Admission criteria and management of critical care patients in a pandemic context: position of the Ethics Commission of the French Intensive Care Society, update of April 2021.

Intensive care unit professionals have experience in critical care and its proportionality, collegial decision-making, withholding or withdrawal of treatment deemed futile, and communication with patients' relatives. These elements rely on ethical values from which we must not deviate in a pandemic situation. The recommendations made by the Ethics Commission of the French Intensive Care Society reflect an approach of responsibility and solidarity towards our citizens regarding the potential impact of a pandemic on critical care resources in France, with the fundamental requirement of respect for human dignity and equal access to health care for all

Spliceosome malfunction causes neurodevelopmental disorders with overlapping features

Pre-mRNA splicing is a highly coordinated process. While its dysregulation has been linked to neurological deficits, our understanding of the underlying molecular and cellular mechanisms remains limited. We implicated pathogenic variants in U2AF2 and PRPF19, encoding spliceosome subunits in neurodevelopmental disorders (NDDs), by identifying 46 unrelated individuals with 23 de novo U2AF2 missense variants (including 7 recurrent variants in 30 individuals) and 6 individuals with de novo PRPF19 variants. Eight U2AF2 variants dysregulated splicing of a model substrate. Neuritogenesis was reduced in human neurons differentiated from human pluripotent stem cells carrying two U2AF2 hyper-recurrent variants. Neural loss of function (LoF) of the Drosophila orthologs U2af50 and Prp19 led to lethality, abnormal mushroom body (MB) patterning, and social deficits, which were differentially rescued by wild-type and mutant U2AF2 or PRPF19. Transcriptome profiling revealed splicing substrates or effectors (including Rbfox1, a third splicing factor), which rescued MB defects in U2af50deficient flies. Upon reanalysis of negative clinical exomes followed by data sharing, we further identified 6 patients with NDD who carried RBFOX1 missense variants which, by in vitro testing, showed LoF. Our study implicates 3 splicing factors as NDD-causative genes and establishes a genetic network with hierarchy underlying human brain development and function

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Retrait social et shizophrénie : rôle de l'anxiété sociale (évaluation standardisée comparative de cinq patients schizophrènes et cinq patients phobiques sociaux)

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Physicochemical characterization of molecular assemblies of miltefosine and amphotericin B.

This study describes the interactions between two amphiphilic molecules with antileishmanial activity, amphotericin B (AmB) and miltefosine [hexadecylphosphocholine (HePC)], the latter being effective by the oral route. The effect of HePC on the aggregation state of AmB in aqueous solution and the interactions between the two agents were monitored using absorption spectroscopy and circular dichroism. Structural characterization of the mixed aggregates formed in water by dynamic light scattering (DLS) and cryofracture electron microscopy was performed. At concentrations above its critical micelle concentration, HePC was shown to interact with AmB, leading to an increase in the proportion of AmB in its monomeric form as a result of a micellar solubilization mechanism with a capacity of 26 +/- 3 mmol of AmB solubilized/mol of HePC, that is, nearly 40 molecules of HePC per molecule of AmB in the mixed micelles. These were revealed as individual and spherical aggregates close to 10 nm in diameter by both electron microscopy and DLS. Such a micellar formulation provides a new AmB-based system which might be useful in delivering AmB orally for visceral leishmaniasis bitherapy

Nouveaux additifs calco-magnésiens pour améliorer la tenue au feu des polymères

peer reviewe

Prise en charge des tentatives de suicide graves : expérience d'un service transdisciplinaire de psychiatrie

International audienceIntroduction: Suicide is the second leading cause of death in young adults. Suicide attempts by violent methods predict later completed suicide and premature mortality. Suicide prevention is a major public health issue in this specific population. The French Student Health Foundation (FSEF) developed a psychiatric ward that includes psychiatric and somatic approaches. This transdisciplinary unit provides mixed psychiatric and rehabilitation treatments for those persons who have attempted suicide and have severe somatic injuries. Methods: We conducted a retrospective study including all subjects admitted into the transdisciplinary unit from 1st January 2011 to 31 December 2017, after a suicide attempt by jumping from a height, in front of a moving object, or by crashing of a motor vehicle. Data was obtained from the medical and administrative records of the clinic. Results: In total, 215 persons were admitted into the transdisciplinary unit after a suicide attempt by a violent mean. Among them, 91.6% had jumped from a height, 7.4% had jumped in front of a train or a metro and 0.9% had crashed a motor vehicle. They were on average 25.5 years old and 50.2% were men. 45.1% had a diagnosis of schizophrenic disorders and 34.4% of mood disorders. A total of 35.6% presented at least one previous suicide attempt, and among them 40.3% had previously attempted suicide with a violent mean. Substance abuse, mostly alcohol and/or cannabis, featured in 40.8% of subject history. The subjects hospitalised in the transdisciplinary unit had multiple, severe injuries: 78.1% had spine fractures, 69.8% had lower limb fractures, 47.9% had pelvic fractures and 43.3% had upper limb fractures. Moreover, 25.5% of them had sacral root damages. The length of stay averaged 184 days and varied in a large range (less than a month to more than two years). The Activities of Daily Living scores were higher than 3 (out of a maximum score of 4) reflecting an important need of assistance. These scores decreased significantly during the hospitalisation for dressing, feeding, continence and locomotion but remained high for comportment and communication. At discharge, the physical sequelae were still important: 61% of people hospitalised had pain that required step 2 or 3 analgesics, 44% had analgesics for neuropathic pain, 80% had lower limb impairments, most often with walking limitation, and 26% had continence disorders. The psychotropic treatments at discharge were related to the psychiatric disorders observed and included 42% antidepressants, 63% neuroleptics and 16% mood stabilizers. Conclusion: This study highlights the severity of the somatic and psychiatric disorders affecting people who are admitted into this transdisciplinary unit. These subjects who have attempted suicide require particular care with multidisciplinary management in order to promote their rehabilitation, reintegration and prevent a suicide reattempt

