The fecal microbiome of 55 obese children and adolescents (BMI-SDS 3.2 ± 0.7) and of 25 normal-weight subjects, matched both for age and sex (BMI-SDS - 0.3 ± 1.1) was analysed. Streptococcus, ...Acidaminococcus, Sutterella, Prevotella, Sutterella wadsworthensis, Streptococcus thermophilus, and Prevotella copri positively correlated with obesity. The inferred pathways strongly associated with obesity concern the biosynthesis pathways of tyrosine, phenylalanine, tryptophan and methionine pathways. Furthermore, polyamine biosynthesis virulence factors and pro-inflammatory lipopolysaccharide biosynthesis pathway showed higher abundances in obese samples, while the butanediol biosynthesis showed low abundance in obese subjects. Different taxa strongly linked with obesity have been related to an increased risk of multiple diseases involving metabolic pathways related to inflammation (polyamine and lipopolysaccharide biosynthesis). Cholesterol, LDL, and CRP positively correlated with specific clusters of microbial in obese patients. The Firmicutes/Bacteroidetes-ratio was lower in obese samples than in controls and differently from the literature we state that this ratio could not be a biomarker for obesity.
Despite the wide availability of novel anti-seizure medications (ASMs), 30% of patients with epilepsy retain persistent seizures with a significant burden in comorbidity and an increased risk of ...premature death. This review aims to discuss the therapeutic strategies, both pharmacological and non-, which are currently in the pipeline.
PubMed, Scopus, and EMBASE databases were screened for experimental and clinical studies, meta-analysis, and structured reviews published between January 2018 and September 2021. The terms "epilepsy," "treatment" or "therapy," and "novel" were used to filter the results.
The common feature linking all the novel therapeutic approaches is the spasmodic rush toward precision medicine, aiming at holistically evaluating patients, and treating them accordingly as a whole. Toward this goal, different forms of intervention may be embraced, starting from the choice of the most suitable drug according to the type of epilepsy of an individual or expected adverse effects, to the outstanding field of gene therapy. Moreover, innovative insights come from
and
studies on the role of inflammation and stem cells in the brain. Further studies on both efficacy and safety are needed, with the challenge to mature evidence into reliable assets, ameliorating the symptoms of patients, and answering the challenges of this disease.
To date, this is the only report showing with close and consecutive magnetic resonance images the extremely rapid response of two types of pediatric low-grade gliomas (PLGG) to vemurafenib and its ...impact on the surgical approach.
We report two cases of symptomatic PLGG treated with vemurafenib, a BRAF inhibitor: in a 12-year-old girl it was used as first-line medical treatment, reducing the tumor by 45% within a month and stabilizing to 76% after a year; in a 3-year-old boy with no improvement after SIOP LGG 2004 Protocol, vemurafenib induced in only one week a 34% shrinkage and solved the hydrocephalus, avoiding surgical operation. DISCUSSION AND CONCLUSIONS: Our cases demonstrate how an early molecular diagnosis of BRAF mutations through the neurosurgical biopsy is essential to promptly start targeted therapies., whose effect can influence both therapeutic and surgical decisions, hopefully reducing the occurrence of second neurosurgery with associated risks of neurological sequelae.
Diabetes mellitus (DM) has been frequently associated with an impaired immune response against infectious agents, making affected patients at risk for more severe disease and sometimes causing worse ...outcomes. The recent COVID-19 pandemic has seriously affected patients with both diabetes, in particular those carrying comorbidities or with poor glycemic control. As regards pediatric diabetes mellitus, the availability of more accurate and technological tools for glycemic management and the improved markers of metabolic control might mitigate the negative impact of infections. Notably, good metabolic control of diabetes since its diagnosis reduces not only the risk of microangiopathic complications but also of impaired immune response to infectious diseases. Therefore, vaccinations are strongly recommended. Our paper aims to provide the most updated evidence regarding infectious diseases in type 1 pediatric DM.
