Acute leukemias (both myeloid and lymphoblastic) are a group of diseases for which each year more successful therapies are implemented. However, in a subset of cases the overall survival (OS) is still exceptionally low due to the infiltration of leukemic cells in the central nervous system (CNS) and the subsequent formation of brain tumors. The CNS involvement is more common in acute lymphocytic leukemia (ALL), than in adult acute myeloid leukemia (AML), although the rates for the second case might be underestimated. The main reasons for CNS invasion are related to the expression of specific adhesion molecules (VLA-4, ICAM-1, VCAM, L-selectin, PECAM-1, CD18, LFA-1, CD58, CD44, CXCL12) by a subpopulation of leukemic cells, called "sticky cells" which have the ability to interact and adhere to endothelial cells. Moreover, the microenvironment becomes hypoxic and together with secretion of VEGF-A by ALL or AML cells the permeability of vasculature in the bone marrow increases, coupled with the disruption of blood brain barrier. There is a single subpopulation of leukemia cells, called leukemia stem cells (LSCs) that is able to resist in the new microenvironment due to its high adaptability. The LCSs enter into the arachnoid, migrate, and intensively proliferate in cerebrospinal fluid (CSF) and consequently infiltrate perivascular spaces and brain parenchyma. Moreover, the CNS is an immune privileged site that also protects leukemic cells from chemotherapy. CD56/NCAM is the most important surface molecule often overexpressed by leukemic stem cells that offers them the ability to infiltrate in the CNS. Although

Aims: The objective of the study was to assess the performance of lung ultrasonography (LUS) as compared to chest radiography and the clinical criteria for the diagnosis of pneumonia in children.Materials and methods: This was a retrospective study in which data were collected from medical files of 81 children admitted with a clinical suspicion of pneumonia in which both an LUS and a chest radiograph during the hospitalization were performed. Reference standard used for the diagnosis of pneumonia were chest radiographs (consolidation, parenchymal infiltrates, and interstitial infiltrate) and clinical criteria. LUSfindings were reported as normal, parenchymal consolidations and pleural effusions. Results: Radiological pneumonia was reported in 72 of the 81 patients (88.9%). LUS identified parenchymal consolidations in 62 cases. LUS correctly identified radiological pneumonia with a sensitivity of 79.2% and a specificity of 44.4%. The positive predictive value (PPV) was 91.9% and the negative predictive value (NPV) was 21.0%. When clinical criteria were used as reference standard, the sensitivity, specificity, PPV and NPV of correctly identifying clinical pneumonia cases by LUS (only consolidations) were 80.0%, 66.7%, 96.8% and 21.0%. When indicative for the presence of pneumonia either the ultrasound consolidation or the ultrasound detected pleural effusion were considered when the sensitivity, PPV and NPV increased to 96.0% (95%CI: 88.8-99.2), 97.3% (95%CI: 92.0-99.1), and 57.1% (95%CI: 27.7-82.2), respectively.Conclusions: In our opinion, our findings together withprevious ones available in the literature recommend LUS as a valuable investigation for the diagnosis of community-acquiredpneumonia in children.

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Prophylactic paracetamol administration impacts vaccine immune response; this study (www.clinicaltrials.gov: NCT01235949) is the first to assess PHiD-CV immunogenicity following prophylactic ibuprofen administration. In this phase IV, multicenter, open-label, randomized, controlled, non-inferiority study in Romania (November 2010–December 2012), healthy infants were randomized 3:3:3:1:1:1 to prophylactically receive immediate, delayed or no ibuprofen (IIBU, DIBU, NIBU) or paracetamol (IPARA, DPARA, NPARA) after each of 3 primary doses (PHiD-CV at age 3/4/5 months co-administered with DTPa-HBV-IPV/Hib at 3/5 and DTPa-IPV/Hib at 4 months) or booster dose (PHiD-CV and DTPa-HBV-IPV/Hib; 12–15 months). Non-inferiority of immune response one month post-primary vaccination in terms of percentage of infants with anti-pneumococcal antibody concentrations ≥0.2 µg/mL (primary objective) was demonstrated if the upper limit (UL) of the 98.25% confidence interval of difference between groups (NIBU vs IIBU, NIBU vs DIBU) was <10% for ≥7/10 serotypes. Immunogenicity and reactogenicity/safety were evaluated, including confirmatory analysis of difference in fever incidences post-primary vaccination in IBU or DIBU group compared to NIBU. Of 850 infants randomized, 812 were included in the total vaccinated cohort. Non-inferiority was demonstrated for both comparisons (UL was <10% for 9/10 vaccine serotypes; exceptions: 6B [NIBU], 23F [IIBU]). However, fever incidence post-primary vaccination in the IIBU and DIBU groups did not indicate a statistically significant reduction. Prophylactic administration (immediate or delayed) of paracetamol decreased fever incidence but seemed to reduce immune response to PHiD-CV, except when given only at booster. Twenty-seven serious adverse events were reported for 15 children; all resolved and were not vaccination-related.

During recent decades, understanding of the molecular mechanisms of acute lymphoblastic leukemia (ALL) has improved considerably, resulting in better risk stratification of patients and increased survival rates. Age, white blood cell count (WBC), and specific genetic abnormalities are the most important factors that define risk groups for ALL. State-of-the-art diagnosis of ALL requires cytological and cytogenetical analyses, as well as flow cytometry and high-throughput sequencing assays. An important aspect in the diagnostic characterization of patients with ALL is the identification of the Philadelphia (Ph) chromosome, which warrants the addition of tyrosine kinase inhibitors (TKI) to the chemotherapy backbone. Data that support the benefit of hematopoietic stem cell transplantation (HSCT) in high risk patient subsets or in late relapse patients are still questioned and have yet to be determined conclusive. This article presents the newly published data in ALL workup and treatment, putting it into perspective for the attending physician in hematology and oncology.