Tamara Belotti

Allergy is not the main trigger of urticaria in children referred to the emergency room

Background  Urticaria is the disease that has the highest impact on quality of life and requires the most visits to the emergency room.

Genomic complexity and dynamics of clonal evolution in childhood acute myeloid leukemia studied with whole-exome sequencing

Despite significant improvement in treatment of childhood acute myeloid leukemia (AML), 30% of patients experience disease recurrence, which is still the major cause of treatment failure and death in these patients. To investigate molecular mechanisms underlying relapse, we performed whole-exome sequencing of diagnosis-relapse pairs and matched remission samples from 4 pediatric AML patients without recurrent cytogenetic alterations. Candidate driver mutations were selected for targeted deep sequencing at high coverage, suitable to detect small subclones (0.12%). BiCEBPα mutation was found to be stable and highly penetrant, representing a separate biological and clinical entity, unlike WT1 mutations, which were extremely unstable. Among the mutational patterns underlying relapse, we detected the acquisition of proliferative advantage by signaling activation (PTPN11 and FLT3-TKD mutations) and the increased resistance to apoptosis (hyperactivation of TYK2). We also found a previously undescribed feature of AML, consisting of a hypermutator phenotype caused by SETD2 inactivation. The consequent accumulation of new mutations promotes the adaptability of the leukemia, contributing to clonal selection. We report a novel ASXL3 mutation characterizing a very small subclone (<1%) present at diagnosis and undergoing expansion (60%) at relapse. Taken together, these findings provide molecular clues for designing optimal therapeutic strategies, in terms of target selection, adequate schedule design and reliable response-monitoring techniques.

Spleen nodules: a potential hallmark of Visceral Leishmaniasis in young children.

BackgroundVisceral leishmaniasis (VL) is a severe disease caused by Leishmania infantum in the Mediterranean basin, and is associated with considerable morbidity and mortality. Infantile VL may begin suddenly, with high fever and vomiting, or insidiously, with irregular daily fever, anorexia, and marked splenomegaly. Delays in diagnosis of VL are common, highlighting the need for increased awareness of clinicians for VL in endemic European countries.Case presentationWe report 4 cases of young children in northern Italy presenting with persistent fever of unknown origin and diagnosed with VL by serological and molecular methods. At the time of diagnosis, these patients showed an unusual echographic pattern characterized by multiple iso-hypoechoic nodules associated with splenomegaly.ConclusionWe suggest that detection of spleen nodules represents a signature of VL in infants, thus helping to diagnose systemic Leishmania infantum infection in children.

Not All Children with Under-Control Asthma are Controlled

Subclinical lung function alterations can sometimes be discovered in asthmatic patients under clinical control. This study aimed to identify the burden of asthmatic children with subclinical airways abnormalities who may benefit from an adjustment in asthma therapy. 134 6-to-17-year-old asthmatic children were enrolled. Of them, 98 presented apparently under clinical control disease and all performed spirometry before and after bronchodilation: 17 (17.3%) had a positive bronchodilation test, in addition to significantly lower lung function indexes as compared to those with under-control asthma who had a negative bronchodilation test. These patients were randomized and re-evaluated: patients (n=8) receiving an adjustment in their therapy showed an improvement in lung function tests and quality of life indexes as compared to 7 without therapy adjustment. In conclusion, a substantial number of apparently-under-control asthmatic children show airways alterations that can be improved by adjusting their therapy, which also seems to enhance their quality of life.

