Le microchimérisme fœtal et son maintienRevue de la littérature

Objective: To estimate through a review of the bibliography to what extent and which quantities a woman holds fetal cells or DNA in her body, after physiological or pathological pregnancy, at term or not. To determine what are the possible factors influencing passage and maintenance of fetal microchimerism.Materials and methods: Literature review conducted from december 2013 to July 2014 allowed a selection of 13 articles With the Keywords "fetal", "chimerism", "microchimerism", "post-partum" "delivery" and "persistence" in the PUBMED database. The 13 articles are detailed and analyzed in the current study.Results: Any woman Who has experienced pregnancy holds genetic tracks from her obstetric history. Either circulating fetal DNA and/or intact cells called pregnancy-associated progenitor cells can be found in the maternal circulation. Fetal microchimerism is kept in biological niches long term postdelivery ant its levels observed in maternal peripheral blood vary according to post-delivery time and to particular prior events such as interruption of pregnancy or to events happening post-delivery such as cancer, inflammation, etc.Conclusion: Microchimerism may play a role on health. Further studies are needed to precise its function and the reasons of its re-apparition long term after delivery. Could its monitoring be a predictive factor for disease diagnosis ?Objectif : Évaluer au travers d'une revue de la bibliographie dans quelle mesure et quelle quantité une femme conserve de l'ADN fœtal dans son organisme, après une grossesse menée ou non à son terme, qu'elle ait été physiologique ou pathologique. Et ainsi déterminer quels sont les possibles facteurs de variation de ce microchimérisme fœtal.Matériels et méthode : Revue de la littérature menée de Décembre 2013 à Juillet 2014 grâce à l'interrogation d'une base de données bibliographiques PUBMED à partir de mots clés. De cette recherche 13 articles ont été sélectionnés.Résultats : Le fait que chaque femme conserve des traces génétiques de ses antécédents obstétricaux est avéré, de l'ADN fœtal circulant et sous forme de cellules intactes appelées pregnancy-associated progenitor cells. Ce microchimérisme fœtal varie en fonction du temps écoulé après un accouchement et de sa conservation dans des niches biologiques.Conclusion : Le microchimérisme pourrait avoir de nombreux enjeux pour la santé, il faudra cependant de nouvelles expérimentations pour conclure sur le rôle précis de celui-ci sur l'apparition ou non d'une maladie chez la femme, cela pourrait permettre d'envisager un éventuel traitement

Lipodystrophic syndromes: From diagnosis to treatment

International audienceLipodystrophic syndromes are acquired or genetic rare diseases, characterised by a generalised or partial lack of adipose tissue leading to metabolic alterations linked to strong insulin resistance. They encompass a variety of clinical entities due to primary defects in adipose differentiation, in the structure and/or regulation of the adipocyte lipid droplet, or due to immune-inflammatory aggressions, chromatin deregulations and/or mitochondrial dysfunctions affecting adipose tissue. Diagnosis is based on clinical examination, pathological context and comorbidities, and on results of metabolic investigations and genetic analyses, which together determine management and genetic counselling. Early lifestyle and dietary measures focusing on regular physical activity and avoiding excess energy intake are crucial. They are accompanied by multidisciplinary follow-up adapted to each clinical form. In case of hyperglycemia, antidiabetic medications, with metformin as a first-line therapy in adults, are used in addition to lifestyle and dietary modifications. When standard treatments have failed to control metabolic disorders, the orphan drug metreleptin, an analog of leptin, can be effective in certain forms of lipodystrophy syndrome. Metreleptin therapy indications, prescription and monitoring were recently defined in France, representing a major improvement in patient care

Toward Microfluidic Label-Free Isolation and Enumeration of Circulating Tumor Cells from Blood Samples

The isolation, analysis, and enumeration of circulating tumor cells (CTCs) from cancer patient blood samples are a paradigm shift for cancer patient diagnosis, prognosis, and treatment monitoring. Most methods used to isolate and enumerate these target cells rely on the expression of cell surface markers, which varies between patients, cancer types, tumors, and stages. Here, we propose a label-free high-throughput platform to isolate, enumerate, and size CTCs on two coupled microfluidic devices. Cancer cells were purified through a Vortex chip and subsequently flowed in-line to an impedance chip, where a pair of electrodes measured fluctuations of an applied electric field generated by cells passing through. A proof-of-concept of the coupling of those two devices was demonstrated with beads and cells. First, the impedance chip was tested as a stand-alone device: (1) with beads (mean counting error of 1.0%, sizing information clearly separated three clusters for 8, 15, and 20 um beads, respectively) as well as (2) with cancer cells (mean counting error of 3.5%). Second, the combined setup was tested with beads, then with cells in phosphate-buffered saline, and finally with cancer cells spiked in healthy blood. Experiments demonstrated that the Vortex HT chip enriched the cancer cells, which then could be counted and differentiated from smaller blood cells by the impedance chip based on size information. Further discrimination was shown with dual high-frequency measurements using electric opacity, highlighting the potential application of this combined setup for a fully integrated label-free isolation and enumeration of CTCs from cancer patient samples. (c) 2019 International Society for Advancement of Cytometr

LIPE-related lipodystrophic syndrome: clinical features and disease modeling using adipose stem cells

