Breastmilk is known to be very important for infants because it provides nutrients and immunological compounds. Among these compounds, human milk oligosaccharides (HMOs) represent the third most ...important component of breastmilk after lipids and lactose. Several experiments demonstrated the beneficial effects of these components on the microbiota, the immune system and epithelial barriers, which are three major biological systems. Indeed, HMOs induce bacterial colonization in the intestinal tract, which is beneficial for health. The gut bacteria can act directly and indirectly on the immune system by stimulating innate immunity and controlling inflammatory reactions and by inducing an adaptive immune response and a tolerogenic environment. In parallel, HMOs directly strengthen the intestinal epithelial barrier, protecting the host against pathogens. Here, we review the molecular mechanisms of HMOs in these different compartments and highlight their potential use as new therapeutic agents, especially in allergy prevention.
Large congenital melanocytic nevi (LCMN) are defined as congenital melanocytic nevi having a projected adult size exceeding 20 cm in diameter. They occur in 1 in 20,000 to 1 in 500,000 newborns. ...Therapeutic management of LCMN remains controversial and is often decided according to melanoma risk.
We sought to synthesize all data available on LCMN-associated melanoma risk, therapeutic assessment, and psychosocial and aesthetic impacts.
A MEDLINE search was conducted (1966-February 2011), and 22 French- and English-language databases were consulted. Case reports and reviews were excluded, as were studies with fewer than 20 patients and insufficient information about the nevi. Studies were qualitatively assessed and analyzed according to predefined criteria.
Fourteen studies were selected (956 references). A total of 52 (2%) melanomas (2 in 1 patient) developed in 2578 patients. Age at diagnosis ranged from birth to 58 (mean 12.6) years. Primary melanomas were mostly cutaneous (82%) and 68% were located on the trunk; 7 melanomas were visceral. Melanoma-associated LCMN size exceeded 40 cm for 74% and 94% had satellite nevi. Of melanomas, 55% were fatal, with age at death ranging from 0.9 to 40 (mean 10) years. Eighteen patients were still alive with a mean follow-up of 10.2 years. Melanoma incidence assessable for 216 cases was estimated at 2.3 per 1000 patient-years. Behavioral/emotional problems independent of the lesion were common in children.
Selected studies were heterogeneous.
LCMN management should be individualized with respect to melanoma risk, and aesthetic and psychosocial aspects.
Asthma, atopic dermatitis and chronic rhinoconjunctivitis are highly heterogeneous. However, epidemiologic associations exist between phenotypic groups of patients. Atopic march is one such ...association but is not the only common point. Indeed, beyond such phenotypes, hallmarks of type 2 immunity have been found in these diseases involving immune dysregulation as well as environmental triggers and epithelial dysfunction. From the canonical Th2 cytokines (IL‐4, IL‐5, IL‐13), new cellular and molecular actors arise, from the epithelium's alarmins to new innate immune cells. Their interactions are now better understood across the different environmental barriers, and slight differences appeared. In parallel, the development of type 2‐targeting biotherapies not only raised hope to treat those diseases but also raised new questions regarding their true pathophysiological involvement. Here, we review the place of type 2 immunity in the different phenotypes of asthma, chronic rhinitis, chronic rhinosinusitis and atopic dermatitis, highlighting nuances between them. New hypotheses rising from the use of biotherapies will be discussed along with the uncertainties and unmet needs of this field.
Heterogenic diseases as asthma, atopic dermatitis and chronic rhinosinusitis with nasal polyposis can be divided into multiple phenotypes. Such clinical presentations share common pathophysiological paths among with type 2 immunity play an important role. Better understanding of the mechanisms underlying type 2 responses allowed the successful development of specific therapeutic strategies. Indeed, biotherapies are now available to target key actors like the immunoglobulin E, the interleukin (IL) 5, the IL‐4 and IL‐13 pathway and more recently, the thymic stromal lymphopoietin. Even though those innovations improve the healthcare of type‐2 mediated diseases, unmet needs remain to be resolved. Graphic created with BioRender.com
Dupilumab subcutaneous injection is approved for treating moderate-to-severe atopic dermatitis (AD) in adolescents, but there has been too little research on an efficacious systemic oral treatment ...with a favorable benefit-risk profile for adolescents with moderate-to-severe AD.
To investigate the efficacy and safety of oral abrocitinib plus topical therapy in adolescents with moderate-to-severe AD.
The phase 3, randomized, double-blind, placebo-controlled study JADE TEEN was conducted in countries of the Asia-Pacific region, Europe, and North America in patients aged 12 to 17 years with moderate-to-severe AD and an inadequate response to 4 consecutive weeks or longer of topical medication or a need for systemic therapy for AD. The study was conducted between February 18, 2019, and April 8, 2020. The data were analyzed after study completion.
Patients were randomly assigned 1:1:1 to receive once-daily oral abrocitinib, 200 mg or 100 mg, or placebo for 12 weeks in combination with topical therapy.
Coprimary end points were achievement of an Investigator's Global Assessment (IGA) response of clear (0) or almost clear (1) with improvement of 2 or more grades from baseline (IGA 0/1) and 75% or greater improvement from baseline in Eczema Area and Severity Index (EASI-75) response at week 12. Key secondary end points included 4-point or greater improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4) at week 12. Adverse events (AEs) were monitored.
