Heterogeneity of pollen food allergy syndrome in seven Southern European countries: The @IT.2020 multicenter study.

BACKGROUND: Pollen food allergy syndrome (PFAS) is a frequently underdiagnosed disease due to diverse triggers, clinical presentations, and test results. This is especially relevant in geographic areas with a broad spectrum of pollen sensitization, such as Southern Europe. OBJECTIVES: To elucidate similarities and differences of PFAS in nine Southern European centers and identify associated characteristics and unique markers of PFAS. METHODS: As part of the @IT.2020 Multicenter Study, 815 patients with seasonal allergic rhinitis (SAR), aged 10-60 years, were recruited in seven countries. They completed questionnaires regarding SAR, comorbidities, family history, and PFAS, and underwent skin prick testing (SPT) and serum IgE testing. RESULTS: Of the 815 patients, 167 (20.5%) reported PFAS reactions. Most commonly, eliciting foods were kiwi (58, 34.7%), peach (43, 25.7%), and melon (26, 15.6%). Reported reactions were mostly local (216/319, 67.7%), occurring within 5 min of contact with elicitors (209/319, 65.5%). Associated characteristics included positive IgE to at least one panallergen (profilin, PR-10, or nsLTP) (p = 0.007), maternal PFAS (OR: 3.716, p = 0.026), and asthma (OR: 1.752, p = 0.073). Between centers, heterogeneity in prevalence (Marseille: 7.5% vs. Rome: 41.4%, p < 0.001) and of clinical characteristics was apparent. Cypress played a limited role, with only 1/22 SPT mono-sensitized patients reporting a food reaction (p < 0.073). CONCLUSIONS: PFAS is a frequent comorbidity in Southern European SAR patients. Significant heterogeneity of clinical characteristics in PFAS patients among the centers was observed and may be related to the different pollen sensitization patterns in each geographic area. IgE to panallergen(s), maternal PFAS, and asthma could be PFAS-associated characteristics.

The effects of Rituximab on Graves'orbitopathy: A retrospective study of 14 patients.

PURPOSE: Management of Graves' ophthalmopathy remains challenging. Over the last decade, previous studies have shown promising results for Rituximab in the treatment of Graves' ophthalmopathy. We present the response of 14 individuals with active moderate-to-severe Graves' ophthalmopathy to Rituximab, representing one of the largest retrospective case series reported to date. METHODS: Rituximab was administered intravenously, 1000 mg twice at a 2-week interval. The primary end point was a clinical activity score reduction (improvement by ⩾ 2 points or disease inactivation: clinical activity score < 3) at 24 weeks. Secondary end points included clinical activity score improved by ⩾ 2 points or inactivation of Graves' ophthalmopathy at 12 weeks, improvement in each item of the clinical activity score, in proptosis, in severity disease by the total eye score and in diplopia according to the Gorman score. RESULTS: A limited improvement in clinical activity score was observed (median improvement at 24 weeks by 1 point, p = 0.002, (5/14 patients, 35.7%). Disease inactivation occurred in 50% of patients (7/14 patients). At 12 weeks, clinical activity score improved by ⩾ 2 points in 2/14 patients (14.3%) and inactivation of Graves' ophthalmopathy occurred in four patients (28.6%). Improvement in proptosis and total eye score was observed in 3/9 patients (33%) and in 4/14 patients (28.6%) at 24 weeks, respectively. Only one patient experienced moderate adverse event. CONCLUSION: Rituximab is a well-tolerated treatment with a good safety profile, but offered limited and partial improvement for active moderate-to-severe Graves' ophthalmopathy with a long duration of disease.

Language, intellectual and educational outcomes after moderate-to-severe traumatic brain injury sustained before the age of 18 months.

