Utility of non-contrast head computed tomography in poisoned patients

Objective: To investigate the utility of non-contrast head computed tomography (CT) in poisoned patients. Methods: A retrospective cohort study of patients referred to a toxicology unit between August 2010 and December 2017. Our database yielded patients who underwent head CT at presentation to the ED. Pre-specified information was compiled from the medical records. Results: There were 6261 presentations of which 1142 underwent head CT (17%). Median age was 41 years, and 437 (38%) were female. There were 492 (43%) recreational ingestions and 466 (41%) deliberate self-poisonings. The commonest agents were sedatives 376 (33%) and opioids 282 (24%); 334 (29%) cases were intubated. Signs of head injury were found in 153 cases (13%) and focal neurological signs in 68 (6%). No acute pathology was reported in 884 head CTs (77%), chronic changes in 193 (17%) and incidental findings in 26 (2%). Acute pathology was found in 39 (4%) patients: 15 with hypoxic-ischaemic injury, three infarctions, nine with intra-cranial haemorrhage, 11 facial bone fractures and one retro-bulbar haematoma. No patient required an immediate surgical intervention, and only one patient had a change to clinical treatment. Acute head CT pathology was associated with at least one of the following clinical features: need for intubation, signs of head injury, seizure, headache, and unexpected neurological signs. Conclusion: Non-contrast head CT is a low-yield investigation in patients presenting with poisoning. Consideration should be given as to whether the clinical presentation is consistent with the expected toxidrome and whether the patient would benefit from head CT

Mesothelioma <i>in situ</i> of the peritoneum: Report of three cases and review of the literature

Aim: Diagnosis of mesothelioma in situ (MIS) is historically controversial and, until recently, specific features defining the entity have not been well characterized. Most reported cases of MIS occurred in the pleura; peritoneal MIS is very rare. This study investigates the morphologic features and results of ancillary testing in peritoneal MIS. Methods: We present three patients with peritoneal MIS, as defined by a single layer of mesothelial cells with loss of nuclear BRCA-1-associated protein-1 (BAP1) immunostaining and without evidence of invasive tumour by microscopic evaluation, imaging, or direct examination of the peritoneum. Histology and immunostains were reviewed by three expert thoracic pathologists with multidisciplinary input. Next-generation sequencing (NGS) was performed in all three cases. A literature review was conducted to characterize this rare precursor lesion. Results: BAP1 was lost in all three lesions, while methylthioadenosine phosphorylase (MTAP) was retained in two (not performed in the third). NGS revealed BAP1 pathogenic alterations in all three cases as well as mutations of SMO, ERCC3, TET2, and U2AF1. Progression to invasive mesothelioma occurred in one patient at 13 months postdiagnosis (case 1). One patient was diagnosed at age 24 and was later found to harbour a BAP1 germline mutation (case 3). Conclusion: This work describes the histologic features and clinicopathologic characteristics of peritoneal MIS in three cases, highlights BAP1 somatic and germline mutations in peritoneal MIS, and strengthens the importance of ancillary studies (including immunohistochemical and molecular studies) in the diagnosis of MIS.</p

Lung adenocarcinomas with isolated TP53 mutation: A comprehensive clinical, cytopathologic and molecular characterization

