Circulating Endothelial Cell Levels Correlate with Treatment Outcomes of Splanchnic Vein Thrombosis in Patients with Chronic Myeloproliferative Neoplasms

Circulating endothelial cells (CECs) are viable, apoptotic or necrotic cells, identified by CD 146 surface antigen expression, considered a biomarker of thrombotic risk, given their active role in inflammatory, procoagulant and immune processes of the vascular compartment. Growing evidence establishes that CECs are also involved in the pathogenesis of several hematological and solid malignancies. The primary aim of this study was to verify if CEC levels could predict both the course and treatment responses of splanchnic vein thrombosis (SVT), either in patients affected by myeloproliferative neoplasms (MPNs) or liver disease. Thus, a retrospective multicenter study was performed; fifteen patients receiving anticoagulant oral treatment with vitamin k antagonists (VKA) for SVT were evaluated. Nine patients were affected by MPN, and all of them received cytoreduction in addition to anticoagulant therapy; four of these patients had primary myelofibrosis (PMF) and were treated with ruxolitinib (RUX), and one patient with primary myelofibrosis, two patients with essential thrombocythemia (ET), and two patients with polycythemia vera (PV) were treated with hydroxyurea (HU). Six patients affected by liver diseases (three with liver cirrhosis and three with hepatocellular carcinoma) were included as the control group. CECs were assayed by flow cytometry on peripheral blood at specific time points, for up to six months after enrollment. The CEC levels were related to C-reactive protein (CRP) levels, splenic volume reduction, and thrombus recanalization, mainly in MPN patients. In patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC), for which the mechanism of SVT development is quite different, the relationship between CEC and SV reduction was absent. In conclusion, the CEC levels showed a significant correlation with the extent of venous thrombosis and endothelial cell damage in myeloproliferative neoplasm patients with splanchnic vein thrombosis. Although preliminary, these results show how monitoring CEC levels during cytoreductive and anticoagulant treatments may be useful to improve SVT outcome in MPN patients

Ruxolitinib rechallenge in resistant or intolerant patients with myelofibrosis: Frequency, therapeutic effects, and impact on outcome

BACKGROUND After ruxolitinib discontinuation, the outcome of patients with myelofibrosis (MF) is poor with scarce therapeutic possibilities. METHODS The authors performed a subanalysis of an observational, retrospective study (RUX-MF) that included 703 MF patients treated with ruxolitinib to investigate 1) the frequency and reasons for ruxolitinib rechallenge, 2) its therapeutic effects, and 3) its impact on overall survival. RESULTS A total of 219 patients (31.2%) discontinued ruxolitinib for >= 14 days and survived for >= 30 days. In 60 patients (27.4%), ruxolitinib was rechallenged for >= 14 days (RUX-again patients), whereas 159 patients (72.6%) discontinued it permanently (RUX-stop patients). The baseline characteristics of the 2 cohorts were comparable, but discontinuation due to a lack/loss of spleen response was lower in RUX-again patients (P = .004). In comparison with the disease status at the first ruxolitinib stop, at its restart, there was a significant increase in patients with large splenomegaly (P < .001) and a high Total Symptom Score (TSS; P < .001). During the rechallenge, 44.6% and 48.3% of the patients had spleen and symptom improvements, respectively, with a significant increase in the number of patients with a TSS reduction (P = .01). Although the use of a ruxolitinib dose > 10 mg twice daily predicted better spleen (P = .05) and symptom improvements (P = .02), the reasons for/duration of ruxolitinib discontinuation and the use of other therapies before rechallenge were not associated with rechallenge efficacy. At 1 and 2 years, 33.3% and 48.3% of RUX-again patients, respectively, had permanently discontinued ruxolitinib. The median overall survival was 27.9 months, and it was significantly longer for RUX-again patients (P = .004). CONCLUSIONS Ruxolitinib rechallenge was mainly used in intolerant patients; there were clinical improvements and a possible survival advantage in many cases, but there was a substantial rate of permanent discontinuation. Ruxolitinib rechallenge should be balanced against newer therapeutic possibilities

