Search

Visual Abstract, Myocardial infarction (MI) is one of the leading causes of death worldwide, and inflammation is central to tissue response and patient outcomes. The 18-kDa translocator protein (TSPO) has been used in PET as an inflammatory biomarker. The aims of this study were to screen novel, fluorinated, TSPO radiotracers for susceptibility to the rs6971 genetic polymorphism using in vitro competition binding assays in human brain and heart; assess whether the in vivo characteristics of our lead radiotracer, 18F-LW223, are suitable for clinical translation; and validate whether 18F-LW223 can detect macrophage-driven inflammation in a rat MI model. Methods: Fifty-one human brain and 29 human heart tissue samples were screened for the rs6971 polymorphism. Competition binding assays were conducted with 3H-PK11195 and the following ligands: PK11195, PBR28, and our novel compounds (AB5186 and LW223). Naïve rats and mice were used for in vivo PET kinetic studies, radiometabolite studies, and dosimetry experiments. Rats underwent permanent coronary artery ligation and were scanned using PET/CT with an invasive input function at 7 d after MI. For quantification of PET signal in the hypoperfused myocardium, K1 (rate constant for transfer from arterial plasma to tissues) was used as a surrogate marker of perfusion to correct the binding potential for impaired radiotracer transfer from plasma to tissue (BPTC). Results: LW223 binding to TSPO was not susceptible to the rs6971 genetic polymorphism in human brain and heart samples. In rodents, 18F-LW223 displayed a specific uptake consistent with TSPO expression, a slow metabolism in blood (69% of parent at 120 min), a high plasma free fraction of 38.5%, and a suitable dosimetry profile (effective dose of 20.5–24.5 μSv/MBq). 18F-LW223 BPTC was significantly higher in the MI cohort within the infarct territory of the anterior wall relative to the anterior wall of naïve animals (32.7 ± 5.0 vs. 10.0 ± 2.4 cm3/mL/min, P ≤ 0.001). Ex vivo immunofluorescent staining for TSPO and CD68 (macrophage marker) resulted in the same pattern seen with in vivo BPTC analysis. Conclusion: 18F-LW223 is not susceptible to the rs6971 genetic polymorphism in in vitro assays, has favorable in vivo characteristics, and is able to accurately map macrophage-driven inflammation after MI.

Background Hospital-based studies have reported variable associations between outcome after spontaneous intracerebral hemorrhage and peri-hematomal edema volume. Aims In a community-based study, we aimed to investigate the existence, strength, direction, and independence of associations between intracerebral hemorrhage and peri-hematomal edema volumes on diagnostic brain CT and one-year functional outcome and long-term survival. Methods We identified all adults, resident in Lothian, diagnosed with first-ever, symptomatic spontaneous intracerebral hemorrhage between June 2010 and May 2013 in a community-based, prospective inception cohort study. We defined regions of interest manually and used a semi-automated approach to measure intracerebral hemorrhage volume, peri-hematomal edema volume, and the sum of these measurements (total lesion volume) on first diagnostic brain CT performed at ≤3 days after symptom onset. The primary outcome was death or dependence (scores 3–6 on the modified Rankin Scale) at one-year after intracerebral hemorrhage. Results Two hundred ninety-two (85%) of 342 patients (median age 77.5 y, IQR 68–83, 186 (54%) female, median time from onset to CT 6.5 h (IQR 2.9–21.7)) were dead or dependent one year after intracerebral hemorrhage. Peri-hematomal edema and intracerebral hemorrhage volumes were colinear ( R2 = 0.77). In models using both intracerebral hemorrhage and peri-hematomal edema, 10 mL increments in intracerebral hemorrhage (adjusted odds ratio (aOR) 1.72 (95% CI 1.08–2.87); p = 0.029) but not peri-hematomal edema volume (aOR 0.92 (0.63–1.45); p = 0.69) were independently associated with one-year death or dependence. 10 mL increments in total lesion volume were independently associated with one-year death or dependence (aOR 1.24 (1.11–1.42); p = 0.0004). Conclusion Total volume of intracerebral hemorrhage and peri-hematomal edema, and intracerebral hemorrhage volume alone on diagnostic brain CT, undertaken at three days or sooner, are independently associated with death or dependence one-year after intracerebral hemorrhage, but peri-hematomal edema volume is not. Data access statement Anonymized summary data may be requested from the corresponding author.

