Clinical characteristics and outcomes of patients with hepatic angiomyolipoma:A literature review

First reported in 1976, hepatic angiomyolipoma (HAML) is a rare mesenchymal liver tumor occurring mostly in middle-aged women. Diagnosis of the liver mass is often incidental on abdominal imaging due to the frequent absence of specific symptoms. Nearly 10% of HAMLs are associated with tuberous sclerosis complex. HAML contains variable proportions of blood vessels, smooth muscle cells and adipose tissue, which renders radiological diagnosis hazardous. Cells express positivity for HMB-45 and actin, thus these tumors are integrated into the group of perivascular epithelioid cell tumors. Typically, a HAML appears on magnetic resonance imaging (or computed tomography scan) as a hypervascular solid tumor with fatty areas and with washout, and can easily be misdiagnosed as other liver tumors, particularly hepatocellular carcinoma. The therapeutic strategy is not clearly defined, but surgical resection is indicated for symptomatic patients, for tumors showing an aggressive pattern (i.e., changes in size on imaging or high proliferation activity and atypical epithelioid pattern on liver biopsy), for large (> 5 cm) biopsy-proven HAML, and if doubts remain on imaging or histology. Conservative management may be justified in other conditions, since most cases follow a benign clinical course. In summary, the correct diagnosis of HAML is challenging on imaging and relies mainly on pathological findings

Sociétés, État, populations en Russie et en URSS

Alain Blum, directeur d’études Sociétés, vie quotidienne et action administrative en Russie et en URSS (XIXe-XXe siècles) L’enseignement a été essentiellement consacré, cette année, à une première approche d’une histoire du quotidien en URSS, construite autour d’une analyse des divers espaces qui se superposent dans l’Union soviétique, professionnel, privé, communautaire, autour des formes de relation qui s’établissent entre les personnes. La réflexion engagée a porté tant sur les approches t..

Prognosis of cirrhotic patients admitted to intensive care unit: a meta-analysis

and METAREACIR GroupInternational audienceBackgroundThe best predictors of short- and medium-term mortality of cirrhotic patients receiving intensive care support are unknown.MethodsWe conducted meta-analyses from 13 studies (2523 cirrhotics) after selection of original articles and response to a standardized questionnaire by the corresponding authors. End-points were in-ICU, in-hospital, and 6-month mortality in ICU survivors. A total of 301 pooled analyses, including 95 analyses restricted to 6-month mortality among ICU survivors, were conducted considering 249 variables (including reason for admission, organ replacement therapy, and composite prognostic scores).ResultsIn-ICU, in-hospital, and 6-month mortality was 42.7, 54.1, and 75.1%, respectively. Forty-eight patients (3.8%) underwent liver transplantation during follow-up. In-ICU mortality was lower in patients admitted for variceal bleeding (OR 0.46; 95% CI 0.36–0.59; p 19 at baseline (OR 8.54; 95% CI 2.09–34.91; p 26 (OR 3.97; 95% CI 1.92–8.22; p < 0.0001; PPV = 0.75), and hepatorenal syndrome (OR 4.67; 95% CI 1.24–17.64; p = 0.022; PPV = 0.88).ConclusionsPrognosis of cirrhotic patients admitted to ICU is poor since only a minority undergo liver transplant. The prognostic performance of general ICU scores decreases over time, unlike the Child–Pugh and MELD scores, even recorded in the context of organ failure. Infection-related parameters had a short-term impact, whereas liver and renal failure had a sustained impact on mortality

Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis

<p>Abstract</p> <p>Background</p> <p>Usher syndrome (USH) combines sensorineural deafness with blindness. It is inherited in an autosomal recessive mode. Early diagnosis is critical for adapted educational and patient management choices, and for genetic counseling. To date, nine causative genes have been identified for the three clinical subtypes (USH1, USH2 and USH3). Current diagnostic strategies make use of a genotyping microarray that is based on the previously reported mutations. The purpose of this study was to design a more accurate molecular diagnosis tool.</p> <p>Methods</p> <p>We sequenced the 366 coding exons and flanking regions of the nine known USH genes, in 54 USH patients (27 USH1, 21 USH2 and 6 USH3).</p> <p>Results</p> <p>Biallelic mutations were detected in 39 patients (72%) and monoallelic mutations in an additional 10 patients (18.5%). In addition to biallelic mutations in one of the USH genes, presumably pathogenic mutations in another USH gene were detected in seven patients (13%), and another patient carried monoallelic mutations in three different USH genes. Notably, none of the USH3 patients carried detectable mutations in the only known USH3 gene, whereas they all carried mutations in USH2 genes. Most importantly, the currently used microarray would have detected only 30 of the 81 different mutations that we found, of which 39 (48%) were novel.</p> <p>Conclusions</p> <p>Based on these results, complete exon sequencing of the currently known USH genes stands as a definite improvement for molecular diagnosis of this disease, which is of utmost importance in the perspective of gene therapy.</p

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

New aspects in the management of liver cirrhosis

La cirrhose est responsable d’environ 17000 décès par an en France. Le seul traitement curatif de la cirrhose reste latransplantation hépatique mais dans le contexte actuel de pénurie de greffons, la prise en charge doit être précoce afin d’interveniravant la décompensation clinique et de prévenir la survenue des complications. Les travaux présentés dans cette thèse s’articulenten deux volets. Le premier volet concerne la prise en charge précoce de deux complications graves de l’hypertension portale. Nousprésentons les résultats d’une enquête nationale de pratiques au sein des CHU et CHG français qui a mis en évidence une grandehétérogénéité dans la prise en charge de la rupture de varice gastrique. Ce travail en apparence anodin a été l’occasion d’une prisede conscience nationale de la nécessité d’élaborer des recommandations notamment concernant la prévention du resaignement. Undeuxième travail a permis de montrer l’intérêt de la calprotectine dosée dans le liquide d’ascite par un test rapide et simple au lit dumalade, pour le diagnostic de l’infection spontanée du liquide d’ascite, une situation courante en pratique clinique aux lourdesconséquences pronostiques. Le second volet concerne l’évaluation pronostique de la cirrhose. Celle-ci a d’abord été abordée sousl’angle de la défaillance viscérale pour éclairer le débat sur l’utilité de la réanimation dans la population des patients atteints decirrhose. La méta-analyse de données internationales multicentriques réalisée sur plus de 2500 patients cirrhotiques a confirmé quele pronostic de ces patients à court terme s’est significativement amélioré ces quinze dernières années, avec une mortalité enréanimation inférieure à 50% mais que le pronostic des patients survivant à la réanimation reste sombre à 6 mois, qui s’expliquesans doute par un accès étonnamment faible à la transplantation hépatique (4%). Notre travail a identifié des éléments prédictifsdisponibles dès l’admission en réanimation, permettant de discriminer d’emblée les candidats à la transplantation hépatique. Lestravaux ultérieurs présentés dans cette thèse ont cherché à identifier des biomarqueurs ayant une signification pronostique dansl’histoire naturelle de la cirrhose. Nous avons jugé pertinent d’explorer avant tout des marqueurs liés à la translocation bactérienneet à l’inflammation systémique. Dans une étude pilote longitudinale, nous avons pu mettre en évidence un impact pronostique desmicroparticules plaquettaires de petite taille et exprimant à leur surface des phosphatidylsérines dont les faibles concentrationsétaient associées à une moindre survie sans transplantation hépatique à 6 mois. Notre hypothèse est que, du fait de leur fortpouvoir procoagulant, ces microparticules sont consommées dans des microthrombi tissulaires et participent à l’extinctionparenchymateuse et à la souffrance intestinale. Nous avons également mis en évidence la valeur pronostique d’une élévationpersistante de la C-réactive protéine (protéine de l’inflammation dont la synthèse hépatique persiste même en cas d’insuffisancehépatique avancée) au cours de l’hospitalisation pour prédire la mortalité à 6 mois des patients cirrhotiques sévèresindépendamment du score MELD. Dans une étude pilote, nous avons montré que les patients attients de cirrhose grave et dontl’évolution est défavorable