Anaesthesia and haemodynamic management of acute ischaemic stroke patients before, during and after endovascular therapy

International audienceEndovascular therapy (EVT) is now standard of care for eligible patients with acute ischaemic stroke caused by large vessel occlusion in the anterior circulation. EVT can be performed with general anaesthesia (GA) or with monitored anaesthesia care, involving local anaesthesia with or without conscious sedation (LA/CS). Controversies remain regarding the optimal choice of anaesthetic strategy and observational studies suggested poorer functional outcome and higher mortality in patients treated under GA, essentially because of its haemodynamic consequences and the delay to put patients under GA. However, these studies are limited by selection bias, the most severe patients being more likely to receive GA and recent randomised trials and meta-analysis showed that protocol-based GA compared with LA/CS is significantly associated with less disability at 3 months. Unlike for intravenous thrombolysis, few data exist to guide management of blood pressure (BP) before and during EVT, but arterial hypotension should be avoided as long as the occlusion persists. BP targets following EVT should probably be adapted to the degree of recanalisation and the extent of ischaemia. Lower BP levels may be warranted to prevent reperfusion injuries even if prospective haemodynamic management evaluations after EVT are lacking

Decision of adjuvant chemotherapy in intermediate risk luminal breast cancer patients: A prospective multicenter trial assessing the clinical and psychological impact of EndoPredict® (EpClin) use (UCBG 2–14)

International audienceGenomic tests can identify ER-positive HER2-negative localized breast cancer patients who may not benefit from adjuvant chemotherapy. Such tests seem especially interesting in "intermediate" clinico-pathological risk categories. The psychological impact of the decision uncertainty in these women remains largely unexplored. We assessed the clinical and psychological impact of EndoPredict® (EpClin), a clinico-genomic test, in these patients

Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis

International audienc

Apoptosis regulation in tetraploid cancer cells

Tetraploidy can result in cancer-associated aneuploidy. As shown here, freshly generated tetraploid cells arising due to mitotic slippage or failed cytokinesis are prone to undergo Bax-dependent mitochondrial membrane permeabilization and subsequent apoptosis. Knockout of Bax or overexpression of Bcl-2 facilitated the survival of tetraploid cells at least as efficiently as the p53 or p21 knockout. When tetraploid cells were derived from diploid p53 and Bax-proficient precursors, such cells exhibited an enhanced transcription of p53 target genes. Tetraploid cells exhibited an enhanced rate of spontaneous apoptosis that could be suppressed by inhibition of p53 or by knockdown of proapoptotic p53 target genes such as BBC3/Puma, GADD45A and ferredoxin reductase. Unexpectedly, tetraploid cells were more resistant to DNA damaging agents (cisplatin, oxaliplatin and camptothecin) than their diploid counterparts, and this difference disappeared upon inhibition of p53 or knockdown of p53-inducible ribonucleotide reductase. Tetraploid cells were also more resistant against UVC and γ-irradiation. These data indicate the existence of p53-dependent alterations in apoptosis regulation in tetraploid cells

Genomics of arbuscular mycorrhizal fungi: Out of the shadows

Chapitre 9International audienceArbuscular mycorrhizal (AM) symbiosis is the most widespread mutualistic association. It concerns 80% of land plants and involves fungi belonging to the phylum Glomeromycota. Benefits to the host plants due to this symbiosis range from nutrient supply to protection against pathogens. AM fungi are important components of the soil microbiome and are of great interest for managing sustainable agriculture, provided that their life cycle is better understood. Recently, major advances in the genomics of the model AM fungus Rhizophagus irregularis DAOM197198 have been published, offering new tools to investigate the biology of this symbiosis. In this chapter, we provide an overview of the efforts that were necessary to reach these results, from the discovery of these fungi and the description of their mutualistic incidence to their in vitro cultivation and on to genomics. The genome of DAOM197198 is estimated at ca. 150 Mb. It is haploid and less polymorphic than expected. Although it is an obligate biotrophic fungus, very little gene loss was observed. We put the Rhizophagus gene repertoire in perspective with previous investigations performed on the physiology of AM fungi: germination, early signalling with host plants, plant invasion, metabolism (phosphorous, carbon and nitrogen) and sexuality. Clearly, the publication of the genome of R. irregularis DAOM197198 is a turning point in the study of AM fungi, and large areas of their biology that still remain to be elucidated will now become accessible for investigation

Noninvasive ventilation in COVID-19 patients aged ≥ 70 years : a prospective multicentre cohort study

