Comparative real-world outcomes of dupilumab versus endoscopic sinus surgery in the treatment of severe CRSwNP patients.

INTRODUCTION: Management of severe chronic rhinosinusitis with nasal polyps (CRSwNP) has changed significantly in recent years, with different treatments now available including biologics and endoscopic sinus surgery (ESS), although there are still few comparative studies. We aimed to compare 1-year outcomes of patients with severe CRSwNP treated with dupilumab or ESS plus intranasal corticosteroids (INCS). METHODS: In this retrospective, real-life, observational, cohort study, we enrolled 101 patients with severe CRSwNP who were treated with INCS and either ESS (n = 49) or dupilumab (n = 52). The following outcomes were considered: nasal polyp score (NPS), Sino Nasal Outcome Test-22 (SNOT-22), visual analogue scale (VAS) for specific symptoms, Sniffin' Sticks identification test (SSIT), need for oral corticosteroids (OCS) and local eosinophilia detected by nasal cytology. RESULTS: ΔNPS was significantly higher in the surgery group up to 12 months when the difference with dupilumab group was no longer significant (ΔNPS: 4 vs. 4.1). ΔVAS rhinorrhoea, ΔVAS smell and ΔSNOT-22 were significantly higher in the dupilumab group at 12 months (p < .05). SSIT scores were significantly better in the dupilumab group starting from the first month of follow-up (p < .05). In the dupilumab group, only 6.1% of patients had detectable local eosinophilia compared to 57% in the surgery group alongside with a lower need for OCS (16.3% vs. 61%). CONCLUSIONS: Both dupilumab and ESS were effective in improving outcomes in patients with severe CRSwNP over 12 months. Nevertheless, patients treated with dupilumab had greater improvement in terms of SNOT-22, VAS rhinorrhoea, VAS smell and SSIT scores, with better control of local inflammation and less need for OCS.

Correlation between inflammatory biomarkers and disease control in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) may have a heterogeneous response to medical/surgical treatments based on endotypes. Data correlating biomarkers and severity of the disease are lacking. We aimed to determine if IL-5 and calprotectin may be useful in defining severity of disease and identifying uncontrolled patients. METHODS: This was a case-control study including 81 patients with diffuse CRSwNP who underwent at least one previous surgery and treated with intranasal steroids. We enrolled 39 uncontrolled patients (SNOT-22 ≥ 40 and two or more cycles of systemic corticosteroids in last year) (Group A) and 42 controlled one (SNOT-22 < 40 and less than two cycles of systemic corticosteroids in last year) (Group B). We analyzed IL-5 and calprotectin in both nasal secretions and nasal polyp tissue. RESULTS: Calprotectin and IL-5 were significantly higher in Group A in both secretions and tissue, and the higher the number of previous surgeries, the higher the levels detected in nasal secretions. At univariate analyses, smoking, asthma, non-steroidal anti-inflammatory drugs-exacerbated respiratory disease (NSAID-ERD), blood eosinophilia, neutrophils, and eosinophils at nasal cytology were significantly associated with uncontrolled disease. Multivariate analyses showed that asthma, NSAID-ERD, and IL-5 in nasal secretion/polyp tissue were significantly related to the risk of uncontrolled disease. CONCLUSIONS: Our data suggest that asthma, NSAID-ERD, and IL-5 in nasal secretions/tissue may be helpful to identify more severe patients, as they are related to the risk of uncontrolled disease. Nonetheless, high levels of calprotectin and neutrophilia were also observed in uncontrolled patients, especially after multiple surgeries.

Temporal trends of blood eosinophilia in severe uncontrolled CRSwNP treated with dupilumab: a real-life study.

PURPOSE: Induced eosinophilia is commonly related to dupilumab treatment. We analysed the temporal trends of blood eosinophilia in patients with severe uncontrolled CRSwNP during the first year of treatment with dupilumab in real-life setting to evaluate its correlation with outcomes of response and adverse events (AEs). METHODS: Seventy-four patients with severe uncontrolled CRSwNP treated with dupilumab at our institution were enrolled. At each visit, we evaluated AEC, outcomes of response to treatment and AEs. RESULTS: A significant increase in AEC was observed since the first month with a peak at 3 months; at 12 months, the values returned comparable to those at baseline. A ≥ 50% increase of the baseline AEC with a value greater than 500 cells/mm3 was documented in 38/74 patients (Group A) regardless of the time of observation, whereas in 36/74 patients (Group B), no changes were observed. Analysing the blood eosinophilia trend over time in group A, we observed a temporary eosinophilia with early onset (within 6 months), persistent eosinophilia with early onset, and eosinophilia with late onset. No differences in terms of outcomes of response to treatment or AEs were found between Group A and Group B, or between patients who developed an AEC ≥ 1500 cells/mm3 or not. CONCLUSION: In our series, we observed that an increase in AEC with different temporal trends may be observed in CRSwNP patients during the first year of treatment with dupilumab. In our series, eosinophilia is not correlated with a negative outcome of response to treatment or a risk of AEs.

