Autologous bilayered self-assembled skin substitutes (SASSs) as permanent grafts: a case series of 14 severely burned patients indicating clinical effectiveness.

Split-thickness skin autografts (AGs) are the standard surgical treatment for severe burn injuries. However, the treatment of patients with substantial skin loss is limited by the availability of donor sites for skin harvesting. As an alternative to skin autografts, our research group developed autologous self-assembled skin substitutes (SASSs), allowing the replacement of both dermis and epidermis in a single surgical procedure. The aim of the study was to assess the clinical outcome of the SASSs as a permanent coverage for full-thickness burn wounds. Patients were recruited through the Health Canada's Special Access Program. SASSs were grafted on debrided full-thickness wounds according to similar protocols used for AGs. The graft-take and the persistence of the SASS epithelium over time were evaluated. 14 patients received surgical care with SASSs. The mean percentage of the SASS graft-take was 98 % (standard deviation = 5) at 5 to 7 d after surgery. SASS integrity persisted over time (average follow-up time: 3.2 years), without noticeable deficiency in epidermal regeneration. Assessment of scar quality (skin elasticity, erythema, thickness) was performed on a subset of patients. Non-homogeneous pigmentation was noticed in several patients. These results indicated that the SASS allowed the successful coverage of full-thickness burns given its high graft-take, aesthetic outcome equivalent to autografting and the promotion of long-term tissue regeneration. When skin donor sites are in short supply, SASSs could be a valuable alternative to treat patients with full-thickness burns covering more than 50 % of their total body surface area.

Towards a global cancer knowledge network: dissecting the current international cancer genomic sequencing landscape.

BACKGROUND: While next generation sequencing has enhanced our understanding of the biological basis of malignancy, current knowledge on global practices for sequencing cancer samples is limited. To address this deficiency, we developed a survey to provide a snapshot of current sequencing activities globally, identify barriers to data sharing and use this information to develop sustainable solutions for the cancer research community. METHODS: A multi-item survey was conducted assessing demographics, clinical data collection, genomic platforms, privacy/ethics concerns, funding sources and data sharing barriers for sequencing initiatives globally. Additionally, respondents were asked as to provide the primary intent of their initiative (clinical diagnostic, research or combination). RESULTS: Of 107 initiatives invited to participate, 59 responded (response rate = 55%). Whole exome sequencing (P = 0.03) and whole genome sequencing (P = 0.01) were utilized less frequently in clinical diagnostic than in research initiatives. Procedures to identify cancer-specific variants were heterogeneous, with bioinformatics pipelines employing different mutation calling/variant annotation algorithms. Measurement of treatment efficacy varied amongst initiatives, with time on treatment (57%) and RECIST (53%) being the most common; however, other parameters were also employed. Whilst 72% of initiatives indicated data sharing, its scope varied, with a number of restrictions in place (e.g. transfer of raw data). The largest perceived barriers to data harmonization were the lack of financial support (P < 0.01) and bioinformatics concerns (e.g. lack of interoperability) (P = 0.02). Capturing clinical data was more likely to be perceived as a barrier to data sharing by larger initiatives than by smaller initiatives (P = 0.01). CONCLUSIONS: These results identify the main barriers, as perceived by the cancer sequencing community, to effective sharing of cancer genomic and clinical data. They highlight the need for greater harmonization of technical, ethical and data capture processes in cancer sample sequencing worldwide, in order to support effective and responsible data sharing for the benefit of patients.

Recommendations on breast cancer screening and prevention in the context of implementing risk stratification: impending changes to current policies.

In recent years, risk stratification has sparked interest as an innovative approach to disease screening and prevention. The approach effectively personalizes individual risk, opening the way to screening and prevention interventions that are adapted to subpopulations. The international perspective project, which is developing risk stratification for breast cancer, aims to support the integration of its screening approach into clinical practice through comprehensive tool-building. Policies and guidelines for risk stratification-unlike those for population screening programs, which are currently well regulated-are still under development. Indeed, the development of guidelines for risk stratification reflects the translational aspects of perspective. Here, we describe the risk stratification process that was devised in the context of perspective, and we then explain the consensus-based method used to develop recommendations for breast cancer screening and prevention in a risk-stratification approach. Lastly, we discuss how the recommendations might affect current screening policies.

Legal liability and the uncertain nature of risk prediction: the case of breast cancer risk prediction models.

BACKGROUND: The rapidity of technological change in genetics is not always matched by the uptake of this new knowledge into practice. Increasing genetic knowledge has already led to legal liability for those who have not used it properly, such as not informing patients or their families of potential genetic risk. A similar outcome is also of concern in the case of risk prediction models used for hereditary breast cancer. RESULTS: No legal case has directly addressed the use of risk prediction models. However, as genetic medicine and risk prediction models become more widely used, the prospect of a lawsuit will also increase. Current case law is instructive on the circumstances under which medical liability actions could be pursued and circumstances under which liability is unlikely, such as the provision of faulty family history information by a patient. CONCLUSIONS: There is existing case law on family history and genetics that parallels in many respects the use of risk prediction models. However, the idea of a bad 'prediction' is a difficult legal concept. Outside of a plain misuse or failure to use a risk prediction model when circumstances clearly required it, there is little legal guidance presently available to determine the risk for medical liability.

Cancer genetics: a model for multifactorial conditions?

Research in the area of genetic susceptibility and cancer is beginning to challenge traditional socio-ethical and legal norms. In particular, increased personal data protection legislation is severely constraining the ability to maintain or initiate new cancer registries for proper epidemiological purposes. Likewise, the principle and obligation of the confidentiality of genetic information cannot remain sacrosanct in the face of the immediate health needs of biological relatives. Finally, participation in research and even the willingness to be tested and treated is constantly threatened by the uncertainty surrounding insurability. What are the new ethical parameters emerging in research in cancer genetics?

Genetic predisposition to cancer--issues to consider.

The importance of molecular genetic events in the development of inherited cancers has evolved from the clinical study, molecular and genetic epidemiology and molecular biology of affected families. As our understanding of the mechanisms of carcinogenesis improves, numerous concerns revolving around the potential impact of laboratory-based predictive genetic testing arise. Through mult-disciplinary approaches supported in part by the Human Genome Project and other research efforts, information is being gathered that may lay the foundation for legislative, scientific and clinical guidelines and recommendations throughout the international community.