In vivo dissection of the mouse tyrosine catabolic pathway with CRISPR-Cas9 identifies modifier genes affecting hereditary tyrosinemia type 1.

Hereditary tyrosinemia type 1 is an autosomal recessive disorder caused by mutations (pathogenic variants) in fumarylacetoacetate hydrolase, an enzyme involved in tyrosine degradation. Its loss results in the accumulation of toxic metabolites that mainly affect the liver and kidneys and can lead to severe liver disease and liver cancer. Tyrosinemia type 1 has a global prevalence of approximately 1 in 100,000 births but can reach up to 1 in 1,500 births in some regions of Québec, Canada.

Identification of divergent placental profiles in clinically distinct pregnancy complications revealed by the transcriptome.

Introduction: Pregnancy complications, including preeclampsia (PE), preterm birth (PTB), and intra-uterine growth restriction (IUGR) have individually been associated with inflammation but the combined comparative analysis of their placental profiles at the transcriptomic and histological levels is lacking.

Methods: Bulk RNA-sequencing of human placental biopsies from uncomplicated term pregnancies (CTL) and pregnancies complicated with early-onset (EO), and late-onset (LO) PE, as well as PTB and term IUGR were used to characterize individual molecular profiles. We also applied immune-cell-specific cellular deconvolution to address local immune cell compositions and analyzed placental lesions by histology to further characterize these complications.

Placenta analysis of Hofbauer cell profile according to the class of antiretroviral therapy used during pregnancy in people living with HIV.

Introduction: The use of antiretroviral therapy drastically reduces vertical transmission of Human Immunodeficiency Virus. However, recent studies demonstrate associations between ART use during pregnancy and placental inflammation, particularly within protease inhibitor (PI)-based regimens. We sought to characterize placental macrophages, namely Hofbauer cells, according to the class of ART used during pregnancy.

Phenotype and outcomes of very early onset and early onset inflammatory bowel diseases in a Montreal pediatric cohort.

Objectives: The incidence of very-early-onset inflammatory bowel disease (VEO-IBD) and early-onset IBD (EO-IBD) is increasing. Here, we report their phenotype and outcomes in a Montreal pediatric cohort.

Methods: We analyzed data from patients diagnosed with IBD between January 2014 and December 2018 from the CHU Sainte-Justine.

Mediators of inflammation at the maternal-fetal interface are altered by SARS-CoV-2 infection and pandemic stress.

Problem: It is now recognized that SARS-CoV-2 infection and pandemic-related stress impacts maternal health. However, their effects at the maternal-fetal interface are still debated.

Method Of Study: We recruited 199 women between March 2020 and July 2021, 79 SARS-CoV-2+ and 120 negative (the latter exposed to pandemic stress only).

Evaluation of a clinical protocol for the management of fever in labor among pregnant women at term: A quality-improvement study.

Objective: To assess the impact of a quality-improvement initiative designed to increase diagnostic accuracy and adequate management of clinical chorioamnionitis (CC) at a tertiary center. Chorioamnionitis occurs in 1%-13% of term pregnancies and increases maternal and neonatal peripartum complications; often over-diagnosed, it leads to unnecessary investigations and treatments.

Methods: This was an interrupted time-series study.

β Cell mass expansion during puberty involves serotonin signaling and determines glucose homeostasis in adulthood.

Puberty is associated with transient insulin resistance that normally recedes at the end of puberty; however, in overweight children, insulin resistance persists, leading to an increased risk of type 2 diabetes. The mechanisms whereby pancreatic β cells adapt to pubertal insulin resistance, and how they are affected by the metabolic status, have not been investigated. Here, we show that puberty is associated with a transient increase in β cell proliferation in rats and humans of both sexes.

Autologous humanized mouse models of iPSC-derived tumors enable characterization and modulation of cancer-immune cell interactions.

Modeling the tumor-immune cell interactions in humanized mice is complex and limits drug development. Here, we generated easily accessible tumor models by transforming either primary skin fibroblasts or induced pluripotent stem cell-derived cell lines injected in immune-deficient mice reconstituted with human autologous immune cells. Our results showed that fibroblastic, hepatic, or neural tumors were all efficiently infiltrated and partially or totally rejected by autologous immune cells in humanized mice.

Impact of Congenital Heart Defects on the Developing Brain.

Objectives: Congenital heart defects (CHD) are responsible for neurodevelopmental delays that were initially attributed to brain injury resulting from cardiac surgery. However, prenatal imaging have shown that brain anomalies are present at birth. The aim of this study was to assess brain injuries before birth in fetuses/neonates with congenital cardiopathies.

Risk Factors of Clinical Relapses in Pediatric Luminal Crohn's Disease: A Retrospective Cohort Study.

