Pediatric extraspinal sacrococcygeal ependymoma (ESE): an Italian AIEOP experience of six cases and literature review

Background: Primary pediatric extraspinal sacrococcygeal ependymoma (ESE) is a very rare disease, poorly described in literature, whose diagnostic, therapeutic, and follow-up approach is still controversial. Methods: We describe six cases of pediatric ESE treated at Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) centers in Italy since 1983, with a review of the literature. Results: All six patients had primary sacrococcygeal disease (two presacral and four subcutaneous) with median age of 10 years. Three patients were males, and two of them are metastatic at diagnosis; 3/6 had myxopapillary ependymoma grade I and 3/6 had classic ependymoma grade II. Five patients underwent surgical resection with complete removal only in one case with coccygectomy. Adjuvant chemoradiotherapy was administered to one metastatic patient obtaining a complete remission. Two patients relapsed at 3 and 8 years from diagnosis: they were treated with salvage chemotherapy (high-dose sequential chemotherapy with myeloablative regimen in one case), surgery, and radiotherapy achieving complete remission (CR). All six patients are in complete continuous remission (CCR) at a median follow-up of 12.8 years. Conclusions: Pediatric patients with this peculiar disease need to be referred to specialized pediatric cancer centers that can provide multidisciplinary treatment after a centralized pathology review. Our experience highlights the role of chemotherapy and radiotherapy in adjuvant and relapse setting. The final prognosis is relatively optimistic, but with a careful follow-up due to the high risk of recurrence

Epidemiology, risk factors and therapy of candidemia in pediatric hematological patients

Invasive fungal infections (IFI) are an important cause of morbidity, increased hospitalization and healthcare costs in critically ill or immunocompromised children. The mortality is comprised between 5 and 20%. In the last 2 decades, the epidemiology of candidemia has changed with an increase of episodes caused by non-Candida albicans species. Central venous catheter, diagnosis of malignancy, and receipt of either vancomycin or antimicrobials with activity against anaerobic organisms for >3 days have been associated with the development of candidemia in the pediatric intensive care unit (PICU). Additional risk factors found in hematological patients were the diagnosis of aplastic anemia, performing an unrelated bone marrow or cord blood transplant, the occurrence of a graft versus host disease and the use of steroids. Early antifungal treatment is recommended to reduce mortality. In neutropenic patients, liposomal amphotericin B, an echinocandin (caspofungin, micafungin), and voriconazole are considered the best option especially for C. glabrata and C. krusei. Fluconazole remains a valid option for infection by Candida albicans in patients not exposed to fluconazole prophylaxis. Amphotericn B deoxy-cholate is generally not recommended because of its nephrotoxicity

Evaluation of energy metabolism and calcium homeostasis in cells affected by Shwachman-Diamond syndrome

Isomorphic mutation of the SBDS gene causes Shwachman-Diamond syndrome (SDS). SDS is a rare genetic bone marrow failure and cancer predisposition syndrome. SDS cells have ribosome biogenesis and their protein synthesis altered, which are two high-energy consuming cellular processes. The reported changes in reactive oxygen species production, endoplasmic reticulum stress response and reduced mitochondrial functionality suggest an energy production defect in SDS cells. In our work, we have demonstrated that SDS cells display a Complex IV activity impairment, which causes an oxidative phosphorylation metabolism defect, with a consequent decrease in ATP production. These data were confirmed by an increased glycolytic rate, which compensated for the energetic stress. Moreover, the signalling pathways involved in glycolysis activation also appeared more activated; i.e. we reported AMP-activated protein kinase hyper-phosphorylation. Notably, we also observed an increase in a mammalian target of rapamycin phosphorylation and high intracellular calcium concentration levels ([Ca2+]i), which probably represent new biochemical equilibrium modulation in SDS cells. Finally, the SDS cell response to leucine (Leu) was investigated, suggesting its possible use as a therapeutic adjuvant to be tested in clinical trials

La experiencia de los bio-distritos: el ejemplo del Bio-Distretto Cilento y las oportunidades para los territorios de la Comunidad Valenciana

El Cilento, zona sur de la provincia de Salerno, en Italia, hace casi quince años apostó por un modelo de desarrollo territorial integrado, basado en la tradición italiana de los distritos industriales, claramente enfocado a la promoción de las producciones agroalimentarias biológicas de la región y que se formó a partir de la participación y del compromiso de un abanico muy amplio de actores. El ejemplo del Bio-Distretto Cilento se ha convertido en un punto de referencia tanto a nivel nacional como internacional, y ha permitido crear un canal de cooperación entre distintas experiencias vinculadas con la protección de áreas rurales, la agroecología y las metodologías participativas. Por otro lado, hay en el País Valenciano muchas potencialidades para la agricultura ecológica en las zonas rurales Por eso, a partir de la experiencia del Cilento se analizan los impactos que tiene un bio-distrito sobre el territorio y se identifica un área dentro de la Comunidad Valenciana, a partir de una investigación sobre los recursos presentes y los posibles actores involucrados y las oportunidades que la iniciativa pueda proporcionar, donde la creación de un biodistrito podría representar una oportunidad única para revitalizar esas comarcas