Background: Noninvasive ventilation (NIV) is a promising alternative to invasive mechanical ventilation (IMV) with a particular importance amidst the shortage of intensive care unit (ICU) beds during the COVID-19 pandemic. We aimed to evaluate the use of NIV in Europe and factors associated with outcomes of patients treated with NIV. Methods: This is a substudy of COVIP study-an international prospective observational study enrolling patients aged >= 70 years with confirmed COVID-19 treated in ICU. We enrolled patients in 156 ICUs across 15 European countries between March 2020 and April 2021.The primary endpoint was 30-day mortality. Results: Cohort included 3074 patients, most of whom were male (2197/3074, 71.4%) at the mean age of 75.7 years (SD 4.6). NIV frequency was 25.7% and varied from 1.1 to 62.0% between participating countries. Primary NIV failure, defined as need for endotracheal intubation or death within 30 days since ICU admission, occurred in 470/629 (74.7%) of patients. Factors associated with increased NIV failure risk were higher Sequential Organ Failure Assessment (SOFA) score (OR 3.73, 95% CI 2.36-5.90) and Clinical Frailty Scale (CFS) on admission (OR 1.46, 95% CI 1.06-2.00). Patients initially treated with NIV (n = 630) lived for 1.36 fewer days (95% CI - 2.27 to - 0.46 days) compared to primary IMV group (n = 1876). Conclusions: Frequency of NIV use varies across European countries. Higher severity of illness and more severe frailty were associated with a risk of NIV failure among critically ill older adults with COVID-19. Primary IMV was associated with better outcomes than primary NIV

Increased 30-day mortality in very old ICU patients with COVID-19 compared to patients with respiratory failure without COVID-19

Purpose The number of patients >= 80 years admitted into critical care is increasing. Coronavirus disease 2019 (COVID-19) added another challenge for clinical decisions for both admission and limitation of life-sustaining treatments (LLST). We aimed to compare the characteristics and mortality of very old critically ill patients with or without COVID-19 with a focus on LLST. Methods Patients 80 years or older with acute respiratory failure were recruited from the VIP2 and COVIP studies. Baseline patient characteristics, interventions in intensive care unit (ICU) and outcomes (30-day survival) were recorded. COVID patients were matched to non-COVID patients based on the following factors: age (+/- 2 years), Sequential Organ Failure Assessment (SOFA) score (+/- 2 points), clinical frailty scale (+/- 1 point), gender and region on a 1:2 ratio. Specific ICU procedures and LLST were compared between the cohorts by means of cumulative incidence curves taking into account the competing risk of discharge and death. Results 693 COVID patients were compared to 1393 non-COVID patients. COVID patients were younger, less frail, less severely ill with lower SOFA score, but were treated more often with invasive mechanical ventilation (MV) and had a lower 30-day survival. 404 COVID patients could be matched to 666 non-COVID patients. For COVID patients, withholding and withdrawing of LST were more frequent than for non-COVID and the 30-day survival was almost half compared to non-COVID patients. Conclusion Very old COVID patients have a different trajectory than non-COVID patients. Whether this finding is due to a decision policy with more active treatment limitation or to an inherent higher risk of death due to COVID-19 is unclear

The impact of frailty on survival in elderly intensive care patients with COVID-19: the COVIP study

Auteurs : COVIP study groupInternational audienceBackground The COVID-19 pandemic has led highly developed healthcare systems to the brink of collapse due to the large numbers of patients being admitted into hospitals. One of the potential prognostic indicators in patients with COVID-19 is frailty. The degree of frailty could be used to assist both the triage into intensive care, and decisions regarding treatment limitations. Our study sought to determine the interaction of frailty and age in elderly COVID-19 ICU patients. Methods A prospective multicentre study of COVID-19 patients ≥ 70 years admitted to intensive care in 138 ICUs from 28 countries was conducted. The primary endpoint was 30-day mortality. Frailty was assessed using the clinical frailty scale. Additionally, comorbidities, management strategies and treatment limitations were recorded. Results The study included 1346 patients (28% female) with a median age of 75 years (IQR 72–78, range 70–96), 16.3% were older than 80 years, and 21% of the patients were frail. The overall survival at 30 days was 59% (95% CI 56–62), with 66% (63–69) in fit, 53% (47–61) in vulnerable and 41% (35–47) in frail patients ( p < 0.001). In frail patients, there was no difference in 30-day survival between different age categories. Frailty was linked to an increased use of treatment limitations and less use of mechanical ventilation. In a model controlling for age, disease severity, sex, treatment limitations and comorbidities, frailty was independently associated with lower survival. Conclusion Frailty provides relevant prognostic information in elderly COVID-19 patients in addition to age and comorbidities. Trial registration Clinicaltrials.gov: NCT04321265 , registered 19 March 2020