Neurofibromatosis type 1 (NF1) is a proteiform genetic condition caused by pathogenic variants in
and characterized by a heterogeneous phenotypic presentation. Relevant genotype-phenotype ...correlations have recently emerged, but only few pertinent studies are available. We retrospectively reviewed clinical, instrumental, and genetic data from a cohort of 583 individuals meeting at least 1 diagnostic National Institutes of Health (NIH) criterion for NF1. Of these, 365 subjects fulfilled ≥2 NIH criteria, including 235 pediatric patients. Genetic testing was performed through cDNA-based sequencing, Next Generation Sequencing (NGS), and Multiplex Ligation-dependent Probe Amplification (MLPA). Uni- and multivariate statistical analysis was used to investigate genotype-phenotype correlations. Among patients fulfilling ≥ 2 NIH criteria, causative single nucleotide variants (SNVs) and copy number variations (CNVs) were detected in 267/365 (73.2%) and 20/365 (5.5%) cases. Missense variants negatively correlated with neurofibromas (
= 0.005). Skeletal abnormalities were associated with whole gene deletions (
= 0.05) and frameshift variants (
= 0.006). The c.3721C>T; p.(R1241*) variant positively correlated with structural brain alterations (
= 0.031), whereas Lisch nodules (
= 0.05) and endocrinological disorders (
= 0.043) were associated with the c.6855C>A; p.(Y2285*) variant. We identified novel NF1 genotype-phenotype correlations and provided an overview of known associations, supporting their potential relevance in the implementation of patient management.
: Plexiform neurofibromas (pNFs) are benign neoplasms, primarily originating from Schwann cells, posing challenges in patients with type 1 neurofibromatosis (NF1) due to pain, disfigurement, ...compression of vital structures and potential for malignancy. Selumetinib, a MEK1/2 inhibitor, has shown promising results in treating inoperable pNFs, with clinical trials demonstrating tumor volume reduction and improved patient-reported outcomes. Despite its efficacy, dermatologic toxicities may impact the quality of life and treatment adherence. Evaluating the frequency and spectrum of such effects is crucial for effective management.
: In a four-year retrospective and prospective study, pediatric NF1 patients with symptomatic, inoperable plexiform neurofibromas (pNFs) were treated with selumetinib. Eligibility criteria included significant morbidity, pNF size exceeding 3 cm or surgical inoperability, and performance status >70%. Hematological, liver, lung and cardiac assessments established baseline health. Selumetinib, orally administered at 25 mg/m
twice, was administered for two years unless a response warranting extension occurred. Cutaneous AEs were documented and graded by severity according to CTCAE v5.0, with evaluations every three to six months. The impact on symptoms and pNF size was systematically recorded, and biopsies characterized histopathological features in those patients requiring surgery.
: Twenty patients were enrolled, with an average age at therapy initiation of 11.6 years. Cutaneous side effects were common, with all patients experiencing at least one and a median of two per patient. Xerosis, paronychia and acneiform rash were prevalent. Notably, pre-pubertal individuals were more susceptible to xerosis. Acneiform rash had a higher incidence in older patients and those with skin phototypes II and III. Successful management involved tailored approaches, such as clindamycin for acneiform rash and topical agents for paronychia. Hair abnormalities, including color changes and thinning, occurred, with female patients at higher risk for the latter. Paronychia presented challenges, necessitating various interventions, including surgical approaches. AEs led to treatment suspension in 20% of patients, with tumor rebound observed in 75%.
: According to our experience, successful management of selumetinib-induced cutaneous AEs requires tailored strategies including surgery. AEs might indirectly determine pNF regrowth due to therapy suspension. We thus emphasize the pivotal role of addressing cutaneous reactions for effective selumetinib management in pediatric patients.
Macrocephaly affects up to 5% of the pediatric population and is defined as an abnormally large head with an occipitofrontal circumference (OFC) >2 standard deviations (SD) above the mean for a given ...age and sex. Taking into account that about 2-3% of the healthy population has an OFC between 2 and 3 SD, macrocephaly is considered as "clinically relevant" when OFC is above 3 SD. This implies the urgent need for a diagnostic workflow to use in the clinical setting to dissect the several causes of increased OFC, from the benign form of familial macrocephaly and the Benign enlargement of subarachnoid spaces (BESS) to many pathological conditions, including genetic disorders. Moreover, macrocephaly should be differentiated by megalencephaly (MEG), which refers exclusively to brain overgrowth, exceeding twice the SD (3SD-"clinically relevant" megalencephaly). While macrocephaly can be isolated and benign or may be the first indication of an underlying congenital, genetic, or acquired disorder, megalencephaly is most likely due to a genetic cause. Apart from the head size evaluation, a detailed family and personal history, neuroimaging, and a careful clinical evaluation are crucial to reach the correct diagnosis. In this review, we seek to underline the clinical aspects of macrocephaly and megalencephaly, emphasizing the main differential diagnosis with a major focus on common genetic disorders. We thus provide a clinico-radiological algorithm to guide pediatricians in the assessment of children with macrocephaly.