Funding: Inflammation in COVID-19: Exploration of Critical Aspects of Pathogenesis (ICECAP) receives funding and support from the Chief Scientist Office (RapidResearch in COVID-19 programme [RARC-19] funding call, “Inflammation in Covid-19: Exploration of Critical Aspects of Pathogenesis; COV/EDI/20/10” to D.A.D., C.D.L., C.D.R., J.K.B., and D.J.H.), LifeArc (through the University of Edinburgh STOPCOVID funding award to K.D., D.A.D., and C.D.L.), UK Research and Innovation (UKRI) (Coronavirus Disease [COVID-19] Rapid Response Initiative; MR/V028790/1 to C.D.L., D.A.D., and J.A.H.), and Medical Research Scotland (CVG-1722-2020 to D.A.D., C.D.L., C.D.R., J.K.B., and D.J.H.). C.D.L. is funded by a Wellcome Trust Clinical Career Development Fellowship(206566/Z/17/Z). J.K.B. and C.D.R. are supported by the Medical Research Council (grant MC_PC_19059) as part of the International Severe AcuteRespiratory Infection Consortium Coronavirus Clinical Characterisation Consortium (ISARIC-4C). D.J.H., I.H.U., and M.E. are supported by the Industrial Centre for Artificial Intelligence Research in Digital Diagnostics. S.P. is supported by Kidney Research UK, and G.T. is supported by the Melville Trust for the Cure and Care of Cancer. Identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and sequencing work was supported by theU.S. Food and Drug Administration grant HHSF223201510104C (“Ebola Virus Disease: correlates of protection, determinants of outcome and clinicalmanagement”; amended to incorporate urgent COVID-19 studies) and contract 75F40120C00085 (“Characterization of severe coronavirus infection inhumans and model systems for medical countermeasure development and evaluation”; awarded to J.A.H.). J.A.H. is also funded by the Centre of Excellence in Infectious Diseases Research and the Alder Hey Charity. R.P.-R. is directly supported by the Medical Research Council Discovery Medicine North Doctoral Training Partnership. The group of J.A.H. is supported by the National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections at the University of Liverpool in partnership with Public Health England and in collaboration with Liverpool School of Tropical Medicine and the University of Oxford. Rationale: In life-threatening Covid-19, corticosteroids reduce mortality, suggesting that immune responses have a causal role in death. Whether this deleterious inflammation is primarily a direct reaction to the presence of SARS-CoV-2 or an independent immunopathologic process is unknown. Objectives: To determine SARS-CoV-2 organotropism and organ-specific inflammatory responses, and the relationships between viral presence, inflammation, and organ injury. Methods: Tissue was acquired from eleven detailed post-mortem examinations. SARS-CoV-2 organotropism was mapped by multiplex PCR and sequencing, with cellular resolution achieved by in situ viral spike protein detection. Histological evidence of inflammation was quantified from 37 anatomical sites, and the pulmonary immune response characterized by multiplex immunofluorescence. Measurements and main results: Multiple aberrant immune responses in fatal Covid-19 were found, principally involving the lung and reticuloendothelial system, and these were not clearly topologically associated with the virus. Inflammation and organ dysfunction did not map to the tissue and cellular distribution of SARS-CoV-2 RNA and protein, both between and within tissues. An arteritis was identified in the lung, which was further characterised as a monocyte/myeloid-rich vasculitis, and occurred along with an influx of macrophage/monocyte-lineage cells into the pulmonary parenchyma. In addition, stereotyped abnormal reticulo-endothelial responses, including excessive reactive plasmacytosis and iron-laden macrophages, were present and dissociated from viral presence in lymphoid tissues. Conclusions: Tissue-specific immunopathology occurs in Covid-19, implicating a significant component of immune-mediated, virus-independent immunopathology as a primary mechanism in severe disease. Our data highlight novel immunopathological mechanisms, and validate ongoing and future efforts to therapeutically target aberrant macrophage and plasma cell responses as well as promoting pathogen tolerance in Covid-19. Publisher PDF

