Congenital hydrocephalus : new Mendelian mutations and evidence for oligogenic inheritance

Peer reviewe

Genotype-phenotype relationships of truncating mutations, p.E297G and p.D482G in bile salt export pump deficiency

Background & Aims: Bile salt export pump (BSEP) deficiency frequently necessitates liver transplantation in childhood. Homozygous p.D482G or p.E297G mutations are associated with relatively mild phenotypes, responsive to surgical interruption of the enterohepatic circulation (siEHC), in contrast to patients with two predicted protein truncating mutations (PPTM). The phenotype of patients with a compound heterozygous genotype of one p.D482G or p.E297G mutation and one PPTM has remained unclear. We aimed to assess their genotype-phenotype relationship. Methods: From the NAPPED database, we selected patients with homozygous p.D482G or p.E297G mutations (BSEP1/1; n=31), with one p.D482G or p.E297G, and one PPTM (BSEP1/3; n=30), and with two PPTMs (BSEP3/3; n=77). We compared presentation, native liver survival (NLS), and effect of siEHC on NLS. Results: The groups had a similar median age at presentation (0.7-1.3 years). Overall NLS at age 10 years was 21% in BSEP1/3 vs. 75% in BSEP1/1 and 23% in BSEP3/3 (P<0.001). Without siEHC in their follow-up, NLS of BSEP1/3 was similar to BSEP3/3 patients, but considerably lower than BSEP1/1 patients (at age 10 years: 38%, 30%, and 71%, resp; P=0.003). After siEHC, BSEP1/3 and BSEP3/3 patients had similarly low NLS, while this was much higher in BSEP1/1 patients (10 years after siEHC, 27%, 14%, and 92%, resp.; P<0.001). Conclusions: BSEP deficiency patients with one p.E297G or p.D482G mutation and one PPTM have a similarly severe disease course and low responsiveness to siEHC as patients with two PPTMs. This identifies a considerable subgroup of patients who are unlikely to benefit from interruption of the enterohepatic circulation by either surgical or ileal bile acid transporter inhibitor treatment

Dynamic Cancer Cell Heterogeneity: Diagnostic and Therapeutic Implications

Though heterogeneity of cancers is recognized and has been much discussed in recent years, the concept often remains overlooked in different routine examinations. Indeed, in clinical or biological articles, reviews, and textbooks, cancers and cancer cells are generally presented as evolving distinct entities rather than as an independent heterogeneous cooperative cell population with its self-oriented biology. There are, therefore, conceptual gaps which can mislead the interpretations/diagnostic and therapeutic approaches. In this short review, we wish to summarize and discuss various aspects of this dynamic evolving heterogeneity and its biological, pathological, clinical, diagnostic, and therapeutic implications, using thyroid carcinoma as an illustrative example

L'hémophilie acquise (à propos de trois cas)

L'hémophilie acquise est une affection rare, liée au développement d'un autoanticorps dirigé contre le facteur VIII de la coagulation, caractérisée par la survenue de complications hémorragiques. Nous rapportons trois observations d'hémophilie acquise survenant chez des hommes âgés de 80 ans, polymédiqués dont deux étaient sous traitement antiagrégants ou anticoagulants. L'hémophilie acquise était associée à d'autres conditions dans deux de nos cas (maladie de Horton et gammapathie monoclonale de signification indéterminée ; diabète) et idiopathique dans un autre cas. Nous observons deux décès. La prise en charge des épisodes hémorragiques inclue les traitements par rFVIIa, FVIII humains, concentrés érythrocytaires et de plasma. L'éradication de l'autoanticorps anti-FVIII a fait appel aux corticoïdes et à l'association corticoïdes-cyclophosphamide. L'étude de ces cas cliniques permet de refaire le point sur les données épidémiologiques, diagnostiques, étiologiques et thérapeutiques de cette pathologie.GRENOBLE1-BU Médecine pharm. (385162101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Lockdown in France: Impact on Families of Young Children With Special Needs

International audienceBackground Families with young children have faced serious challenges during the first lockdown as a result of the COVID-19 pandemic. In addition to remote working, parents have had to monitor their children’s schoolwork and manage their daily lives. When one of the children also has neuro-developmental disorders, this results in an increased burden. We can therefore wonder how these families with one or more young children (under 6 years old) with special needs have experienced and dealt with this lockdown. Aim of the Study In this context, the “COVJEUNENFANT” study focused more specifically on the subjective experience, as a parent, of those who cared for children with special needs (i.e., with developmental disorders, neurodevelopmental disorders, proven disabilities or chronic health conditions) compared to the general population. We wished to see if the consequences of the health crisis were significantly different from those perceived by respondents in the general population ( n = 490) and if the sociodemographic structure of these families differed from those of other respondents. Methods Ninety three French families with at least one child under 6 years old and one with developmental difficulties or a chronic illness, from a cohort of 490 control families, participated in a web-based survey during the first lockdown, from the 28th April 2020 to 29th May 2020. Results After presenting the participants’ sociodemographic characteristics, the results show that these French families ( n = 93) are less wealthy than the control population “without special needs” ( n = 397), have felt more pressures originating from their environment (families, friends, colleagues, media, social networks…), have suffered from more health issues (other than COVID-19), have taken more measures to protect themselves (social-distancing), and were less likely to feel happy. A significantly larger number of them lamented the lack of free time and voiced a larger need for information regarding children’s education. However, their parental role was felt as being more satisfying and their family relations strengthened more than in the general population of participants. Conclusion It is apparent that urgent prioritisation is needed in order to support and care for these families by continuing to provide care for their children in one way or another, and by ensuring that their need to adapt again does not exceed their own abilities and resources, especially as young children, who have high levels of requirements, are present in the home

Questionnaire as an alternative of skin prick tests to differentiate allergic from non-allergic rhinitis in epidemiological studies

National audienc

Visible moulds, smoking, rhinitis and asthma in adults: the EGEA study

International audienc

Visible moulds, non-allergic and allergic rhinitis and asthma in adults: the EGEA study

International audienc

Long-term air pollution exposure, greenness and health-related quality of life (HRQOL) in ECRHS

International audienc