Intact FGF23 concentration in healthy infants, children, and adolescents, and diagnostic usefulness in patients with X-linked hypophosphatemic rickets.

OBJECTIVE: FGF23 measurement may have a diagnostic role to investigate patients with phosphate disorders. However, normal values for infants, children, and adolescents have not been defined. METHODS: In a total of 282 (males 145, females 137) healthy infants (n = 30), prepubertal (n = 147), pubertal (n = 59), and postpubertal (n = 46), and in twenty patients with X-linked hypophosphatemic rickets (XLH, age 10.2 ± 5.6 years) serum phosphate (automated analyzer), and plasma intact FGF23 (immunochemiluminescent sandwich assay, DiaSorin) concentrations were measured. RESULTS: Intact FGF23 concentrations were higher in healthy infants than in prepubertal (P < 0.01) and postpubertal subjects (P < 0.05); pubertal subjects showed higher values (P < 0.05) than postpubertal subjects. Serum phosphate concentrations were higher (P < 0.001) in healthy infants than in prepubertal, pubertal, and postpubertal subjects. Pubertal subjects had higher (P < 0.001) serum phosphate concentrations than postpubertal subjects. Intact FGF23 and serum phosphate concentrations did not differ (P = NS) by sex, age of menarche, and time after menarche. In healthy subjects, there was no correlation between intact FGF23 and serum phosphate concentrations. Intact FGF23 concentrations were higher (P < 0.0001) in patients with XLH than in healthy subjects according to chronological age and pubertal development. In all patients, intact FGF23 concentrations were above 40 pg/mL; intact FGF23 concentrations were inversely correlated with serum phosphate concentrations (r = -0.65; P < 0.01). CONCLUSION: In healthy subjects, chronological age and puberty were main determinants of intact FGF23 concentrations. Intact FGF23 concentrations may be a useful marker for the early diagnosis of XLH in pediatric patients.

Allergic rhinitis and COVID-19: friends or foes?

Summary: Allergic rhinitis (AR) is a common disease affecting up to 40% of the general population worldwide. In the Coronavirus 2019 (COVID-19) pandemic era, many observational studies analysing the effect of asthma and chronic obstructive pulmonary disease on the risk of developing COVID-19 were conducted, while data on AR are limited.In this paper, we review the risk of developing SARS-Cov-2 infection carried by AR patients, the outcomes of those with COVID-19 disease, and the COVID-19 influence on the allergic and nasal symptoms and the psychological status of AR patients, in both adult and paediatric populations.AR patients seem to be protected from COVID 19 infection. Even if data about the influence of AR on the severity of COVID-19 disease are still not conclusive, it seems that being an AR patient does not increase the risk of poor COVID-19 prognoses. The clinical manifestation of AR can be distinguished by COVID-19 symptoms. Treating AR adequately is also strongly recommended, especially during pandemic.

OM-85 in the prevention of respiratory infections: State-of-the-art and future perspectives in clinical practice.

Respiratory infections (RI) significantly burden patients, their families, and society. Respiratory infection recurrence (RRI) usually depends on a defect of the immune response, which can be more or less transient and/or selective. In particular, children, older people, heavy smokers, and patients with chronic diseases, characterized by an inadequate immune response, may be at risk of developing RRI. In this context, OM- 85 could represent a valuable option in the management of RRI. OM-85 is a bacterial lysate containing the extracts of some common pathogens, including Branhamella catarrhalis, Klebsiella pneumoniae, Klebsiella ozaenae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, and Staphylococcus aureus. Methodologically rigorous studies have documented the mechanism of action, efficacy, and safety of OM-85. OM-85 enhances the natural and acquired immune response through multifaceted mechanisms. Substantial evidence has shown that OM-85 can prevent respiratory infections, reduce the number of COPD exacerbations, and shorten the disease duration at home or in hospital. OM-85 can enhance the effectiveness of the 'flu vaccination without affecting the vaccine tolerability. The preventive use of OM-85 can reduce the use of antibiotics, contributing to contrast antibiotic resistance and saving the high cost of chronic respiratory diseases. Further studies should define the ideal candidate to OM-85 treatment.

Post-traumatic stress, anxiety, and depressive symptoms in caregivers of children tested for COVID-19 in the acute phase of the Italian outbreak.

