Polarizers, optical bridges and Sagnac interferometers for nanoradian polarization rotation measurements

The ability to measure nanoradian polarization rotations, $\theta_F$, in the photon shot noise limit is investigated for partially crossed polarizers (PCP), a static Sagnac interferometer and an optical bridge, each of which can in principal be used in this limit with near equivalent figures-of-merit (FOM). In practice a bridge to PCP/Sagnac source noise rejection ratio of $1/4\theta_F^2$ enables the bridge to operate in the photon shot noise limit even at high light intensities. The superior performance of the bridge is illustrated via the measurement of a 3 nrad rotation arising from an axial magnetic field of 0.9 nT applied to a terbium gallium garnet. While the Sagnac is functionally equivalent to the PCP in terms of the FOM, unlike the PCP it is able to discriminate between rotations with different time ($T$) and parity ($P$) symmetries. The Sagnac geometry implemented here is similar to that used elsewhere to detect non-reciprocal ($\overline{T}P$) rotations like those due to the Faraday effect. Using a Jones matrix approach, novel Sagnac geometries uniquely sensitive to non-reciprocal $\overline{TP}$ (e.g. magneto-electric or magneto-chiral) rotations, as well as to reciprocal rotations (e.g. due to linear birefringence, $TP$, or to chirality, $T\overline{P}$) are proposed.Comment: 12 pages, 7 figure

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

Surgical management of obese and morbid obese : consequences on non-alcoholic fatty liver disease and on access to liver transplantation

L’obésité est dorénavant considérée comme une maladie par l’OMS et touche l’ensemble du globe. Responsable d’une diminution de l’espérance de vie en raison de l’augmentation de la mortalité cardiovasculaire et carcinologique, l’obésité a des conséquences métaboliques endocrines avec la survenue du diabète de type 2 et hépatiques avec la stéatopathie métabolique. La stéatopathie métabolique et notamment sa forme sévère, la NASH, provoquent l’accroissement du nombre de cirrhose et du carcinome hépatocellulaire. La prise en charge de la stéatopathie métabolique implique de considérer le traitement de l’obésité. La chirurgie bariatrique apparait aujourd’hui comme le meilleur traitement de l’obésité. Chez le patient atteint de stéatohépatite, la chirurgie bariatrique permet la résolution de la NASH dans près 80% des cas. La disparition du processus inflammatoire initie la diminution de la fibrose. L’importance de la réponse histologie est associée à la perte de poids et à l’amélioration de l’insulinorésistance. Après 5 ans de suivi, il n’y a pas de récidive de la maladie, et la fibrose continue de s’améliorer. A titre d’exemple, la fibrose disparait totalement chez près de 45% des patients atteints de fibrose avancée à baseline. Pour les patients souffrants de carcinome hépatocellulaire et/ou d’insuffisance hepatocellulaire, la greffe apparait comme le traitement de référence. Néanmoins, l’analyse du devenir sur liste d’attente prétransplantation des patients révèle que les patients obèses morbides ont plus de risque de mortalité sur liste, et moins d’accès à la greffe. Cet effet n’est pas dû à une plus faible attribution des greffons, mais à un taux de refus plus important en raison d’incompatibilités morphologiques entre le donneur et le receveur. Idéalement, il faudrait pouvoir proposer des greffons provenant de donneurs obèses à ces receveurs, mais ces premiers sont stéatosiques et plus sensibles à l’ischémie reperfusion. La modulation de l’ischémie reperfusion apparait comme un enjeu majeur pour améliorer l’accès à la greffe, en utilisation des greffons dit marginaux. La protéine NOD1 semble être une cible idéale pour réduire le processus lésions de l’ischémie reperfusion. A l’échelle hépatique, la voie NOD1 influence l’expression des molécules d’adhérences ICAM-1 et VCAM-1 à la surface des cellules endothéliales et des hépatocytes. Les antagonistes NOD1 réduisent ainsi l’expression de ICAM-1 et VCAM-1, l’interaction entre hépatocytes et polynucléaires neutrophiles et ainsi que les aires de nécrose hépatique secondaire à la l’ischémie reperfusion. NOD1 se positionne comme une cible intéressante méritant d’être évaluer sur des foies stéatosiques afin de les protéger du processus lésionnel de l’ischémie reperfusion.Obesity is now considered as a disease by WHO with a Global threat. Responsible for a decrease in life expectancy due to increased cardiovascular and carcinologic mortality, obesity has endocrine metabolic consequences with the onset of type 2 diabetes and hepatic consequences with non-alcoholic fatty liver disease (NAFLD). NAFLD and in particular its severe form, non-alcoholic steatohepatitis (NASH), cause an increase in the number of cirrhosis and hepatocellular carcinoma. Management of NASH involves considering treatment for obesity. Bariatric surgery is emerging as the best treatment for obesity today. In patients with steatohepatitis, bariatric surgery resolves NASH in nearly 80% of cases. The disappearance of the inflammatory process initiates the decrease in fibrosis. The magnitude of the histological response is associated with weight loss and improvement in insulin resistance. After 5 years of follow-up, there is no recurrence of the disease, and the fibrosis continues to improve. For example, fibrosis resolves completely in nearly 45% of patients with advanced baseline fibrosis. For patients suffering from hepatocellular carcinoma and / or hepatocellular insufficiency, the liver transplantation appears to be the best therapeutic option. Nonetheless, analysis of the pre-transplant waiting list outcome of patients reveals that morbidly obese patients have a higher risk of on-list mortality, and less access to transplantation. This effect is not due to a lower allocation of grafts, but to a higher refusal rate due to morphological incompatibilities between the donor and the recipient. Ideally, it should be possible to offer grafts from obese donors to these recipients, but the formers disclose frequently steatosis and thus more susceptible to ischemia reperfusion. The modulation of ischemia reperfusion appears to be a major issue in improving access to grafts, using so-called marginal grafts. The NOD1 protein appears to be an ideal target for reducing the ischemia reperfusion injury process. At the hepatic level, the NOD1 pathway influences the expression of ICAM-1 and VCAM-1 adhesion molecules on the surface of endothelial cells and hepatocytes. The NOD1 antagonists thus reduce the expression of ICAM-1 and VCAM-1, the interaction between hepatocytes and polymorphonuclear neutrophils and as well as the areas of hepatic necrosis secondary to ischemia reperfusion. NOD1 is positioned as an interesting target deserving to be evaluated on fatty livers in order to protect them from the injury process of ischemia reperfusion

