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Background: MiRNAs are a class of small non-coding RNAs that are involved in the post-transcriptional regulation of gene expression. MiRNAs are considered a class of epigenetic biomarkers. These biomarkers can investigate disease at different stages: diagnosis, therapy or clinical follow-up. Objective: The aim of this paper is to highlight the innovative use of miRNAs in several childhood diseases. Methods: We conducted a literature review to search the usage of miRNAs in pediatric clinical routine or experimental trials. Results: We found a possible key role of miRNAs in different pediatric illnesses (metabolic alterations, coagulation defects, cancer). Conclusion: The modest literature production denotes that further investigation is needed to assess and validate the promising role of miRNAs as non-invasive biomarkers in pediatric disorders.

Background and Objective: Immune thrombocytopenia (ITP) is a common bleeding disorder in childhood. The management of ITP in children is controversial, requiring personalized assessment of patients and therapeutic choices. Thrombopoietin receptor agonists (TPO-RAs), eltrombopag and romiplostim, have been shown to be safe and effective for the treatment of pediatric ITP. The aim of our research is to define the role of thrombopoietin receptor agonists in the management of pediatric ITP. Methods: This review focuses on the use of TPO-RAs in pediatric ITP, in randomized trials and in clinical routine, highlighting their key role in the management of the disease. Results: Eltrombopag and romiplostim appear effective treatment options for children with ITP. Several clinical studies have assessed that the use of TPO-RAs increases platelet count, decreases bleeding symptoms and improves health-related quality of life. Moreover, TPO-RAs are well tolerated with minor side effects. Conclusion: Although long term efficacy and safety of TPO-RAs still require further investigations, their use is gradually expanding in the clinical practice of children with ITP.

Sickle bone disease (SBD) is a chronic complication of sickle cell disease (SCD) whose pathogenesis is not completely understood. Chronic inflammation associated with SCD could alter bone remodeling. Our aim was to analyze the serum levels of bone remodeling markers in a group of SCD children to evaluate their involvement in the SBD.We enrolled 26 SCD subjects and 26 age-matched controls, who lived in the same geographic area. DKK-1, sclerostin, RANKL, and OPG serum levels were evaluated. Neutrophil-lymphocyte ratio (NLR) was also evaluated as a marker of inflammation.The analysis of bone remodeling markers did not show any significant difference between the two groups except for DKK-1 levels that were significantly higher in the patients than controls (p .05). A significant direct correlation between NLR and DKK-1 (p = .004) was found. An inverse correlation between NLR and osteocalcin (p = .01) has also been observed.The chronic inflammation, which represents a peculiar characteristic in SCD patients, would represent the primary causal agent of the activation of osteoblastogenesis inhibitors responsible of bone impairment in these subjects. Further studies will be needed to better explain the role of these inhibitors in SCD, to prevent or treat bone damage in this population.

Hemophilias are hemorrhagic congenital rare diseases. The gold standard of therapy in hemophilics is the intravenously replacement therapy. We can infuse intravenously plasma derived factors (FVIII for Hemophilia A and FIX for Hemophilia B) or recombinant products (i.e., clotting factor synthetically produced). Venipuncture is not a safe procedure in subjects with hemorrhagic diseases. It is considered an invasive technique with potential massive bleeding and it requires standardized procedures to prevent complications. Local pressure after the procedure (with eventually ice rest) must be always done. In case of bleeding a rapid replacement therapy must be conducted. A severe complication in hemophilia is compartment syndrome. We report a case of massive bleeding in a hemophilic newborn after venipuncture and a literature review of compartment syndrome in hemophiliacs. The aim of this paper is to help physicians in the clinical management to prevent the evolution of a massive bleeding in compartment syndrome.

Venous thromboembolism (VTE) in children is a rare occurrence, although in recent decades we have seen an increase due to several factors, such as the rise in survival of subjects with chronic conditions, the use of catheters, and the increased sensitivity of diagnostic tools. Besides inherited thrombophilia, acquired conditions such as cardiovascular diseases, infections, chronic disorders, obesity and malignancy are also common risk factors for paediatric VTE. The treatment of paediatric VTE consists of the use of heparins and/or vitamin K antagonists to prevent dissemination, embolization, and secondary VTE. Randomized clinical trials of direct oral anticoagulants in paediatric VTE are ongoing, with the aim to improve the compliance and the care of patients. We reviewed the physiological and pathological mechanisms underlying paediatric thrombosis and updated the current diagnosis and treatment options.

Autoimmune thyroid disorders, including Graves’ disease and Hashimoto’s thyroiditis, have been reported in patients with primary immune thrombocytopenia (ITP). Several etiopathogenetic mechanisms connecting thyroid diseases and thrombocytopenia have been described. Thrombocytopenia is often documented in patients with Graves’ disease, due to reduced platelet life span in hyperthyroidism, immune dysregulation and genetic predisposition (HLA B8 presence). We present the case of a 14-years old girl, who was referred to our Pediatrics Unit, because of contemporary appearance of weight loss, profuse sweating and episodes of recurrent epistaxis. A complete health team, made up of hematologists and endocrinologists, met in consultation in order to reach a diagnosis. A suppression of serum Thyroid-stimulating hormone (TSH) concentrations, the presence of anti-TSH receptor antibodies, and at the same time an immune thrombocytopenia with positive anti-platelet antibodies, have been detected. Furthermore, a positive direct and indirect Coombs test without hemolytic anemia, antinuclear antibodies (ANA) positivity, and a C4 consumption have been documented. The patient started treatment with thiamazole with progressive improvement of thyroid function and thrombocytopenia, requiring only an intravenous immunoglobulin infusion on one time. A multidisciplinary follow-up has been scheduled, in order to monitor the multi-organ immune dysregulation. This report documents a significant improvement of thrombocytopenia after antithyroid treatment in a young subject affected with Graves’ disease. (www.actabiomedica.it)

