This report assesses the impact of the COVID-19 pandemic on pediatric cancer patients over an 8-week period elapsing from the day of the Italian outbreak (February 20, 2020) to the time of writing (April 15, 2020) in Lombardia region, the epicenter of the pandemic in Italy and one of the worst-hit areas in Europe. During the 8-week period, 155 467 confirmed COVID-19 diagnoses and 19 508 deaths due to the virus were reported in Italy, while Lombardia registered 63 098 positive cases (40% of all Italians affected) and 11 384 deaths. Lombardia is the central region of northern Italy, covering an area of 23 863 km 2 with a population of 10 million (population density 421.6/km 2 ). The region has six pediatric onco-hematology centers.Cancer incidence in the region's population aged 0-18 years is approximately 19/100 000, with 320 new cases expected to occur each year. 1In addition, 40-50% additional patients come from other Italian regions

The diagnosis of cow’s milk allergy (CMA) is particularly challenging in infants, especially with non-Immunoglobulin E (IgE)-mediated manifestations, and inaccurate diagnosis may lead to unnecessary dietary restrictions. The aim of this study was to assess the accuracy of the cow’s milk-related symptom score (CoMiSSTM) in response to a cow’s milk-free diet (CMFD). We prospectively recruited 47 infants (median age three months) who had been placed on a CMFD due to persisting unexplained gastrointestinal symptoms. We compared data with 94 healthy controls (median age three months). The CoMiSSTM score was completed at recruitment and while on the exclusion diet. In 19/47 (40%) cases a response to the diet occurred. At recruitment CoMiSSTM was significantly higher in cases compared to controls (median score 8 vs. 3; p-value: <0.05), 9 cases had a score ≥12 and 8/9 normalized on CMFD. An oral milk challenge was performed in all 19 responders and six of these had a positive reaction to cow’s milk (CM). In eight infants IgE allergy tests were positive. The receiver operation characteristic (ROC) curve identified a CoMISSTM score of 9 to be the best cut-off value (84% sensitivity, 85% specificity, 80% positive (PPV) and 88% negative predictive value (NPV)) for the response to CMFD. We found CoMiSSTM to be a useful tool to help identify infants with persisting gastrointestinal symptoms and suspected CMA that would benefit from CMFD.

SummaryAutoimmune diseases are more represented in Down syndrome (DS) individuals compared to chromosomally normal people. Natural T regulatory cells (nTreg) have been considered to be primary in the role of controlling the intensity and targets of the immune response. We have investigated the phenotypical and functional alteration of nTreg in a group of DS people. The phenotypical characteristic of Treg cells of 29 DS was analysed and compared with an age-matched healthy control group. The inhibitory potential of CD4 + CD25 high CD127 low T regulatory cells was evaluated on autologous CD4+ CD25 -T cell proliferation in response to activation with a mytogenic pan-stimulus (anti-CD2, anti-CD3 and anti-CD28 antibodies). The CD4 + CD25 high cells in the DS and control groups were 2·692 Ϯ 0·3808%, n = 29 and 1·246 Ϯ 0·119, n = 29%, respectively (P = 0.0007), with a percentage of forkhead box protein 3 (FoxP3)-expressing cells of 79·21 Ϯ 3·376%, n = 29 and 59·75 Ϯ 4·496%, respectively (P = 0.0015). CD4 + CD25 + FoxP3 + cells were increased in peripheral blood from DS subjects (DS mean 5·231 Ϯ 0·6065% n = 29, control mean 3·076 Ϯ 0·3140% n = 29). The majority of CD4 + CD25 high were CD127 low and expressed a high percentage of FoxP3 (natural Treg phenotype). While the proliferative capacity of DS T cells was not altered significantly compared to normal individuals, a reduced inhibitory potential of Treg compared to healthy controls was clearly observed (mean healthy control inhibition in Teff : Treg 1:1 co-culture: 58·9% Ϯ 4·157%, n = 10 versus mean DS inhibition in Teff : Treg 1:1 co-culture: 39·8 Ϯ 4·788%, n = 10, P = 0.0075; mean healthy control inhibition in Teff : Treg 1:0·5 co-culture: 45·10 Ϯ 5·858%, n = 10 versus DS inhibition in Teff : Treg 1:0·5 co-culture: 24·10 Ϯ 5·517%, n = 10, P = 0.0177). DS people present an over-expressed peripheral nTreg population with a defective inhibitory activity that may partially explain the increased frequency of autoimmune disease.

Background: X-linked agammaglobulinemia (XLA) is the prototype of primary humoral immunodeficiencies. Long-term follow-up studies regarding disease-related complications and outcome are scarce. Objective: Our aim was to describe the natural history of XLA. Methods: A nationwide multicenter study based on the Italian Primary Immunodeficiency Network registry was established in 2000 in Italy. Affected patients were enrolled by documenting centers, and the patients' laboratory, clinical, and imaging data were recorded on an annual base.Results: Data on the patients (N 5 168) were derived from a cumulative follow-up of 1370 patient-years, with a mean followup of 8.35 years per patient. The mean age at diagnosis decreased after establishment of the Italian Primary Immunodeficiency Network registry (84 months before vs 23 months after). Respiratory, skin, and gastrointestinal manifestations were the most frequent clinical symptoms at diagnosis and during long-term follow-up. Regular immunoglobulin replacement treatment reduced the incidence of invasive infections. Affected patients developed chronic lung