Prise en charge chirurgicale de l’obèse et de l’obèse morbide : conséquences sur la stéatopathie métabolique et sur l’accès à la transplantation hépatique

Obesity is now considered as a disease by WHO with a Global threat. Responsible for a decrease in life expectancy due to increased cardiovascular and carcinologic mortality, obesity has endocrine metabolic consequences with the onset of type 2 diabetes and hepatic consequences with non-alcoholic fatty liver disease (NAFLD). NAFLD and in particular its severe form, non-alcoholic steatohepatitis (NASH), cause an increase in the number of cirrhosis and hepatocellular carcinoma. Management of NASH involves considering treatment for obesity. Bariatric surgery is emerging as the best treatment for obesity today. In patients with steatohepatitis, bariatric surgery resolves NASH in nearly 80% of cases. The disappearance of the inflammatory process initiates the decrease in fibrosis. The magnitude of the histological response is associated with weight loss and improvement in insulin resistance. After 5 years of follow-up, there is no recurrence of the disease, and the fibrosis continues to improve. For example, fibrosis resolves completely in nearly 45% of patients with advanced baseline fibrosis. For patients suffering from hepatocellular carcinoma and / or hepatocellular insufficiency, the liver transplantation appears to be the best therapeutic option. Nonetheless, analysis of the pre-transplant waiting list outcome of patients reveals that morbidly obese patients have a higher risk of on-list mortality, and less access to transplantation. This effect is not due to a lower allocation of grafts, but to a higher refusal rate due to morphological incompatibilities between the donor and the recipient. Ideally, it should be possible to offer grafts from obese donors to these recipients, but the formers disclose frequently steatosis and thus more susceptible to ischemia reperfusion. The modulation of ischemia reperfusion appears to be a major issue in improving access to grafts, using so-called marginal grafts. The NOD1 protein appears to be an ideal target for reducing the ischemia reperfusion injury process. At the hepatic level, the NOD1 pathway influences the expression of ICAM-1 and VCAM-1 adhesion molecules on the surface of endothelial cells and hepatocytes. The NOD1 antagonists thus reduce the expression of ICAM-1 and VCAM-1, the interaction between hepatocytes and polymorphonuclear neutrophils and as well as the areas of hepatic necrosis secondary to ischemia reperfusion. NOD1 is positioned as an interesting target deserving to be evaluated on fatty livers in order to protect them from the injury process of ischemia reperfusion.L’obésité est dorénavant considérée comme une maladie par l’OMS et touche l’ensemble du globe. Responsable d’une diminution de l’espérance de vie en raison de l’augmentation de la mortalité cardiovasculaire et carcinologique, l’obésité a des conséquences métaboliques endocrines avec la survenue du diabète de type 2 et hépatiques avec la stéatopathie métabolique. La stéatopathie métabolique et notamment sa forme sévère, la NASH, provoquent l’accroissement du nombre de cirrhose et du carcinome hépatocellulaire. La prise en charge de la stéatopathie métabolique implique de considérer le traitement de l’obésité. La chirurgie bariatrique apparait aujourd’hui comme le meilleur traitement de l’obésité. Chez le patient atteint de stéatohépatite, la chirurgie bariatrique permet la résolution de la NASH dans près 80% des cas. La disparition du processus inflammatoire initie la diminution de la fibrose. L’importance de la réponse histologie est associée à la perte de poids et à l’amélioration de l’insulinorésistance. Après 5 ans de suivi, il n’y a pas de récidive de la maladie, et la fibrose continue de s’améliorer. A titre d’exemple, la fibrose disparait totalement chez près de 45% des patients atteints de fibrose avancée à baseline. Pour les patients souffrants de carcinome hépatocellulaire et/ou d’insuffisance hepatocellulaire, la greffe apparait comme le traitement de référence. Néanmoins, l’analyse du devenir sur liste d’attente prétransplantation des patients révèle que les patients obèses morbides ont plus de risque de mortalité sur liste, et moins d’accès à la greffe. Cet effet n’est pas dû à une plus faible attribution des greffons, mais à un taux de refus plus important en raison d’incompatibilités morphologiques entre le donneur et le receveur. Idéalement, il faudrait pouvoir proposer des greffons provenant de donneurs obèses à ces receveurs, mais ces premiers sont stéatosiques et plus sensibles à l’ischémie reperfusion. La modulation de l’ischémie reperfusion apparait comme un enjeu majeur pour améliorer l’accès à la greffe, en utilisation des greffons dit marginaux. La protéine NOD1 semble être une cible idéale pour réduire le processus lésions de l’ischémie reperfusion. A l’échelle hépatique, la voie NOD1 influence l’expression des molécules d’adhérences ICAM-1 et VCAM-1 à la surface des cellules endothéliales et des hépatocytes. Les antagonistes NOD1 réduisent ainsi l’expression de ICAM-1 et VCAM-1, l’interaction entre hépatocytes et polynucléaires neutrophiles et ainsi que les aires de nécrose hépatique secondaire à la l’ischémie reperfusion. NOD1 se positionne comme une cible intéressante méritant d’être évaluer sur des foies stéatosiques afin de les protéger du processus lésionnel de l’ischémie reperfusion

