A study protocol to characterise pathophysiological and molecular markers of rheumatic heart disease and degenerative aortic stenosis using multiparametric cardiovascular imaging and multiomics techniques.

INTRODUCTION: Rheumatic heart disease (RHD), degenerative aortic stenosis (AS), and congenital valve diseases are prevalent in sub-Saharan Africa. Many knowledge gaps remain in understanding disease mechanisms, stratifying phenotypes, and prognostication. Therefore, we aimed to characterise patients through clinical profiling, imaging, histology, and molecular biomarkers to improve our understanding of the pathophysiology, diagnosis, and prognosis of RHD and AS. METHODS: In this cross-sectional, case-controlled study, we plan to recruit RHD and AS patients and compare them to matched controls. Living participants will undergo clinical assessment, echocardiography, CMR and blood sampling for circulatory biomarker analyses. Tissue samples will be obtained from patients undergoing valve replacement, while healthy tissues will be obtained from cadavers. Immunohistology, proteomics, metabolomics, and transcriptome analyses will be used to analyse circulatory- and tissue-specific biomarkers. Univariate and multivariate statistical analyses will be used for hypothesis testing and identification of important biomarkers. In summary, this study aims to delineate the pathophysiology of RHD and degenerative AS using multiparametric CMR imaging. In addition to discover novel biomarkers and explore the pathomechanisms associated with RHD and AS through high-throughput profiling of the tissue and blood proteome and metabolome and provide a proof of concept of the suitability of using cadaveric tissues as controls for cardiovascular disease studies.

A retrospective study of death scene investigation practices for sudden unexpected death of infants (SUDI) in Cape Town, South Africa.

A death scene investigation (DSI) forms an integral part of the inquiry into death, particularly for sudden unexpected death of infants (SUDI). Global guidelines exist for DSI, however, previous studies have shown that South Africa does not routinely perform DSI for SUDI cases, nor is there a standard protocol in this regard. This was largely attributed to the large burden of SUDI cases as well as the lack of resources, due to South Africa being a developing country. This study assessed DSI practices at one of the largest mortuaries in Cape Town (Salt River Mortuary) to assess the scope of these practices within a resource-constrained context. Data were collected by retrospectively reviewing medico-legal case files (n = 454) from SUDI cases investigated at Salt River Mortuary over a two-year period. The results showed that SUDI death scenes were visited in 59.2% of cases at Salt River Mortuary, with poor and inconsistent levels of documentation. Death scenes were never investigated in cases where the infant was pronounced dead on arrival at a medical facility. The findings support the need for a locally relevant approach to DSI, coupled with specialized training for staff. Based on the limited resources, this should focus on the training of staff using the available resources and accurate use of documentation.

Global trends in the extent of death scene investigation performed for sudden and unexpected death of infant (SUDI) cases: A systematic review.

Sudden unexpected death of infants (SUDI) is the rapid and unexpected death of an infant aged less than 1year old. These deaths are referred for a medico-legal investigation to establish cause of death. National and regional protocols for the investigation of SUDI cases have been established in some countries and these typically include a death scene investigation component. However, there is a paucity of literature detailing the nature and extent of death scene investigation protocols. A systematic review was conducted to review the scope of death scene investigation of SUDI cases worldwide. Relevant articles (n=74) were identified by searching four literature databases, three discipline-specific journals, as well as each article's reference list, until saturation was reached. Of the 16 countries represented by the included articles, seven made specific reference to the standardised protocol used, which included photography, interviews and/or scene re-enactments. The remaining 54 studies appeared to include a subset of these analyses during death scene investigation, which varied between countries, and between SUDI admissions. This may be attributed to the differing socio-economic standings of countries, and the resources available. Only four studies were from developing countries, three of which originated from South Africa. Overall, where a standardised death scene investigation was performed, it added value to the post-mortem investigation; as such, death scene investigation should be encouraged in SUDI investigation. To this end, protocols should be established nationally, and contain core analyses, which could be expanded depending on the needs and resources of the country.

