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.

Funding considerations for the disclosure of genetic incidental findings in biobank research.

The use of biobanks in biomedical research has grown considerably in recent years. As a result of the increasing analysis of tissue samples stored in biobanks, there has also been an increase in the probability of discovering-in addition to the research target-incidental findings (IF). We identified 23 laws, policies and guidelines from international, regional and national organizations that provide guidance or identify the need for the disclosure of IF to research participants. We analyzed these instruments to determine their contemplation of the funding considerations for the disclosure of IF, examining their guidance for who discloses and the extent of researcher responsibilities. We found that the available normative documents provide little guidance to researchers and biobanks for how they should address cost and funding concerns associated with IF disclosure. It is therefore essential that the research and policy communities think through the financial implications of imposing an ethical responsibility to disclose IF. Concerted efforts should be made by policymakers, ethicists, researchers, clinicians and research institutions to develop detailed funding recommendations, potentially universal in application, to aid in the disclosure of IF, and we provide recommendations on steps that can be taken to ensure full consideration of these issues.

Status, sale and patenting of human genetic material: an international survey.

Following a decade of debate, the European Directive on the Legal Protection of Biotechnological Inventions was adopted by the European Parliament and the Council of the European Union on July 6, 1998. The Directive constitutes a legal and social policy landmark in biotechnology, taking an explicit position on the contentious issue of the patentability of higher life forms. It fails, however, to provide definitive statements on the legal status of human genetic material or the possibility of personal financial gain in relation to such material. An overview of the international, regional and national positions (as found in laws and official policy statements) on the status, commodification and patentability of human genetic material indicates that, although the Directive represents a consolidation of opinions, many issues remain unresolved.

HostSeq: a Canadian whole genome sequencing and clinical data resource.

HostSeq was launched in April 2020 as a national initiative to integrate whole genome sequencing data from 10,000 Canadians infected with SARS-CoV-2 with clinical information related to their disease experience. The mandate of HostSeq is to support the Canadian and international research communities in their efforts to understand the risk factors for disease and associated health outcomes and support the development of interventions such as vaccines and therapeutics. HostSeq is a collaboration among 13 independent epidemiological studies of SARS-CoV-2 across five provinces in Canada. Aggregated data collected by HostSeq are made available to the public through two data portals: a phenotype portal showing summaries of major variables and their distributions, and a variant search portal enabling queries in a genomic region. Individual-level data is available to the global research community for health research through a Data Access Agreement and Data Access Compliance Office approval. Here we provide an overview of the collective project design along with summary level information for HostSeq. We highlight several statistical considerations for researchers using the HostSeq platform regarding data aggregation, sampling mechanism, covariate adjustment, and X chromosome analysis. In addition to serving as a rich data source, the diversity of study designs, sample sizes, and research objectives among the participating studies provides unique opportunities for the research community.

Points to consider for laboratories reporting results from diagnostic genomic sequencing.

Although NGS technologies are well-embedded in the clinical setting for identification of genetic causes of disease, guidelines issued by professional bodies are inconsistent regarding some aspects of reporting results. Most recommendations do not give detailed guidance about whether variants of uncertain significance (VUS) should be reported by laboratory personnel to clinicians, and give conflicting messages regarding whether unsolicited findings (UF) should be reported. There are also differences both in their recommendations regarding whether actively searching for secondary findings (SF) is appropriate, and in the extent to which they address the duty (or lack thereof) to reanalyse variants when new information arises. An interdisciplinary working group considered the current guidelines, their own experiences, and data from a recent qualitative study to develop a set of points to consider for laboratories reporting results from diagnostic NGS. These points to consider fall under six categories: (i) Testing approaches and technologies used, (ii) Approaches for VUS; (iii) Approaches for reporting UF, (iv) Approaches regarding SF; (v) Reanalysis of data & re-contact; and vi) Minors. While it is unclear whether uniformity in reporting across all laboratories is desirable, we hope these points to consider will be useful to diagnostic laboratories as they develop their processes for making decisions about reporting VUS and UF from NGS in the diagnostic context.

Harmonizing Global Biospecimen Consent Practices to Advance Translational Research: A Call to Action.

One of the many challenges of translational medicine is working with research participants to donate biospecimens through an ethical informed consent framework. The increasingly complex ethical and regulatory differences across jurisdictions translates into limitations on use and potential value of biological specimens and their associated data in clinical research. We introduce a call to action for more uniform global standards for collection of biological specimen informed consent data to enable greater advancements in medical research.

Recent advances in medically assisted conception: legal, ethical and social issues.

A review of reports, bills and legislation from around the world, during the period from 1987 to 1991, reveals certain areas of consensus on the possible or actual, ethical and legal regulation of medically assisted conception. Other areas remain controversial, due not only to cultural and religious differences but also to the social significance of the very implementation of these new technologies. Irrespective of these differences, the reformulation of certain shared international principles of human rights permits a greater specificity both in their translation and in their application to medically assisted conception. Areas discussed include the dignity of the person, the security of human genetic material, the quality of services, the inviolability of the person and the inalienability of the person.

Confidentiality in genetic testing: legal and ethical issues in an international context.

This comparative legal study on confidentiality in genetic testing examines three levels of communication of genetic information: the personal; the familial; and the institutional third parties. At the first two levels, it is argued that the approach is one that recognizes genetic individuality and reciprocity within the physician-patient relationship without legislative interference. This stands in contrast to the possible use of genetic information by economic third parties or, even, that of the state with respect to the DNA profiling of the genetic identity of criminals, the approach for both areas being the promulgation of 'genetic-specific' or human rights legislation with the hope of preventing discrimination. This rush to constrain the impact of genetic information through legislation is criticized since it may well lead to further stigmatization. The author proposes the promotion of the concept of genetic privacy within the broader rubric of informational self-determination.

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?

Physicians and genetic malpractice.

Primary care physicians are unprepared for the increase in demands for prenatal genetic testing. Often, they do not possess the necessary knowledge, skills or attitudes to provide genetic counselling. Yet, since the demand for prenatal genetic services is growing faster than the number of genetic professionals, the responsibility of genetic counselling will fall to these physicians. Physicians who lack genetic literacy may find themselves the targets of lawsuits for wrongful birth and wrongful life. Wrongful birth and wrongful life claims (in the context of genetics) both assert that but for the physician's negligence, the handicapped child would not have been born. Such medical malpractice suits against physicians exist in the United States, the United Kingdom, Canada and Australia. This paper discusses the case law on wrongful birth/life cases in these four countries. The authors conclude that as the number and availability of prenatal genetic tests increases, so too will the number of genetic malpractice claims, unless the education of physicians and medical students in genetics is promoted, possibly with the Internet as the new educational paradigm.