The Clinical Impact of Methotrexate-Induced Stroke-Like Neurotoxicity in Paediatric Departments: An Italian Multi-Centre Case-Series

Introduction: Stroke-like syndrome (SLS) is a rare subacute neurological complication of intrathecal or high-dose (≥500 mg) Methotrexate (MTX) administration. Its clinical features, evoking acute cerebral ischaemia with fluctuating course symptoms and a possible spontaneous resolution, have elicited interest among the scientific community. However, many issues are still open on the underlying pathogenesis, clinical, and therapeutic management and long-term outcome. Materials and Methods: We retrospectively analyzed clinical, radiological and laboratory records of all patients diagnosed with SLS between 2011 and 2021 at 4 National referral centers for Pediatric Onco-Hematology. Patients with a latency period that was longer than 3 weeks between the last MTX administration of MTX and SLS onset were excluded from the analysis, as were those with unclear etiologies. We assessed symptom severity using a dedicated arbitrary scoring system. Eleven patients were included in the study. Results: The underlying disease was acute lymphoblastic leukemia type B in 10/11 patients, while fibroblastic osteosarcoma was present in a single subject. The median age at diagnosis was 11 years (range 4–34), and 64% of the patients were women. Symptoms occurred after a mean of 9.45 days (± 0.75) since the last MTX administration and lasted between 1 and 96 h. Clinical features included hemiplegia and/or cranial nerves palsy, paraesthesia, movement or speech disorders, and seizure. All patients underwent neuroimaging studies (CT and/or MRI) and EEG. The scoring system revealed an average of 4.9 points (± 2.3), with a median of 5 points (maximum 20 points). We detected a linear correlation between the severity of the disease and age in male patients. Conclusions: SLS is a rare, well-characterized complication of MTX administration. Despite the small sample, we have been able to confirm some of the previous findings in literature. We also identified a linear correlation between age and severity of the disease, which could improve the future clinical management

Microbiome Composition and Its Impact on the Development of Allergic Diseases

Allergic diseases, such as food allergy (FA), atopic dermatitis (AD), and asthma, are heterogeneous inflammatory immune-mediated disorders that currently constitute a public health issue in many developed countries worldwide. The significant increase in the prevalence of allergic diseases reported over the last few years has closely paralleled substantial environmental changes both on a macro and micro scale, which have led to reduced microbial exposure in early life and perturbation of the human microbiome composition. Increasing evidence shows that early life interactions between the human microbiome and the immune cells play a pivotal role in the development of the immune system. Therefore, the process of early colonization by a “healthy” microbiome is emerging as a key determinant of life-long health. In stark contrast, the perturbation of such a process, which results in changes in the host-microbiome biodiversity and metabolic activities, has been associated with greater susceptibility to immune-mediated disorders later in life, including allergic diseases. Here, we outline recent findings on the potential contribution of the microbiome in the gastrointestinal tract, skin, and airways to the development of FA, AD, and asthma. Furthermore, we address how the modulation of the microbiome composition in these different body districts could be a potential strategy for the prevention and treatment of allergic diseases

Primary Prevention of Pediatric Asthma through Nutritional Interventions

Asthma is the most common chronic non-communicable disease in children, the pathogenesis of which involves several factors. The increasing burden of asthma worldwide has emphasized the need to identify the modifiable factors associated with the development of the disease. Recent research has focused on the relationship between dietary factors during the first 1000 days of life (including pregnancy)—when the immune system is particularly vulnerable to exogenous interferences—and allergic outcomes in children. Specific nutrients have been analyzed as potential targets for the prevention of childhood wheeze and asthma. Recent randomized controlled trials show that vitamin D supplementation during pregnancy, using higher doses than currently recommended, may be protective against early childhood wheezing but not school-age asthma. Omega-3 fatty acid supplementation during pregnancy and infancy may be associated with a reduced risk of childhood wheeze, although the evidence is conflicting. Data from observational studies suggest that some dietary patterns during pregnancy and infancy might also influence the risk of childhood asthma. However, the quality of the available evidence is insufficient to allow recommendations regarding dietary changes for the prevention of pediatric asthma. This review outlines the available high-quality evidence on the role of prenatal and perinatal nutritional interventions for the primary prevention of asthma in children and attempts to address unmet areas for future research in pediatric asthma prevention

Dietary Interventions and Nutritional Factors in the Prevention of Pediatric Asthma

Asthma is the most frequent chronic disease in children, and its pathogenesis involves genetic, epigenetic, and environmental factors. The rapid rise in the prevalence of asthma registered over the last few decades has stressed the need to identify the environmental and modifiable factors associated with the development of the disease. In particular, there is increasing interest in the role of modifiable nutritional factors specific to both the prenatal and post-natal early life as, during this time, the immune system is particularly vulnerable to exogenous interferences. Several dietary factors, including maternal diet during pregnancy, the duration of breastfeeding, the use of special milk formulas, the timing of the introduction of complementary foods, and prenatal and early life supplementation with vitamins and probiotics/prebiotics, have been addressed as potential targets for the prevention of asthma. In this review, we outline recent findings on the potential role of prenatal and perinatal dietary and nutritional interventions for the primary prevention of pediatric asthma. Moreover, we addressed unmet needs and areas for future research in the prevention of childhood-onset asthma

Probiotics in the prevention and treatment of atopic dermatitis

The use of probiotic supplements might change the composition of the intestinal flora of children, subsequently modulating the immune system's reactivity. The effects of probiotic administration for the prevention/treatment of allergic diseases and atopic dermatitis, in particular, are still so controversial that no definitive recommendation can be made at this stage. Differences in strain specificity, timing, and length of administration all contribute to diversifying the conclusions of this review

Probiotics in the prevention and treatment of atopic dermatitis

The use of probiotic supplements might change the composition of the intestinal flora of children, subsequently modulating the immune system's reactivity. The effects of probiotic administration for the prevention/treatment of allergic diseases and atopic dermatitis, in particular, are still so controversial that no definitive recommendation can be made at this stage. Differences in strain specificity, timing, and length of administration all contribute to diversifying the conclusions of this review

Prevention of recurrent respiratory infections: Inter-society Consensus

Recurrent respiratory infections (RRIs) are a common clinical condition in children, in fact about 25% of children under 1 year and 6% of children during the first 6 years of life have RRIs. In most cases, infections occur with mild clinical manifestations and the frequency of episodes tends to decrease over time with a complete resolution by 12 years of age. However, RRIs significantly reduce child and family quality of life and lead to significant medical and social costs. Despite the importance of this condition, there is currently no agreed definition of the term RRIs in the literature, especially concerning the frequency and type of infectious episodes to be considered. The aim of this consensus document is to propose an updated definition and provide recommendations with the intent of guiding the physician in the complex process of diagnosis, management and prevention of RRIs