Thrombosis in essential thrombocytemia and early/prefibrotic primary myelofibrosis: the role of the WHO histological diagnosis

BACKGROUND: Vascular events represent the most frequent complications of thrombocytemias. We aimed to evaluate their risk in the WHO histologic categories of Essential Thrombocytemia (ET) and early Primary Myelofibrosis (PMF). METHODS: From our clinical database of 283 thrombocytemic patients, we selected those with available bone marrow histology performed before any treatment, at or within 1 year from diagnosis, and reclassified the 131 cases as true ET or early PMF, with or without fibrosis, according to the WHO histological criteria. Vaso-occlusive events at diagnosis and in the follow-up were compared in the WHO-groups. RESULTS: Histologic review reclassified 61 cases as ET and 72 cases as early PMF (26 prefibrotic and 42 with grade 1 or 2 fibrosis). Compared to ET, early PMF showed a significant higher rate of thrombosis both in the past history (22% vs 8%) and at diagnosis (15.2% vs 1.6%), and an increased leukocyte count (8389 vs 7500/mmc). Venous thromboses (mainly atypical) were relatively more common in PMF than in ET. Patients with prefibrotic PMF, although younger, showed a significant higher 15-year risk of developing thrombosis (48% vs 16% in fibrotic PMF and 17% in ET). At multivariate analysis, age and WHO histology were both independent risk-factors for thrombosis during follow-up; patients >60 yr-old or with prefibrotic PMF showed a significantly higher risk at 20 years than patients <60 yr-old with ET or fibrotic PMF (47% vs 4%, p = 0.005). CONCLUSIONS: Our study support the importance of WHO histologic categories in the thrombotic risk stratification of patients with thrombocytemias. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2020211863144412

When is it worth waiting for? Food quantity, but not food quality, affects delay tolerance in tufted capuchin monkeys

When faced with choices between smaller sooner options and larger later options (i.e. intertemporal choices), both humans and non-human animals discount future rewards. Apparently, only humans consistently show the magnitude effect, according to which larger options are discounted over time at a lower rate than smaller options. Most of the studies carried out in non-human animals led instead to negative results. Here, we tested ten tufted capuchin monkeys (Sapajus spp.) in a delay choice task to evaluate whether they show a magnitude effect when choosing between different quantities of the same food or when the options are represented by high- and low-preferred foods in different conditions. Whereas food quality did not play a role, we provided the first evidence of an effect of the reward amount on temporal preferences in a non-human primate species, a result with potential implications for the validity of comparative studies on the evolution of delay tolerance. In contrast with human results, but as shown in other animal species, capuchins’ choice of the larger later option decreased as the amount of the smaller sooner option increased. Capuchins based their temporal preferences on the quantity of the smaller sooner option, rather than on that of the larger later option, probably because in the wild they virtually never have to choose between the above two options at the same time, but they more often encounter them consecutively. Thus, paying attention to the sooner option and deciding on the basis of its features may be an adaptive strategy rather than an irrational response

Costituenti bioattivi degli alimenti di origine vegetale

La parola «nutraceutica» è la crasi, non solo semantica, tra i termini nutrienti e farmaceutica, e la disciplina corrispondente richiede la conoscenza di aspetti chimici e biologici, oltre a mostrare che tipo di declinazione ha impresso alla chimica degli alimenti. A partire dal 1990 infatti, anno in cui si è tenuto in Italia il primo Congresso nazionale di Chimica degli alimenti, l'attenzione in questo campo ha cominciato a orientarsi verso la presenza di contaminanti organici e inorganici nei cibi, di metaboliti secondari e di microcostituenti di interesse nutraceutico e salutistico. Da allora sono stati fatti molti passi avanti e questo settore si è rivelato strategico dal punto di vista economico, della salute della popolazione e dell'ampliamento delle conoscenze riguardanti il nostro metabolismo. Oggi abbiamo a disposizione la possibilità di svolgere indagini approfondite sugli aspetti compositivi degli alimenti e sulla loro tracciabilità, grazie a sistemi innovativi quali le tecniche multidimensionali, per esempio quelle heart-cutting e comprehensive, o le nuove tecniche di spettrometria di massa, per citarne alcune. Gli alimenti sono così descrivibili per la loro composizione, o per le loro proprietà tecnologiche, reologiche o per le caratteristiche commerciali e sensoriali, ma anche per il contributo che possono dare alla salute e al benessere, cosa che intende fare questo libro. "La chimica e gli alimenti. Nutrienti e aspetti nutraceutici" è un testo che unisce la descrizione della composizione chimica degli alimenti in termini di micro e macronutrienti e di metaboliti secondari, e dei loro effetti salutistici, all'aspetto legislativo, passando in rassegna le tappe più significative che ha attraversato la legislazione in materia negli ultimi anni; dà anche conto degli aspetti analitici più avanzati, oltre a non trascurare il tema della sicurezza e l'importanza della componente sensoriale degli alimenti

