Ethical and Clinical Aspects of Intensive Care Unit Admission in Patients with Hematological Malignancies: Guidelines of the Ethics Commission of the French Society of Hematology

Admission of patients with hematological malignancies to intensive care unit (ICU) raises recurrent ethical issues for both hematological and intensivist teams. The decision of transfer to ICU has major consequences for end of life care for patients and their relatives. It also impacts organizational human and economic aspects for the ICU and global health policy. In light of the recent advances in hematology and critical care medicine, a wide multidisciplinary debate has been conducted resulting in guidelines approved by consensus by both disciplines. The main aspects developed were (i) clarification of the clinical situations that could lead to a transfer to ICU taking into account the severity criteria of both hematological malignancy and clinical distress, (ii) understanding the process of decision-making in a context of regular interdisciplinary concertation involving the patient and his relatives, (iii) organization of a collegial concertation at the time of the initial decision of transfer to ICU and throughout and beyond the stay in ICU. The aim of this work is to propose suggestions to strengthen the collaboration between the different teams involved, to facilitate the daily decision-making process, and to allow improvement of clinical practice

Exome-wide association study to identify rare variants influencing COVID-19 outcomes : Results from the Host Genetics Initiative

Publisher Copyright: Copyright: © 2022 Butler-Laporte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75–10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.Peer reviewe

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Microangiopathies thrombotiques associées au virus de l'immunodéficience humaine (présentation clinique et pronostic en fonction de l'activité d'ADAMTS13)

L'infection par le VIH constitue un facteur de risque de développer une microangiopathie thrombotique. Dans ce travail, nous avons étudié la présentation clinique et l'évolution des patients atteints de MAT dans un contexte d'infection par le VIH en fonction de l'activité d'ADAMTS13. Dans cette étude, 29 patients, présentaient des MAT liée au VIH, 17 patients avec un déficit sévère en ADAMTS13, ont été comparé à 12 patients avec une activité ADAMTS13 détectable. La présentation clinique, les antécédents de pathologies opportunistes, les données biologiques, et le pronostic ont été comparés entre ces 2 groupes. Ces patients VIH ont également été comparés à 62 patients présentant des MAT idiopathiques. Nous avons pu observé que, chez les patients souffrant de MAT liées au VIH, un déficit sévère en ADAMTS13 est associé, à un taux de CD4+ plus élevé (p=0.05), à une moindre prévalence de pathologies opportunistes (23.5% versus 91.6%, respectivement, p=0.0005) et à un meilleur pronostic du syndrome de MAT (mortalité: 11.7% versus 50%, p=0.04), comparable à celui des patients présentant des MAT idiopathiques.Human immunodeficiency virus (VIH) infection is a risk factor for thrombotic microangiopathy; We sought whether a severe deficiency in ADAMTS13, the enzyme specifically involved in the cleavage of von Willebrand factor, was associated with specific presenting features and outcome in HIV associated TMA. In this prospective, multicenter, case-control study, 29 patients of 236 in the French network on TMA had a HIV associated TMA.17 patients with severe ADAMTS13 deficiency were compared to 12 patients with a detectable ADAMTS13 activity. HIV patients were also compared to 62 patients with idiopathic TMA, either with or without severe ADAMTS13 deficiency.HIV associated TMA with severe ADAMTS13 deficiency have less AIDSrelated complications and a higher CD4 T cell count. TMA prognosis is better and comparable to this of idiopathic forms.ST QUENTIN EN YVELINES-BU (782972101) / SudocSudocFranceF

Síndrome de lise tumoral: uma revisão abrangente da literatura Acute tumor lysis syndrome: a comprehensive review