Effectiveness of Dupilumab in the Treatment of Adult and Older Adult Patients with Severe, Uncontrolled CRSwNP.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial disease that significantly impacts patients' quality of life. New therapeutic strategies and in particular biologic treatments are now available for these patients. It has been demonstrated that Dupilumab (an anti IL-4/IL-13 biologic drug) is effective in reducing the size of nasal polyps and in improving patients' symptoms and thus, quality of life. No real-world studies examining Dupilamab's efficacy in the elderly with respect to other adult age groups have as yet been carried out. The aim of this multicentric study was to evaluate Dupilumab's efficacy in young-middle adults as opposed to an older adult population affected by severe, uncontrolled CRSwNP. Of the 96 patients included in the study, 22 were 65 years old or older. Significant improvements were observed in all the parameters considered in both age groups after treatment was begun (T0 mean values for SNOT-22 = 58.5 ± 20.3, VAS NO = 7.6 ± 2.2, VAS smell = 8.6 ± 2.1, NPS = 5.6 ± 1.4, PNIF = 101.6 ± 59.4, S'S = 5.1 ± 3.1), T4 mean values for SNOT-22 = 15.1 ± 12.7, VAS NO = 1.7 ± 1.8, VAS smell = 2.4 ± 3, NPS = 1.7 ± 1.7, PNIF = 162.4 ± 43.2, S'S = 10.4 ± 3.7) (p < 0.0001). No differences in the variables considered were observed between the two age groups during the study, with the exception of the Peak Nasal Inspiratory Flow (PNIF), which was marginally higher; this was also the case according to multivariate analyses (p = 0.008) in the young-middle adult group with respect to the elderly one (p = 0.07). At multivariate analyses, asthma and the female sex negatively influenced the PNIF values (p = 0.001 and p = 0.012, respectively). Age negatively influenced the Visual Analog Scale (VAS) for nasal obstruction (p = 0.0032) and Endoscopic Sinus Surgery (ESS) negatively influenced the patents' olfactory performance (p = 0.028) to the same degree in both groups. Dupilumab was found to be effective to the same degree in both age groups. It can be considered a safe and reliable option for the treatment of elderly patients with severe, uncontrolled CRSwNP.

"I feel your fear": superior fear recognition in organised crime members.

Individuals who deviate from social norms by committing crimes may have reduced facial emotion recognition abilities. Nevertheless, a specific category of offenders - i.e. organised crime (OC) members - is characterised by hierarchically organised social networks and a tendency to manipulate others to reach their illicit goals. Since recognising emotions is crucial to building social networks, OC members may be more skilled in recognising the facial emotion expressions of others to use this information for their criminal purposes. Evidence of a difference between OC and non-organised crime (NOC) offenders in terms of facial emotion recognition is still lacking. To fill this gap in the literature, we tested 50 OC, 50 NOC offenders, and 50 non-offender controls for their ability to identify six basic emotions (happiness, sadness, fear, anger, disgust, and surprise). All participants underwent a cognitive and psychological evaluation to avoid alternative explanations. Results show that OC members were more able to detect the expression of fear in others as compared to NOC. We interpreted this finding in light of the social context and the behavioural criminal attitude of OC members.

Galvanic Vestibular Stimulation influences risk-taking behaviour.

Risk-taking behaviour is an essential aspect of our interactions with the environment. Here we investigated whether vestibular inputs influence behavioural measurement of risk-taking propensity. We have combined bipolar Galvanic Vestibular Stimulation (GVS) with a well-known and established risk-taking behaviour task, namely the Balloon Analogue Risk Task (BART). A sham stimulation was used to control for non-specific effects. Left-anodal and right-cathodal GVS (L-GVS), which preferentially activates the vestibular projections in the right hemisphere, decreased the willingness to take risk during the BART compared with right-anodal and left-cathodal GVS (R-GVS), which activates the left hemisphere. This proved a specific vestibular effect which depends on GVS polarity. Conversely, no generic vestibular effect, defined as the adjusted average of L-GVS and R-GVS conditions compared to sham, emerged, excluding non-specific vestibular effects. Our results confirmed recent findings of a vestibular contribution to decision-making and strategy control behaviour. We suggest that the vestibular-mediated balancing of risk seeking behaviour is an important element of the brain's capacity to adapt to the environment.

Low dose oral corticosteroids, microneedling, and topical 5-fluorouracil: A novel treatment for recalcitrant pediatric vitiligo.

