Early liver transplantation for severe alcohol-related hepatitis not responding to medical treatment: a prospective controlled study

peer reviewedBackground: Early liver transplantation for severe alcohol-related hepatitis is an emerging treatment option. We aimed to assess the risk of alcohol relapse 2 years after early liver transplantation for alcohol-related hepatitis compared with liver transplantation for alcohol-related cirrhosis after at least 6 months of abstinence. Methods: We conducted a multicentre, non-randomised, non-inferiority, controlled study in 19 French and Belgian hospitals. All participants were aged 18 years or older. There were three groups of patients recruited prospectively: patients with severe alcohol-related hepatitis who did not respond to medical treatment and were eligible for early liver transplantation according to a new selection scoring system based on social and addiction items that can be quantified in points (early transplantation group); patients with alcohol-related cirrhosis listed for liver transplantation after at least 6 months of abstinence (standard transplantation group); patients with severe alcohol-related hepatitis not responding to medical treatment not eligible for early liver transplantation according to the selection score (not eligible for early transplantation group), this group did not enter any further liver transplantation processes. We also defined a historical control group of patients with severe alcohol-related hepatitis unresponsive to medical therapy and non-transplanted. The primary outcome was the non-inferiority of 2-year rate of alcohol relapse after transplantation in the early transplantation group compared with the standard transplantation group using the alcohol timeline follow back (TLFB) method and a prespecified non-inferiority margin of 10%. Secondary outcomes were the pattern of alcohol relapse, 2-year survival rate post-transplant in the early transplantation group compared with the standard transplantation group, and 2-year overall survival in the early transplantation group compared with patients in the not eligible for early transplantation group and historical controls. This trial is registered with ClinicalTrials.gov, NCT01756794. Findings: Between Dec 5, 2012, and June 30, 2016, we included 149 patients with severe alcohol-related hepatitis: 102 in the early transplantation group and 47 in the not eligible for early transplantation group. 129 patients were included in the standard transplantation group. 68 patients in the early transplantation group and 93 patients in the standard transplantation group received a liver transplant. 23 (34%) patients relapsed in the early transplantation group, and 23 (25%) patients relapsed in the standard transplantation group; therefore, the non-inferiority of early transplantation versus standard transplantation was not demonstrated (absolute difference 9·1% [95% CI –∞ to 21·1]; p=0·45). The 2-year rate of high alcohol intake was greater in the early transplantation group than the standard transplantation group (absolute difference 16·7% [95% CI 5·8–27·6]) The time spent drinking alcohol was not different between the two groups (standardised difference 0·24 [95% CI −0·07 to 0·55]), but the time spent drinking a large quantity of alcohol was higher in the early transplantation group than the standard transplantation group (standardised difference 0·50 [95% CI 0·17–0·82]). 2-year post-transplant survival was similar between the early transplantation group and the standard transplantation group (hazard ratio [HR] 0·87 [95% CI 0·33–2·26]); 2-year overall survival was higher in the early transplantation group than the not eligible for early transplantation group and historical controls (HR 0·27 [95% CI 0·16–0·47] and 0·21 [0·13–0·32]). Interpretation: We cannot conclude non-inferiority in terms of rate of alcohol relapse post-transplant between early liver transplantation and standard transplantation. High alcohol intake is more frequent after early liver transplantation. This prospective controlled study confirms the important survival benefit related to early liver transplantation for severe alcohol-related hepatitis; and this study provides objective data on survival and alcohol relapse to tailor the management of patients with severe alcohol-related hepatitis. Funding: The present study has been granted by the French Ministry of Health—Programme Hospitalier de Recherche Clinique 2010

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/)

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Transport tunnel polarisé en spin dans le système épitaxié Fe/MgO/Fe (interactions magnétiques et symétries électroniques)