Investigation into abandoned neonates admitted to Salt River Forensic Pathology Mortuary, Cape Town.

The high rates of abandoned neonatal remains admitted to Salt River Mortuary (SRM), Cape Town, and the dearth of literature published in South Africa prompted a retrospective assessment of these cases to describe the profile and assess the scope of the post-mortem investigation of abandoned neonates, as well as determine the prosecution rate of abandoned live births. Demographic details, scene information and post-mortem findings were obtained from medico-legal case files concerning non-viable fetuses, stillbirths and concealment of birth cases admitted to SRM between 1 January 2012 and 31 December 2016 (n=249). Despite the majority of the cases being natural deaths, the cause of death frequently remained 'undetermined' in these cases, often due to the presence of decomposition. Histological analyses were only performed in a small fraction of undetermined cases. Furthermore, the hypothesis that the prosecution rate of abandoned live births is extremely low was supported by this study, with only one case prosecuted in the 5-year period. For the remainder of the cases, the court status was given as either 'under investigation' (47.8%) or 'case closed' (47.8%). In the majority of the instances, the case was closed due to the unknown identity of the biological mother; however, DNA analyses were not performed in all of these cases. Overall, the data highlighted the need for the development and implementation of standard protocols, and recommendations were made for conducting the medico-legal investigation of abandoned neonates in a South African setting.

A systematic review exploring the relationship between infection and sudden unexpected death between 2000 and 2016: A forensic perspective.

Death due to infectious diseases is a major health concern worldwide. This is of particular concern in developing countries where poor-socio economic status and a lack of healthcare resources contribute to the high burden of disease. In some cases death due to infection can be acute and aggressive, and death may occur without a diagnosis whilst the person is still alive. These deaths may ultimately lead to a medico-legal autopsy being performed. There are various mechanisms by which sudden death due to infection may occur. In addition, there are many risk factors associated with sudden death due to infection, which differ between infants and older individuals. However, it is unclear which pathogens and risk factors are most frequently associated with sudden death due to infection. Therefore a systematic review of articles and case reports published between 1 January 2000 and 30 June 2016 was undertaken in order to (1) explore the relationship between pathogens and their causative role and (2) identify the relationship between predisposing and/or risk factors associated with sudden death due to infection. Major databases were searched and after critical appraisal 143 articles were identified. It was found that respiratory infections and deaths involving bacterial pathogens were most commonly associated with these deaths. In addition the most common risk factors in infants were exposure to tobacco smoke and co-sleeping. In adults the most common risk factors were co-morbid conditions and illnesses. This information aids in a better understanding of these deaths and highlights the need for more research in this field, particularly in developing countries.

Ethical considerations in forensic genetics research on tissue samples collected post-mortem in Cape Town, South Africa.

BACKGROUND: The use of tissue collected at a forensic post-mortem for forensic genetics research purposes remains of ethical concern as the process involves obtaining informed consent from grieving family members. Two forensic genetics research studies using tissue collected from a forensic post-mortem were recently initiated at our institution and were the first of their kind to be conducted in Cape Town, South Africa. MAIN BODY: This article discusses some of the ethical challenges that were encountered in these research projects. Among these challenges was the adaptation of research workflows to fit in with an exceptionally busy service delivery that is operating with limited resources. Whilst seeking guidance from the literature regarding research on deceased populations, it was noted that next of kin of decedents are not formally recognised as a vulnerable group in the existing ethical and legal frameworks in South Africa. The authors recommend that research in the forensic mortuary setting is approached using guidance for vulnerable groups, and the benefit to risk standard needs to be strongly justified. Lastly, when planning forensic genetics research, consideration must be given to the potential of uncovering incidental findings, funding to validate these findings and the feedback of results to family members; the latter of which is recommended to occur through a genetic counsellor. CONCLUSION: It is hoped that these experiences will contribute towards a formal framework for conducting forensic genetic research in medico-legal mortuaries in South Africa.