BACKGROUND AND OBJECTIVES: There are several lung ultrasound scores (LUS) for evaluating lung aeration in critically ill adults with restrictive lung disorders. A modified LUS adapted for neonates correlates well with oxygenation and is able to be used to predict the need for surfactant in preterm neonates with respiratory distress syndrome (RDS). However, no data are available for extremely preterm neonates for whom timely surfactant administration is especially important. We hypothesized that LUS might be reliable in extremely preterm neonates with RDS who are treated with continuous positive airway pressure. We aimed to determine the diagnostic accuracy of LUS in predicting the need for surfactant treatment and re-treatment in this population. METHODS: We performed a prospective cohort diagnostic accuracy study between 2015 and 2016 in a tertiary-care academic center. Inborn neonates at ≤30 weeks’ gestation with RDS treated with continuous positive airway pressure were eligible. Surfactant was given on the basis of oxygen requirement thresholds derived from European guidelines, and a LUS was not used to guide surfactant treatment. We calculated the LUS after admission and analyzed its diagnostic accuracy to predict surfactant treatment and re-treatment. RESULTS: We enrolled 133 infants; 68 (51%) received 1 dose of surfactant and 19 (14%) received 2 surfactant doses. A LUS is significantly correlated with oxygenation index (ρ = 0.6; P < .0001) even after adjustment for gestational age (P < .0001). A LUS can be used to accurately predict the need for the first surfactant dose (area under the curve = 0.94; 95% confidence interval: 0.90–0.98; P < .0001) and also the need for surfactant redosing (area under the curve = 0.803; 95% confidence interval: 0.72–0.89; P < .0001). The global accuracy for the prediction of surfactant treatment and re-treatment is 89% and 72%, respectively. CONCLUSIONS: LUS may be used to predict the need for surfactant replacement in extremely preterm neonates with RDS.

Background: The question of whether children with subclinical hypothyroidism (SH) should be treated or not is controversial due to the lack of studies on outcomes of SH children treated with L-thyroxine (L-T4) versus those receiving no therapy. Objectives: (a) To evaluate thyroid tests under L-T4 and after therapy withdrawal in 69 SH children (group A) and (b) to compare our results with those recorded in 92 untreated children (group B). Design: Group A children were treated for 24 months and TSH and FT4 levels 3 months after therapy withdrawal were compared with those measured in group B at the end of follow-up in order to investigate treatment effects. Results: The prevalence of children who had normalized TSH at the end of follow-up was higher in group A, but the prevalence of those who had normalized or maintained unchanged TSH was similar in the two groups, as was the prevalence of children who exhibited a TSH increase >10 mU/l. In group A, TSH values at 27 months were associated with baseline values. Conclusions: (a) Two-year treatment in SH children is unable to modify posttherapy outcome of hyperthyrotropinemia; (b) therapy is unable to prevent the risk of further TSH increase after treatment withdrawal, and (c) posttherapy TSH outcome is conditioned by baseline TSH.

Bovine surfactants are known to be clinically equivalent but it is unclear if porcine or bovine surfactants at their licensed dose should be preferred to treat respiratory distress syndrome in preterm neonates. We performed a comprehensive review of biochemical and pharmacological features of surfactants to understand the biological plausibility of any clinical effect. We then performed a pragmatic meta-analysis comparing internationally marketed porcine and bovine surfactants for mortality and respiratory outcomes. Search for randomised controlled trials with no language/year restrictions and excluding “grey” literature, unpublished or non-peer reviewed reports was conducted, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the most recent methodological recommendations. Sixteen articles were included in the review and 14 in the meta-analysis (1491 neonates). 200 mg/kg poractant-α (a porcine surfactant) was associated with lower BPD/mortality (OR 0.632[95%CI:0.494, 0.809];p < 0.001),BPD (OR 0.688[95%CI:0.512, 0.925];p = 0.013), retreatment (OR 0.313[95%CI:0.187, 0.522];p < 0.0001), airleaks (OR 0.505[95%CI:0.308, 0.827];p = 0.006) and lung haemorrhage (OR 0.624[95%CI:0.388, 1];p = 0.051). Gestational age is associated with effect size for BPD (coefficient: 0.308 [95%CI:0.063, 0.554];p = 0.014) and surfactant retreatment (coefficient: -0.311 [95%CI:-0.595, − 0.028];p = 0.031). 200 mg/kg poractant-α is associated with better respiratory outcomes compared to bovine surfactants at their licensed dose. The effect of poractant-α on BPD and surfactant retreatment is greater at lowest and highest gestational ages, respectively. PROSPERO n.42017075251 .