Early microcalcification is a feature of coronary plaques with an increased propensity to rupture and to cause acute coronary syndromes. In this ex vivo imaging study of coronary artery specimens, the non-invasive imaging radiotracer, 18F-fluoride, was highly selective for hydroxyapatite deposition in atherosclerotic coronary plaque. Specifically, coronary 18F-fluoride uptake had a high signal to noise ratio compared with surrounding myocardium that makes it feasible to identify coronary mineralisation activity. Areas of 18F-fluoride uptake are associated with osteopontin, an inflammation-associated glycophosphoprotein that mediates tissue mineralisation, and Runt-related transcription factor 2, a nuclear protein involved in osteoblastic differentiation. These results suggest that 18F-fluoride is a non-invasive imaging biomarker of active coronary atherosclerotic mineralisation.

Traffic incidents are one of the most frequent causes of death in young adults worldwide. Depending on the location of the incident, the velocity of the vehicle(s), the weather condition, traffic incidents are often complicated making the investigation of the circumstances difficult. Here we report a case of an incinerated body involved in a vehicle incident. Differential diagnosis included natural cause of death during driving, fatal traumatic injuries, death due to fire and positional asphyxia. The body was submitted to PMCT prior to autopsy as part of a research protocol (N. 1388/2016) at the Department of Medical Imaging of the University Hospital of Heraklion in Crete, Greece. Unenhanced PMCT revealed craniofacial fractures, a thin film of subdural haemorrhage and an epidural fluid collection. The findings were interpreted as consistent with an impact to the face, causing craniofacial fractures mainly on the right side, and an acute subdural hematoma. Autopsy findings corroborated the diagnosis. The epidural hematoma was deemed to be post-mortem heat-induced. This case is an excellent example of the diagnostic value of PMCT in the medicolegal investigation of death.

Forensic and legal medicine focuses on the interaction between law and medicine. All medical practitioners should have knowledge about the basics of forensic and legal medicine to call upon in the absence of specialists; hence, it is important for any practitioner to be fully aware of laws, statutes, codes of practice, regulations, and professional standards within their own geographic region of practice. This chapter focuses on (1) diagnosis and forensic aspects of death, including death certification and the role (in the United Kingdom) of the coroner; (2) assessment of allegations of physical and sexual abuse, and of torture; (3) how to perform a postmortem (where pathology services may be limited); and (4) forensic use of medical biological tests, particularly genetic tests that can be helpful in determining the likely cause of otherwise unexplained deaths.

Unexpected active Tuberculosis (TB) at autopsy represents a serious transmissible health risk to mortuary and laboratory staff. Post Mortem CT (PMCT) is widely accepted as a valuable adjunct to autopsy throughout the world, but the uptake and implementation varies from country to country. We present a case of unexpected active TB on PMCT and review the literature on the incidence of and risks from the condition. We use this unexpected finding, and the fact that PMCT was in this case also able to provide the information for parts I and II of the Death Certificate as a further argument for the routine use of PMCT by all Forensic Institutes.

Introduction Sudden unexpected death is a leading cause of cardiovascular mortality worldwide. Coronary plaque rupture is the most frequent cause of all cardiac deaths, however the assessment of coronary artery disease at autopsy is remains a technical challenge. The use of post-mortem computed tomography coronary angiography (CTCA) has been shown to increase the diagnostic accuracy of post-mortem autopsy findings. This study aims to assess the validity of vulnerable plaque imaging using post-mortem CTCA. Methods A cohort of sudden death victims underwent double contrast-enhanced CT coronary angiography. Cannulation of the right common carotid artery with Foley catheter balloon occlusion of the ascending aorta facilitated air injection and contrast enhancement (10% Iohexol, Omnipaque 300, GE Healthcare) of the aortic root and coronary arteries. Contrast enhanced CT images were assessed for features of coronary plaque vulnerability including positive remodelling, spotty calcification, low CT attenuation, napkin ring sign and intra-coronary thrombus in proximal coronary artery segments. Results Eight sudden death victims had a mean age of 63.6 (±8.8) years and 37.5% (n=3) were male. Features of vulnerable plaque (Positive remodelling and low attenuation) were present in 50% of sudden death victims. Obstructive coronary artery disease with vulnerable plaque features were the most frequent observation in sudden death victims. Conclusion Vulnerable plaque can be detected in victims of sudden death. Post-mortem CTCA can be used to identify the coronary pathophysiological mechanisms that result in sudden cardiac death.