Objective: The aim of this study was to assess long-term outcomes in terms of oral language, intellectual ability, education, following very early moderate-to-severe TBI. Methods: Children who had been hospitalized in rehabilitation after moderate-to-severe TBI sustained before 18 months of age were contacted once they had reached school age. Detailed oral language and intellectual ability assessment were performed, and information on ongoing education was collected. Results: 52 children met inclusion criteria; 21 (40.4%) participated [13 males, mean age 7.5 years (SD = 1.9), age at injury 0.7 years (SD = 0.5), time since injury 6.8 years (SD = 1.8)]. Performance was in the clinical range (<-2SD) for: syntactic comprehension (67%; mean z-scores -2.6; SD = 3.1), syntactic expression (62%; -2.1; SD = 1.3), lexical stock extent (57%; -1.5; SD = 1.5), lexical access skills (48%; -1.9; SD = 2), and semantic organization (32%; -0.9; SD = 1.2). Full-scale IQ was <90 for 91%. Only eight children followed mainstream education without adaptations. Performance on all language tests (except lexical stock extent) was significantly poorer for children with a personal school aid or those in specialized education. Conclusions: Early moderate-to-severe TBI causes significant delayed language (especially syntactic aspects of language) and cognitive disabilities, with consequences on long-term educational outcome. These children require long-term follow-up and timely interventions.

Assessment of executive functions in children and adolescents with acquired brain injury (ABI) using a novel complex multi-tasking computerised task: The Jansari assessment of Executive Functions for Children (JEF-C©).

Objectives: The Jansari assessment of Executive Functions for Children (JEF-C©) is a new non-immersive computerised assessment of executive functions. The objectives of the study were to test the feasibility and validity of JEF-C© in children and adolescents with acquired brain injury (ABI). Methods: Twenty-nine patients with ABI aged 10-18 years and 30 age-and gender-matched controls were tested. Participants performed JEF-C©, Wechsler Abbreviated Scale of Intelligence (WASI) and the Behavioural Assessment of the Dysexecutive Syndrome for Children (BADS-C), while parents completed the Behaviour Rating Inventory of Executive Function (BRIEF) questionnaire. Results: The JEF-C© task proved feasible in patients with ABI. The internal consistency was medium (Cronbach's alpha = 0.62 and significant intercorrelations between individual JEF-C© constructs). Patients performed significantly worse than controls on most of the JEF-C© subscales and total score, with 41.4% of participants with ABI classified as having severe executive dysfunction. No significant correlations were found between JEF-C© total score, the BRIEF indices, and the BADS-C. Significant correlations were found between JEF-C© and demographic characteristics of the sample and intellectual ability, but not with severity/medical variables. Conclusion: JEF-C© is a playful complex task that appears to be a sensitive and ecologically valid assessment tool, especially for relatively high-functioning individuals.

Benefit of Switching Dual Antiplatelet Therapy After Acute Coronary Syndrome According to On-Treatment Platelet Reactivity: The TOPIC-VASP Pre-Specified Analysis of the TOPIC Randomized Study.

OBJECTIVES: This study sought to evaluate the impact of initial platelet reactivity on the benefit of switched strategy. BACKGROUND: TOPIC (Timing Of Platelet Inhibition after acute Coronary Syndrome) study suggested that switched dual antiplatelet therapy (DAPT) could improve net clinical benefit after acute coronary syndrome by preventing bleeding. METHODS: Acute coronary syndrome patients, 1 month after coronary stenting and event free, were randomly assigned to aspirin and clopidogrel (switched DAPT) or continuation of drug regimen (unchanged DAPT). All patients underwent platelet function testing at this time and were classified as low on-treatment platelet reactivity (LTPR) (platelet reactivity index vasodilator-stimulated phosphoprotein ≤20%) or non-LTPR (platelet reactivity index vasodilator-stimulated phosphoprotein >20%). The primary endpoint aimed to evaluate the impact of platelet reactivity on clinical outcomes and benefit of switched DAPT strategy. RESULTS: A total of 645 patients were included, 305 (47%) of whom were classified as LTPR. LTPR patients were less often diabetic (p = 0.01), had lower body mass index (p < 0.01), and were more often on ticagrelor (p < 0.01). Patients defined as LTPR and randomized to unchanged DAPT were at the highest risk of primary endpoint occurrence (31%; p < 0.01). Conversely, in the switched arm, LTPR patients had no significant difference in primary outcome incidence compared with non-LTPR patients (hazard ratio [HR]: 0.78; 95% confidence interval [CI]: 0.40 to 1.49; p = 0.45). The switched strategy was associated with important reduction in primary endpoint incidence in LTPR patients (HR: 0.29; 95% CI: 0.17 to 0.51; p < 0.01) and only numerically lower incidence in non-LTPR patients (HR: 0.79; 95% CI: 0.46 to 1.35; p = 0.39). CONCLUSIONS: Switched DAPT was superior regardless of initial platelet reactivity but the benefit was greater in LTPR patients. Indeed, the switched strategy was highly effective in this group, which had impaired prognosis with unchanged DAPT but similar prognosis after switching.

Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (timing of platelet inhibition after acute coronary syndrome) randomized study.

AIMS: Newer P2Y12 blockers (prasugrel and ticagrelor) demonstrated significant ischaemic benefit over clopidogrel after acute coronary syndrome (ACS). However, both drugs are associated with an increase in bleeding complications. The objective of the present study was to evaluate the benefit of switching dual antiplatelet therapy (DAPT) from aspirin plus a newer P2Y12 blocker to aspirin plus clopidogrel 1 month after ACS. METHODS AND RESULTS: We performed an open-label, monocentric, and randomized trial. From March 2014 to April 2016, patients admitted with ACS requiring coronary intervention, on aspirin and a newer P2Y12 blocker and without adverse event at 1 month, were assigned to switch to aspirin and clopidogrel (switched DAPT) or continuation of their drug regimen (unchanged DAPT). The primary outcome was a composite of cardiovascular death, urgent revascularization, stroke and bleeding as defined by the Bleeding Academic Research Consortium (BARC) classification ≥2 at 1 year post ACS. Six hundred and forty six patients were randomized and 645 analysed, corresponding to 322 patients in the switched DAPT and 323 in the unchanged DAPT group. The primary endpoint occurred in 43 (13.4%) patients in the switched DAPT group and in 85 (26.3%) patients in the unchanged DAPT (HR 95%CI 0.48 (0.34-0.68), P < 0.01). No significant differences were reported on ischaemic endpoints, while BARC ≥ 2 bleeding occurred in 13 (4.0%) patients in the switched DAPT and in 48 (14.9%) in the unchanged DAPT group (HR 95%CI 0.30 (0.18-0.50), P < 0.01). CONCLUSION: A switched DAPT is superior to an unchanged DAPT strategy to prevent bleeding complications without increase in ischaemic events following ACS.

Impact of obesity and the metabolic syndrome on response to clopidogrel or prasugrel and bleeding risk in patients treated after coronary stenting.

This study aimed to analyze the impact of body mass index (BMI) and the metabolic syndrome (MS) on responses to clopidogrel or prasugrel and bleeding risk after acute coronary syndrome. The study included 1,542 consecutive patients who underwent coronary stenting (287 clopidogrel 75 mg, 868 clopidogrel 150 mg, and 387 prasugrel 10 mg). Platelet reactivity was assessed 1 month after discharge using platelet reactivity index vasodilator stimulated phosphoprotein (PRI VASP). Three hundred thirty-six patients (21.8%) were obese (BMI ≥30), and we observed higher platelet reactivity associated with higher BMI across thienopyridine regimens. Incidence of high on-treatment platelet reactivity (PRI VASP >50%) was higher in obese than nonobese patients (p <0.05 for all regimens). Conversely, incidence of low on-treatment platelet reactivity with prasugrel therapy (PRI VASP <20%) was lower in obese than nonobese patients: 13% (12 of 93) versus 33% (97 of 294); odds ratio 0.30, 95% confidence interval 0.16 to 0.58; p <0.001. Accordingly, incidence of Bleeding Academic Research Consortium bleeding complications was higher in nonobese than in obese patients: 10% (119 of 1,206) versus 6% (20 of 336); odds ratio 1.7, 95% confidence interval 1.1 to 2.8; p = 0.03. This impaired response was only observed in obese patients with the MS, and obese with the MS had significantly higher platelet reactivity than other obese patients with all regimens (p <0.01). Obese patients without the MS had no significant difference in platelet reactivity compared with nonobese patients. In conclusion, the present study confirmed that BMI has a strong impact on response to clopidogrel and prasugrel with higher incidence of high on-treatment platelet reactivity, lower incidence of low on-treatment platelet reactivity, and lower bleeding complication in obese patients. However, among obese patients, the presence of the MS strongly affects response to antiplatelet agents, indicating that the metabolic status might be a better predictor of platelet inhibition than BMI.