Risk factors associated with development and mortality by invasive fungal diseases in pediatric allogeneic stem cell transplantation. A pediatric subgroup analysis of data from a prospective study of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO)

Allogeneic hemopoietic stem cell transplant (HSCT) is a high-risk procedure for development of invasive fungal diseases (IFD) in children. Pre-engraftment neutropenia and severe Graft vs. host disease (GvHD) represent probably the most known, risk factors [1–3], but other factors like age, type of donor, and immunosuppressive therapy have also been reported [1, 3–9]. In 2014 the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) published a nationwide prospective survey performed in the period 2008–2010 on risk factors for IFD and IFD-related mortality in the first year after allogeneic HSCT [10]. This original study included both adults and children, but a specific pediatric subpopulation analysis was not performed. The present study retrospectively analyzed epidemiology, risk factors for IFD, and IFD-related mortality in the subpopulation of patients aging ≤18 years. Results were compared with that of the original study, and not specifically with those strictly observed in adults, that in any case represented near 90% of patients enrolled, suggesting a high strength of the results of that study at least for the adults’ population. Data collected and definitions were the same adopted in the original study for IFD, time of occurrence after HSCT and GvHD, as well as for the analyzed variables [10]. However, since the number of patients aging ≤18 years were a fraction (205/1858, 11%) of all included in the original one, some simplifications were introduced in the analyzed variables (underlying disease and its phase, previous HSCT, donor type, type of conditioning regimen, mold active antifungal prophylaxis, status of a pretransplant IFD, center HSCT activity) in order to avoid the presence of categories with too few subjects. Qualitative data were reported as absolute frequencies and percentages and quantitative data as median values and interquartile range (IQR). Cumulative incidence of IFD was calculated considering a possible competing risk of IFD with underlying disease relapse, or death. Overall mortality was estimated by the Kaplan–Meier method and the log-rank test was applied to assess differences between curves. Multivariable analysis was adopted to identify risk factors for IFD and IFD-associated mortality [11]: sub-distribution hazard ratio (SHR) with the 95% confidence interval (CI) was calculated to analyze risk factors and hazard ratio (HR) with 95% for mortality. Likelihood ratio test (LRT) was performed to measure the effect of each predictor. All tests were two-tailed and a p value <0.05 was considered * Elio Castagnola eliocastagnola@gaslini.org

A New Formulation of an Old Drug: A Potential New Therapy in the Management of Oral cGvHD

Oral chronic graft versus host disease (cGVHD) is often refractory to systemic therapies. Additional topical treatment is commonly required. The potency of the agent, the vehicle and formulation in which it is delivered are all critical factors in determining the effectiveness of topical therapies. High potency of budesonide, combined with its very low bioavailability when absorbed through mucosal surfaces, increased the potential role in topical application for oral cGVHD. Viscous formulation increases mucosal contact time resulting in a greater decrease in mucosal inflammation. This short communication suggests that oral viscous budesonide should be considered as a potential new therapy in the management of oral cGVHD.

Anterior Mediastinal Tumors

The mediastinum is the most common site of chest masses in children. Mediastinal masses are placed in one of three mediastinal compartments (anterior, middle, posterior) on the basis of a lateral chest radiograph [1] They comprise a wide spectrum of disease, and around 40% occur in children aged <2 years of age. Mediastinal masses are usually assigned to a single mediastinal compartment to limit the differential diagnosis. Large mediastinal masses can cause compression of adjacent structures. Patients may have airway compression or cardiovascular compromise. A total of 39% of mediastinal masses are benign and 61% are malignant, with more than half of these being lymphoma [2]. A total of 44% of all mediastical lesions are anterior mediastinal tumors [3], which are relatively rare in the pediatric population. Most are due to hematogenous malignancy and about half of these patients are asymptomatic. Anterior mediastinal masses represent a heterogeneous group of congenital and neoplastic lesions, many of which are malignant [4, 5].

Tumors of the Chest Wall

Chest wall tumors (CWTs) in children comprise a wide range of benign and malignant neoplasms. These tumors are rare in infants, children and young adults, accounting for 1.8% of solid tumors [1]. However, high proportions of CWTs are malignant, and represent a diagnostic and therapeutic challenge to pediatric thoracic surgeons. The chest wall can be affected by: primary malignant neoplasms arising from different structures; secondary tumors which can invade the chest wall from the adjacent structures (e.g., breast, pleura, mediastinum, lung); metastatic tumors [2].