Forensic age estimation of the knee by post-mortem DR, CT, and MR imaging: a comparative study.

It is believed by many that reference data for age estimation purposes must be imaging-modality specific. A study from our department has however proven otherwise. We therefore found it interesting to investigate this further by looking at the level of agreement between different imaging modalities. The aim of this study was to investigate the level of agreement between the three radiological modalities, computed tomography (CT), magnetic resonance imaging (MRI), and digital radiography (DR), in assessing the ossification of the epiphyses of the knee. A total of 34 deceased individuals of 10-25 years of age, brought in for a medicolegal autopsy at our department, were scanned by CT, MRI, and DR. The ossification stages of the three bones of the right knee, distal femoral, proximal tibial, and proximal fibular epiphysis were assessed using the established combined staging method by Schmeling et al. and Kellinghaus et al. Analysis of the results by Cohen's weighted kappa showed a good agreement between CT and DR (K = 0.61-0.70), and MRI and DR (K = 0.68-0.79) but only moderate agreement between CT and MRI (K = 0.55-0.57). This leads us to conclude that different radiological images cannot be used interchangeably for age estimation purposes, so reference material needs to be imaging-modality specific. However, to make a more general conclusion research on a larger population is needed.

Translational deep phenotyping of deaths related to the COVID-19 pandemic: protocol for a prospective observational autopsy study.

INTRODUCTION: The COVID-19 pandemic is an international emergency with an extreme socioeconomic impact and a high mortality and disease burden. The COVID-19 outbreak is neither fully understood nor fully pictured. Autopsy studies can help understand the pathogenesis of COVID-19 and has already resulted in better treatment of patients. Structured and systematic autopsy of COVID-19-related deaths will enhance the mapping of pathophysiological pathways, not possible in the living. Furthermore, it provides an opportunity to envision factors translationally for the purpose of disease prevention in this and future pandemics. This is the protocol for an autopsy study that offers an umbrella for deep and diverse investigations of COVID-19-related deaths, including a systematic investigation of 'long' COVID-19 by means of extensive and systematic tissue sampling. METHODS AND ANALYSIS: A COVID-19-specific autopsy algorithm has been created to cover all cases undergoing clinical or forensic autopsy in Denmark. The algorithm describes advanced tissue sampling and a translational analytical follow-up for deep phenotyping. The translational approach covers registry data, postmortem imaging, gross autopsy findings, microscopic organ changes, postmortem toxicology, postmortem biochemical investigation, microbiological profiling and immunological status at the time of death, and future research projects covering genetics and epigenetics on an organ level. ETHICS AND DISSEMINATION: This study has been approved by the Regional Ethics Committee of the Region of Greater Copenhagen (No: H-20078436) and the Danish Data Protection Agency (No: 2002-54-1080). Next of kin gave informed consent to research. The study results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: This study is purely observational and, as such, does not meet the criteria of the International Committee of Medical Journal Editors for clinical trials; thus, there is no need for registration in a database of research trials, such as clinical trials. To facilitate cooperation in research, provide transparency on case recruitment for publications to come and to avoid unnecessary duplicate work, we nevertheless wish to publish our protocol.

Autopsies in pandemics - a perspective on barriers and benefits. Is it time for a revival?

Influenza virus and coronavirus pandemics regularly sweep the globe, at great cost of health and economy. Our aim was to conduct a PubMed search for autopsy studies on influenza and coronavirus to investigate the contribution of autopsies during pandemics, focussing on autopsy methods and procedures and the role of autopsy findings in pandemics. The retrieved autopsy studies generally relied on microscopy, polymerase chain reaction (PCR), immunostaining and electron microscopy. Most were small and reported on lung effects, including diffuse alveolar damage (DAD), pneumonia and tracheobronchitis. Antibiotic therapy has diminished a role for bacterial pneumonia, whereas obesity is an emerging risk factor. Autopsy studies have provided new insights into coronavirus disease 2019 (COVID-19) treatments like anti-coagulative therapy. Unfortunately, autopsies during pandemics are hampered by lack of guidelines, facilities and expertise for handling potentially infectious corpses and by widely varying recommendations for personal protective equipment and procedures. The Department of Forensic Pathology, at the Forensic Institute, at the University of Copenhagen in Denmark has, in collaboration with the Department of Pathology, Rigshospitalet, Copenhagen, initiated a prospective observational study on COVID-19-related deaths encompassing postmortem imaging, standardized autopsy procedures/reporting and extensive tissue sampling for histological, chemical, microbiological and genetic analysis. The study involves a diverse array of research groups at the University of Copenhagen, and the clinical field.

The calcineurin inhibitor cyclosporine A improves lipopolysaccharide-induced vascular dysfunction but does not rescue from cardiovascular collapse in endotoxemic mice.

The calcineurin inhibitor cyclosporine A (CsA) improves survival in endotoxemic mice. It was hypothesized that CsA counteracts the bradycardia and hypotension characteristic of endotoxemia. Vascular reactivity was determined in lipopolysaccharide (LPS; 50 µg/mL)-treated mouse aortic rings suspended in a myograph. Arterial blood pressure and heart rate were measured continuously with indwelling catheters in conscious mice treated with CsA and a bolus injection of LPS (2 mg/kg). The α1-adrenoceptor agonist phenylephrine induced stable tension of aortic rings that were attenuated significantly by LPS. Co-incubation of rings with LPS and CsA (1 × 10(-7) mol/L-1 × 10(-5) mol/L) restored vascular reactivity to phenylephrine. Intravenous administration of CsA (20 and 40 mg/kg/day) to mice induced a significant increase (by approximately 10 mmHg) in mean arterial blood pressure (MAP), with no effect on heart rate. An LPS bolus led to significant decreases in MAP (by approximately 30 mmHg) and heart rate (to 50 % of baseline). CsA-treated LPS-mice exhibited higher MAP at some (20 mg/kg) or all (40 mg/kg) time points after LPS. The decrease in MAP (Δ pressure) was similar between vehicle- and CsA-treated groups. The 50 % decrease in heart rate was not affected by CsA. Inducible nitric oxide synthase (iNOS) mRNA and protein levels in LPS-treated mice organs and plasma NO x concentration were significantly reduced by CsA. It is concluded that in a murine model of endotoxemia, increased peripheral vascular resistance and suppression of systemic NO formation by cyclosporine A are not sufficient to prevent cardiovascular collapse, which is caused primarily by compromised cardiac function.