BACKGROUND: The recent COVID-19 pandemic pointed out new burdens for researchers on mental health and that evidence-based (EB) studies on vulnerable populations are timely needed. The present paper aims at analysing the impact of suspicious of SARS-COV-2 infection in a cohort of parents presented at 3 major hospitals (spread between north and center of Italy) during the Italian COVID-19 pandemic phase 1. METHODS: Participants of the present cross-sectional, multicenter study were parental couples of children suspected to have COVID-19 who underwent testing with nasopharyngeal swabbing. All subjects were assessed by means of the: Impact of Event Scale-Revised (IES-R), Generalized Anxiety Disorder 7-Item (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) in order to evaluate Post-traumatic stress (PTSS), anxiety, and depressive symptoms, respectively. OUTCOMES: Results evidenced that parents whose children tested positive for COVID-19 were more prone to developing PTSS, anxiety and depressive symptoms. The same results emerged for parents who had quarantined as opposed to those who had not. Moreover, patients who suffered economic damage showed a higher prevalence of anxiety and depressive symptoms, whereas PTSS was more common among unemployed subjects and among mothers. INTERPRETATION: This study identified a mental health strain represented by parenting a child who tested positive for SARS-CoV-2 infection. Further EB research is needed to develop evidence-driven strategies to reduce adverse psychological impacts and related psychiatric symptoms in caregivers of COVID-19 infected children during the next phases of the pandemic.

Disorders of sexual development with XY karyotype and female phenotype: clinical findings and genetic background in a cohort from a single centre.

PURPOSE: 46, XY disorders (or differences) of sex development (DSD) are a group of clinical conditions with variable genetic background; correct diagnosis is often difficult, but it permits to optimize the management. The aim of this study is to identify clinical and genetics features of a group of women with 46, XY DSD to define some issues characterizing people with 46, XY DSD in Italy. METHODS: Retrospective analysis of girls and women with 46, XY DSD and female phenotype evaluated between year 2000 and 2016, performed by anonymised database, focusing on the clinical features and management, including presentation, first diagnostic suspect, gonadal surgery and molecular diagnostic delay. RESULTS: A total of 84 records were collected (mean age at clinical presentation: 9.1 ± 7.9 years; mean age at definitive diagnosis: 20.1 ± 15.0 years). Complete androgen insensitivity syndrome was the most common diagnosis (60%). Only 12 patients (14.3%) did not receive a molecular diagnosis. Early misdiagnoses frequently occurred; diagnostic delay was 10.2 ± 11.2 years, being reduced in patients presenting from 2007 to 2016. The discordance between genotypic and phenotypic sex during pregnancy or at birth determined early reason for referral in a considerable percentage (4.9%). CONCLUSION: Misdiagnosis and long diagnostic delays are present in females with 46, XY DSD in Italy, but the new genetic techniques permit faster right diagnoses in the last years. The centralization in dedicated third level units permits to reduce the number of patients without a molecular diagnosis, allowing better clinical management and appropriate genetic counselling.

Posterior dynamic neutralization and hybrid stabilization in degenerative spine diseases: long-term clinical and radiological outcomes.

Dynamic spinal stabilization aims to reduce some of the problems inherent with traditional fusion. The aim of our study is to analyse clinical and radiological outcomes and to identify the causes of clinical failure in patients who underwent posterior dynamic neutralization or posterior hybrid stabilization because of degenerative lumbar spine diseases. We retrospectively analysed 80 patients at 7.1 years mean follow-up (Range: 5.1 - 8.3 years): 50 were treated with Dynamic Stabilization System (Dynesys) (mean age 47 years old) and 30 with Dynamic Transition Option (mean age 48 years old). We performed clinical pre-and post-operative evaluation using Visual Analogue Scale (VAS), Oswestry Low Back Pain Scale (ODI) and X-rays study. Results: we reported an important reduction of VAS from 7 to 2 (p<.001) and minimal disability in 65% of the patients, moderate disability in 18.2%, severe disability in 12.5% and crippling back pain in 4.3%. X-ray analysis showed a significative decrease of 3.5° with respect to the preoperative values, exactly 2° in neutral position postop, 1.2° in flexion postop and 2.5° in extension postop. Data showed greater reduction of extension than flexion in postoperative period. Dynamic neutralization limits more the extension than flexion. The correct preoperative planning, the careful selection of patients and the meticulous surgical technique are mandatory to avoid clinical failures. It is very important to identify the correct screw positioning and to avoid excessive pre-tensioning of the implant. Posterior dynamic neutralization and hybrid stabilization are valid alternative to spinal fusion in degenerative spine disease.

