Congenital rhabdomyosarcoma: a different clinical presentation in two cases

Background: Rhabdomyosarcoma (RMS), one of the most common soft tissue sarcomas of childhood, is very rare in the neonatal period (0.4-2% of cases). In order to gain a deeper understanding of this disease at such age, patient and tumor features, as well as treatment modality and outcome need to be reported. Case presentation: We describe two cases with congenital RMS treated at Bambino Gesù Children's Hospital between 2000 and 2016. They represent only 2.24% of all RMS patients diagnosed during that period in our Institution; this data is in agreement with the incidence reported in the literature. They reflect the two different clinical forms in which the disease may manifest itself. One patient, with the alveolar subtype (positive for specific PAX3-FOXO1 fusion transcript) and disseminated disease, had a fatal outcome with central nervous system (CNS) progression despite conventional and high dose chemotherapy. The other child, with the localized embryonal subtype, was treated successfully with conservative surgery and conventional chemotherapy, including prolonged maintenance therapy. He is disease free at 7 years of follow-up. Conclusions: RMS can also be diagnosed during the neonatal period. Given the young age, disease management is often challenging, and especially for the alveolar subtype, the outcome is dismal despite intensified multimodality therapy. In fact, it characteristically manifests with multiple subcutaneous nodules and progression most commonly occurs in the CNS (Rodriguez-Galindo et al., Cancer 92(6):1613-20, 2001). In this context, CNS prophylaxis could play a role in preventing leptomeningeal dissemination, and molecular studies can allow a deeper tumor characterization, treatment stratification and identification of new potential therapeutic targets

Current Trends in Gelatin-Based Drug Delivery Systems

Gelatin is a highly versatile natural polymer, which is widely used in healthcare-related sectors due to its advantageous properties, such as biocompatibility, biodegradability, low-cost, and the availability of exposed chemical groups. In the biomedical field, gelatin is used also as a biomaterial for the development of drug delivery systems (DDSs) due to its applicability to several synthesis techniques. In this review, after a brief overview of its chemical and physical properties, the focus is placed on the commonly used techniques for the development of gelatin-based micro- or nano-sized DDSs. We highlight the potential of gelatin as a carrier of many types of bioactive compounds and its ability to tune and control select drugs' release kinetics. The desolvation, nanoprecipitation, coacervation, emulsion, electrospray, and spray drying techniques are described from a methodological and mechanistic point of view, with a careful analysis of the effects of the main variable parameters on the DDSs' properties. Lastly, the outcomes of preclinical and clinical studies involving gelatin-based DDSs are thoroughly discussed

Current evidence of antifungal prophylaxis and therapy in pediatric patients

Invasive fungal infections (IFI) are an important complication in pediatric haematological and oncological patients who undergo intensive chemotherapy for leukemia, solid tumour at advanced stage or relapsed, and hematopoietic stem cell transplantation. The incidence of IFI is lower than bacterial infection but mortality rate remains high. This review is designed to help paediatric oncologists in choosing the appropriate anti-fungal strategy and agents for prophylaxis, empirical, pre-emptive and specific therapy on the basis of published evidence

Modelling Load Stochastic Jumps for Power Systems Dynamic Analysis

This letter proposes an approach to model power system loads as stochastic processes that incorporate both continuous and event-driven dynamics. The letter provides a brief theoretical background on the stochastic differential equations defining Ornstein-Uhlenbeck processes with jumps used for the stochastic modeling of power system voltage-dependent loads. The all-island 1479-bus Irish transmission system serves to illustrate and test the proposed jump-diffusion model

SDE-based wind speed models with Weibull distribution and exponential autocorrelation

This paper discusses three approaches to construct wind speed models based on Stochastic Differential Equations (SDEs). The methods are applied to construct models able to simulate wind speed trajectories that are statistically described by means of the Weibull distribution and the exponential autocorrelation. The ability of the three models to reproduce stochastic processes with the above indicated statistical properties is duly studied and compared. With this aim, wind speed measurements recorded in a weather station located in Ireland are analyzed. The parameters obtained in this analysis are used to set up the developed models. Finally, the statistical properties of the trajectories generated by the three models are compared with the statistical properties of the considered wind speed data set