Etude prospective de l'évolution lésionnelle hépatique (inflammation, ballonisation et fibrose) après chirurgie bariatrique des patients obèses morbides atteints de stéatopathie métabolique sévère et/ou de stéatohépatique

LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

Quelle place pour la chirurgie bariatrique dans le traitement de la stéatohépatite non alcoolique ?

International audienceBariatric surgery is indicated for patients with BMI≥35kg/m2 and associated steatohepatitis. Bariatric surgery induces NASH disappearance for nearly 80% of patients after 1 year of follow up. Bariatric surgery is associated with low morbidity and mortality if patients are well selected. Bariatric surgery is contraindicated in patients with cirrhosis. Long-term data are needed to determine the risk of recurrence of NASH. The extension of indications for bariatric surgery to patients with BMI less than 35kg/m2 will depend on the results of randomized trials

Benefits of tailored hepatocellular carcinoma screening in patients with cirrhosis on cancer‐specific and overall mortality: A modeling approach

International audienc

Un modèle pour identifier les buveurs excessifs à haut risque de progression de la maladie du foie

International audienceBACKGROUND & AIMS:Alcohol-related liver disease (ALD) causes chronic liver disease. We investigated how information on patients' drinking history and amount, stage of liver disease, and demographic feature can be used to determine risk of disease progression.METHODS:We collected data from 2334 heavy drinkers (50 g/day or more) with persistently abnormal results from liver tests who had been admitted to a hepato-gastroenterology unit in France from January 1982 through December 1997; patients with a recorded duration of alcohol abuse were assigned to the development cohort (n=1599; 75% men) or the validation cohort (n=735; 75% men), based on presence of a liver biopsy. We collected data from both cohorts on patient history and disease stage at the time of hospitalization. For the development cohort, severity of the disease was scored by the METAVIR (due to the availability of liver histology reports); in the validation cohort only the presence of liver complications was assessed. We developed a model of ALD progression and occurrence of liver complications (hepatocellular carcinoma and/or liver decompensation) in association with exposure to alcohol, age at the onset of heavy drinking, amount of alcohol intake, sex and body mass index. The model was fitted to the development cohort and then evaluated in the validation cohort. We then tested the ability of the model to predict disease progression for any patient profile (baseline evaluation). Patients with a 5-y weighted risk of liver complications greater than 5% were considered at high risk for disease progression.RESULTS:Model results are given for the following patient profiles: men and women, 40 y old, who started drinking at an age of 25 y, drank 150 g/day, and had a body mass index of 22 kg/m2 according to the disease severity at baseline evaluation. For men with baseline F0-F2 fibrosis, the model estimated the probabilities of normal liver, steatosis, or steatohepatitis at baseline to be 31.8%, 61.5% and 6.7%, respectively. The 5-y weighted risk of liver complications was 1.9%, ranging from 0.2% for men with normal liver at baseline evaluation to 10.3% for patients with steatohepatitis at baseline. For women with baseline F0-F2 fibrosis, probabilities of normal liver, steatosis, or steatohepatitis at baseline were 25.1%, 66.5% and 8.4%, respectively; the 5-y weighted risk of liver complications was 3.2%, ranging from 0.5% for women with normal liver at baseline to 14.7% for patients with steatohepatitis at baseline. Based on the model, men with F3-F4 fibrosis at baseline have a 24.5% 5-y weighted risk of complications (ranging from 20.2% to 34.5%) and women have a 30.1% 5-y weighted risk of complications (ranging from 24.7% to 41.0%).CONCLUSIONS:We developed a Markov model that integrates data on level and duration of alcohol use to identify patients at high risk of liver disease progression. This model might be used to adapt patient care pathways