à 12 mois ont des taux plasmatiques plus élevés de 3-hydroxymyristate (nouveau marqueurd’endotoxinémie dont la quantification directe a été récemment mise au point).In France, cirrhosis results in about 17 000 deaths per year. Liver transplantation is the only curative treatment. In the context oforgan shortage, the management of cirrhosis must be early in order to intervene before clinical decompensation and to prevent theoccurrence of complications. The clinical research presented in this thesis is divided into two parts. The first part concerns the earlymanagement of two serious complications of portal hypertension. We present the results of a French national survey in general andacademic hospitals which revealed a great heterogeneity of practices in the management of gastric variceal bleeding. Thisseemingly anodyne work has raised for a national awareness about the need to develop guidelines particularly regarding theprevention of rebleeding. A second study showed the pertinence of calprotectin measured in ascitic fluid by a rapid, simple, bedsidetest, for the diagnosis of spontaneous bacterial peritonitis, a common situation in clinical practice. The second part of the researchconcerns the prognostic evaluation of cirrhosis. This was first approached from the perspective of organ failure in an attempt toenrich the debate about the utility/futility of resuscitation in patients with cirrhosis. The meta-analysis of multicenter internationaldata on more than 2500 cirrhotic patients confirmed that the short term prognosis of these patients has improved significantly inthe last fifteen years, with a mortality in ICU lower than 50% but that the prognosis of patients surviving the ICU stays remains poorat 6 months, with a very low access to liver transplantation (4%). Our work has enabled us to identify some predictive elementsavailable on ICU admission, that allow an early identification of patients who are candidates for liver transplantation. Subsequentworks presented in this thesis sought to identify biomarkers with prognostic significance in the natural history of cirrhosis. Weconsidered it important to explore, first and foremost, markers related to bacterial translocation and systemic inflammation. In alongitudinal pilot study, we were able to demonstrate a prognostic impact of plasma levels of circulating small platelet-derivedmicroparticles expressing on their surface phosphatidylserine, whose low concentrations were associated with a reduced transplant-free survival at 6 months. Our hypothesis is that, because of their strong procoagulant capacities, these microparticles areintegrated into tissular microthrombi and thus contribute to the liver parenchymal extinction and to the alteration of the gut barrier.We have also demonstrated the prognostic value of persistently elevated levels of C-reactive protein (acute phase protein whosesynthesis persists even in case of advanced liver failure) during hospitalization, to predict 6 months mortality in patients with severecirrhosis. In a pilot study, we showed that patients with advanced cirrhosis who had poor outcome at 12 months had higher plasmalevels of 3-hydroxymyristate (a new surrogate of endotoxemia whose direct quantification was recently developed) at baseline.Finally, we have confirmed that patients with severe cirrhosis have a higher serum concentration of copeptin (a hormone released inparticular in case of inflammatory stress), and that this biomarker is a predictor of 6 and 12 months mortality independently of theusual prognostic scores. Our research thus optimizes the prognostic evaluation of cirrhosis. Although some biomarkers requirefurther investigation and external validation, the prognostic involvement of systemic inflammation during cirrhosis seems promisingenough to be incorporated into the prognostic scores in the next futur

La femme 8 semaines après l'accouchement et si l'on s'intéressait au rein ?

Acupuncture obstétricaleQuelles sont les perturbations physiques et émotionnelles que les femmes décrivent 8 semaines après la naissance de leur enfant ? Vu sous l’angle de la Médecine Traditionnelle Chinoise, le Rein a été extrêmement sollicité durant la période périnatale. Si le Rein se trouve être encore insuffisant à cette distance de l’accouchement, les répercussions impliqueront l’ensemble de l’organisme. Pouvons-nous envisager d’améliorer le bien-être physique tout autant que psychologique des femmes 8 semaines après l’accouchement par le biais d’une thérapeutique basée sur le Rein ? C’est la question que nous nous sommes posés en interrogeant les femmes à ce moment clef de leur vie. Par le biais d’un questionnaire remis aux patientes, nous avons pu corréler cette hypothèse aux symptômes décrits fréquemment, et ainsi proposer des démarches thérapeutiques en acupuncture basées sur le retour à l’équilibre du Rein. Nous avons ensuite proposé de renforcer ces thérapeutiques par le biais de la diététique et de plusieurs pratiques complémentaire

Linear Differential Equations, Differential Galois Groups, First Integrals of Differential Systems

International audienceÉcole thématiqu