Background and Purpose— The characteristics of intracerebral hemorrhage (ICH) may vary by ICH location because of differences in the distribution of underlying cerebral small vessel diseases. Therefore, we investigated the incidence, characteristics, and outcome of lobar and nonlobar ICH. Methods— In a population-based, prospective inception cohort study of ICH, we used multiple overlapping sources of case ascertainment and follow-up to identify and validate ICH diagnoses in 2010 to 2011 in an adult population of 695 335. Results— There were 128 participants with first-ever primary ICH. The overall incidence of lobar ICH was similar to nonlobar ICH (9.8 [95% confidence interval, 7.7–12.4] versus 8.6 [95% confidence interval, 6.7–11.1] per 100 000 adults/y). At baseline, adults with lobar ICH were more likely to have preceding dementia (21% versus 5%; P =0.01), lower Glasgow Coma Scale scores (median, 13 versus 14; P =0.03), larger ICHs (median, 38 versus 11 mL; P P P =0.02) than those with nonlobar ICH. One-year case fatality was lower after lobar ICH than after nonlobar ICH (adjusted odds ratio for death at 1 year: lobar versus nonlobar ICH 0.21; 95% confidence interval, 0.07–0.63; P =0.006, after adjustment for known predictors of outcome). There were 4 recurrent ICHs, which occurred exclusively in survivors of lobar ICH (annual risk of recurrent ICH after lobar ICH, 11.8%; 95% confidence interval, 4.6%–28.5% versus 0% after nonlobar ICH; log-rank P =0.04). Conclusions— The baseline characteristics and outcome of lobar ICH differ from other locations.

Blast lung injury is a well documented barotrauma pulmonary pressure insult, often seen in victims and survivors of high pressure extrinsic explosions, such as those caused by extrinsic explosive devices or gas leaks. In this case we present a case of blast lung injury secondary to internal barotrauma, namely suicide by intra-oral shotgun use, and provide correlative post-mortem CT and autopsy images.

The examination of the body of a murdered adult female found in her apartment revealed the presence of a 6-inch screwdriver in the skull cavity that had been inserted through the medial border of the left eye. The presence of a small bruise around the medial aspect of the eye together with the absence of fresh hemorrhage along the tract of the screwdriver was consistent with a postmortem origin. Death, however, was caused by a large incised wound of the neck and multiple skull fractures consistent with hammer blows.

Aims: To determine whether galectin-3 is a sensitive indicator of thyroid malignancy. It has been suggested as a potential marker for differentiating thyroid carcinoma from benign or non-neoplastic lesions in preoperative fine-needle aspirates (FNAs). Methods: Galectin-3 protein expression was assessed by immunohistochemistry in formalin-fixed thyroid tissues from 124 patients with histological diagnoses of papillary carcinoma (n = 38), follicular carcinoma (n = 19), follicular adenoma (n = 32) and dominant nodules of multinodular goitre (n = 35). Expression of galectin-3 was also assessed by Western blotting in 24 fresh thyroid tissues. Results: Galectin-3 expression was observed in the majority of carcinomas (papillary 92%; follicular 74%). However, a large proportion of follicular adenomas (72%) and multinodular goitres (57%) also expressed galectin-3. In addition, galectin-3 expression was observed in epithelial cells of normal thyroid tissue and Hashimoto's thyroiditis. Galectin-3 immunopositivity was significantly greater in papillary carcinomas than in dominant nodules or follicular adenomas (P

