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are employees of Genentech, Inc, a member of the Roche group, and own Roche stock. C. E. Brightling is a consultant with fees paid to his institution from Genentech, Inc, and Regeneron; received research grants and was a consultant with fees paid to his institution from AstraZeneca, GlaxoSmithKline, Sanofi, Boehringer Ingelheim, Roche/Genentech, Chiesi, 4D Pharma, Mologics, and Novartis.Background: The IL-33/ST2 pathway is linked with asthma susceptibility. Inhaled allergens, pollutants, and respiratory viruses, which trigger asthma exacerbations, induce release of IL-33, an epithelial-derived ''alarmin.'' Astegolimab, a human IgG 2 mAb, selectively inhibits the IL-33 receptor, ST2. Approved biologic therapies for severe asthma mainly benefit patients with elevated blood eosinophils (type 2-high), but limited options are available for patients with low blood eosinophils (type 2-low). Inhibiting IL-33 signaling may target pathogenic pathways in a wider spectrum of asthmatics. Objectives: This study evaluated astegolimab efficacy and safety in patients with severe asthma. Methods: This double-blind, placebo-controlled, dose-ranging study (ZENYATTA [A Study to Assess the Efficacy and Safety of MSTT1041A in Participants With Uncontrolled Severe Asthma]) randomized 502 adults with severe asthma to subcutaneous placebo or 70-mg, 210-mg, or 490-mg doses of astegolimab every 4 weeks. The primary endpoint was the annualized asthma exacerbation rate (AER) at week 54. Enrollment caps ensured 30 patients who were eosinophil-high (> _300 cells/mL) and 95 patients who were eosinophil-low (<300 cells/mL) per arm. Results: Overall, adjusted AER reductions relative to placebo were 43% (P 5 .005), 22% (P 5 .18), and 37% (P 5 .01) for 490mg, 210-mg, and 70-mg doses of astegolimab, respectively. Adjusted AER reductions for patients who were eosinophil-low were comparable to reductions in the overall population: 54% (P 5 .002), 14% (P 5 .48), and 35% (P 5 .05) for 490-mg, 210mg, and 70-mg doses of astegolimab. Adverse events were similar in astegolimab-and placebo-treated groups. Conclusions: Astegolimab reduced AER in a broad population of patients, including those who were eosinophil-low, with inadequately controlled, severe asthma. Astegolimab was safe and well tolerated. (J Allergy Clin Immunol 2021;nnn:nnnnnn.)

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OBJECTIVE: To investigate if long-term caloric restriction under controlled conditions adversely affects cognitive function in obese women. SUBJECTS: Healthy, premenopausal women between 23±42 y. Dieting group: n 14. Control group: n 11. DESIGN: Longitudinal weight loss study (repeated measures within-subject design) with 3 weeks of baseline, 15 weeks of 50% caloric restriction, and 3 weeks of weight stabilization. MEASUREMENTS: Computerized cognitive function tests (sustained attention, short-term memory, simple reaction time, motor performance and attentional focus), height, body weight, body composition (TOBEC) and behavioral questionnaires (Dutch Eating Behaviour Questionnaire, Eating Attitudes Test, and State-Trait Anxiety Inventory). RESULTS: Dieting women lost 12.3 AE 5.5 kg (mean AE s.d.) of body weight. Controlled long-term caloric restriction signi®cantly slowed simple reaction time but did not diminish sustained attention, motor performance or immediate memory. Word recall performance signi®cantly improved by 24% at the end of caloric restriction. CONCLUSIONS: The slowing of simple reaction time is a short-term and long-term consequence of caloric restriction. In contrast to previous short-term dieting studies, sustained attention and immediate memory were not impaired with long-term caloric restriction.

Mycophenolate mofetil (MMF) is widely used to prevent acute rejection in adults after renal, cardiac, and liver transplantation. This study investigated the safety, tolerability, and pharmacokinetics of MMF suspension in pediatric renal allograft recipients. One hundred renal allograft recipients were enrolled into three age groups (33 patients, 3 months to <6 years; 34 patients, 6 to <12 years; 33 patients, 12 to 18 years). Patients received MMF 600 mg/m2 b.i.d. concomitantly with cyclosporine and corticosteroids with or without antilymphocyte antibody induction. One year after transplantation, patient and graft survival (including death) were 98% and 93%, respectively. Twenty-five patients (25%) experienced a biopsy-proven (Banff grade borderline or higher) or presumptive acute rejection within the first 6 months post-transplantation. Analysis of pharmacokinetic parameters for mycophenolic acid (MPA) and mycophenolic acid glucuronide showed no clinically significant differences among the age groups. The dosing regimen of MMF 600 mg/m2 b.i.d. achieved the targeted early post-transplantation MPA 12-h area under concentration-time curve (AUC0-12) of 27.2 microg h per ml. Adverse events had similar frequencies among the age groups (with the exception of diarrhea, leukopenia, sepsis, and anemia, which were more frequent in the <6 years age group) and led to withdrawal of MMF in about 10% of patients. Administration of MMF 600 mg/m2 b.i.d. is effective in prevention of acute rejection, provides predictable pharmacokinetics, and is associated with an acceptable safety profile in pediatric renal transplant recipients.