Introduction: There is currently little knowledge on factors associated with the relapse of Crohn's disease (CD) in children. The aims of this study were to describe the risk factors associated with relapse in pediatric CD and the changes in the relapse rate over the past decade.

Methods: Patients younger than 18 years and diagnosed between 2009 and 2019 were included in this retrospective cohort study.

Factors associated with time to clinical remission in pediatric luminal Crohn's disease: A retrospective cohort study.

Background And Aim: Data on factors influencing time to remission in pediatric Crohn's disease (CD) are very limited in the literature. The aim of this retrospective cohort study was to describe the trends of time to clinical remission over the past decade and to identify factors associated with time to clinical remission in children with luminal CD.

Methods: Patients under 18 years old diagnosed between 2009 and 2019 were included.

Association between proteinuria and placental pathology in preeclampsia: A retrospective study.

Introduction: Preeclampsia develops due to placental insufficiency and systemic proinflammatory and antiangiogenic mediator release, with ensuing systemic endothelial dysfunction. Nephrotic-range proteinuria appears to be associated with worse pregnancy outcomes. The relationship between differing degrees of proteinuria and the severity of placental alterations has not been studied.

Changes in the clinical phenotype and behavior of pediatric luminal Crohn's disease at diagnosis in the last decade.

Background And Aims: The aims of this study were to describe the trends in the behavior of pediatric CD during the last decade and to describe the seasonal variation of disease presentation.

Methods: Patients under 18 years old and diagnosed between 2009 and 2019 were included. The clinical, endoscopic, histological, and laboratory data were collected from the medical records.

Molecular Profiling of Hard-to-Treat Childhood and Adolescent Cancers.

Importance: Little progress in pediatric cancer treatment has been noted in the past decade, urging the development of novel therapeutic strategies for adolescents and children with hard-to-treat cancers. Use of comprehensive molecular profiling in the clinical management of children and adolescents with cancer appears a suitable approach to improve patient care and outcomes, particularly for hard-to-treat cases.

Objective: To assess the feasibility of identifying potentially actionable mutations using next-generation sequencing-based assays in a clinically relevant time frame.

Rapamycin as an Adjunctive Therapy for NLRC4 Associated Macrophage Activation Syndrome.

Gain of function (GOF) mutations affecting the inflammasome component NLRC4 are known to cause early-onset macrophage activation syndrome (MAS) and neonatal enterocolitis. Here we report a patient with a NLRC4 GOF mutation presenting with neonatal MAS efficiently treated with a combination of anakinra and rapamycin. Through studies, we show that rapamycin reduces both IL-1β and IL-18 secretion by the patient's phagocytic cells.

[All large necrotic and hemorrhagic kidney tumors in children are not necessarily malignant: A case of a 7-month-old child].

We report the case of a large tumor in the left kidney with necrotic and hemorrhagic features in a 7-month-old child, which was clinically and radiologically suggestive of a nephroblastoma. The tumor was a nodular mass measuring 8cm in diameter occupying two thirds of the kidney and presenting areas of necrosis and hemorrhage. No capsular rupture or renal sinus infiltration were found.

Intestinal Metaplasia of the Esophagus in Children With Esophageal Atresia.

Objectives: Patients with esophageal atresia/tracheoesophageal fistula (EA-TEF) can develop Barrett esophagus as a long-term consequence of their condition. Intestinal metaplasia (IM), a risk factor for developing adenocarcinoma of the esophagus, has not been well characterized in the pediatric population.

Methods: Retrospective review of patients with EA-TEF followed at 3 academic pediatric centers between the years 1997 and 2014.

Revisiting Pathological Criteria for Earlier Diagnosis of Coeliac Disease.

Objectives: The diagnosis of coeliac disease (CD) remains sometimes difficult because the histological criteria are not fully met. The aim of this study was to refine histological diagnostic criteria of CD.

Methods: One hundred seventy-five duodenal bulb D1 (n = 79) and duodenal D2 (n = 96) biopsies of 96 patients with CD (58 girls, mean age 7 years), 135 normal D2 biopsies (69 girls, mean age 12 years), and 64 D2 biopsies of other digestive disorders (DDs) (39 girls, mean age 13 years) obtained from children during a period of 4 years were reviewed.

Juvenile respiratory papillomatosis: risk factors for severity.

Juvenile recurrent respiratory papillomatosis is caused mainly by human papillomavirus genotypes 6 or 11, acquired at birth or during pregnancy from an infected mother. Recurrent respiratory papillomatosis is characterized by recurring warts growing most commonly in the larynx. Multiple surgical procedures and the risk of airway obstruction contribute to the devastating impact of this disease.