Corticotroph tumor progression after bilateral adrenalectomy (Nelson’s syndrome):systematic review and expert consensus recommendations

Corticotroph tumor progression (CTP) leading to Nelson's syndrome (NS) is a severe and difficult-to-treat complication subsequent to bilateral adrenalectomy (BADX) for Cushing's disease. Its characteristics are not well described, and consensus recommendations for diagnosis and treatment are missing

Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma

SummaryWe describe a comprehensive genomic characterization of adrenocortical carcinoma (ACC). Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1. Genome wide DNA copy-number analysis revealed frequent occurrence of massive DNA loss followed by whole-genome doubling (WGD), which was associated with aggressive clinical course, suggesting WGD is a hallmark of disease progression. Corroborating this hypothesis were increased TERT expression, decreased telomere length, and activation of cell-cycle programs. Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68-CpG probe DNA-methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers

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 < 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

Caractérisation clinique et paraclinique de deux groupes de corticosurrénalomes identifiés par le transcriptome

Les tumeurs corticosurrénaliennes posent une double problématique, clinique et physiopathologique. Au plan clinique le diagnostic de malignité est parfois difficile et lr pronostic des formes malignes (ou corticosurrénalomes) est le plus souvent imprévisible. Au plan physiopathologique, les mécanismes à l'origine de ces tumeurs sont inconnus. Le classement des tumeurs en fonction de la proximité de leur transcriptome distingue parfaitement adénomes et corticosurrénalomes. Deux groupes de corticosurrénalomes associés à un pronostic différent ont été identifiés par des études de transcriptome. Ce travail a repris les caractéristiques cliniques et paracliniques des patients de ces deux groupes. Les patients du groupe de mauvais pronostic présentent au diagnostic une maladie plus agressive : tumeur plus volumineuse, extension plus importante, anomalies histologiques plus nombreuses, métastases plus fréquentes. Le déséquilibre du sexe ratio entre les deux groupes, avec un enrichissement en hommes du groupe de mauvais pronostic, est une observation plus originale, qui doit être confirmée, et dont la signification physiopathologique éventuelle n est pas connue. L information pronostique apportée par le transcriptome est indépendante des facteurs pronostiques classiques des corticosurrénalomes, notamment de l extension tumorale. Ce résultat est en faveur de l existence de deux types de corticosurrénalomes distincts, ayant une biologie et un pronostic différents.Adrenocortical tumors pose a dual problem, clinical and pathophysiological. Diagnosis of malignancy is sometimes difficult, and prognosis of malignant tumors is most often unpredictable. At a pathophysiological level, mechanisms at the origin of these tumors are unknown. The classification of tumors according to the proximity of their transcriptome perfectly distinguishes adrenocortical adenomas and cancers, and identifies within these two groups of very different prognosis. To resume the clinical and paraclinical characteristics of adrenocortical cancers of two groups of different prognoses obtained by the transcriptome, in search of their commonalities and differences. As expected patients in the poor prognosis group have a more aggressive disease at diagnosis (tumor larger, deeper extension, histological features more numerous, more frequent metastasis). The imbalance of sex ratiobetween the two groups, with enrichment in men in the group with poor prognosis, is a more original observation, to be confirmed, and whose potential pathophysiological significance is unknown. The prognostic information provided by the transcriptome is independent of conventional prognostic factors in adrenocortical carcinomas, including tumor extension. These results support the existence of two distinct types of adrenocortica carcinomas, with a different biology and prognosisST QUENTIN EN YVELINES-BU (782972101) / SudocSudocFranceF

Tumeurs de la corticosurrénale (du transcriptome aux phénotypes de sécrétion et de malignité)

PARIS5-BU Méd.Cochin (751142101) / SudocSudocFranceF

Métaphylaxie : théorie et pratique lors d'affections respiratoires

National audienceLa métaphylaxie correspond à un usage mixte curatif et préventif des antibiotiques sur un lot d'animaux exposés au même risque infectieux. La métaphylaxie regroupe des pratiques très diverses notamment en fonction des pays et du type de production, de plus non codifiées et sans consensus à ce jour. Son intérêt théorique repose sur une thérapeutique précoce des animaux aux premiers stades cliniques discrets et des animaux infectés en incubation, sur la thérapeutique des animaux en phase clinique aiguë et sur la prévention de l'infection des animaux au contact. Les principes de la métaphylaxie, ses objectifs en pathologie respiratoire bovine et des exemples de modalités pratiques sont discutés, ainsi que le bien-fondé de cette pratique dans le cadre d'EcoAntibio 2017, le choix des molécules et les intérêts médicaux et économiques réels ou supposés

Approche lors d'affections respiratoires des bovins adultes

D'après une communication présentée au Wolrd Buiatrics Congress 2006National audienc

Antibioprévention en élevage bovin : prescrire ou proscrire

National audienceLes données relative à l'antibioprévention en élevage bovin sont rares, alors que cette pratique est courante en élevages de veaux de boucherie, et à un moindre degré en élevages de bovins à l'engrais. La définition de l'antibioprévention mérite tout d'abord d'être clarifiée. En particulier, il convient de cesser de la confondre avec la métaphylaxie traitée dans cette session. La première question qui se pose est celle de la justification de l'antibioprévention dans ces contextes. Les pratiques actuelles d'antibioprévention décrites en élevages naisseurs ou de veaux de boucherie paraissent en effet contradictoires avec les principes de l'usage prudent et raisonné des antibiotiques, promues en particulier par le plan national EcoAntibio 2017. Ces pratiques ont des conséquences que l'on peut qualifier de néfastes en termes de santé publique. Des alternatives sont heureusement envisageables, qu'il convient même de privilégier pour contribuer à atteindre les objectifs fixé par le plan EcoAntibio 2017

DNA Methylation Is an Independent Prognostic Marker of Survival in Adrenocortical Cancer

Context Adrenocortical cancer (ACC) is an aggressive tumor with a heterogeneous outcome. Prognostic stratification is difficult even based on tumor stage and Ki67. Recently integrated genomics studies have demonstrated that CpG islands hypermethylation is correlated with poor survival. Objective The goal of this study was to confirm the prognostic value of CpG islands methylation on an independent cohort. Design Methylation was measured by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). Setting MS-MLPA was performed in a training cohort of 50 patients with ACC to identify the best set of probes correlating with disease-free survival (DFS) and overall survival (OS). These outcomes were validated in an independent cohort from 21 ENSAT centers. Patients The validation cohort included 203 patients (64% women, median age 50 years, 80% localized tumors). Main Outcome Measures DFS and OS. Results In the training cohort, mean methylation of 4 genes (PAX5, GSTP1, PYCARD, PAX6) was the strongest methylation marker. In the validation cohort, methylation was a significant prognostic factor of DFS (P < 0.0001) and OS (P < 0.0001). Methylation, Ki67, and ENSAT stage were combined in multivariate models. For DFS, methylation (P = 0.0005) and stage (P < 0.0001) but not Ki67 (P = 0.19) remained highly significant. For OS, methylation (P = 0.0006), stage (P < 0.0001), and Ki67 (P = 0.024) were independent prognostic factors. Conclusions Tumor DNA methylation emerges as an independent prognostic factor in ACC. MS-MLPA is readily compatible with clinical routine and should enhance our ability for prognostication and precision medicine

Pregnancy does not accelerate corticotroph tumor progression in Nelson's syndrome

Pituitary surgery is the first line of treatment for Cushing's disease; when surgery fails, bilateral adrenalectomy may be proposed, particularly for women with a desire for pregnancy. Little is known about the impact of pregnancy on corticotroph tumor progression after bilateral adrenalectomy