Les jonctions tunnel magnétiques monocristallines Fe(1 00)/MgO(1 00)/Fe(1 00) élaborées par Epitaxie par Jet Moléculaire sont des systèmes modèles pour la va1idation de concepts spécifiques au transport polarisé en ( spin dans les multicouches cristallines. L'analyse de la structure de bande montre que le Fe(100) apparaît comme un demi-métal au regard de la symétrie 01 : cette nouvelle notion de polarisation en terme de symétrie électronique explique les formidables effets magnétorésistifs prédits dans ce système. Nos résultats magnétorésistifs valident les effets de filtrage en symétrie et montrent l'influence de la structure électronique sur le transport dont les mécanismes dépassent le modèle des électrons libres. Parallèlement, la croissance bidimensionnelle du MgO a permis "élaboration de fines couches de MgO pour lesquelles nous avons fourni la première mise en évidence expérimentale d'une interaction antiferromagnétique entre deux couches magnétiques par effet tunnel polarisé en spin.Monocrystalline Fe(1 00)/MgO(1 00)/Fe(1 00) magnetic tunnel junctions (MT J), elaborated by Molecular Beam Epitaxy constitute ideal systems for validation of specific concepts related to the spin polarized transport in crystalline multilayers. The analysis of the band structure shows that the Fe(100) behaves as a half-metal with respect to the 01 electronic symmetry; this new concept of spin polarization/filtering in terms of symmetry being at the origin of huge magnetoresistive effects theoretically predicted in these systems. Our magnetotransport results validate the effects of electronic symmetry filtering. Moreover, they illustrate the influence of the electronic structure on tunnel transport, whose complex mechanisms go weil beyond the free- electron framework. The precise control of the bidimensional epitaxial growth of MgO allowed us the elaboration of extremely thin insulating barriers for which we provide a first experimental proof of magnetic coupling by spin polarized tunneling.NANCY-INPL-Bib. électronique (545479901) / SudocSudocFranceF

How to overcome the electrical conductivity limitation of carbon nanotube yarns drawn from carbon nanotube arrays

International audienceA complete literature review of carbon nanotube (CNT) yarn conductivities is presented, highlighting that CNT yarns made from CNT arrays grown by Chemical Vapor Deposition show a resistivity limitation of around 1 mΩ cm. We bring a deep understanding of the conduction limitation in CNT yarns spun from arrays thanks to systematic electrical transport studies in a large temperature range (3 K - 350 K) in CNT yarns made in different conditions of densification, doping and CNT lengths. The analysis of the electrical transport by the reduced activation energy clearly uncouples the effects of the inter-CNT contacts, prevailing below 70 K and the intrinsic CNT resistivity (prevailing above 70 K). Contrary to what is commonly accepted, we show that the contacts between CNTs have no impact on the CNT yarn resistivity at room temperature. In addition, we present a unique study of the structural and electrical properties of the CNT web which reveals that the CNT bundles are very well connected with each other. We estimate the CNT bundle resistivity (0.8 mΩ cm) to be close to that of the CNT yarn (1.1 mΩ cm). We conclude that, at room temperature, the CNT yarn resistivity is limited by that of the CNT bundle

A unified electrical model based on experimental data to describe electrical transport in carbon nanotube-based materials

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N-type semiconducting polymers for dual applications in organic solar cells and thermoelectricity

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Large improvement of CNT yarn electrical conductivity by varying chemical doping and annealing treatment

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A new high performance ionic liquid mixture electrolyte for large temperature range supercapacitor applications (−70 °C to 80 °C) operating at 3.5V cell voltage

International audienceIn this work, we propose a new eutectic ionic liquid mixture based on 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide and 1-propyl-3-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide to be employed as electrolyte in large temperature range supercapacitor applications. The electrolyte exhibited excellent thermal properties in terms of high temperature decomposition (440 °C), a very low melting temperature (no phase transition up to −70 °C) as well as a wide electrochemical window (4.4 V vs Pt). Accordingly, a symmetric coin cell supercapacitor device was performed using porous Ni-foam electrodes in presence of the corresponding mixture at an extended working temperature range from −70 °C to 80 °C. The electrochemical performance of the device was characterised by a wide electrochemical window of 3.5 V maintaining an excellent electrochemical double layer capacitive behavior in all the range. In addition, areal capacitance values between 5 μF cm−2 (−70 °C) and 100 μF cm−2 (80 °C) were obtained at a high scan rate of 20 V s−1, evidencing the rapid and extraordinary electrochemical response even at such extreme temperatures with an excellent cycling stability

New "one-step" method for the simultaneous synthesis and anchoring of organic monolith inside COC microchip channels

The present process is under French patent pending no. FR1156586.International audienceA new method for monolith synthesis and anchoring inside cyclic olefin copolymer (COC) microchannels in a single step is proposed. It is shown that type I photoinitiators, typically used in a polymerization mixture to generate free radicals during monolith synthesis, can simultaneously act as type II photoinitiators and react with the plastic surface through hydrogen abstraction. This mechanism is used to "photograft" poly(ethylene glycol) methacrylate (PEGMA) on COC surfaces. Contact angle measurements were used to observe the changes in surface hydrophilicity when increasing initiator concentration and irradiation duration. The ability of type I photoinitiators to synthesize and anchor a monolith inside COC microchannels in a single step was proved through SEM observations. Different concentrations of photoinitiators were tried. Finally, electrochromatographic separations of polycyclic aromatic hydrocarbons were realized to illustrate the beneficial effect of anchoring on chromatographic performances. The versatility of the method was demonstrated with two widely used photoinitiators: benzoin methyl ether (BME) and azobisisobutyronitrile (AIBN)