Real-practice thromboprophylaxis in atrial fibrillation

This retrospective observational study was based on databases of the Local Health Authority of Treviso, Italy. It evaluated the prevalence and the effectiveness of oral anticoagulation treatment (OAT) for the management of nonvalvular atrial fibrillation (NVAF) in everyday clinical practice. Out of 6,138 NVAF patients, only 3,024 received Vitamin K antagonist (VKA). Potential barriers decreasing the probability of being treated with VKA were female sex, older age, antiplatelet treatment and history of bleeding. In addition, VKA-treatment was not in line with current ESC and AIAC guidelines, since the patients at high or low risk of stroke were under-or over-treated, resp. Among VKAtreated patients, 73 % of subjects were not at target with anticoagulation. OAT resulted to be effective in reducing stroke risk. However, stroke events were significantly influenced also by previous stroke or transient ischemic attack (hazard ratio, HR = 2.99, p < 0.001) and by previous bleeding events (HR = 1.60, p < 0.001)

Role of Oxidative Stress Mediated by Glutathione-S-transferase in Thiopurines' Toxic Effects

Azathioprine (AZA), 6-mercaptopurine (6-MP), and 6-thioguanine (6-TG) are antimetabolite drugs, widely used as immunosuppressants and anticancer agents. Despite their proven efficacy, a high incidence of toxic effects in patients during standard-dose therapy is recorded. The aim of this study is to explain, from a mechanistic point of view, the clinical evidence showing a significant role of glutathione-S-transferase (GST)-M1 genotype on AZA toxicity in inflammatory bowel disease patients. To this aim, the human nontumor IHH and HCEC cell lines were chosen as predictive models of the hepatic and intestinal tissues, respectively. AZA, but not 6-MP and 6-TG, induced a concentration-dependent superoxide anion production that seemed dependent on GSH depletion. N-Acetylcysteine reduced the AZA antiproliferative effect in both cell lines, and GST-M1 overexpression increased both superoxide anion production and cytotoxicity, especially in transfected HCEC cells. In this study, an in vitro model to study thiopurines' metabolism has been set up and helped us to demonstrate, for the first time, a clear role of GST-M1 in modulating AZA cytotoxicity, with a close dependency on superoxide anion production. These results provide the molecular basis to shed light on the clinical evidence suggesting a role of GST-M1 genotype in influencing the toxic effects of AZA treatment

Safety and anti-tumour activity of the IgE antibody MOv18 in patients with advanced solid tumours expressing folate receptor-alpha: a phase I trial

All antibodies approved for cancer therapy are monoclonal IgGs but the biology of IgE, supported by comparative preclinical data, offers the potential for enhanced effector cell potency. Here we report a Phase I dose escalation trial (NCT02546921) with the primary objective of exploring the safety and tolerability of MOv18 IgE, a chimeric first-in-class IgE antibody, in patients with tumours expressing the relevant antigen, folate receptor-alpha. The trial incorporated skin prick and basophil activation tests (BAT) to select patients at lowest risk of allergic toxicity. Secondary objectives were exploration of anti-tumour activity, recommended Phase II dose, and pharmacokinetics. Dose escalation ranged from 70 μg–12 mg. The most common toxicity of MOv18 IgE is transient urticaria. A single patient experienced anaphylaxis, likely explained by detection of circulating basophils at baseline that could be activated by MOv18 IgE. The BAT assay was used to avoid enrolling further patients with reactive basophils. The safety profile is tolerable and maximum tolerated dose has not been reached, with evidence of anti-tumour activity observed in a patient with ovarian cancer. These results demonstrate the potential of IgE therapy for cancer

B cell profiles, antibody repertoire and reactivity reveal dysregulated responses with autoimmune features in melanoma

B cells are known to contribute to the anti-tumor immune response, especially in immunogenic tumors such as melanoma, yet humoral immunity has not been characterized in these cancers to detail. Here we show comprehensive phenotyping in samples of circulating and tumor-resident B cells as well as serum antibodies in melanoma patients. Memory B cells are enriched in tumors compared to blood in paired samples and feature distinct antibody repertoires, linked to specific isotypes. Tumor-associated B cells undergo clonal expansion, class switch recombination, somatic hypermutation and receptor revision. Compared with blood, tumor-associated B cells produce antibodies with proportionally higher levels of unproductive sequences and distinct complementarity determining region 3 properties. The observed features are signs of affinity maturation and polyreactivity and suggest an active and aberrant autoimmune-like reaction in the tumor microenvironment. Consistent with this, tumor-derived antibodies are polyreactive and characterized by autoantigen recognition. Serum antibodies show reactivity to antigens attributed to autoimmune diseases and cancer, and their levels are higher in patients with active disease compared to post-resection state. Our findings thus reveal B cell lineage dysregulation with distinct antibody repertoire and specificity, alongside clonally-expanded tumor-infiltrating B cells with autoimmune-like features, shaping the humoral immune response in melanoma

Prime osservazioni sull\u2019afide asiatico Tuberocephalus (T.) tianmushanensis Zhang in Italia.