International audienceObjective: The term Multiple Symmetric Lipomatosis (MSL) describes a heterogeneous group of rare monogenic disorders and multifactorial conditions, characterized by upper-body adipose masses. Biallelic variants in LIPE encoding hormone-sensitive lipase (HSL), a key lipolytic enzyme, were implicated in three families worldwide. We aimed to further delineate LIPE-related clinical features and pathophysiological determinants.Methods: A gene panel was used to identify pathogenic variants. The disease features were reviewed at the French lipodystrophy reference center. The immunohistological, ultrastructural, and protein expression characteristics of lipomatous tissue were determined in surgical samples from one patient. The functional impact of variants was investigated by developing a model of adipose stem cells (ASCs) isolated from lipomatous tissue.Results: We identified new biallelic LIPE null variants in three unrelated patients referred for MSL and/or partial lipodystrophy. The hallmarks of the disease, appearing in adulthood, included lower-limb lipoatrophy, upper-body and abdominal pseudo-lipomatous masses, diabetes and/or insulin resistance, hypertriglyceridemia, liver steatosis, high blood pressure, and neuromuscular manifestations. Ophthalmological investigations revealed numerous auto-fluorescent drusen-like retinal deposits in all patients. Lipomatous tissue and patient ASCs showed loss of HSL and decreased expression of adipogenic and mature adipocyte markers. LIPE-mutated ASCs displayed impaired adipocyte differentiation, decreased insulin response, defective lipolysis, and mitochondrial dysfunction.Conslusions: Biallelic LIPE null variants result in a multisystemic disease requiring multidisciplinary care. Loss of HSL expression impairs adipocyte differentiation, consistent with the lipodystrophy/MSL phenotype and associated metabolic complications. Detailed ophthalmological examination could reveal retinal damage, further pointing to the nervous tissue as an important disease target

Apathy in depression: An arterial spin labeling perfusion MRI study

International audienceIntroductionApathy, as defined as a deficit in goal-directed behaviors, is a critical clinical dimension in depression associated with chronic impairment. Little is known about its cerebral perfusion specificities in depression. To explore neurovascular mechanisms underpinning apathy in depression by pseudo-continuous arterial spin labeling (pCASL) magnetic resonance imaging (MRI).MethodsPerfusion imaging analysis was performed on 90 depressed patients included in a prospective study between November 2014 and February 2017. Imaging data included anatomical 3D T1-weighted and perfusion pCASL sequences. A multiple regression analysis relating the quantified cerebral blood flow (CBF) in different regions of interest defined from the FreeSurfer atlas, to the Apathy Evaluation Scale (AES) total score was conducted.ResultsAfter confound adjustment (demographics, disease and clinical characteristics) and correction for multiple comparisons, we observed a strong negative relationship between the CBF in the left anterior cingulate cortex (ACC) and the AES score (standardized beta = −0.74, corrected p value = 0.0008).ConclusionOur results emphasized the left ACC as a key region involved in apathy severity in a population of depressed participants. Perfusion correlates of apathy in depression evidenced in this study may contribute to characterize different phenotypes of depression

Type 1 Diabetes in People Hospitalized for COVID-19: New Insights From the CORONADO Study

International audienc

The association between macrovascular complications and intensive care admission, invasive mechanical ventilation, and mortality in people with diabetes hospitalized for coronavirus disease-2019 (COVID-19)

International audienceAbstract Background It is not clear whether pre-existing macrovascular complications (ischemic heart disease, stroke or peripheral artery disease) are associated with health outcomes in people with diabetes mellitus hospitalized for COVID-19. Methods We conducted cohort studies of adults with pre-existing diabetes hospitalized for COVID-19 infection in the UK, France, and Spain during the early phase of the pandemic (between March 2020—October 2020). Logistic regression models adjusted for demographic factors and other comorbidities were used to determine associations between previous macrovascular disease and relevant clinical outcomes: mortality, intensive care unit (ICU) admission and use of invasive mechanical ventilation (IMV) during the hospitalization. Output from individual logistic regression models for each cohort was combined in a meta-analysis. Results Complete data were available for 4,106 (60.4%) individuals. Of these, 1,652 (40.2%) had any prior macrovascular disease of whom 28.5% of patients died. Mortality was higher for people with compared to those without previous macrovascular disease (37.7% vs 22.4%). The combined crude odds ratio (OR) for previous macrovascular disease and mortality for all four cohorts was 2.12 (95% CI 1.83–2.45 with an I 2 of 60%, reduced after adjustments for age, sex, type of diabetes, hypertension, microvascular disease, ethnicity, and BMI to adjusted OR 1.53 [95% CI 1.29–1.81]) for the three cohorts. Further analysis revealed that ischemic heart disease and cerebrovascular disease were the main contributors of adverse outcomes. However, proportions of people admitted to ICU (adjOR 0.48 [95% CI 0.31–0.75], I 2 60%) and the use of IMV during hospitalization (adjOR 0.52 [95% CI 0.40–0.68], I 2 37%) were significantly lower for people with previous macrovascular disease. Conclusions This large multinational study of people with diabetes mellitus hospitalized for COVID-19 demonstrates that previous macrovascular disease is associated with higher mortality and lower proportions admitted to ICU and treated with IMV during hospitalization suggesting selective admission criteria. Our findings highlight the importance correctly assess the prognosis and intensive monitoring in this high-risk group of patients and emphasize the need to design specific public health programs aimed to prevent SARS-CoV-2 infection in this subgroup