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a rare autosomal recessive disease, caused by mutations of a single gene named autoimmune regulator gene (AIRE) which results in a failure of T cell tolerance within the thymus. Chronic mucocutaneous candidiasis, chronic hypoparathyroidism, and Addison’s disease are the hallmarks of the syndrome. APECED is also characterized by several autoimmune endocrine and nonendocrine manifestations, and the phenotype is often complex. Moreover, even though APECED is a monogenic disease, its clinical picture is generally dominated by a wide heterogeneity both in the severity and in the number of components even among siblings with the sameAIREgenotype. The variability of its clinical expression implies that diagnosis can be challenging, and a considerable delay often occurs between the appearance of symptoms and the diagnosis. Since a prompt diagnosis is essential to prevent severe complications, clinicians should be aware of all symptoms and signs of suspicion. The aim of this paper is to give an overview on the clinical presentation and diagnostic criteria of APECED and to focus on current knowledge on genotype-phenotype correlation.

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a rare autosomal recessive disease, caused by mutations of a single gene named Autoimmune regulator gene (AIRE) which results in a failure of T cell tolerance. Central tolerance takes place within the thymus and represents the mechanism by which potentially autoreactive T cells are eliminated through the negative selection process. The expression of tissue-specific antigens (TSAs) by medullary thymic epithelial cells (mTECs) in the thymus is a key process in the central tolerance and is driven by the protein encoded by AIRE gene, the transcription factor autoimmune regulator (Aire). A failure in this process caused by AIRE mutations is thought to be responsible of the systemic autoimmune reactions of APECED. APECED is characterized by several autoimmune endocrine and non-endocrine manifestations and the phenotype is often complex. Although APECED is the paradigm of a monogenic autoimmune disorder, it is characterized by a wide variability of the clinical expression even between siblings with the same genotype, thus implying that additional mechanisms, other than the failure of Aire function, are involved in the pathogenesis of the disease. Unraveling open issues of the molecular basis of APECED, will help improve diagnosis, management and therapeutical strategies of this complex disease.

Malignant spinal cord compression (MSCC) is associated withpoor prognosis and may lead to permanent paralysis, sensory loss, and sphincter dysfunction. Very limited data are available on incidence and etiology of MSCC in pediatric population. We aimed to examine etiology, clinical presentation and treatment of pediatric patient with MSCC admitted to the Santobono-Pausilipon Children’s Hospital, Naples, Italy. Forty-four children under 18 yearsadmitedsince 2007 and assessed for MSCC clinical presentations, evaluation, and treatment.were retrospectively collected from our institutional pediatric oncology and neurosurgery database. The median age at time of MSCC diagnosis was 52 months, with a peak in young (≤3 years) patients. The leading cause of MSCC was extramedullary tumors (63.6%), in particular neuroblastoma (27.2%) followed by Ewing sarcomas (15.9%). Cord compression was the presenting feature of a new malignancy in 33 (75%) patients, and a consequence of metastatic disease progression or relapse in the remaining 11 (25%) patients. Motor deficit was the initial symptoms of spinal compression in all patients, while pain was present in about 60% of patients, followed by sphincteric deficit (43.2%). The primary tumor site was located in the neck in 3 (6.8%) patients, thorax in 16 (36.4%), cervico-thoracic region in 3 (6.8%), thoraco-lumbar region in 8 (18.2%), abdomen in 5 (11.4%), lumbar-sacral region in 7 (15.9%) and thoracic-lumbar-sacral region in 1 (2.3%). The median length of the interval between symptom onset and tumor diagnosis varied widely from 0 to 360 days in the entire population, however this interval was significantly shorter in patients with known neoplasia in comparisonto patients with new diagnosis (at relapse 7 days [interquartile range 3–10] vs at diagnosis 23 days [7–60]). Pre and post-operative spine magnetic resonance imagingwas performed in all cases, and most(95%) patients underwent neurosurgical treatment as first treatment. Severe motor deficit was associated with younger age and severe motor deficit at diagnosis was associated withworst motor outcomes at discharge from neurosurgery. Patients with progression or relapsed disease showed a worst prognosis, while the majority of patients (70.5%) were alive at 5 years after diagnosis. The natural history of MSCC in children is associated to permanent paralysis, sensory loss, and sphincter dysfunction, thus prompt diagnosis and correct management are needed to minimize morbidity. Treatment strategies differed widely among cancer types and study groups in the absence of optimal evidence-based treatment guidelines. When the diagnosis is uncertain, surgery provides an opportunity to biopsy the lesion in addition to treating the mass.