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Introduction: Allergen-specific immunotherapy (IT) is emerging as a viable option for treatment of peanut allergy. Yet, prophylactic IT remains unexplored despite early introduction of peanut in infancy was shown to prevent allergy. There is a need to understand how allergens interact with the immune system depending on the route of administration, and how different dosages of allergen may protect from sensitisation and a clinical active allergy. Here we compared peanut allergen delivery via the oral, sublingual (SL), intragastric (IG) and subcutaneous (SC) routes for the prevention of peanut allergy in Brown Norway (BN) rats. Methods: BN rats were administered PBS or three different doses of peanut protein extract (PPE) via either oral IT (OIT), SLIT, IGIT or SCIT followed by intraperitoneal (IP) injections of PPE to assess the protection from peanut sensitisation. The development of IgE and IgG1 responses to PPE and the major peanut allergens were evaluated by ELISAs. The clinical response to PPE was assessed by an ear swelling test (EST) and proliferation was assessed by stimulating splenocytes with PPE. Results: Low and medium dose OIT (1 and 10 mg) and all doses of SCIT (1, 10, 100 µg) induced sensitisation to PPE, whereas high dose OIT (100 mg), SLIT (10, 100 or 1000 µg) or IGIT (1, 10 and 100 mg) did not. High dose OIT and SLIT as well as high and medium dose IGIT prevented sensitisation from the following IP injections of PPE and suppressed PPE-specific IgE levels in a dose-dependent manner. Hence, administration of peanut protein via different routes confers different risks for sensitisation and protection from peanut allergy development. Overall, the IgE levels toward the individual major peanut allergens followed the PPE-specific IgE levels. Discussion: Collectively, this study showed that the preventive effect of allergen-specific IT is determined by the interplay between the specifi

Background: The authors hypothesized that both perineural and systemic dexamethasone as adjuncts to bupivacaine increase the duration of an ulnar nerve block compared with bupivacaine alone, and that systemic dexamethasone is noninferior to perineural dexamethasone. Methods: The authors performed bilateral ulnar nerve blocks with 3 ml bupivacaine 5 mg/ml in 16 healthy volunteers on two trial days. According to randomization, subjects received adjunct treatment with 1 ml dexamethasone 4 mg/ml + 1 ml of saline (perineural condition) in one arm and 2 ml saline in the other arm (systemic condition, through absorption and redistribution of the contralaterally administered perineural dexamethasone) on one trial day; and 2 ml saline in one arm (placebo condition) and 2 ml of lidocaine in the other arm (lidocaine condition) on the other trial day. The primary outcome was the duration of the sensory nerve block assessed by temperature discrimination. Results: Mean sensory block duration was 706 ± 94 min for the perineural condition, 677 ± 112 min for the systemic condition, and 640 ± 121 min for the placebo condition. The duration of the sensory nerve block was greater with perineural dexamethasone versus placebo (mean difference 66 min (95% CI, 23 to 108). Block duration was similar between systemic dexamethasone and placebo (mean difference 36 min; 95% CI, -30 to 103). Conclusions: Perineural dexamethasone as an adjunct to bupivacaine in healthy volunteers resulted in a greater duration of an ulnar nerve block when compared with placebo. Systemic dexamethasone resulted in a similar duration as placebo.

The multicenter observational BiRD study investigated the real-world effectiveness and safety of ibrutinib in patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL) and Waldenström's macroglobulinemia (WM) in Belgium. This interim analysis reports results for patients with CLL, with a median follow-up of 34 months. Overall, patients had predominantly relapsed/refractory disease (73%) and were elderly (median age 72 years) with high-risk features such as del17p and/or TP53 mutations (59%). Patients were included either prospectively or retrospectively, and the total patient population effectiveness results were adjusted with left truncation. In the effectiveness population (N = 221: prospective, n = 71; retrospective, n = 150), the overall response rate was 90.0%. Median progression-free survival was 38.3 months (prospective, not estimable; retrospective, 51.5 months) and median overall survival was not yet estimable in the total, prospective and retrospective groups. Treatment-emergent adverse events (TEAEs) for the prospective and retrospective groups are reported separately. Any-grade TEAEs of interest in the prospective/retrospective groups included infections (67.1%/60.1%), diarrhea (20.5%/10.5%), hypertension (16.4%/9.8%) and atrial fibrillation (12.3%/7.2%). Major bleeding was reported in 5.5%/3.3% of prospective/retrospective patients, with little difference observed between those receiving versus not receiving antithrombotic treatment. Discontinuations due to toxicity were reported in 10.5% of patients. Results from this interim analysis show treatment with ibrutinib to be effective and tolerable, with no new safety signals observed. Future analyses will report on longer-term follow-up.