue engineering and regenerative medicine away from the use of biomaterials, currently questions the value of histopathologic methods in the evaluation of biological changes. To date, the available tools of evaluation are not fully consistent and satisfactory for these advanced therapies. We have developed a new, simple and inexpensive quantitative digital approach that provides key metrics for structural and compositional characterization of the regenerated tissues. For example, metrics provide the tissue ingrowth rate (TIR) which integrates two separate indicators; the cell ingrowth rate (CIR) and the total collagen content (TCC) as featured in the equation, TIR% = CIR% + TCC%. Moreover a subset of quantitative indicators describing the directional organization of the collagen (relating structure and mechanical function of tissues), the ratio of collagen I to collagen III (remodeling quality) and the optical anisotropy property of the collagen (maturity indicator) was automatically assessed as well. Using an image analyzer, all metrics were extracted from only two serial sections stained with either Feulgen & Rossenbeck (cell specific) or Picrosirius Red F3BA (collagen specific). To validate this new procedure, three-dimensional (3D) scaffolds were intraperitoneally implanted in healthy and in diabetic rats. It was hypothesized that quantitatively, the healing tissue would be significantly delayed and of poor quality in diabetic rats in comparison to healthy rats. In addition, a chemically modified 3D scaffold was similarly implanted in a third group of healthy rats with the assumption that modulation of the ingrown tissue would be quantitatively present in comparison to the 3D scaffold-healthy group. After 21 days of implantation, both hypotheses were verified by use of this novel computerized approach. When the two methods were run in parallel, the quantitative results revealed fine details and differences not detected by the semi-quantitative assessment, demonstrating the importance of quantitative analysis in the performance evaluation of soft tissue healing. This automated and supervised method reduced operator dependency and proved to be simple, sensitive, cost-effective and time-effective. It supports objective therapeutic comparisons and helps to elucidate regeneration and the dynamics of a functional tissue.

The multilayer flow modulator (MFM; Cardiatis, Isnes, Belgium) is a self-expandable mesh of braided cobalt alloy wires, used for treatment of aortic and peripheral aneurysms. To further improve our understanding of this novel technology, the endothelialization kinetics of the MFM was investigated and compared with those of two marketed single-layer stents. Five porcine animal models were used in which a total of 19 stents were implanted in the iliac and carotid arteries between one and five weeks before sacrifice. All 19 stents were successfully delivered. For all devices, nonsignificant signs of inflammation or thrombosis were noted, and there was no evidence of local intolerance. The MFM developed a thin layer of endothelial cells earlier and was associated with less neointimal development than the two single-layer stents. A differing phenomenon of integration was also revealed and hypothesized as endothelialization from adhesion of circulating endothelial progenitor cells, as well as adhesion from the arterial wall, and also by the differences in trauma exposed to the arterial wall.

Background/Aims: The short stature homeobox-containing (SHOX) gene is one of many genes that regulate longitudinal growth. The SHOX deficiency (SHOX-D) phenotype, caused by intragenic or regulatory region defects, ranges from normal stature to mesomelic skeletal dysplasia. We investigated differences in radiological anomalies between patients with SHOX-D and Turner syndrome (TS) and the effect of 2 years of growth hormone (GH) treatment on these anomalies. Methods: Left hand/wrist, forearm and lower leg radiographs were assessed at baseline and after 2 years in children with genetically confirmed SHOX-D (GH-treated and untreated groups) and TS (GH-treated) in a randomised, controlled, multinational study. Results: Radiological anomalies of hand, wrist and forearm were common in SHOX-D and TS. Radial bowing appeared more prevalent in SHOX-D, while lower leg anomalies were more common in TS. There were no significant differences in radiological findings between GH-treated and untreated patients with SHOX-D after 2 years. Conclusion: GH treatment had no systematic effect on skeletal findings in SHOX-D, based on limited radiological differences between the GH-treated and untreated groups at 2 years. Bone age radiographs allow assessment of radiological signs indicating a potential diagnosis of SHOX-D and may lead to earlier genetic confirmation and initiation of GH therapy.

The Tissue Engineering & Regenerative Medicine International Society-Europe (TERMIS-EU) Industry Committee as well as its TERMIS-Americas (AM) counterpart intend to address the specific challenges and needs facing the industry in translating academic research into commercial products. Over the last 3 years, the TERMIS-EU Industry Committee has worked with commercial bodies to deliver programs that encourage academics to liaise with industry in proactive collaborations. The TERMIS-EU 2013 Industry Symposium aimed to build on this commercial agenda by focusing on two topics: Operations Management (How to move a process into the good manufacturing practice [GMP] environment) and Clinical Translation (Moving a GMP process into robust trials). These topics were introduced by providing the synergistic business perspective of partnering between the multiple regenerative medicine stakeholders, throughout the life cycle of product development. Seven industry leaders were invited to share their experience, expertise, and strategies. Due to the complex nature of regenerative medicine products, partnering for their successful commercial development seems inevitable to overcome all obstacles by sharing experiences and expertise of all stakeholders. When ideally implemented, the "innovation quotient" of a virtual team resulting from the combination of internal and external project teams can be maximized through maximizing the three main dimensions: core competences, technology portfolio, and alliance management.