From time series to visibility algorithms: A novel approach to study the spread of SARS-CoV-2 in wastewater

The detection of SARS-CoV-2 in faeces encouraged various studies exploring wastewater as a disease surveillance tool from a wastewater-based epidemiology (WBE) perspective. Virus concentration data in wastewater are collected and arranged in time series and generally analysed by using statistical approaches. However, for studying complex and non-linear phenomena, this procedure may not be effective. In this regard, the present work introduces an alternative and innovative approach to analyse time series of SARS-CoV-2 concentration in wastewater based on visibility algorithms. The temporal evolution of the epidemic is transformed into a visibility graph that allows the study of time series from a nonlinear perspective. The connectivity structure of the visibility graph encapsulates significant information of the starting time series. By investigating the topological characteristics of the graph, it is possible to extract nontrivial evidence to give a physical interpretation of the phenomenon and to identify the factors that mainly influence the virus transmission. The proposed approach has been applied to the time series data collected at ten wastewater treatment plants to interpret the trend of the epidemic and attempt to forecast the phenomenon in the analysed basins. Overall, using visibility algorithms to study COVID-19 in sewage is a valuable tool for monitoring the community, with potential for predicting epidemics and community behaviours

Prophylaxis and therapy of viral infections in pediatric patients treated for malignancy

Infections are still an important cause of mortality and morbidity in pediatric cancer patients. Most of the febrile episodes in immunocompromised patients are classified as a fever of unknown origin (FUO) while bacteria are the more frequent causes of documented infections. Viral infections are also feared during chemotherapy but less data are available on their incidence and morbidity. We reviewed the literature on incidence, morbidity, and mortality of viral infections in children undergoing chemotherapy and discussed the evidence concerning the prophylaxis and the therapy

Biosimilars in the management of neutropenia: focus on filgrastim

Advances in chemotherapy and surgery allows the majority of patients to survive cancer diseases. Yet, the price may be a proportion of patients dying of complications due to treatment-induced infectious complications, such as neutropenia. With the aim of decreasing morbidity and mortality related to infectious complications, recombinant human granulocyte colony-stimulating factor (G-CSF), filgrastim, and pegylated filgrastim have been used to reduce time and degree of neutropenia. A biosimilar is a copy of an approved original biologic medicine whose data protection has expired. The patent for filgrastim expired in Europe in 2006 and in the US in 2013. This review analyses the available evidence to be considered in order to design a strategy of use of G-CSF and its biosimilars. The clinical and safety outcomes of biosimilars are well within the range of historically reported data for originator filgrastim. This underscores the clinical effectiveness and safety of biosimilar filgrastim in daily clinical practice. Biosimilars can play an important role by offering the opportunity to reduce costs, thus contributing to the financial sustainability of treatment programs

Cidofovir for BK Virus-Associated Hemorrhagic Cystitis: A Retrospective Study

Background.BK virus-associated hemorrhagic cystitis (BKV-HC) is a severe complication after allogeneic hematopoietic stem cell transplantation (HSCT), but antiviral treatment for this condition has not been evaluated. Methods.We conducted a retrospective survey on the safety and outcome of cidofovir treatment for patients with BKV-HC in centers affiliated with the European Group for Blood and Marrow Transplantation. Results.From 1 April 2004 to 31 December 2007, 62 patients received a diagnosis of BKV-HC after a median interval of 35 days after HSCT (range, 3-577 days). Fifty-seven patients (92%) received intravenous cidofovir, whereas 5 patients received cidofovir intravesically. Complete response (CR) was recorded in 38 (67%) of 57 patients with HC treated with intravenous cidofovir, whereas partial response (PR) was documented in 7 patients (12%). CR was documented in 3 patients and PR in 1 patient with HC treated with intravesical cidofovir. A reduction of 1-3 logs in BKV load was documented in 8 of the 10 patients achieving CR. Mild-to-moderate toxic effects were recorded in 18 of 57 patients who received intravenous cidofovir administration. In a multivariate analysis, the factors significantly associated with response to cidofovir were the stem cell source (P=.01) and the use of total body irradiation (P=.03). After a median follow-up of 287 days, overall survival and total treatment-related mortality rates were 63% and 40% for patients achieving CR, compared with 14% and 72% for patients with PR or no response to cidofovir, respectively (P<.001 and P=.001, respectively). Conclusions.Cidofovir may be a potentially effective therapy for BKV-HC, but evidence supporting its use requires randomized controlled trial

Monitoring planning for urban drainage networks

Urban drainage network (UDN) monitoring is an important task whose planning can be related to various purposes, as for example contaminant detection and epidemiological studies. This paper proposes two different strategies for the identification of a monitoring system for UDNs. The optimal solution, in terms of location and number of sensors, is firstly addressed using a deterministic approach. A new mathematical model is developed and a global optimization solver is employed to perform the optimization procedure. Secondly, the position of devices is also investigated using a new strategy based on the complex network theory (CNT) tools. The comparison between the results achieved by both the strategies is finally presented with reference to a benchmark network