The anti-IgE monoclonal antibody omalizumab as adjuvant treatment in desensitization to carboplatin in patients with ovarian cancer

• Ovarian cancer is the most lethal among gynecological cancers. • Carboplatin-based chemotherapy identifies as the main systemic treatment for ovarian cancer patients. • Almost one every three patients treated with carboplatin experiences hypersensitivity reactions. • Patients may experience breakthrough reactions during drug desensitization. • Omalizumab represents a promising new treatment to overcome carboplatin hypersensitivity

A practical guide to recognize allergic and immunologic skin diseases: diagnosis at first sight

Allergic and immunologic skin diseases are becoming increasingly common and this requires clinicians to be able to recognize and diagnose them. A joint meeting (GET TOGETHER 2022) of the Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC) and the Italian Society of Allergological, Occupational and Environmental Dermatology (SIDAPA) aimed to review the current knowledge on the differential diagnosis of contact dermatitis, atopic dermatitis, hereditary angioedema, urticaria, and cutaneous mastocytosis. The most important aspects to take into consideration when faced with a new cutaneous manifestation are the clinical features of the lesions, their distribution, age of onset, and comorbidities/aggravating factors. The document does not aim to provide an exhaustive and comprehensive description of all allergic and immunologic skin diseases. Instead, it should be a reference tool for the clinician who is faced with the onset of a new skin manifestation and its differential diagnosis

Dissociable Effects of Reward on Attentional Learning: From Passive Associations to Active Monitoring

Visual selective attention (VSA) is the cognitive function that regulates ongoing processing of retinal input in order for selected representations to gain privileged access to perceptual awareness and guide behavior, facilitating analysis of currently relevant information while suppressing the less relevant input. Recent findings indicate that the deployment of VSA is shaped according to past outcomes. Targets whose selection has led to rewarding outcomes become relatively easier to select in the future, and distracters that have been ignored with higher gains are more easily discarded. Although outcomes (monetary rewards) were completely predetermined in our prior studies, participants were told that higher rewards would follow more efficient responses. In a new experiment we have eliminated the illusory link between performance and outcomes by informing subjects that rewards were randomly assigned. This trivial yet crucial manipulation led to strikingly different results. Items that were associated more frequently with higher gains became more difficult to ignore, regardless of the role (target or distracter) they played when differential rewards were delivered. Therefore, VSA is shaped by two distinct reward-related learning mechanisms: one requiring active monitoring of performance and outcome, and a second one detecting the sheer association between objects in the environment (whether attended or ignored) and the more-or-less rewarding events that accompany them

Attentional Biases for Smoking Cues in Smokers

Gli stimoli motivazionali dell\u2019ambiente, associati alle ricompense, sono in grado di innescare cambiamenti plastici nel cervello, facendo in modo che l\u2019attenzione sia prioritaria verso questi stimoli. Di conseguenza il sistema attentivo \ue8 spesso anomalo nei soggetti con dipendenza da sostanze d\u2019abuso. Gli stimoli correlati alla sostanza d\u2019abuso attirano l\u2019attenzione in modo automatico. Per esempio i fumatori mostrano bias attenzionali verso stimoli associati al fumo. I meccanismo alla base di questo fenomeno sono ancora dibattuti. Abbiamo indagato l\u2019influenza del genere e di altri fattori associati alla dipendenza da nicotina sui fenomeni di cattura dell\u2019attenzione provocata da stimoli associati al fumo di sigaretta in una popolazione di giovani fumatori. Abbiamo trovato una differenza di genere e pi\uf9 precisamente, solo i maschi mostravano una cattura attenzionale per gli stimoli associati al fumo di sigaretta. Inoltre sia per i maschi che per le femmine abbiamo trovato una forte associazione del fenomeno di cattura attenzionale con le abitudini di fumo. Nel complesso questi risultati svelano un influsso determinante di vari predittori, in particolare il genere, nel determinare il fenomeno di cattura attenzionale verso stimoli associati alla dipendenza da nicotina nei fumatori cronici.The activation of motivational systems by stimuli in the environment which are associated with rewarding experiences is able to trigger plastic changes in the brain, thereby altering the attentional priority of those stimuli. As a result, attentional deployment is often abnormal in addiction, with drug-related stimuli attracting attention automatically and gaining control over behavior. For example, smokers show attentional biases towards smoke-related cues, but the mechanisms underlying these effects and the nature of their link to addiction are still debated. Here we investigated the influence of gender and individual factors on the temporal dynamics of attentional deployment towards smoke-related stimuli in young smokers. Crucially, we found a striking gender difference, with only males exhibiting a typical attentional bias for smoke-related items, and the bias revealed strong time dependency. Additionally, for both males and females, various personality traits and smoking habits predicted the direction and strength of the measured bias. Overall, these results unveil a crucial influence of several predictors \u2013 notably gender, on the biases of attention towards smoke-related items in chronic smokers

Biases of attention in chronic smokers: men and women are not alike.