Abstract Background TP53 mutation is present in about 50.8% of lung adenocarcinomas, frequently in combination with other genetic alterations. However, a rare subset harbors the TP53 mutation alone. Methods Next‐generation sequencing was performed in 844 lung adenocarcinomas diagnosed by fine needle aspiration. Fourteen cases (1.7%) showed isolated TP53 alteration and were subjected to a comprehensive analysis. Results The average age at diagnosis was 65.7 years (range 48–79); 9 males and 5 females. All were smokers with an average pack‐year of 40.7 (range 10–70). Ten had metastases, mostly in the brain (n = 4) and pleura (n = 4). After a follow‐up period of up to 102 months, 9 died, 3 were alive free of disease, 1 was alive with disease, and 1 was lost to follow‐up. The median survival was 12.2 months. Most tumors exhibited poor differentiation, composed of solid sheets with moderate to severe atypia, increased mitotic activity, and necrotic background. Half were positive for TTF‐1 and showed p53 overexpression. PD‐L1 was positive in 5 cases. Most alterations were missense mutations in exons 5–8, and this mutation type was associated with p53 overexpression. Tumors with combined missense mutation and truncated protein had higher PD‐L1 expression along with a trend towards an increase in tumor mutational burden (TMB). CEBPA deletion of undetermined significance was the most common copy number alteration. Conclusion Isolated TP53 mutation was seen in association with smoking, high‐grade cytomorphologic features, adverse prognosis, and recurrent CEBPA deletions. These tumors tend to have strong PD‐L1 expression and high TMB, suggesting potential benefit from immune checkpoint inhibitors. Hence, the recognition of this molecular group has prognostic and therapeutic implications

A multi-taxon analysis of European Red Lists reveals major threats to biodiversity.

Acknowledgements: The European Red List assessments have been compiled by numerous species experts, many of whom are affiliated with the IUCN Species Survival Commission and are listed as co-authors of the assessments on the IUCN Red List of Threatened Species. The views expressed in this publication do not necessarily reflect those of IUCN or those of the EC. The designation of geographical entities in this paper, and the presentation of the material, do not imply the expression of any opinion whatsoever on the part of IUCN or the EC concerning the legal status of any country, territory, or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries.Funder: European Commission; funder-id: http://dx.doi.org/10.13039/501100000780Funder: National Parks and Wildlife Service; funder-id: http://dx.doi.org/10.13039/100012733Funder: Republic of IrelandFunder: Ministry of Economic Affairs; funder-id: http://dx.doi.org/10.13039/501100004725Funder: Department of Nature & Biodiversity (Ministerie van Economische Zaken, Directie Natuur & Biodiversiteit), the NetherlandsFunder: Council of EuropeFunder: Office fédéral de l’environnement, SwitzerlandFunder: Swedish Environmental Protection Agency (Naturvardsverket), SwedenFunder: British Entomological Society, United KingdomFunder: Ministry of Sustainable Development and Infrastructure, Government of the Grand-Duché of LuxembourgFunder: Ministry of the Environment of the Czech RepublicFunder: ArtDatabanken from the Swedish University of Agricultural SciencesBiodiversity loss is a major global challenge and minimizing extinction rates is the goal of several multilateral environmental agreements. Policy decisions require comprehensive, spatially explicit information on species' distributions and threats. We present an analysis of the conservation status of 14,669 European terrestrial, freshwater and marine species (ca. 10% of the continental fauna and flora), including all vertebrates and selected groups of invertebrates and plants. Our results reveal that 19% of European species are threatened with extinction, with higher extinction risks for plants (27%) and invertebrates (24%) compared to vertebrates (18%). These numbers exceed recent IPBES (Intergovernmental Platform on Biodiversity and Ecosystem Services) assumptions of extinction risk. Changes in agricultural practices and associated habitat loss, overharvesting, pollution and development are major threats to biodiversity. Maintaining and restoring sustainable land and water use practices is crucial to minimize future biodiversity declines

A multi-taxon analysis of European Red Lists reveals major threats to biodiversity.

Biodiversity loss is a major global challenge and minimizing extinction rates is the goal of several multilateral environmental agreements. Policy decisions require comprehensive, spatially explicit information on species’ distributions and threats. We present an analysis of the conservation status of 14,669 European terrestrial, freshwater and marine species (ca. 10% of the continental fauna and flora), including all vertebrates and selected groups of invertebrates and plants. Our results reveal that 19% of European species are threatened with extinction, with higher extinction risks for plants (27%) and invertebrates (24%) compared to vertebrates (18%). These numbers exceed recent IPBES (Intergovernmental Platform on Biodiversity and Ecosystem Services) assumptions of extinction risk. Changes in agricultural practices and associated habitat loss, overharvesting, pollution and development are major threats to biodiversity. Maintaining and restoring sustainable land and water use practices is crucial to minimize future biodiversity declines