- La governance dei corridoi TEN-T transalpini: esperienze e riflessioni strategiche

L’obiettivo del paper è quello di permettere una valutazione sistemica degli strumenti di governance dei corridoi transalpini inseriti nelle reti di trasporto trans europee (TEN-T), evidenziando le relazioni che intercorrono tra gli specifici sistemi di pre-funding, finanziamento e tariffazione e le più ampie politiche dei trasporti e dell’ambiente attivate anche durante la fase di messa a regime e gestione delle infrastrutture. L’analisi si avvale di una matrice di valutazione che tiene conto degli effetti di politica economica ampia oltreché degli impatti trasportistici e delle conseguenze in termini di governance, soffermandosi sull’esame di meccanismi di competizione verticale e orizzontale delle scelte degli enti pubblici coinvolti dai corridoi TEN-T. I casi studio relativi alla Nuova Linea Torino-Lione fra Italia e Francia, della direttrice del Gottardo in Svizzera e del corridoio del Brennero fra Italia e Austria, permettono di comprendere l’ampia valenza di politica economica che sottende queste scelte e come le iniziative attivate da parte dell’Unione Europea sui temi del finanziamento e sulla governance possono offrire spunti di efficientamento dal punto di vista economico

Nutritional modulation of the gut microbiome in allogeneic hematopoietic stem cell transplantation recipients

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents a potentially curative strategy for many oncological and non-oncological diseases, but it is associated with marked morbidity and mortality. The disruption of gut microbiota (GM) eubiosis has been linked to major allo-HSCT complications, including infections and acute graft vs. host disease (aGvHD), and correlates with mortality. This increasing knowledge on the role of the GM in the allo-HSCT procedure has led to fascinating ideas for modulating the intestinal ecosystem in order to improve clinical outcomes. Nutritional strategies, either by changing the route of nutritional supplementation or by administering specific molecules, are increasingly being considered as cost- and risk-effective methods of modulating the GM. Nutritional support has also emerged in the past several years as a key feature in supportive care for allo-HSCT recipients, and deterioration of nutritional status is associated with decreased overall survival and higher complication rates during treatment. Herein we provide a complete overview focused on nutritional modulation of the GM in allo-HSCT recipients. We address how pre transplant diet could affect GM composition and its ability to withstand the upsetting events occurring during transplantation. We also provide a complete overview on the influence of the route of nutritional administration on the intestinal ecosystem, with a particular focus on the comparison between enteral and parenteral nutrition (PN). Moreover, as mounting evidence are showing how specific components of post-transplant diet, such as lactose, could drastically shape the GM, we will also summarize the role of prebiotic supplementation in the modulation of the intestinal flora and in allo-HSCT outcomes

Exploiting Plant Volatile Organic Compounds (VOCs) in Agriculture to Improve Sustainable Defense Strategies and Productivity of Crops

There is an urgent need for new sustainable solutions to support agriculture in facing current environmental challenges. In particular, intensification of productivity and food security needs require sustainable exploitation of natural resources and metabolites. Here, we bring the attention to the agronomic potential of volatile organic compounds (VOCs) emitted from leaves, as a natural and eco-friendly solution to defend plants from stresses and to enhance crop production. To date, application of VOCs is often limited to fight herbivores. Here we argue that potential applications of VOCs are much wider, as they can also protect from pathogens and environmental stresses. VOCs prime plant’s defense mechanisms for an enhanced resistance/tolerance to the upcoming stress, quench reactive oxygen species (ROS), have potent antimicrobial as well as allelopathic effects, and might be important in regulating plant growth, development, and senescence through interactions with plant hormones. Current limits and drawbacks that may hamper the use of VOCs in open field are analyzed, and solutions for a better exploitation of VOCs in future sustainable agriculture are envisioned

ERCC6L2-related disease: a novel entity of bone marrow failure disorder with high risk of clonal evolution