Factors influencing the length of stay in a unit with mixed rehabilitation and psychiatric care after a suicide attempt by jumping: a cohort observational retrospective study

International audienceBACKGROUND: Persons who have attempt suicide by jumping often require intensive treatment for their somatic injuries and the high risk of future completed suicide. The FSEF (French Student Health Foundation) developed a Transdisciplinary unit specifically designed for these people. AIM: The aim of this study was to investigate psychiatric and somatic factors associated with Length Of Stay (LOS) in this unit. DESIGN: Cohort observational retrospective study. SETTING: The Transdisciplinary unit provide a dual approach, combining rehabilitation (physiotherapy, balneotherapy, occupational therapy, speech therapy, cognitive rehabilitation, social and family support) and psychiatric care. POPULATION: Men and women admitted into the Transdisciplinary unit, after a suicide attempt by jumping from a height with severe somatic injuries. METHODS: We examined the associations between potential predictors and LOS with Stepwise regressions: model 1 included all variables assessed at admission (age, sex, occupational status, psychiatric disorder history, height of the fall, type of injury, LOS in acute care units and dependences at admission); model 2: all variables at discharge (main psychiatric diagnosis, orientation at discharge, psychotropic treatments, pain treatments, arms mobility limitation, legs mobility limitation, sphincter disorders and dependences at discharge); final model: all significant variables in models 1 and 2. RESULTS: One hundred ninety-seven subjects were included (49.7% of men; mean age: 25.6 years, ±6.21). Most factors associated with LOS were related to injuries due to the suicide attempt. LOS in the Transdisciplinary unit increased with longer LOS in acute care (β=0.589; P=0.003), higher dependence for continence at admission (β=44.640; P<0.001) and sphincter disorders at discharge (β=78.034; P<0.001). LOS was also longer with higher dependence for behavior at discharge (β=30.182; P=0.042) and unemployed status (β=59.496; P=0.008), which could reflect psychiatric disorders severity. LOS was shorter when subjects had arms mobility limitation at discharge (β=-42.591; P=0.018). CONCLUSIONS: The persons admitted into this unit have serious physical injuries due to their fall. These injuries require intensive rehabilitation and their severity is the largest contributing factor to the LOS. Some findings also advocate for influence of psychiatric factors on LOS, underlying the need for both concomitant psychiatric and somatic care for these people. CLINICAL REHABILITATION IMPACT: People should ideally receive both psychiatric and rehabilitation care after a suicide attempt by jumpi

Influence of polymer behaviour in organic solution on the production of polylactide nanoparticles by nanoprecipitation.

International audienceThe aim of this study was to define the parameters determining an optimized yield of monodisperse, nanosized particles after nanoprecipitation of a biodegradable polymer, with a view to industrial scale-up the process. Poly(d,l)-lactides (PLAs) from a homologous series of different molar masses were nanoprecipitated at different initial polymer concentrations from two organic solvents, acetone and tetrahydrofuran (THF), into water without surfactant according to a standardized procedure. Quasi-elastic light scattering and gel permeation chromatography with universal detection were used respectively to size the particles and to determine the molar mass distribution of the polymeric chains forming both nanoparticles and bulk aggregates. The intrinsic viscosity of the polymers as a function of molar mass and solvent were determined by kinematic viscosity measurements in organic solutions. High yields of small nanoparticles were obtained with polymers of lower molar mass (22600 and 32100g/mol). For a given polymer concentration in organic solution, the particle diameter was always lower from acetone than from THF. For initial molar masses higher than 32100g/mol, only dilute organic solutions gave significant yields of nanoparticles. Furthermore, polymer mass fractionation occurred with increasing initial molar mass and/or concentration: the nanoparticles were formed by polymeric chains of molar masses significantly lower than the average initial one. In general, nanoparticle production was satisfactory when the initial organic solution of polymer was in the dilute rather than the semi-dilute regime. Moreover, acetone, which acted as a theta solvent for PLA, always led to smaller particles and better yields than THF