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Alterations in nuclear factor kappa B (NF-κB) essential modulator (NEMO; HUGO-approved symbol IKBKG) underlie most cases of ectodermal dysplasia with immune deficiency (EDI), a human disorder characterized by anhidrosis with diminished immunity. EDI has also been associated with a single heterozygous mutation at position Ser32 of the NF-κB inhibitor IκBα, one of two phosphorylation sites that are essential for targeting IκBα for proteasomal degradation and hence for activation of NF-κB. We report a novel heterozygous nonsense mutation in the IKBA (HUGO-approved symbol, NFKBIA) gene of a 1-year-old male child with EDI that introduces a premature termination codon at position Glu14. An in-frame methionine downstream of the nonsense mutation allows for reinitiation of translation. The resulting N-terminally truncated protein lacks both serine phosphorylation sites and inhibits NF-κB signaling by functioning as a dominant negative on NF-κB activity in lymphocytes and monocytes. These findings support the scanning model for translation initiation in eukaryotes and confirm the critical role of the NF-κB in the human immune response.

Background Few studies have examined how developing obesity in early adulthood affects the course of asthma. Objective We analyzed lung function and asthma impairment and risk among non-obese children with asthma, comparing those who were obese in young adulthood to those who remained non-obese. Methods Post-hoc analysis of 771 subjects with mild-moderate asthma who were not obese (pediatric definition, body mass index (BMI) <95th percentile) when enrolled in the Childhood Asthma Management Program at ages 5–12 years. Subjects were then followed to age ≥ 20 years. For visits at ages ≥ 20 years, spirometry values as percent predicted and recent asthma symptom scores and prednisone exposure were compared between 579 subjects who were non-obese at all visits and 151 who obese (adult definition of BMI ≥ 30 kg/m2) on at least one visit (median number of visits when obese = 4, IQR 2–7). Results Compared to participants who were non-obese (BMI 23.4 ± 2.6 kg/m2), those who became obese (BMI 31.5 ± 3.8 kg/m2) had significant decreases in FEV1/FVC (p<0.0003) and FEV1 (p = 0.001), without differences in FVC (p=0.15) during visits at ages ≥ 20 years. For each unit increase of BMI, FEV1 percent predicted decreased by 0.29 (p=0.0009). The relationship between BMI and lung function was not confounded by sex or BMI at baseline. Asthma impairment (symptom scores) and risk (prednisone use) did not differ between the two groups. Conclusion Becoming obese in early adulthood was associated with increased airway obstruction, without impact on asthma impairment or risk.

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Background β-Lactam antibiotics are first-line therapy for perioperative prophylaxis; however, patient-reported allergies often lead to increased prescribing of alternative antibiotics that may increase the incidence of surgical site infections. The R-group side chain of the β-lactam ring is responsible for allergic cross-reactivity and experts recommend the use of β-lactams that are structurally dissimilar. Methods An internally developed, antibiotic side-chain–based cross-reactivity chart was developed and implemented alongside enhanced allergy assessment processes. This single-center, quasi-experimental study analyzed antibiotic prescribing in all adult patients with a documented β-lactam allergy undergoing an inpatient surgical procedure between quartile (Q) 1 (2012)–Q3 (2014) (historical group) and Q3 (2016)–Q3 (2018) (intervention group). Propensity-weighted scoring analyses compared categorical and continuous outcomes. Interrupted time-series analysis further analyzed key outcomes. Results A total of 1119 and 1089 patients were included in the historical and intervention cohorts, respectively. There was a significant difference in patients receiving a β-lactam alternative antibiotic between cohorts (84.9% vs 15.1%; P &lt; .001). There was a decrease in 30-day readmissions in the intervention cohort (7.9% vs 6.3%; P = .035); however, there was no difference in the incidence of SSIs in patients readmitted (14.8% vs 13%; P = .765). No significant differences were observed in allergic reactions (0.5% vs 0.3%; P = .323), surgical site infections, in-hospital and 30-day mortality, healthcare facility–onset Clostridiodes difficile infection, acute kidney injury, or hospital costs. Conclusions Implementation of an antibiotic cross-reactivity chart combined with enhanced allergy assessment processes significantly improved the prescribing of β-lactam antibiotics for surgical prophylaxis.

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In the past decade the rise in life-threatening allergic reactions to foods in young children has necessitated increased interaction among personnel in the psychosocial, medical, and educational arenas regarding the multifaceted aspects of this concerning problem. Schools and childcare facilities are vital venues for the continued growth and development of children outside the home. However, these facilities offer unique challenges to caring for the food-allergic child, requiring that the medical, educational, and caretaking communities work in unison to provide the safest environment for all children. Despite the potential obstacles, these settings offer a tremendous opportunity for the development and implementation of strategies to provide for proper identification of children at risk, to increase awareness and prevention, and for the provision of optimal treatment of food-related anaphylactic reactions occurring outside the home.