A síndrome de lise tumoral é caracterizada pela destruição maciça de células malignas e conseqüente liberação do seu conteúdo no espaço extracelular. Embora possa ocorrer de modo espontâneo, a síndrome de lise tumoral aparece em geral, logo após o início do tratamento com agentes quimioterápicos citotóxicos. Uma vez liberados, estes metabólitos podem subjugar os mecanismos homeostáticos resultando em hiperuricemia, hipercalemia, hiperfosfatemia, e hipocalcemia. Estas alterações biológicas podem levar à ocorrência de diversas manifestações clínicas, incluindo lesão renal aguda, convulsões e morte súbita, que podem requerer cuidados intensivos. Como a síndrome de lise tumoral está associada a um prognóstico reservado, prevenção de sua ocorrência per se e também de suas conseqüências é obrigatória. O objetivo desta revisão foi descrever os mecanismos fisiopatológicos, e as manifestações clínicas e biológicas da síndrome de lise tumoral aguda, e fornecer recomendações atualizadas para sua prevenção. Foram selecionados artigos sobre síndrome de lise tumoral publicados nos últimos 20 anos no PubMed www.pubmed.gov. Estudos referenciados nos artigos selecionados na busca, também foram utilizados. Resultados: A síndrome de lise tumoral é uma complicação grave e freqüente em pacientes com neoplasias de diagnóstico recente. Estratégias de prevenção incluem hidratação vigorosa, agentes uricolíticos, identificação dos fatores que predispõem à lesão renal aguda e, nos pacientes críticos, a indicação profilática de métodos de substituição da função renal necessários para prevenir ou limitar suas conseqüências. Entretanto, o momento adequado assim como as modalidades de prevenção a serem oferecidas ainda são desconhecidos e podem ser inclusive modificadas por alterações no espectro de pacientes em risco de desenvolvê-la. O desenvolvimento e a validação de estratégias baseadas no risco dos pacientes são necessários para limitar a alta morbidade e mortalidade desta complicação.<br>Tumor lysis syndrome is characterized by the massive destruction of malignant cells and the release in the extra-cellular space of their content. While Tumor lysis syndrome may occur spontaneously before treatment, it usually develops shortly after the initiation of cytotoxic chemotherapy. These metabolites can overwhelm the homeostatic mechanisms with development of hyperuricaemia, hyperkalaemia, hyperphosphataemia, and hypocalcaemia. These biological manifestations may lead to clinical manifestations including, acute kidney injury, seizure, or sudden death that require intensive care. Since clinical tumor lysis syndrome is associated with a poor prognosis both prevention of tumor lysis syndrome and prevention of clinical consequences of tumor lysis syndrome are mandatory. The objective of this review is to describe pathophysiological mechanisms, biological and clinical manifestations of tumor Lysis syndrome, and to provide upto-date guidelines to ensure prevention of tumor lysis syndrome. Review of selected studies on tumor lysis syndrome published at the PubMed database www.pubmed.gov during the last 20 years. Additional references were retrieved from the studies initially selected. Tumor lysis syndrome is a frequent and life-threatening complication of the newly diagnosed malignancies. Preventive measures, including hydration, uricolytic agents, eviction of factors predisposing to acute kidney injury and, in the more severe patients, on prophylactic renal replacement therapy, are required to prevent or limit clinical consequences of Tumor lysis syndrome. However optimal timing and modalities of prevention remains unknown and may be modified by the changing spectrum of patients at risk of tumor lysis syndrome. Development and validation of risk based strategies is required to limit the high morbidity and mortality of this complication

Emotional competencies in emerging adolescence: relations between teacher ratings and student self-reports

This cross-sectional study examines gender-informed teachers’ and early adolescents’ reports of emotional competencies within the school setting. The sample for the current study consisted of 290 emerging adolescents (114 boys, 170 girls) recruited from 24 schools. Social-emotional competencies were assessed by students’ self-report questionnaires and teacher and parent reports. Results showed significant positive associations between teacher-rated emotional competencies and emerging adolescents’ self-reports with three of the four Interpersonal Reactivity Index subscales (Perspective Taking, r = .231, p = .000; Fantasy, r = .303, p = .000; and Empathetic Concern, r = .196, p = .007). Significant gender differences were also found as both adults and adolescents’ rated girls as showing greater emotional competencies than boys. Results are discussed in terms of future research directions and implications for educational strategies and practices to help build prosocial and emotional abilities and behaviours