Alagille syndrome is an autosomal dominant multisystem disorder with variable phenotypic penetrance, caused by heterozygous mutations in JAG1 or NOTCH2, encoding for the components of the Notch signaling pathway. In this paper, we described a novel mutation not yet reported in literature. This 3-years old male child was referred to our Clinical Genetics Unit because of delayed psychomotor development, systolic murmur, dysmorphic facial features, and hypertransaminasemia. The novel JAG1 heterozygous c.2026delT variant in exon 16 was found. JAG1 mutations are classified as protein truncating and non-protein truncating, without any genotype-phenotype correlation. The detected mutation determines a stop codon (p.Cys676AlafsTer67) in the gene sequence, encoding a truncated protein. Our report broadens the spectrum of JAG1 gene mutations.

Objective: Immune thrombocytopenia (ITP) is an acquired immuno-mediated disorder characterized by thrombocytopenia with an increased risk of bleeding. In recent years 1,25[OH]2D3 has been rediscovered as an immune modulator. We decided to evaluate serum Vitamin D levels in a cohort of children with immune thrombocytopenia in order to discover if Vitamin D concentrations may predict ITP duration. Methods: Thirty children were enrolled in this study (sixteen with chronic ITP and fourteen with newly diagnosed ITP) to assess serum Vitamin D levels. Results:: The results showed that 80% of the enrolled children presented a D hypovitaminosis status. Children with newly diagnosis ITP showed no statistically significantly higher median values of Vitamin D compared to chronic ITP. Conclusions:: This study may suggest that Vitamin D deficiency does not represent a chronicity factor for ITP. However, further studies are needed to understand the role of Vitamin D in ITP pathogenesis.

Pediatric patients with Prader-Willi syndrome (PWS) can be treated with recombinant human GH (rhGH). These patients are highly sensitive to rhGH and the standard doses suggested by the international guidelines often result in IGF-1 above the normal range. We aimed to evaluate 1 the proper rhGH dose to optimize auxological outcomes and to avoid potential overtreatment, and 2 which patients are more sensitive to rhGH. In this multicenter real-life study, we recruited 215 patients with PWS older than 1 year, on rhGH at least for 6 months, from Italian Centers for PWS care. We collected auxological parameters, rhGH dose, IGF-1 at recruitment and (when available) at start of treatment. The rhGH dose was 4.3 (0.7/8.4) mg/m2/week. At recruitment, IGF-1 was normal in 72.1% and elevated in 27.9% of the patients. In the group of 115 patients with IGF-1 available at start of rhGH, normal pretreatment IGF-1 and uniparental disomy were associated with elevated IGF-1 during the therapy. No difference in height and growth velocity was found between patients treated with the highest and the lowest range dose. The rhGH dose prescribed in Italy seems lower than the recommended one. Normal pretreatment IGF-1 and uniparental disomy are risk factors for elevated IGF-1. The latter seems to be associated with higher sensitivity to GH. In case of these risk factors, we recommend a more accurate titration of the dose to avoid overtreatment and its potential side effects.

Human coronaviruses (HCoVs) commonly cause mild upper-respiratory tract illnesses but can lead to more severe and diffusive diseases. A variety of signs and symptoms may be present, and infections can range in severity from common cold and sore throat to more serious laryngeal or tracheal infections, bronchitis, and pneumonia. Among the seven coronaviruses that affect humans, (SARS)-CoV, the Middle East respiratory syndrome (MERS)-CoV and the most recent coronavirus disease 2019 (COVID-19) represent potential life-threatening diseases worldwide. In adults they may cause severe pneumonia that evolve in distress respiratory syndrome and multiorgan failure with a high mortality rate. Children appear to be less susceptible to develop severe clinical disease and present usually with mild and aspecific symptoms similar to other respiratory infections typical of childhood. However, some children such as infants, adolescents or those with underlying diseases may be more at-risk categories and require greater caution from clinicians. Available data on pediatric coronavirus infections are rare and scattered in the literature. The purpose of this review is to provide to clinicians a complete and updated panel useful to recognize and characterize the broad spectrum of clinical manifestations of coronavirus infections in the pediatric age.

Letter to Editor

Shiga toxin-producing Escherichia Coli (STEC) infections routinely run as a common gastroenteritis, but in many cases they may evolve towards hemolytic uremic syndrome (HUS). HUS is a rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Gut microorganisms have a fundamental impact on human physiology, because they modulate normal intestinal functions and play a pivotal role in influencing the local and systemic immune responses. Despite surveillance established in many countries and major progresses in the understanding of STEC-HUS mechanisms, no specific treatment is currently available. Targeting the gut microbiota could represent a new potential therapeutic strategy in STEC infection. In this paper, we reviewed the current knowledge about microbiota characteristics of patients with STEC infections, as well as in vitro and in vivo evidence of probiotic supplementation in managing STEC gastroenteritis and in HUS onset prevention.