L\u2019afide asiatico Tuberocephalus ( Trichosiphoniella ) tianmushanensis Zhang (Hemiptera Aphididae) \ue8 stato osservato per la prima volta in Italia nel maggio 2012 su due esemplari di Prunus subhirtella cv. pendula presenti nell\u2019Orto Botanico di Padova, sui quali sono state notate molte foglie con caratteristiche galle di color rosa - rossastro. Tempo addietro la specie era stata segnalata in Francia ed eradicata con successo nell\u2019anno successivo. Il presente studio si \ue8 proposto di verificare, mediante controllo dei ciliegi ornamentali presenti nel territorio veneto, l\u2019eventuale presenza e diffusione della specie, la sua fenologia e l\u2019identificazione dell\u2019ospite secondario, trattandosi di un afide con ciclo biologico dioico. I rilievi sono stati effettuati sia sull\u2019ospite primario, Prunus subhirtella cv. pendula , sia sul presunto ospite secondario, Artemisia vulgar is , a partire dal mese di ottobre 2012 al mese di ottobre 2014. Dalle prime ricerche effettuate la specie appare presente sul territorio in modo limitato e frammentario. La sua presenza, verificata in un vivaio di piante ornamentali sito nel comune di Saon ara (PD), \ue8 indice dell\u2019importante ruolo che i vivai di piante ornamentali hanno nell\u2019introduzione e nella diffusione di specie esotiche. La popolazione all\u2019interno delle galle \ue8 stata monitorata per due anni successivi. La prova di trasferimento delle fem mine fondatrigenie alate (migranti) su Artemisia vulgaris , riportata in letteratura come ospite secondario, non ha avuto esito positivo, per cui l\u2019ospite secondario della specie rimane incerto . Tuttavia il ritrovamento, per due anni consecutivi, della spec ie sull\u2019ospite primario \ue8 un indice certo del completamento dell\u2019olociclo e quindi della presenza dell\u2019ospite secondario nella zona di studio. Dalle osservazioni effettuate \ue8 possibile affermare che la specie risulta acclimatata nel nostro ambiente in quan to la sua popolazione \ue8 presente in misura numerica sufficiente a persistere indefinitamente nel nuovo territori

Prime osservazioni sull\u2019afide asiatico Tuberocephalus (T.) tianmushanensis Zhang in Italia.

L\u2019afide asiatic Tuberocephalus ( Trichosiphoniella ) tianmushanensis Zhang (Hemiptera Aphididae) \ue8 stato osservato per la prima volta in Italia nel maggio 2012 su due esemplari di Prunus subhirtella cv. pendula presenti nell\u2019Orto Botanico di Padova, sui quali sono state notate molte foglie con caratteristiche galle di color rosa - rossastro. Tempo addietro la specie era stata segnalata in Francia ed eradicata con successo nell\u2019anno successivo. Il presente studio si \ue8 proposto di verificare, mediante controllo dei ciliegi ornamentali presenti nel territorio veneto, l\u2019eventuale presenza e diffusione della specie, la sua fenologia e l\u2019identificazione dell\u2019ospite secondario, trattandosi di un afide con ciclo biologico dioico. I rilievi sono stati effettuati sia sull\u2019ospite primario, Prunus subhirtella cv. pendula , sia sul presunto ospite secondario, Artemisia vulgar is , a partire dal mese di ottobre 2012 al mese di ottobre 2014. Dalle prime ricerche effettuate la specie appare presente sul territorio in modo limitato e frammentario. La sua presenza, verificata in un vivaio di piante ornamentali sito nel comune di Saon ara (PD), \ue8 indice dell\u2019importante ruolo che i vivai di piante ornamentali hanno nell\u2019introduzione e nella diffusione di specie esotiche. La popolazione all\u2019interno delle galle \ue8 stata monitorata per due anni successivi. La prova di trasferimento delle fem mine fondatrigenie alate (migranti) su Artemisia vulgaris , riportata in letteratura come ospite secondario, non ha avuto esito positivo, per cui l\u2019ospite secondario della specie rimane incerto . Tuttavia il ritrovamento, per due anni consecutivi, della spec ie sull\u2019ospite primario \ue8 un indice certo del completamento dell\u2019olociclo e quindi della presenza dell\u2019ospite secondario nella zona di studio. Dalle osservazioni effettuate \ue8 possibile affermare che la specie risulta acclimatata nel nostro ambiente in quan to la sua popolazione \ue8 presente in misura numerica sufficiente a persistere indefinitamente nel nuovo territorio

Therapeutic targets and new directions for antibodies developed for ovarian cancer

Antibody therapeutics against different target antigens are widely used in the treatment of different malignancies including ovarian carcinomas, but this disease still requires more effective agents. Improved understanding of the biological features, signaling pathways, and immunological escape mechanisms involved in ovarian cancer has emerged in the past few years. These advances, including an appreciation of the cross-talk between cancer cells and the patient's immune system, have led to the identification of new targets. In turn, potential antibody treatments with various mechanisms of action, including immune activation or toxin-delivery, that are directed at these targets have been developed. Here, we identify established as well as novel targets for antibodies in ovarian cancer, and discuss how they may provide fresh opportunities to identify interventions with enhanced therapeutic potential