Antihistamines in children and adolescents: A practical update

Histamine is a chemical mediator, released predominantly by tissue mast cells, circulating basophils, and neurons, which are activated in response to various immunological and non-immunological stimuli. Histamine has to bind to specific receptors to exert its physiological and pathophysiological functions. Endogenous histamine is the main mediator of the immediate allergic response, which moreover, performs other multiple functions, including regulation of gastric secretion, neurotransmission in the central nervous system, and immunomodulatory activity. The involvement of histamine in various disorders and the importance of receptors in the clinical features have relevant implications in clinical practice. Anti-H1 antihistamines contrast the histamine-dependent effects, mainly concerning nasal symptoms and cutaneous itching and wheal. Antihistamines are among the most prescribed drugs in pediatric care. This review updates the practical use of antihistamines in children and adolescents

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Rasmussen's encephalitis: From immune pathogenesis towards targeted-therapy.

Rasmussen encephalitis (RE) is a unilateral hemispheric encephalitis whose main clinical features include refractory focal epilepsy or epilepsia partialis continua, hemiparesis, and progressive cognitive decline. Despite the autoimmune pathogenesis of RE, the only definitive therapeutic option is currently represented by surgery. We review the clinical features, the immune pathogenesis, and the available therapeutic options for RE, with special focus on immunosuppressive agents. The research includes systematic reviews, meta-analyses, observational studies, clinical trials, cases series and reports, until 2020. The use of immunosuppressive agents in RE is supported by the evidence of an autoimmune involvement of the central nervous system in this condition. Although often insufficient to modify the disease course and to achieve symptomatic control, immune therapy can be effective in patients with slow disease progression or in patients in which surgery is not applicable. Moreover, the documentation of T-cell involvement in the pathogenesis of RE, with a specific cytokine pattern, opens a window of opportunity for the use of T-targeted therapies and biologic drugs (i.e. anti-TNFα agents) in the treatment of this disease.

Post-traumatic stress spectrum symptoms in parents of children affected by epilepsy: Gender differences.

PURPOSE: To investigate psychopathological reaction to traumatic stress, addressing in particular gender difference, in parental couples of children affected by epilepsy. METHODS: 50 mothers and 50 fathers, paired for one's child, of children followed at the Pediatric Unit of a major Italian University Hospital with a diagnosis of epilepsy were enrolled, screened by means of the Semi-structured Clinical Interview for DSM-5 (SCID-5) and filled the Trauma and Loss Spectrum Self-Report (TALS-SR), an international instrument to evaluate post-traumatic stress symptomatology. RESULTS: 25 % of the total sample presented a diagnosis of PTSD with a statistically higher prevalence of mothers (36 % and 14 %, respectively; p = .021). Furthermore, 44 % (48 % mothers and 40 % fathers) presented a partial PTSD. Important gender differences emerged also for all cluster dimensions of the TALS-SR except for the Avoidance. Finally, the analysis of the single items of the TALS-SR evidenced that in mothers subgroup prevail cognitive symptoms of fear and sadness as well as somatic manifestations. CONCLUSIONS: Our results point out the differences between mothers and fathers in trauma response and underline the need to develop gender targeted models of healthcare prevention and assistance.

Antihistamines in children and adolescents: A practical update.

Histamine is a chemical mediator, released predominantly by tissue mast cells, circulating basophils, and neurons, which are activated in response to various immunological and non-immunological stimuli. Histamine has to bind to specific receptors to exert its physiological and pathophysiological functions. Endogenous histamine is the main mediator of the immediate allergic response, which moreover, performs other multiple functions, including regulation of gastric secretion, neurotransmission in the central nervous system, and immunomodulatory activity. The involvement of histamine in various disorders and the importance of receptors in the clinical features have relevant implications in clinical practice. Anti-H1 antihistamines contrast the histamine-dependent effects, mainly concerning nasal symptoms and cutaneous itching and wheal. Antihistamines are among the most prescribed drugs in pediatric care. This review updates the practical use of antihistamines in children and adolescents.

17ß-hydroxysteroid dehydrogenase type 3 deficiency: female sex assignment and follow-up.

