Metabolomic profile of patients with left ventricular assist devices: a pilot study

Background: Metabolomic profiling has important diagnostic and prognostic value in heart failure (HF). We investigated whether left ventricular assist device (LVAD) support has an impact on the metabolomic profile of chronic HF patients and if specific metabolic patterns are associated with the development of adverse events. Methods: We applied untargeted metabolomics to detect and analyze molecules such as amino acids, sugars, fatty acids and other metabolites in plasma samples collected from thirty-three patients implanted with a continuous-flow LVAD. Data were analyzed at baseline, i.e., before implantation of the LVAD, and at long-term follow-up. Results: Our results reveal significant changes in the metabolomic profile after LVAD implant compared to baseline. In detail, we observed a pre-implant reduction in amino acid metabolism (aminoacyl-tRNA biosynthesis) and increased galactose metabolism, which reversed over the course of support [median follow-up 187 days (63–334 days)]. These changes were associated with improved patient functional capacity driven by LVAD therapy, according to NYHA functional classification of HF (NYHA class I-II: pre-implant =0% of the patients; post-implant =97% of the patients; P<0.001). Moreover, patients who developed adverse thromboembolic events (n=4, 13%) showed a pre-operative metabolomic fingerprint mainly associated with alterations of fatty acid biosynthesis and mitochondrial beta-oxidation of short-chain saturated fatty acids. Conclusions: Our data provide preliminary evidence that LVAD therapy is associated with changes in the metabolomic profile of HF and suggest the potential use of metabolomics as a new tool to stratify LVAD patients in regard to the risk of adverse events

Human protein C concentrate in pediatric septic patients

Severe sepsis and septic shock are leading causes of morbidity and mortality in the pediatric population. Unlike what is suggested for the adult population, recombinant human activated protein C (rhAPC) is contraindicated in children. Long before rhAPC was considered for use in pediatric patients, case reports appeared on the safe administration of protein C zymogen. Therefore, we conducted a systemic review of currently available data on protein C zymogen (PC) use among children affected by severe sepsis or septic shock. A total number of 13 case series or case reports and a dose-finding study were found on the use of PC in the pediatric intensive care unit, reporting on 118 treated children, with an overall survival of 84%. There was no bleeding complication, the only reported complication being a single mild allergic reaction. These studies show that PC is safe, not associated with bleeding and possibly useful for improving coagulation abnormalities of sepsis

Human protein C concentrate in pediatric septic patients

Severe sepsis and septic shock are leading causes of morbidity and mortality in the pediatric population. Unlike what is suggested for the adult population, recombinant human activated protein C (rhAPC) is contraindicated in children. Long before rhAPC was considered for use in pediatric patients, case reports appeared on the safe administration of protein C zymogen. Therefore, we conducted a systemic review of currently available data on protein C zymogen (PC) use among children affected by severe sepsis or septic shock. A total number of 13 case series or case reports and a dose-finding study were found on the use of PC in the pediatric intensive care unit, reporting on 118 treated children, with an overall survival of 84%. There was no bleeding complication, the only reported complication being a single mild allergic reaction. These studies show that PC is safe, not associated with bleeding and possibly useful for improving coagulation abnormalities of sepsis

Adjuvant Treatment in Pancreatic Cancer: Shaping the Future of the Curative Setting

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease even in the early stages, despite progresses in surgical and pharmacological treatment in recent years. High potential for metastases is the main cause of therapeutic failure in localized disease, highlighting the current limited knowledge of underlying pathological processes. However, nowadays research is focusing on the search for personalized approaches also in the adjuvant setting for PDAC, by implementing the use of biomarkers and investigating new therapeutic targets. In this context, the aim of this narrative review is to summarize the current treatment scenario and new potential therapeutic approaches in early stage PDAC, from both a preclinical and clinical point of view. Additionally, the review examines the role of target therapies in localized PDAC and the influence of neoadjuvant treatments on survival outcomes

Cerebral Perfusion and Neuromonitoring during Complex Aortic Arch Surgery: A Narrative Review

: Complex ascending and aortic arch surgery requires the implementation of different cerebral protection strategies to avoid or limit the probability of intraoperative brain damage during circulatory arrest. The etiology of the damage is multifactorial, involving cerebral embolism, hypoperfusion, hypoxia and inflammatory response. These protective strategies include the use of deep or moderate hypothermia to reduce the cerebral oxygen consumption, allowing the toleration of a variable period of absence of cerebral blood flow, and the use of different cerebral perfusion techniques, both anterograde and retrograde, on top of hypothermia, to avoid any period of intraoperative brain ischemia. In this narrative review, the pathophysiology of cerebral damage during aortic surgery is described. The different options for brain protection, including hypothermia, anterograde or retrograde cerebral perfusion, are also analyzed, with a critical review of the advantages and limitations under a technical point of view. Finally, the current systems of intraoperative brain monitoring are also discussed

Genomic properties of chromosomal bands are linked to evolutionary rearrangements and new centromere formation in primates

