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/)

A simple characterization methodology for the identification of the visco-elastic behavior of thermoset adhesives during cure

International audienceThe identification of the mechanical behavior of adhesives is necessary to describe the development of residual stresses during their curing, which might impact their mechanical strength and lead to early failure of the bonding. A simple characterization and modeling approach is therefore developed and presented, which permits to monitor and identify the mechanical behavior of a thermosetting adhesive during the whole curing process. The test method is based on a compressive test, which consists in applying a periodic displacement and recording the subsequent load variations during cure. The test set-up relies on a simple apparatus as it consists in steel cylinders mounted on a standard tensile test machine. The analysis of the mechanical behavior is based on an analytical description of a visco-elastic constitutive law following the Maxwell model, leading to the identification of the material apparent viscosity and Young’s modulus. This characterization methodology is applied to an epoxy adhesive during cure. The obtained mechanical properties are in good agreement with values provided by the material supplier, which permits to validate the developed methodology

Jean-Baptiste Bouffet / N.H. Jacob, d'après Alexandre Péron

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Effects of food deprivation and particle size of ground wheat on digestibility of food components in broilers fed on a pelleted diet

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DIY your captures when everything else fails: Description of an artisanal dart launcher with an assessment of the medium-term response in a primate

International audienceWhen our dart guns failed in Morocco, we devised an artisanal pressurised air launcher to replace them. The effective shooting range was between 12 and 20 m, which made it possible to capture wild Barbary macaques (Macaca sylvanus), from groups that would not allow for a closer approach or enter any trap. To assess the effect of that method of capture, we monitored the groups on foot before and after the captures. We looked for evidence of a change in risk perception after the captures. We did not uncover any such evidence in the step lengths, turning angles, home range area, frequency of rest while on the ground or frequency of social interactions. We conclude that for the study animals, being captured with our artisanal dart launcher, had a similar effect to being darted with a professional gun, and we intend this note as an inspiration to other field operators finding themselves in a similar predicament

Effect of -based Direct-fed Microbial on Performance, Nutrient Utilization, Intestinal Morphology and Cecal Microflora in Broiler Chickens

The present study was conducted to evaluate the effect of the dietary supplementation of Bacillus amyloliquefaciens-based direct-fed microbial (DFM) on growth performance, nutrient utilization, intestinal morphology and cecal microflora in broiler chickens. A total of two hundred and eighty eight 1-d-old Arbor Acres male broilers were randomly allocated to one of four experimental treatments in a completely randomized design. Each treatment was fed to eight replicate cages, with nine birds per cage. Dietary treatments were composed of an antibiotic-free basal diet (control), and the basal diet supplemented with either 15 mg/kg of virginiamycin as antibiotic growth promoter (AGP), 30 mg/kg of Bacillus amyloliquefaciens-based DFM (DFM 30) or 60 mg/kg of Bacillus amyloliquefaciens-based DFM (DFM 60). Experimental diets were fed in two phases: starter (d 1 to 21) and finisher (d 22 to 42). Growth performance, nutrient utilization, morphological parameters of the small intestine and cecal microbial populations were measured at the end of the starter (d 21) and finisher (d 42) phases. During the starter phase, DFM and virginiamycin supplementation improved the feed conversion ratio (FCR; p<0.01) compared with the control group. For the finisher phase and the overall experiment (d 1 to 42) broilers fed diets with the DFM had better body weight gain (BWG) and FCR than that of control (p<0.05). Supplementation of virginiamycin and DFM significantly increased the total tract apparent digestibility of crude protein (CP), dry matter (DM) and gross energy during both starter and finisher phases (p<0.05) compared with the control group. On d 21, villus height, crypt depth and villus height to crypt depth ratio of duodenum, jejunum, and ileum were significantly increased for the birds fed with the DFM diets as compared with the control group (p<0.05). The DFM 30, DFM 60, and AGP groups decreased the Escherichia coli population in cecum at d 21 and d 42 compared with control group (p<0.01). In addition, the population of Lactobacillus was increased in DFM 30 and DFM 60 groups as compared with control and AGP groups (p<0.01). It can be concluded that Bacillus amyloliquefaciens-based DFM could be an alternative to the use of AGPs in broilers diets based on plant protein

Effects of two wheat cultivars on physico-chemical properties of wheat flours and digesta from two broiler chicken lines (D+ and D-) differing in digestion capacity.

International audience1. The current experiment is the second part of a study about the effects of wheat quality on digestibility of pelleted diets for broiler chickens. In the first part, it was previously shown that a hard cultivar resulted in a negative effect on starch digestibility in two divergent lines of chickens (D+ and D-) selected for digestion capacity. The aim of this second part was to investigate the reasons for this negative effect of a hard cultivar (Baltimor) compared to a soft one (Scipion) in D+ and D- lines. 2. Proventriculus pepsin activity, pancreas proteolytic and amylolytic activities were estimated in four pools of birds: "D+ line (Baltimor fed)", "D+ line (Scipion fed)", "D- line (Baltimor fed)" and "D- line (Scipion fed)". Results suggested greatest amount of pepsin units per g BW for D+ birds and lowest amount of pancreas proteolytic units per g BW for D+ birds fed Scipion wheat. Pancreas showed very similar α-amylase activities among treatments. 3. In vitro hydrolyses of wheat gluten proteins with proventriculus extracts from pools of D+ and D- birds did not show any differences between hard and soft cultivars, whatever the origin of pools. 4. Pepsin hydrolysis of fine (300 to 425 µm) and coarse (1180 to 1600 µm) fractions from wheat flours (Baltimor or Scipion) showed that the 30 min proteolysis rate was highest for the fine fraction in both cultivars. No difference was observed with extended hydrolysis time. 5. In vitro digestion simulation of whole wheat flours confirmed the results previously obtained in vivo, with a negative effect of hard cultivar on starch digestion rate, and no effect on protein digestion. 6. Laser particle size analyses showed that ileum digesta from birds fed with hard wheat cultivar showed highest proportion of coarse particles. 7. Microscopic analyses of D+ ileum digesta revealed that the concentration of undigested starch granules in subaleurone area of wheat bran particles was the highest with hard cultivar. 8. The results suggested that physical entrapment of starch granules in coarse particles was a major explanation for decreased starch digestibility values in chickens fed hard wheat diets

Nutritional effects of feed form, and wheat compared to maize, in the D+ and D- chicken lines selected for divergent digestion capacity

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Effects of wheat quality on digestion differ between the D+ and D- chicken lines selected for divergent digestion capacity

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