BACKGROUND: Deficiency of 17ß-hydroxysteroid dehydrogenase type 3 (17ß-HSD3) is a rare autosomal recessive 46,XY disorder of sex development (DSD). It is due to pathogenetic variants in the HSD17B3 gene. Mutated genes encode an abnormal enzyme with absent or reduced ability to convert Δ4-androstenedione (Δ4-A) to testosterone (T) in the fetal testis. Affected individuals are usually raised as females and diagnosis is made at puberty, when they show virilization. METHODS: A girl with a presumptive diagnosis of complete androgen insensitivity syndrome underwent endocrine and genetic assessment. Long-term follow-up was reported. RESULTS: The diagnosis of 17ß-HSD3 deficiency was made (stimulated T/Δ4-A ratio: 0.15; HSD17B3 gene analysis: c.277+4A>T in intron 3/c.640_645del (p.Glu214_Glu215del) in exon 9. After extensive information, parents decided to maintain female sex. Gonadal removal was performed and histological evaluation demonstrated deep fibrosis of testicular tissue. Follow-up till 8.5 years of age showed somatic and neuro-psychological development fitting with the female sex. CONCLUSIONS: Management of a child with the rare 17ß-HSD3 deficiency remains challenging. Any decision must be carefully evaluated with parents. Long-term follow-up must be warranted by a multidisciplinary DSD team to evaluate the adequacy of the choices made on quality of life in later life.

Efficacy and tolerability of mycophenolate mofetil in a pediatric Rasmussen syndrome.

Rasmussen syndrome (RS) is a chronic encephalopathy with uncertain etiology and immune-mediated pathogenesis. The only definitive treatment is represented by functional hemispherectomy. We describe the case of a 6.5-year-old female patient who developed several episodes of focal, unilateral clonic seizures. Following laboratory and instrumental investigations, the patient was diagnosed as having RS. A treatment with corticosteroids, intravenous immunoglobulin, and the antiseizure medication (carbamazepine and levetiracetam) did not completely control the seizures. Therefore, the patient was treated with mycophenolate mofetil (MMF), showing a good clinical response, with reduction of the seizures, and stability of the radiological findings. This case suggests the potential utility of MMF in the immune approach to RS.

Pregnenolone and pregnenolone-methyl-ether rescue neuronal defects caused by dysfunctional CLIP170 in a neuronal model of CDKL5 Deficiency Disorder.

Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene are responsible for the onset of CDKL5 Deficiency Disorder (CDD), a neurological pathology characterised by severe infantile seizures, intellectual disability, impairment of gross motor skills, sleep and gastrointestinal disturbances. CDKL5 is a serine/threonine kinase the molecular network of which is not yet fully understood. Loss of CDKL5 both in vitro and in vivo leads to altered neuronal morphology including axon specification and outgrowth, dendritic arborisation and spine morphology suggesting a link between CDKL5 and the regulation of proper cytoskeleton functioning. Recently, we found that CDKL5 regulates the binding of CLIP170 to microtubules (MT). CLIP170 is a MT-plus end tracking protein (+TIP) that associates with MTs when present in its open, active conformation. Here we present evidence suggesting CLIP170 contributes to neuronal CDKL5-dependent defects and that it represents an important novel druggable target for CDD; indeed, CLIP170 is directly targeted by the neuroactive steroid pregnenolone (PREG), which induces the active conformation of the protein thus promoting MT-dynamics. We here show that PREG and a synthetic derivative pregnenolone-methyl-ether (PME) can restore the MT association of CLIP170 and revert morphological and molecular defects in Cdkl5-KO neurons at different stages of maturation. All together, these findings identify CLIP170 as possible novel druggable target for CDKL5 related disorders providing an intriguing prospective for future disease-modifying drug-based therapies.

Pediatric mastocytosis: report of 23 cases in 5 years / Mastocitosis cutánea en niños: reporte de 23 casos en 5 años

RESUMEN Introducción: Las mastocitosis son un conjunto de trastornos clínicos, producidos todos ellos por una proliferación de mastocitos y su acumulación en varios órganos, entre los cuales el más común es la piel. Objetivo: Presentar la experiencia de pacientes con mastocitosis oriundos de Neuquén atendidos en el consultorio de Dermatología pediátrica en un período de 5 años. Detallar formas clínicas, presentación, topografía de las lesiones y evolución. Diseño: Se realizó un estudio descriptivo, retrospectivo de corte transversal, en el período comprendido entre abril de 2013 y marzo de 2018. Materiales y Método: Se revisaron las Historias clínicas digitales de pacientes con diagnóstico de mastocitosis cutánea que concurrieron al consultorio de dermatología infantil en la ciudad de Neuquén. Resultados: Se reunieron 23 casos de mastocitosis cutánea; de ellos el 60,87% corresponden a mastocitosis maculopapular y el 39,13%, a mastocitomas. No hubo diferencias significativas en cuanto al sexo. La mayoría de ellos presentó lesiones localizadas en tronco y miembros. El 95% tuvo signo de Darier positivo. Conclusiones: En nuestra muestra la presentación clínica más frecuente fue la mastocitosis maculopapular y la edad de inicio fue antes del año de vida en la totalidad de los pacientes. Las lesiones se distribuyeron en tronco y miembros en la mayoría de los casos. Los pacientes con mastocitomas solitarios permanecieron estables; en los casos de mastocitosis maculopapular se utilizaron antihistamínicos, con buena evolución.