This study included 285 adolescents with moderate-to-severe AD (145 boys 50.9% and 140 girls 49.1%), of whom 160 (56.1%) were White and 94 (33.0%) were Asian; the median age was 15 years (interquartile range 13-17 years). Substantially more patients treated with abrocitinib (200 mg or 100 mg) vs placebo achieved an IGA response of 0/1 (46.2%; 41.6% vs 24.5%; P < .05 for both), EASI-75 (72.0%; 68.5% vs 41.5%; P < .05 for both), and PP-NRS4 (55.4%; 52.6% vs 29.8%; P < .01 for 200 mg vs placebo) at week 12. Adverse events were reported for 59 (62.8%), 54 (56.8%), and 50 (52.1%) patients in the 200 mg, 100 mg, and placebo groups, respectively; nausea was more common with abrocitinib, 200 mg (17 18.1%) and 100 mg (7 7.4%). Herpes-related AEs were infrequent; 1 (1.1%), 0, and 2 (2.1%) patients had serious AEs.
This randomized clinical trial found that oral abrocitinib combined with topical therapy was significantly more effective than placebo with topical therapy in adolescents with moderate-to-severe AD, with an acceptable safety profile.
ClinicalTrials.gov identifier: NCT03796676.
Allergic diseases now affect over 30% of individuals in many communities, particularly young children, underscoring the need for effective prevention strategies in early life. These allergic ...conditions have been linked to environmental and lifestyle changes driving the dysfunction of three interdependent biological systems: microbiota, epithelial barrier and immune system. While this is multifactorial, dietary changes are of particular interest in the altered establishment and maturation of the microbiome, including the associated profile of metabolites that modulate immune development and barrier function. Prebiotics are non-digestible food ingredients that beneficially influence the health of the host by 1) acting as a fermentable substrate for some specific commensal host bacteria leading to the release of short-chain fatty acids in the gut intestinal tract influencing many molecular and cellular processes; 2) acting directly on several compartments and specifically on different patterns of cells (epithelial and immune cells). Nutrients with prebiotic properties are therefore of central interest in allergy prevention for their potential to promote a more tolerogenic environment through these multiple pathways. Both observational studies and experimental models lend further credence to this hypothesis. In this review, we describe both the mechanisms and the therapeutic evidence from preclinical and clinical studies exploring the role of prebiotics in allergy prevention.
Neurofibromatosis type 1 (NF1) is a genetic pathology that can lead to impaired social functioning that has a negative impact on patients' quality of life. To date, although the hypothesis of ...impaired social cognition has been proposed as a potential explanation for these difficulties, very few studies have focused on theory of mind in children with NF1. Furthermore, other complex sociocognitive abilities have never been investigated. The aim of the present study was to assess theory of mind, moral reasoning, and social information processing in children with NF1 compared with a control group.
We administered the Paediatric Evaluation of Emotions, Relationships and Socialization® to 38 children with NF1 aged between 8 years and 16 years 11 months (mean = 11.4,
= 2.3) and 43 control children with comparable sociodemographic characteristics.
Patients performed significantly worse than controls on moral reasoning and social information processing tests, but there was no significant difference on theory of mind.
These results seem to confirm the presence of social cognition difficulties in NF1 that could explain, at least in part, their social difficulties, although not all dimensions are concerned. The differences between the processes we assessed are discussed in relation to the methodologies used to measure them, and raises questions about the complementarity of traditional tools and more ecological assessments.
Neurofibromatosis type 1 (NF1) is a genetic disorder in which the most frequent complication in children is learning disabilities. Over the past decade, growing arguments support the idea that ...executive dysfunction is a core deficit in children with NF1. However, some data remain inconsistent. The aim of this study was to determine the magnitude of impairment for each executive function (EF) and clarify the impact of methodological choices and participant's characteristics on EFs.
In this meta-analysis, 19 studies met the selection criteria and were included with data from a total of 805 children with NF1 and 667 controls. Based on the Diamond's model (2013), EF measures were coded separately according to the following EF components: working memory, inhibitory control, cognitive flexibility, planning/problem solving. The review protocol was registered with PROSPERO (International prospective register of systematic reviews; CRD42017068808).
A significant executive dysfunction in children with NF1 is demonstrated. Subgroup analysis showed that the impairment varied as a function of the specific component of executive functioning. The effect size for working memory and planning/problem solving was moderate whereas it was small for inhibitory control and cognitive flexibility. Executive dysfunction seems to be greater with increasing age whereas assessment tool type, intellectual performance, attention deficit hyperactivity disorder and control group composition did not seem to affect EF results.
EF deficits are a core feature in children with NF1 and an early identification of executive dysfunctions is essential to limit their impact on the quality of life. (JINS, 2018, 24, 977-994).
Neurofibromatosis type 1 (NF1) is a genetic disease that can lead to impaired social adaptation and functioning, thus affecting quality of life. To date, studies of these children's social cognition ...abilities have been scant and far from exhaustive. Therefore, the purpose of the present study was to assess the ability of children with NF1, compared with controls, to process facial expressions of emotions - not only including the usual primary emotions (happiness, anger, surprise, fear, sadness and disgust), but secondary emotions, too. To do so, the links between this ability and the characteristics of the disease (mode of transmission, visibility, and severity) were examined. A total of 38 children with NF1 aged 8-16 years 11 months (mean = 11.4, SD = 2.3) and 43 sociodemographically comparable control children performed the emotion perception and recognition tests of a social cognition battery. Results confirmed that the processing of primary and secondary emotions is impaired in children with NF1, but there were no significant links with either mode of transmission, severity, or visibility. These results encourage further comprehensive assessments of emotions in NF1, and suggest that investigations should be extended to higher level social cognition skills, such as theory of mind and moral judgments.
PDF