The activation of motivational systems by stimuli in the environment that are associated with rewarding experiences is able to trigger plastic changes in the brain, thereby altering the attentional priority of those stimuli. As a result, attentional deployment is often abnormal in addiction, with drug-related stimuli attracting attention automatically and gaining control over behavior. For example, smokers show attentional biases toward smoke-related cues, but the mechanisms underlying these effects and the nature of their link to addiction are still debated. Here, we investigated the influence of gender and individual factors on the temporal dynamics of attentional deployment toward smoke-related stimuli in young smokers. Crucially, we found a striking gender difference, with only males exhibiting a typical attentional bias for smoke-related items, and the bias revealed strong time dependency. Additionally, for both males and females, various personality traits and smoking habits predicted the direction and strength of the measured bias. Overall, these results unveil a crucial influence of several predictors-notably, gender-on the biases of attention toward smoke-related items in chronic smokers

Rewards teach visual selective attention

AbstractVisual selective attention is the brain function that modulates ongoing processing of retinal input in order for selected representations to gain privileged access to perceptual awareness and guide behavior. Enhanced analysis of currently relevant or otherwise salient information is often accompanied by suppressed processing of the less relevant or salient input. Recent findings indicate that rewards exert a powerful influence on the deployment of visual selective attention. Such influence takes different forms depending on the specific protocol adopted in the given study. In some cases, the prospect of earning a larger reward in relation to a specific stimulus or location biases attention accordingly in order to maximize overall gain. This is mediated by an effect of reward acting as a type of incentive motivation for the strategic control of attention. In contrast, reward delivery can directly alter the processing of specific stimuli by increasing their attentional priority, and this can be measured even when rewards are no longer involved, reflecting a form of reward-mediated attentional learning. As a further development, recent work demonstrates that rewards can affect attentional learning in dissociable ways depending on whether rewards are perceived as feedback on performance or instead are registered as random-like events occurring during task performance. Specifically, it appears that visual selective attention is shaped by two distinct reward-related learning mechanisms: one requiring active monitoring of performance and outcome, and a second one detecting the sheer association between objects in the environment (whether attended or ignored) and the more-or-less rewarding events that accompany them. Overall this emerging literature demonstrates unequivocally that rewards “teach” visual selective attention so that processing resources will be allocated to objects, features and locations which are likely to optimize the organism’s interaction with the surrounding environment and maximize positive outcome

How to Prevent and Mitigate Hypersensitivity Reactions to Biologicals Induced by Anti-Drug Antibodies?

Biologicals are widely used therapeutic agents for rheumatologic diseases, cancers, and other chronic inflammatory diseases. They are characterized by complex structures and content of variable amounts of foreign regions, which may lead to anti-drug antibodies (ADA) development. ADA onset may limit the clinical usage of biologicals because they may decrease their safety. In fact they are mainly associated with immediate hypersensitivity reactions (HSRs). Development of ADAs is reduced by concomitant immunosuppressive treatment, while it is increased by longer intervals between drug administrations; thus, regular infusion regimens should be preferred to reduce HSRs. Once ADAs have formed, some procedures can be implemented to reduce the risk of HSRs. ADAs may belong to different isotype; the detection of IgE ADA is advisable to be assessed when high and early ADAs are detected, in order to reduce the risk of severe HRs. In patients who need to reintroduce the biological culprit, as alternative therapies are not available, drug desensitization (DD) may be applied. Desensitization should be conceptually dedicated to patients with an IgE-mediated HSR; however, it can be performed also in patients who had developed non-IgE-mediated HSRs. Although the underlying mechanisms behind successful DD has not been fully clarified, the DD procedure is associated with the inhibition of mast cell degranulation and cytokine production. Additionally, some data are emerging about the inhibition of drug-specific immune responses during DD.</jats:p

Behavioral results.

<p>a) Results obtained in our previous research, showing that the effect of reward bias depended on the attentional role of each stimulus during biased reward delivery (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0019460#pone.0019460-DellaLibera2" target="_blank">[28]</a> Exp. 1). b) Results obtained in the present Experiment, showing a generalized effect of reward bias, unaffected by the associated attentional roles. Note that the y-axes scales in a) and b) slightly differ. In all plots error bars denote SEM.</p

EGPA Phenotyping: Not Only ANCA, but Also Eosinophils

Background: Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a small-vessel necrotizing vasculitis. The anti-neutrophil cytoplasmic antibodies&rsquo; (ANCA) role in defining clinical EGPA phenotypes is well established. Although the role of eosinophils in disease pathogenesis has been clearly demonstrated, the value of blood eosinophil count (BEC) as a biomarker of disease phenotypes is currently uncertain. Methods: We retrospectively analyzed EGPA patients referred to our Immunology Clinic. Demographic, laboratory and clinical features were retrieved from clinical records, and a Logistic Regression was fitted to evaluate the predictive power of all baseline clinical and laboratory features to define EGPA phenotypes. Results: 168 patients were recruited. BEC &le; 1500 cells/mL was predictive of a clinical involvement characterized by asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and lung opacities (OR 0.18, 95% CI 0.07&ndash;0.43; respiratory-limited phenotype); BEC &gt; 3500/mL was predictive of extrapulmonary organ involvement (OR 3.5, 95% CI 1.7&ndash;7.1; systemic phenotype). BEC was also predictive of peripheral nervous system (PNS) involvement, with a positive trend with increasing BEC (&lt;1500/mL: OR 0.17, 95%CI, 0.06&ndash;0.47; &gt;3500/mL: OR 2.8, 95% CI, 1.5&ndash;5.28). ANCA positivity was also predictive of extrapulmonary involvement (OR 4.7, 95% CI 1.9&ndash;11.99). Conclusions: according to BEC and irrespective of the ANCA status, two EGPA phenotypes could be identified, named systemic and respiratory-limited phenotypes, with different organ involvement and possibly different prognoses