A micro-bead device to explore Plasmodium falciparum-infected, spherocytic or aged red blood cells prone to mechanical retention by spleen endothelial slits

Présentation oraleInternational audiencen.

A functionally impaired missense variant identified in French Canadian families implicates FANCI as a candidate ovarian cancer-predisposing gene.

BACKGROUND: Familial ovarian cancer (OC) cases not harbouring pathogenic variants in either of the BRCA1 and BRCA2 OC-predisposing genes, which function in homologous recombination (HR) of DNA, could involve pathogenic variants in other DNA repair pathway genes. METHODS: Whole exome sequencing was used to identify rare variants in HR genes in a BRCA1 and BRCA2 pathogenic variant negative OC family of French Canadian (FC) ancestry, a population exhibiting genetic drift. OC cases and cancer-free individuals from FC and non-FC populations were investigated for carrier frequency of FANCI c.1813C>T; p.L605F, the top-ranking candidate. Gene and protein expression were investigated in cancer cell lines and tissue microarrays, respectively. RESULTS: In FC subjects, c.1813C>T was more common in familial (7.1%, 3/42) than sporadic (1.6%, 7/439) OC cases (P = 0.048). Carriers were detected in 2.5% (74/2950) of cancer-free females though female/male carriers were more likely to have a first-degree relative with OC (121/5249, 2.3%; Spearman correlation = 0.037; P = 0.011), suggesting a role in risk. Many of the cancer-free females had host factors known to reduce risk to OC which could influence cancer risk in this population. There was an increased carrier frequency of FANCI c.1813C>T in BRCA1 and BRCA2 pathogenic variant negative OC families, when including the discovery family, compared to cancer-free females (3/23, 13%; OR = 5.8; 95%CI = 1.7-19; P = 0.005). In non-FC subjects, 10 candidate FANCI variants were identified in 4.1% (21/516) of Australian OC cases negative for pathogenic variants in BRCA1 and BRCA2, including 10 carriers of FANCI c.1813C>T. Candidate variants were significantly more common in familial OC than in sporadic OC (P = 0.04). Localization of FANCD2, part of the FANCI-FANCD2 (ID2) binding complex in the Fanconi anaemia (FA) pathway, to sites of induced DNA damage was severely impeded in cells expressing the p.L605F isoform. This isoform was expressed at a reduced level, destabilized by DNA damaging agent treatment in both HeLa and OC cell lines, and exhibited sensitivity to cisplatin but not to a poly (ADP-ribose) polymerase inhibitor. By tissue microarray analyses, FANCI protein was consistently expressed in fallopian tube epithelial cells and only expressed at low-to-moderate levels in 88% (83/94) of OC samples. CONCLUSIONS: This is the first study to describe candidate OC variants in FANCI, a member of the ID2 complex of the FA DNA repair pathway. Our data suggest that pathogenic FANCI variants may modify OC risk in cancer families

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/)

MISE AU POINT DE MILIEUX DE CULTURE SELECTIFS ET ETUDE EPIDEMIOLOGIQUE DU PORTAGE DE BACTERIES MULTIRESISTANTES CHEZ LES PATIENTS ADMIS DANS LE SERVICE DE REANIMATION DU CENTRE HOSPITALIER DE TOURCOING (DES BIOL. MED.)

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Dyserythropoïèse acquise et anémie hémolytique auto-immune:à propos de 6 cas pédiatriques

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Hereditary Spherocytosis: Indication of splenectomy and its long-term complications

International audienceHereditary spherocytosis (HS) is the most frequent cause of constitutional hemolytic anemia among Caucasians. It is due to a quantitative or qualitative defect of some of the proteins composing the skeleton of the red blood cell membrane. Destabilization of this membrane causes spherisation of the red blood cells and hemolysis, occurring mainly in the spleen. Splenectomy is consequently very efficient in this disease. Recent guidelines aimed at defining the place of splenectomy in HS: it is always indicated in severe cases, preferentially after the age of 6 years old; it should be discussed in mild presentations, and is never indicated in asymptomatic cases. Subtotal splenectomy may be an interesting option in children under 6 years old with severe presentation, but its place is not well defined yet. However, splenectomy is associated with long-term complications. Infectious complications are well known, and can be prevented with vaccination, education of the patient and his family, and with the systematic use of prophylactic antibiotics after splenectomy. It is noteworthy that the risk of overwhelming post-splenectomy infection persists all life long in splenectomized patients. There is also an increased thrombo embolic risk after splenectomy, including early splenic and portal thrombosis (often asymptomatic), and delayed arterial or venous events. A slightly increased risk of cancer has also been described in splenectomized patients, but this is still controversial, and has not been studied specifically in HS patients. All these complications should be taken into account when a splenectomy is discussed, but keeping in mind its clear benefits in symptomatic forms of HS

Treatment of Erdheim–Chester disease with canakinumab

International audienc

Un rare cas de céramique commune saintongeaise signée: les jattes à collerette Santrot

International audienc