Thrombosis in essential thrombocytemia and early/prefibrotic primary myelofibrosis: The role of the WHO histological diagnosis

none12noBACKGROUND: Vascular events represent the most frequent complications of thrombocytemias. We aimed to evaluate their risk in the WHO histologic categories of Essential Thrombocytemia (ET) and early Primary Myelofibrosis (PMF). METHODS: From our clinical database of 283 thrombocytemic patients, we selected those with available bone marrow histology performed before any treatment, at or within 1 year from diagnosis, and reclassified the 131 cases as true ET or early PMF, with or without fibrosis, according to the WHO histological criteria. Vaso-occlusive events at diagnosis and in the follow-up were compared in the WHO-groups. RESULTS: Histologic review reclassified 61 cases as ET and 72 cases as early PMF (26 prefibrotic and 42 with grade 1 or 2 fibrosis). Compared to ET, early PMF showed a significant higher rate of thrombosis both in the past history (22% vs 8%) and at diagnosis (15.2% vs 1.6%), and an increased leukocyte count (8389 vs 7500/mmc). Venous thromboses (mainly atypical) were relatively more common in PMF than in ET. Patients with prefibrotic PMF, although younger, showed a significant higher 15-year risk of developing thrombosis (48% vs 16% in fibrotic PMF and 17% in ET). At multivariate analysis, age and WHO histology were both independent risk-factors for thrombosis during follow-up; patients >60 yr-old or with prefibrotic PMF showed a significantly higher risk at 20 years than patients <60 yr-old with ET or fibrotic PMF (47% vs 4%, p = 0.005). CONCLUSIONS: Our study support the importance of WHO histologic categories in the thrombotic risk stratification of patients with thrombocytemiasRupoli, S; Goteri, G; Picardi, P; Micucci, G; Canafoglia, L; Scortechini A.R; Federici, I; Giantomassi, F; Da Lio, L; Zizzi, A; Honorati, E; Leoni, P.Rupoli, S; Goteri, Gaia; Picardi, P; Micucci, Giorgia; Canafoglia, Lucia; Scortechini A., R; Federici, I; Giantomassi, F; Da Lio, L; Zizzi, A; Honorati, Elisa; Leoni, Pietr

Antioxidant Activity of Citrus Limonoids and Investigation of Their Virucidal Potential against SARS-CoV-2 in Cellular Models

: The COVID-19 pandemic represents an unprecedented global emergency. Despite all efforts, COVID-19 remains a threat to public health, due to the complexity of mass vaccination programs, the lack of effective drugs, and the emergence of new variants. A link has recently been found between the risk of developing a severe COVID-19 infection and a high level of oxidative stress. In this context, we have focused our attention on natural compounds with the aim of finding molecules capable of acting through a dual virucidal-antioxidant mechanism. In particular, we studied the potential of grapefruit seed extracts (GSE) and their main components, belonging to the class of limonoids. Using chemical and biological approaches including isolation and purification of GSE, antioxidant and virucidal assays, we have shown that grapefruit seed constituents, belonging to the class of limonoids, are endowed with remarkable virucidal, antioxidant and mitoprotective activity