ABSTRACT Introduction: Mastocytosis is a heterogeneous group of disorders, characterized by a proliferation of mast cells and its accumulation in several organs, being the skin the most frequently affected one. Design: A descriptive, retrospective cross-sectional study, was conducted in the period from April 2013 to March 2018 in Neuquen city. Materials and Method: Electronic medical records of patients diagnosed with cutaneous mastocytosis who attended to the pediatric dermatology clinic in Neuquen city were reviewed. Results: We present 23 cases of cutaneous mastocytosis, of which 60,87% were maculopapular and 39,13% mastocytomas. There were no significant differences in terms of sexes. Most of them presented localized lesions in trunk and limbs. 95% had positive Darier´s sign. Conclusions: In our sample, the most frequent clinical presentation was maculopapular mastocytosis, and the age of onset was during the first year of life in all patients. The majority of lesions were distributed over the trunk and limbs. Patients with mastocytoma remained stable; maculopapular patients recieved antihistamines, with good evolution.

The clinical relevance of molecular diagnosis in children allergic to grass pollen and treated with allergen immunotherapy

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Current therapeutic paradigm in pediatric atopic dermatitis: Practical guidance from a national expert panel

Introduction and Objectives: Atopic dermatitis (AD) is the most common cutaneous inflammatory disease in both adults and children. Although emerging therapeutic approaches are being investigated for the management of pediatric AD, it still needs to be managed with conventional treatments. This consensus document is aimed at providing an update on general management and therapies of pediatric AD, defining practical recommendations for using both topical and systemic agents. Material and Methods: A panel of experts consisting of dermatologists and pediatricians were convened in order to define statements, through a Delphi process, standardizing the management of AD in pediatric subjects in a real-world setting. Results: A set of practical recommendations obtaining an at least 75% agreement was presented. Conclusions: This set of practical recommendations represents a simple and fast snapshot on the pediatric use of common anti-AD therapeutics

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Post-traumatic stress and major depressive disorders in parent caregivers of children with a chronic disorder.

Post-traumatic Stress Disorder (PTSD) and Major Depressive Disorder (MDD) are the most common psychiatric consequences among caregivers of pediatric patients affected by severe chronic illnesses. The aims of this study were to describe rates of PTSD and MDD in a sample of parents of epileptic children, and to examine the correlations between symptoms of post-traumatic stress and depression. Parents of children with epilepsy were enrolled and screened by means of the PTSD module of the Semi-Structured Clinical Interview for DSM-5 (SCID-5) and of the Hamilton Rating Scale for depression (HAM-D). They also completed the Trauma and Loss Spectrum Self-Report (TALS-SR), an international instrument to evaluate post-traumatic stress spectrum symptoms. Results revealed PTSD rates of 15.7% (19.5% mothers, 8,1% fathers; p = .043) and MDD rates of 7.5% (10.2% mothers,1.8% fathers; p = .064). A model of multiple linear regression indicated a significant B linear regression coefficient between being mothers (p = .012), witnessing tonic-clonic seizures (p = .015) and having higher TALS-SR total score (p < .001) as predictors of HAM-D total score. Our findings highlight the relationship between PTSD and MDD, evidencing the need for further studies on pediatric caregivers aimed to develop specific intervention programs of healthcare prevention and assistance.

Allergic manifestations to local anaesthetic agents for dental anaesthesia in children: a review and proposal of a new algorithm.

AIM: The purpose of this review was to evaluate allergic manifestations to dental local anaesthetic (LA) in children and to propose an algorithm for the diagnosis of LA allergy, in order to minimise the number of children who are wrongly categorised as allergic. MATERIALS AND METHODS: A comprehensive literature survey was performed on LA allergy in children before a dental treatment. In proposing a diagnostic algorithm, evidences from literature have been integrated with personal experience. RESULTS: Data from literature showed that overall less than 1% of young patients tested for suspected LA have a positive subcutaneous test and have a positive diagnosis. A complete diagnostic procedure should include: clinical history reported by patients, objective medical records, results of skin tests and provocation test with the suspected drug. Patients with negative skin tests should perform a subcutaneous challenge, while patients with a positive skin test should be tested for a different unrelated LA. CONCLUSION: Allergy to LA is a rare condition. A complete diagnostic algorithm will allow to identify paediatric patients correctly.