Wieacker-Wolff syndrome (WWS) is an X-linked Arthrogryposis Multiplex Congenita (AMC) disorder associated with broad neurodevelopmental impairment. The genetic basis of WWS lies in hemizygous ...pathogenic variants in
, encoding a C4H2 type zinc-finger nuclear factor abundantly expressed in the developing human brain. The main clinical features described in WWS families carrying
pathogenic variants encompass having a short stature, microcephaly, birth respiratory distress, arthrogryposis, hypotonia, distal muscle weakness, and broad neurodevelopmental delay. We hereby report a Sicilian family with a boy clinically diagnosed with WWS and genetically investigated with exome sequencing (ES), leading to the identification of a c.593G>A (p. R198Q) hemizygous pathogenic variant in the
gene. During the first year of life, the onset of central hypoadrenalism led to recurrent hypoglycemic events, which likely contributed to seizure susceptibility. Also, muscle biopsy studies confirmed a pathology of the muscle tissue and revealed peculiar abnormalities of the neuromuscular junction. In conclusion, we expand the phenotypic spectrum of the WWS-related neurodevelopmental disorders and discuss the role of
in the context of the potential neuroendocrinological and neuromuscular features associated with this condition.
BRAF inhibitors, in recent years, have played a central role in the disease control of unresectable BRAF-mutated pediatric low-grade gliomas (LGGs). The aim of the study was to investigate the acute ...and long-term effects of vemurafenib on the lipid metabolism in children treated for an LGG. In our cohort, children treated with vemurafenib (
= 6) exhibited alterations in lipid metabolism a few weeks after starting, as was demonstrated after 1 month (
= 4) by the high plasma levels of the total cholesterol (TC = 221.5 ± 42.1 mg/dL), triglycerides (TG = 107.8 ± 44.4 mg/dL), and low-density lipoprotein (LDL = 139.5 ± 51.5 mg/dL). Despite dietary recommendations, the dyslipidemia persisted over time. The mean lipid levels of the TC (222.3 ± 34.7 mg/dL), TG (134.8 ± 83.6 mg/dL), and LDL (139.8 ± 46.9 mg/dL) were confirmed abnormal at the last follow-up (45 ± 27 months,
= 6). Vemurafenib could be associated with an increased risk of dyslipidemia. An accurate screening strategy in new clinical trials, and a multidisciplinary team, are required for the optimal management of unexpected adverse events, including dyslipidemia.
Background
In the pediatric population, the knowledge of the acute presentation of SARS-CoV-2 infection is mainly limited to small series and case reports, particularly when dealing with neurological ...symptoms. We describe a large cohort of children with acute SARS-CoV-2 infection, focusing on the neurological manifestations and investigating correlations between disease severity and population demographics.
Methods
Patients aged 0–18 years with a positive molecular swab were recruited between April 2020 and March 2021 from a tertiary Italian pediatric centre. Clinical data, imaging, and laboratory test results were retrieved from our local dataset and statistically analyzed.
Results
A total of 237 patients with a median age of 3.2 years were eligible; thirty-two (13.5%) presented
with
neurological symptoms, including headache (65.6%), altered awareness (18.8%), ageusia/anosmia (12.5%), seizures (6.3%), and vertigo (6.3%), combined in 7 (21.9%) cases. Respiratory (59.5%) and gastrointestinal (25.3%) symptoms were the most common among the 205 (86.5%) patients
without
neurological involvement. Neurological symptoms did not significantly influence the severity of the triage access codes. Moreover, pre-existing medical conditions were not higher in the group
with
neurological manifestations. Overall, fifty-nine patients (25%, 14/59
with
neurological symptoms) required treatment, being antibiotics, systemic steroids, and heparin those most prescribed.
Conclusion
Our study supports the overall benign course of the SARS-CoV-2 infection in children. Neurological manifestations, except for headache, remain a rare presenting symptom, and disease severity seems unrelated to pre-existing medical conditions.
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