Association between proton-pump inhibitors (PPI) and metronomic capecitabine (MCAP) as salvage treatment for patients with advanced gastro-intestinal tumoursa. A randomized phase II study

Background: Several researches have shown that acidification of tumor microenvironment is the basis for tumor invasiveness, ability to metastasize S382 Abstracts and cytotoxic agents resistance; therefore proton pump inhibitors (PPI) could significantly increase the chemosensitivity. In our retrospective work we have investigated the role of capecitabine (mCAP) at metronomic dosage of 1500 mg/die as salvage chemotherapy in patients with metastatic colorectal cancer, showing a moderately activity and well tolerability. In this prospective study we evaluated safety and activity of mCAP in the advanced gastro-intestinal patients and the putative chemosensitizing activity of a specific PPI (Rabeprazole) in association to this therap

Low Level of Her-2 Locus Amplification by Fluorescent In Situ Hybridization Does Not Correlate with Her-2 Protein Overexpression by Immunohistochemistry in Barrett's Esophagus

An accurate evaluation of the Her-2 status has important prognostic and therapeutic implications in many carcinomas. The aim of the study was to correlate Her-2 locus (17q11.2) amplification and chromosome 17 gains as assessed by fluorescent in situ hybridization (FISH) with Her-2 protein overexpression by immunohistochemistry (IHC) in patients with Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). We analyzed 34 patients with Her-2 amplification and/or chromosome 17gains using FISH on brush cytology specimens. Seven patients (21%) showed high Her-2 locus amplification (Her-2: Cep17 ≥ 5 : 1), 5 (15%) showed low Her-2 locus amplification (Her-2: Cep17 ≥ 2 < 5 : 1), and 22 (65%) displayed gains of chromosome 17 only. Further, we confirmed Her-2 amplification on corresponding biopsies that were taken at the same occasion as the cytologybrushings. Then, we compared the FISH results with IHC data obtained from the corresponding biopsies and showed that low level of Her-2 amplification does not correlate with Her-2 protein overexpression (score +3/+2; P = 1), in contrast to the high amplification level (P = .001). Thus, in our population of BE and EAC patients, low level of Her-2 amplification does not result in detectable level of Her-2 protein as assessed by IHC

Impact of Variability, Uncertainty and Frequency Regulation on Power System Frequency Distribution

This work originates from the observation of the frequency distribution of the Irish system as obtained from a Frequency Disturbance Recorder lent to the last author by the University of Tennessee. The probability density function of such a distribution appears to be bimodal. The paper first investigates how stochastic sources, in particular, load and wind power estimation errors, impact on the distribution of the frequency of a high-voltage transmission system. Then, possible routes to obtain a bimodal distribution of the frequency are explored and the most likely cause that leads to the observed behaviour of the Irish system is identified. Finally, the paper presents a comparison of different frequency regulation strategies and their impact on the distribution of the frequency. A sensitivity analysis of wind speed and load parameters is presented and discussed based on the IEEE-14 bus system

A pSMAD/CDX2 Complex Is Essential for the Intestinalization of Epithelial Metaplasia

The molecular mechanisms leading to epithelial metaplasias are poorly understood. Barrett's esophagus is a premalignant metaplastic change of the esophageal epithelium into columnar epithelium, occurring in patients suffering from gastroesophageal reflux disease. Mechanisms behind the development of the intestinal subtype, which is associated with the highest cancer risk, are unclear. In humans, it has been suggested that a nonspecialized columnar metaplasia precedes the development of intestinal metaplasia. Here, we propose that a complex made up of at least two factors needs to be activated simultaneously to drive the expression of intestinal type of genes. Using unique animal models and robust in vitro assays, we show that the nonspecialized columnar metaplasia is a precursor of intestinal metaplasia and that pSMAD/CDX2 interaction is essential for the switch toward an intestinal phenotype