Background Peanut oral immunotherapy (OIT) is a promising approach to peanut allergy but reactions are frequent and some patients cannot be desensitized. The anti-IgE medication omalizumab (Xolair) may allow more rapid peanut updosing and decrease reactions. Objective To evaluate if omalizumab facilitated rapid peanut desensitization in highly allergic patients. Methods Thirty-seven subjects were randomized to omalizumab (n=29) or placebo (n=8). After 12 weeks of treatment subjects underwent a rapid one-day desensitization of up to 250 mg of peanut protein, followed by weekly increases up to 2000 mg. Omalizumab was then discontinued and subjects continued on 2000 mg of peanut protein. They underwent an open challenge to 4000 mg peanut protein twelve weeks after stopping study drug. If tolerated, subjects continued on 4000 mg of peanut protein daily. Results The median peanut dose tolerated on the initial desensitization day was 250 mg for omalizumab versus 22.5 mg for placebo treated subject. Subsequently 23 of 29 (79%) subjects randomized to omalizumab tolerated 2000 mg peanut protein 6 weeks after stopping omalizumab versus 1 of 8 (12%) receiving placebo (p<0.01). Twenty-three subjects on omalizumab versus 1 on placebo passed the 4000 mg food challenge. Overall reaction rates were not significantly lower in omalizumab versus placebo treated subjects (OR=0.57 p=0.15), although omalizumab treated subjects were exposed to much higher doses of peanut. Conclusion Omalizumab allows subjects with peanut allergy to be rapidly desensitized over as little as 8 weeks of peanut OIT. In the majority of subjects, this desensitization is sustained after omalizumab is discontinued. Additional studies will help clarify which patients would benefit most from this approach.

Ptpn6 is a cytoplasmic phosphatase that functions to prevent autoimmune and interleukin 1 receptor (IL-1R)-dependent caspase-1-independent inflammatory disease. Conditional deletion of Ptpn6 in neutrophils (Ptpn6 ΔPMN ) is sufficient to initiate IL-1R-dependent cutaneous inflammatory disease, but the source of IL-1 and the mechanisms behind IL-1 release remain unclear. Here, we investigated the mechanisms controlling IL-1α/β release from neutrophils by inhibiting caspase-8-dependent apoptosis and Ripk1-Ripk3-Mlkl-regulated necroptosis. Loss of Ripk1 accelerated disease onset, whereas combined deletion of caspase-8, and either Ripk3 or Mlkl, strongly protected Ptpn6 ΔPMN mice. Ptpn6 ΔPMN neutrophils displayed increased p38 MAP kinase-dependent Ripk1-independent IL-1 and tumor necrosis factor (TNF) production, and were prone to cell death. Together, these data emphasize dual functions for Ptpn6 in the negative regulation of p38 MAP kinase activation to control TNF and IL-1α/β expression, and in maintaining Ripk1 function to prevent caspase-8-and Ripk3-Mlkl-dependent cell death and concomitant IL-1α/β release.

Objective Transition readiness assessment has focused attention on adolescent knowledge and skills, but data-driven benchmarks have not been established. Methods Patients with IBD, aged 25–55 years, attending an outpatient gastroenterology clinic, were recruited to complete a voluntary, confidential survey asking patients to recall medications and potential side effects, and to rate their degree of independence performing health maintenance tasks. Results The 141 respondents (48% response rate) had mean age of 36 years with median disease duration of 11 years. They were 60% female, 54% had Crohn’s disease, and 23% were diagnosed before age 18. Nearly all patients were fully independent answering doctor’s questions during the visit (93%) and scheduling office visits (92%). Excluding pharmacy pick up, full independence seen in only 57%, while 16% significantly delegated tasks. No differences by gender, disease type, medication class, age at disease onset, or disease duration were found across levels of self-management. Almost all (97%) respondents could recall medication name, while fewer were able to recall dose (63%) or frequency (65%). Side effect knowledge was poor; among 81 patients on a biologic or immunomodulator, only 17 (21%) cited cancer and 22 (27%) cited infection. Conclusions Adolescent IBD transition programs now have empiric data from this study about adult benchmarks for independence in self-management skills. Further research can establish which skills correlate with medication adherence and active collaboration with the medical team. This study also exposes important gaps in medication risk knowledge and may allow improved patient education for subgroups of adult IBD patients.

A research team from Boston Children's Hospital and Harvard Medical School conducted a community-based feeding study in collaboration with Framingham State University (FSU) and Sodexo, the food service contractor at FSU. The study was a randomized controlled trial, implemented on the FSU campus. For the final year of the study, a satellite feeding site was established at Assabet Valley Regional Technical High School. The purpose of the study was to assess the biological effects of different macronutrient diets. An academia-industry partnership was developed to overcome common challenges associated with hospital-based feeding studies. Benefits included the following: a study site outside of Boston (reducing inconvenience for participants), access to a large commercial kitchen and study-specific kiosk (promoting efficiency), collaboration with Sodexo chefs (ensuring palatability of meals), and opportunity to procure food from contracted vendors. The research (academia) and food service (industry) teams worked together to design, plan, and execute intervention protocols using an integrated approach. During execution, the research team was primarily responsible for overseeing treatment fidelity, whereas the food service team provided culinary expertise, with a strong focus on hospitality and food quality. The study was conducted in 3 cohorts between August 2014 and May 2017. Participants received all of their food for ∼30 wk, totaling >160,000 meals. For all 3 cohorts combined, 234 participants provided informed consent, 229 started a standard run-in weight-loss diet, 164 lost a mean ± SD 12% ± 2% of baseline body weight and were randomly assigned to different macronutrient diets for weight-loss maintenance, and 148 completed the study. During the final and largest cohort, as many as 114 participants received daily meals concurrently. The daily cost per participant for preparation and service of weighed meals and snacks was ∼$65. This academia-industry partnership provides a model for controlled feeding protocols in nutrition research, potentially with enhanced cost-effectiveness, practicality, and generalizability. This trial was registered at http://www.clinicaltrials.gov as NCT02068885.

Navigating health care systems can be a challenge for families. A retrospective descriptive cohort analysis was conducted assessing referrals to patient navigators (PNs) in one urban academic pediatric primary care practice. PNs tracked referral processes and a subset of PN referrals was assessed for markers of successful referrals. The most common reasons for referral were assistance overcoming barriers to care (46%), developmental concerns (38%), and adherence/care coordination concerns (14%). Significant predictors of referral were younger age, medical complexity, public insurance, male sex, and higher rates of no-show to visits in primary or subspecialist care. The majority of referrals were resolved. The referrals for process-oriented needs were significantly more successful than those for other concerns. PNs were more effective for discrete process tasks than for those that required behavior change by patients or families. Future directions include analysis of cost effectiveness of the PN program and analysis of parent and primary care provider experience.