Light TD, Royer NA, Zabell J, Le MB, Thomsen TA, Kealey GP, Alpen MA, Nashelsky MB. Autopsy after Traumatic Death: A Shifting Paradigm. J Surg Res 2009, online first, doi:10.1016/j.jss.2009.07.009. The authors performed a prospective, descriptive cohort study in order to analyze the frequency of incidental findings, which are under recognized and reported by trauma surgeons, and missed trauma diagnoses. Of 496 trauma deaths identified over a 4-year period, 229 were subjected to autopsy (46%), and 204 complete autopsies were available for review. Diagnoses from the autopsy reports were compared to abstracted medical records to identify injuries known ante mortem and confirmed by autopsy, injuries not known ante mortem and incidental autopsy findings. 74% of deaths were due to blunt force trauma in motor vehicle collisions or falls. Class 3 missed diagnoses (minor, would not have changed outcome if identified) were common (33%). Class 1 (major, would have changed outcome) and 2 (major, would not have changed outcome) missed diagnoses were identified in 21% of all cases and consisted of traumatic brain injury, spine fractures and skull fractures in moribund patients. In 14% of the cases, important incidental findings were reported at autopsy. These included infectious disease, severe premature atherosclerosis, neoplasms and others such as cardiomyopathy. The authors conclude that incidental autopsy findings might have implications for family members and public health, and that autopsies are a valuable tool to validate clinical diagnoses and reveal unknown diagnoses, and they contribute to the education of health professionals. Their results should be followed up as are the results of other procedures and should be communicated to the next of kin.

With the rapid and continuous development of information technology, policing faces new challenges. As computer equipments are becoming cheaper and the internet more readily available, computer crime and criminal exploitation is on the increase. Investigating such crimes requires identification, preservation, analysis and presentation of digital evidence, the key elements of forensic computing. This is helped by the fact that Locard’s principle is applicable to this branch of science as much as in other areas of forensic science. This webwatch considers the ever evolving area of Forensic Computing.

This is a case report of a 30-year-old man found dead in his flat lying on the floor with multiple stab wounds over the body, surrounded by an extensive volume of blood. Examination of the scene of death showed a secure flat, locked from inside. A blood-stained knife was present close to the body and two unstained notes left on the sofa at the locus. A small plastic bag containing white powder (which following toxicological examinations appeared to be cocaine) and an almost full bottle of beer were present on a table. Autopsy revealed more than 40 stab wounds to neck, chest, and abdomen arranged in isolated groups within which the wounds showed similar directions and had a transverse orientation. Together with hesitation marks located on the neck and wrists these characteristics allowed to interpret this case as a suicide.

Mobile multi-detector computed tomography (MDCT) scanners are potentially available to temporary mortuaries and can be operational within 20 min of arrival. We describe, to our knowledge, the first use of mobile MDCT for a mass fatality incident. A mobile MDCT scanner attended the disaster mortuary after a five vehicle road traffic incident. Five out of six bodies were successfully imaged by MDCT in c. 15 min per body. Subsequent full radiological analysis took c. 1 h per case. The results were compared to the autopsy examinations. We discuss the advantages and disadvantages of imaging with mobile MDCT in relation to mass fatality work, illustrating the body pathway process, and its role in the identification of the pathology, personal effects, and health and safety hazards. We propose that the adoption of a single modality of mobile MDCT could replace the current use of multiple radiological sources within a mass fatality mortuary.

At times the boundaries between medicine and other allied health care professions becomes blurred such that roles historically undertaken by doctors are today undertaken by others often, in fact, more suited to the role. At the time of conception and implementation this exchange of duties may not be accepted by those trapped within the traditions of the hierarchy of medicine which often leads to conflict between the two groups who initially have to work side by side. A good example of the exchange of duties and the differences of forensic practice throughout the world is that of the role of the nurse in death and forensic investigation. This web watch will draw attention to sites dedicated to forensic nursing and highlight the roles which have been taken on by nurses, predominately within the United States, which have traditionally been viewed as the arena of the doctor.