Chromosomal rearrangements in humans are largely related to pathological conditions, and phenotypic effects are also linked to alterations in the expression profile following nuclear relocation of genes between functionally different compartments, generally occupying the periphery or the inner part of the cell nuclei. On the other hand, during evolution chromosomal rearrangements may occur apparently without damaging phenotypic effects, and are visible in currently phylogenetically-related species. To increase our insight into chromosomal reorganisation in the cell nucleus, we analysed eighteen chromosomal regions endowed with different genomic properties in cell lines derived from eight primate species covering the entire evolutionary tree. We show that homologous loci, in spite of their evolutionary relocation along the chromosomes, generally remain localised to the same functional compartment of the cell nuclei. We conclude that evolutionarily succesfull chromosomal rearrangements are those that leave the nuclear position of the regions involved unchanged. On the contrary, in pathological situations, the effect typically observed is on gene structure alteration or gene nuclear reposition. Moreover, our data indicate that new centromere formation could potentially occur everywhere in the chromosomes, but only those emerging in very GC-poor/gene-poor regions, generally located in the nuclear periphery, have a high probability of being retained through evolution. This suggests that, in the cell nucleus of related species, evolutionary chromosomal reshufflings or new centromere formation does not alter the functionality of the regions involved or the interactions between different loci, thus preserving the expression pattern of orthologous genes

Costruire geo-competenze, apprendimento permanente, lavoro decente, quale ruolo per la GIScience e i Sistemi a Pilotaggio Remoto nella promozione degli obiettivi di sostenibilità al 2030?

La Geographic Information Science è stata considerata la “causa comune per la ricerca interdisciplinare” (Onsrud, Kuhn, 2015). Nell'era dei sistemi aerei a pilotaggio remoto, l’Università di Padova ha avviato con l’anno accademico 2015/2016 un nuovo master di secondo livello in “GIScience e Sistemi a Pilotaggio Remoto (SAPR) per la gestione integrata del territorio e delle risorse naturali”. Il master vede la collaborazione di cinque dipartimenti universitari, aziende che operano nel campo della GIScience e dei droni, ONG. Con il volume del 2016 Education for people and planet: Creating sustainable futures for all, l'UNESCO ha avviato il monitoraggio dell'obiettivo 4 dei Sustainable development goals: "Garantire l'educazione di qualità, inclusiva ed equa e promuovere opportunità di apprendimento permanente per tutti". In questo contributo si indagano, alla luce degli obiettivi di sostenibilità al 2030, le possibili integrazioni tra apprendimento permanente, lavoro decente, sviluppo sostenibile, innovazione tecnologica ed il ruolo della GIScience e delle opportunità di utilizzare la piattaforma offerta da un master di secondo livello per facilitare le interazioni tra giovani, imprese, territorio

Niveles altos del mar durante el Último Máximo Interglacial deducidos mediante muescas de abrasión y márgenes internos de terrazas marinas en Puerto Deseado, Provincia de Santa Cruz, Argentina

A detailed geomorphological survey was undertaken in the area of Puerto Deseado (Santa Cruz Province, Argentina) to reconstruct the Relative Sea-level (RSL) position during the Last Interglacial highstand. The presence of active and well-preserved abrasive notches and inner margins of terraces related to the MIS5e and to the Holocene, measured with DGPS, allowed to accurately estimate the RSL change from the present to the MIS5e highstand at ca. 21 m. The geomorphological and geochronological analyses support the notion of the presence of a significant regional tectonic uplift in the Atlantic Patagonia, which can be locally estimated at ca. 0.12 mm/yr.Se realizó un estudio geomorfológico detallado en la zona de Puerto Deseado (provincia de Santa Cruz, Argentina) para reconstruir la posición relativa del nivel (RNM) del mar durante el Último Máximo Interglacial. La presencia de muescas de abrasión activas y bien conservadas, y la posición de los márgenes internos de las terrazas relacionadas con el MIS5e y el Holoceno, medido con GPS diferencial, permitió estimar con precisión el cambio RNM desde el presente hasta la transgresión MIS5e en aproximadamente 21 m. Los análisis geomorfológicos y geocronológicos sustentan la noción de la presencia de un significativo levantamiento tectónico regional en la Patagonia Atlántica, que puede estimarse localmente en alrededor de 0,12 mm/año.Facultad de Ciencias Naturales y Muse

Clinical scenarios for use of transvalvular microaxial pumps in acute heart failure and cardiogenic shock – A European experienced users working group opinion

Abstract For patients with myocardial infarct-related cardiogenic shock (CS), urgent percutaneous coronary intervention is the recommended treatment strategy to limit cardiac and systemic ischemia. However, a specific therapeutic intervention is often missing in non-ischemic CS cases. Though drug treatment with inotropes and/or vasopressors may be required to stabilize the patient initially, their ongoing use is associated with excess mortality. Coronary intervention in unstable patients often leads to further hemodynamic compromise either during or shortly after revascularization. Support devices like the intra-aortic balloon pump failed to improve clinical outcomes in infarct-related CS. Currently, more powerful and active hemodynamic support devices unloading the left ventricle such as transvalvular microaxial pumps are available and are being increasingly used. However, as for other devices large randomized trials are not yet available, and device use is based on registry data and expert consensus. In this article, a multidisciplinary group of experienced users of transvalvular microaxial pumps outlines the pathophysiological background on hemodynamic changes in CS, the available mechanical support devices, and current guideline recommendations. Furthermore, different hemodynamic situations in several case-based scenarios are used to illustrate candidate settings and to provide the theoretic and scientific rationale for left-ventricular unloading in these scenarios. Finally, organization of shock networks, monitoring, weaning, and typical complications and their prevention are discussed