Enquête nationale sur la prévalence des troubles mentaux en Égypte : étude préliminaire RÉSUMÉ Cette étude constitue une première étape de l'enquête nationale sur la prévalence des troubles mentaux en Égypte. Nous avons réalisé une enquête auprès des ménages par porte à porte dans cinq régions d'Égypte et avons interrogé 14 640 adultes âgés de 18 à 64 ans. Les troubles mentaux ont été diagnostiqués sur la base de l'interrogatoire MINI-Plus. La prévalence globale a été estimée à 16,93 % de la population adulte étudiée. Les principaux problèmes étaient des troubles de l'humeur (6,43 %), des troubles anxieux (4,75 %) et des troubles multiples (4,72 %). Les troubles mentaux étaient associés à des facteurs sociodémographiques (par exemple le fait d'être une femme, de ne pas avoir de travail et d'être divorcé) et à des maladies physiques (par exemple une cardiopathie, une maladie rénale ou une hypertension).

Identifying cancer predisposition syndromes in children with tumors is crucial, yet few clinical guidelines exist to identify children at high risk of having germline mutations. The McGill Interactive Pediatric OncoGenetic Guidelines project aims to create a validated pediatric guideline in the form of a smartphone/tablet application using algorithms to process clinical data and help determine whether to refer a child for genetic assessment. This paper discusses the initial stages of the project, focusing on its overall structure, the methodology underpinning the algorithms, and the upcoming algorithm validation process.

Key PointsEngineered human models of high-fatality pediatric leukemia are relevant to uncover disease biomarkers and therapeutic vulnerabilities. NUP98-KDM5A–associated AMKL expresses SELP, MPIG6B, and NEO1 biomarkers and is sensitive to pharmacologic inhibition with ruxolitinib.

Over 10% of children with Wilms tumor (WT) have an underlying cancer predisposition syndrome (CPS). Cognizant of increasing demand for genetic evaluation and limited resources across health care settings, there is an urgent need to rationalize genetic referrals for this population. The McGill Interactive Pediatric OncoGenetic Guidelines study, a Canadian multi‐institutional initiative, aims to develop an eHealth tool to assist physicians in identifying children at elevated risk of having a CPS. As part of this project, a decisional algorithm specific to WT consisting of five tumor‐specific criteria (age <2 years, bilaterality/multifocality, stromal‐predominant histology, nephrogenic rests, and overgrowth features) and universal criteria including features of family history suspicious for CPS and congenital anomalies, was developed. Application of the algorithm generates a binary recommendation—for or against genetic referral for CPS evaluation. To evaluate the algorithm's sensitivity for CPS identification, we retrospectively applied the tool in consecutive pediatric patients (n = 180) with WT, diagnosed and/or treated at The Hospital for Sick Children (1997–2016). Odds ratios were calculated to evaluate the strengths of associations between each criterion and specific CPS subtypes. Application of the algorithm identified 100% of children with WT and a confirmed CPS (n = 27). Age <2 years, bilaterality/multifocality, and congenital anomalies were strongly associated with pathogenic variants in WT1. Presence of >1 overgrowth feature was strongly associated with Beckwith‐Wiedemann syndrome. Stromal‐predominant histology did not contribute to CPS identification. We recommend the incorporation of the WT algorithm in the routine assessment of children with WT to facilitate prioritization of genetic referrals in a sustainable manner.

No abstract

Pediatric acute myeloid leukemia (AML) is a heterogeneous disease that requires a multifaceted treatment approach. Although outcomes for low-risk AML have improved significantly over recent decades, high-risk AML continues to be associated with an adverse prognosis. Recent advances in molecular diagnostics, risk stratification, and supportive care have contributed to improvements in outcomes in pediatric AML. Targeted approaches, for example, the use of tyrosine kinase inhibitors to treat FLT3-ITD AML, offer promise and are currently undergoing clinical investigation in pediatric patients. New approaches to hematopoietic stem cell transplantation, including the use of haploidentical donors, are significantly expanding donor options for patients with high-risk AML. This review provides an overview of recent advances in the treatment of pediatric AML that are likely to have clinical impact and reshape the standard of care. K E Y W O R D Sacute myeloid leukemia, childhood AML, HSCT, pediatric AML Historically, risk stratification rested on blast morphology and cytogenetics. Improvement of cytogenetic techniques, flow cytometry, and introduction of molecular techniques, such as targeted sequencing and the detection of fusion transcripts, have identified a larger number of prognostic markers. 5 A summary is shown in Table 1. Mutations of uncertain prognostic significance in pediatric AML include point mutations targeting the c-KIT receptor tyrosine kinase and the FLT3

Shwachman-Diamond syndrome (SDS) is a rare and systemic disease mostly caused by mutations in the SBDS gene and characterized by pancreatic insufficiency, skeletal abnormalities, and a bone marrow dysfunction. In addition, SDS patients are predisposed to develop myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), typically during adulthood and associated with TP53 mutations. Although most SDS diagnoses are established in childhood, the nature and frequency of serial bone marrow cell investigations during the patients' lifetime remain a debatable topic. The precise molecular mechanisms leading to AML progression in SDS patients have not been fully elucidated because the patient cohorts are small and most disease monitoring is conducted using standard histological and cytogenetic approaches. Here we report a rare case of a patient with SDS who was diagnosed with AML at 5 years of age and survived. Intermittent neutropenia preceded the AML diagnostic but serial bone marrow monitoring according to the standard of care revealed no cytogenetic anomalies nor signs of clonal hematopoiesis. Using next generation sequencing approaches to find cytogenetically cryptic pathogenic mutations, we identified the cancer hotspot mutation c.394C>T/p.Arg132Cys in IDH1 with high variant allelic frequency in bone marrow cells, suggesting clonal expansion of a major leukemic clone karyotypically normal, in the SDS-associated AML. The mutation was somatic and likely occurred at the leukemic transformation stage, as it was not detected in a matched normal tissue nor in bone marrow smear prior to AML diagnosis. Gain-of-function mutations in IDH1 , such as c.394C>T/p.Arg132Cys, create a neo-activity of isocitrate dehydrogenase 1 converting α-ketoglutarate into the oncometabolite D-2-hydroxyglutarate, inhibiting α-ketoglutarate-dependent enzymes, such as histone and DNA demethylases. Overall, our results suggest that along with previously described abnormalities such as TP53 mutations or monosomy7, 7q-, which are all absent in this patient, additional mechanisms including IDH1 mutations drive SDS-related AML and are likely associated with variable outcomes. Sensitive techniques complementary to standard cytogenetics, such as unbiased or targeted panel-based next generation sequencing approaches, warrant testing for monitoring of myelodysplasia, clonal hematopoiesis, and leukemia in the context SDS. Such analyses would also assist treatment decisions and allow to gain insight into the disease biology.

In the chinchilla, when a tympanic perforation is present, almond oil does not seem to cause ototoxicity. Further studies are needed to better assess the effect of almond oil on hearing in humans.