ERCC excision repair 6 like 2 (ERCC6L2) gene encodes for different helicase-like protein members of the Snf2 family involved in transcription-coupled nucleotide excision repair and in cell proliferation. Germline homozygous mutations in children and adults predispose to a peculiar bone marrow failure phenotype characterized by mild hematological alterations with a high risk of developing acute myeloid leukemia. The outcome for patients with leukemia progression is dismal while patients undergoing hematopoietic stem cell transplantation in the early stage have better outcomes. The ERCC6L2-related hematological disease presents a high penetrance, posing important questions regarding the treatment strategies and possible preemptive approaches. This review describes the biological function of ERCC6L2 and the clinical manifestations of the associated disease, trying to focus on the unsolved clinical questions

Chemotherapy-free treatment for acute promyelocytic leukemia: the pediatric view of a revolutionary tale

The addition of all-trans retinoic acid (ATRA) to the standard anthracycline-base chemotherapy has revolutionized the treatment of acute promyelocytic leukemia (APL) over the last decades, becoming a model for precision medicine. The protocols based on the combination of ATRA and chemotherapy allowed obtaining excellent response rates both for children and adults. However, the persistence of anthracycline chemotherapy as a backbone was a matter of concern for both acute and long-term complications. Efforts in reducing anthracycline cumulative dose or even eliminating anthracycline have been pursued in more recent pediatric protocols thanks to the introduction of arsenic trioxide (ATO). The impressive results of the ATRA/ATO combinations led to the introduction of protocols completely chemotherapy-free for standard-risk adult patients as the standard of care, whereas pediatric chemo-free protocols are still currently under evaluation. In this Review, we will critically retrace the history of this unique revolution in precision medicine, discussing the peculiar advantages for pediatric patients with APL

The emerging role of nutritional support in the supportive care of pediatric patients undergoing hematopoietic stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) represents a potentially curative strategy for many oncological, hematological, metabolic, and immunological diseases in children. The continuous effort in ameliorating supportive care represents one of the cornerstones in the improvement of outcome in these patients. Nowadays, more than ever nutritional support can be considered a key feature. Oral feeding in the early post-transplant period is severely impaired because of mucositis due to conditioning regimen, characterized by, mainly by vomiting, anorexia, and diarrhea. Gastrointestinal acute graft-versus-host-disease (GvHD), infections and associated treatments, and other medications, such as opioids and calcineurin inhibitors, have also been correlated with decreased oral intake. The consequent reduction in caloric intake combined with the catabolic effect of therapies and transplantation-related complications with consequent extended immobilization, results in a rapid deterioration of nutritional status, which is associated with decreased overall survival and higher complication rates during treatment. Thus, nutritional support during the early post-transplantation period becomes an essential and challenging issue for allo-HSCT recipients. In this context, the role of nutrition in the modulation of the intestinal flora is also emerging as a key player in the pathophysiology of the main complications of HSCT. The pediatric setting is characterized by less evidence, considering the challenge of addressing nutritional needs in this specific population, and many questions are still unanswered. Thus, we perform a narrative review regarding all aspects of nutritional support in pediatric allo-HSCT recipients, addressing the assessment of nutritional status, the relationship between nutritional status and clinical outcomes and the evaluation of the nutritional support, ranging from specific diets to artificial feeding

Effectiveness of Quinolone Prophylaxis in Pediatric Acute Leukemia and Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-analysis

The effectiveness of quinolone prophylaxis in high-risk hematological pediatric patients is controversial. A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, including studies that involved children and young adults undergoing chemotherapy for acute leukemia or hematopoietic stem cell transplantation (HSCT) who received quinolone prophylaxis compared with no prophylaxis. A meta-analysis was performed on bloodstream infections and neutropenic fever. Data regarding the impact of prophylaxis on overall survival, antibiotic exposure, antibiotic-related adverse effects, antibiotic resistance, Clostridium difficile infections, fungal infections, length of hospitalization, and costs were reviewed in the descriptive analysis. Sixteen studies were included in the qualitative analysis, and 10 of them met the criteria for quantitative analysis. Quinolone prophylaxis was effective in reducing the rate of bloodstream infections and neutropenic fever in pediatric acute leukemia compared with no prophylaxis, but it had no significant effect in HSCT recipients. Prophylaxis was associated with a higher rate of bacterial resistance to fluoroquinolones and higher antibiotic exposure

Venetoclax-based therapies in pediatric advanced MDS and relapsed/refractory AML: a multicenter retrospective analysis

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