A 10-year-old boy was referred to our outpatient clinic with a 2-year history of vitiligo minimally responsive to topical corticosteroids and phototherapy. Low dose oral corticosteroids were prescribed in combination with sessions of microneedling and 5-fluourouracil 5% cream applied immediately after needling on a monthly basis. Repigmentation was initially noted after the first cycle at week 4. After 3 sessions of treatment (week 16), the patient showed a complete repigmentation of the knees.

Autonomic responses to emotional linguistic stimuli and amplitude of low-frequency fluctuations predict outcome after severe brain injury.

An accurate prognosis on the outcome of brain-injured patients with disorders of consciousness (DOC) remains a significant challenge, especially in the acute stage. In this study, we applied a multiple-technique approach to provide accurate predictions on functional outcome after 6 months in 15 acute DOC patients. Electrophysiological correlates of implicit cognitive processing of verbal stimuli and data-driven voxel-wise resting-state fMRI signals, such as the fractional amplitude of low-frequency fluctuations (fALFF), were employed. Event-related electrodermal activity, an index of autonomic activation, was recorded in response to emotional words and pseudo-words at baseline (T0). On the same day, patients also underwent a resting-state fMRI scan. Six months later (T1), patients were classified as outcome-negative and outcome-positive using a standard functional outcome scale. We then revisited the baseline measures to test their predictive power for the functional outcome measured at T1. We found that only outcome-positive patients had an earlier, higher autonomic response for words compared to pseudo-words, a pattern similar to that of healthy awake controls. Furthermore, DOC patients showed reduced fALFF in the posterior cingulate cortex (PCC), a brain region that contributes to autonomic regulation and awareness. The event-related electrodermal marker of residual cognitive functioning was found to have a significant correlation with residual local neuronal activity in the PCC. We propose that a residual autonomic response to cognitively salient stimuli, together with a preserved resting-state activity in the PCC, can provide a useful prognostic index in acute DOC.

Pathological risk-propensity typifies Mafia members' cognitive profile.

Since the recruitment process, Italian Mafias impose on their members a strict code of conduct. These rigid rules regulate their private and public behavior, implying a total adhesion to the group's values. Such juridical and social aspects substantially distinguish organized crime (OC) from ordinary crime. It is still unknown whether these two categories of offenders also show distinctive cognitive traits. Here we investigated the frontal lobe cognitive functions of 50 OC prisoners from the Mafia and 50 non-OC prisoners based on the performance of 50 non-prisoner controls. We found that OC members were more likely to show pathological risk-propensity than non-OC prisoners. We interpret this finding as the result of the internal dynamics of Mafia groups. OC is a worldwide threat, and the identification of cognitive traits behind criminal behavior will help in devising focused prevention policies.

Interoceptive sensibility tunes risk-taking behaviour when body-related stimuli come into play.

In everyday life, we continuously make decisions, assuming the risk by making choices on material possessions or our body. Bodily signals may support the decision-making process, informing us about possible outcomes. Sensibility for such internal bodily changes influences the way we perceive the environment, and it can boost the body-related stimuli processing. Thus, the question arises of whether the individual sensibility to interoceptive signals modulates decision-making in the presence of biological stimuli. To test this hypothesis, we administered 50 healthy subjects with the Balloon Analogue Risk Task, in which participants were required to inflate a virtual balloon, and a modified version of it, in which they inflated a virtual body. We found that interoceptive sensibility predicted risk-taking behaviour only in the presence of body-related stimuli. Our results provided new evidence on the role of interoceptive sensibility in complex cognitive functions, such as risk-taking behaviour, which impacts the way we act within our society.

Exploring biased attention towards body-related stimuli and its relationship with body awareness.

Stimuli of great social relevance exogenously capture attention. Here we explored the impact of body-related stimuli on endogenous attention. Additionally, we investigate the influence of internal states on biased attention towards this class of stimuli. Participants were presented with a body, face, or chair cue to hold in memory (Memory task) or to merely attend (Priming task) and, subsequently, they were asked to find a circle in an unrelated visual search task. In the valid condition, the circle was flanked by the cue. In the invalid condition, the pre-cued picture re-appeared flanking the distracter. In the neutral condition, the cue item did not re-appear in the search display. We found that although bodies and faces benefited from a general faster visual processing compared to chairs, holding them in memory did not produce any additional advantage on attention compared to when they are merely attended. Furthermore, face cues generated larger orienting effect compared to body and chairs cues in both Memory and Priming task. Importantly, results showed that individual sensitivity to internal bodily responses predicted the magnitude of the memory-based orienting of attention to bodies, shedding new light on the relationship between body awareness and visuo-spatial attention.