CD4+Foxp3+ regulatory T cells (Tregs) are indispensable negative regulators of immune responses. To understand Treg biology in health and disease, it is critical to elucidate factors that affect Treg homeostasis and suppressive function. Tregs express several costimulatory TNF receptor family members that activate non-canonical NF-κB via accumulation of NF-κB inducing kinase (NIK). We previously showed that constitutive NIK expression in all T cells causes fatal multi-organ autoimmunity associated with hyperactive conventional T cell responses and poor Treg-mediated suppression. Here, we show that constitutive NIK expression that is restricted to Tregs via a Cre-inducible transgene causes an autoimmune syndrome. We found that constitutive NIK expression decreased expression of numerous Treg signature genes and microRNAs involved in Treg homeostasis and suppressive phenotype. NIK transgenic Tregs competed poorly with WT Tregs in vivo and produced pro-inflammatory cytokines upon stimulation. Lineage tracing experiments revealed accumulation of ex-Foxp3+ T cells in mice expressing NIK constitutively in Tregs, and these former Tregs produced copious IFNγ and IL-2. Our data indicate that under inflammatory conditions in which NIK is activated, Tregs may lose suppressive function and may actively contribute to inflammation.

Introduction: Pelvic fractures are diverse injuries with varying degrees of severity. Treatment recommendations are determined by the associated instability. For likely stable patterns, postmobilization imaging is used to assess for occult instability. This study assesses the utility of postmobilization images and determines how often they alter the recommendations for treatment. Methods: Records at a single level 1 trauma center from January 2007 through December 2014 were reviewed, and patients with Current Procedural Terminology codes and International Classification of Diseases, Ninth Revision codes for pelvic and acetabular fractures were identified. For those chosen for nonsurgical treatment at presentation, a detailed chart review was performed to identify patients who had postmobilization radiographs and to determine whether this imaging led to a change in treatment recommendations. Results: Inclusion criteria were met by 762 patients whose average age was 50 years. Of 331 patients planned for nonsurgical treatment at presentation, 168 (51%) had postmobilization images. The postmobilization radiographs did not alter treatment recommendations in any of these patients; however, three of these patients underwent surgical stabilization based on the patients' report of pain with attempted mobilization. Discussion: Routine postmobilization imaging has limited value for patients with pelvic injuries and a low likelihood for instability, such as those with incomplete sacral fractures. Eliminating this step would reduce cost and decrease radiation exposure. The need for change in treatment plan or further imaging should be based on the patient's clinical progress with weight bearing. Level of Evidence: Level 4

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INTRODUCTION: Advanced maternal age (AMA) and obesity have been shown to independently influence maternal and neonatal outcomes. We sought to determine if obese AMA women had greater risk for adverse outcomes compared to non-obese AMA women. METHODS: A retrospective cohort study of non-anomalous, singleton AMA (age 35+) pregnancies at Oregon Health & Science University from 2009–2014 to assess if obesity (pre-pregnancy BMI 30+) impacted outcomes above AMA status alone. Maternal outcomes included gestational diabetes (GDM), pre-eclampsia (PET), and cesarean section (CS). Neonatal outcomes included NICU admission, SGA/LGA, preterm birth, and hypoglycemia. Univariate analyses were used to determine significant differences between groups (P<.05), and multivariate logistic regression adjusting for biologically plausible confounders was utilized to determine strength of association. RESULTS: Of the 7,953 deliveries during the study period, 1,712 were to AMA women with 459 obese (27%) and 1,253 non-obese (73%). Obese AMA women were associated with significantly increased rates of GDM (aOR 3.04, 95% CI 2.23–4.40), PEC (aOR 1.64, 95% CI 1.09–2.47), and CS (aOR 1.42, 95% CI 1.12–1.85). Neonates born to obese AMA women were associated with significantly increased rates of LGA (aOR 2.66, 95% CI 1.86–3.80) and hypoglycemia (aOR 1.98, 95% CI 1.10–3.58). There was no significant association between obesity in AMA women and SGA, preterm birth, or NICU admission. CONCLUSION: In AMA pregnancies, obesity is associated with significantly increased rates of GDM, PEC, CS, LGA neonates, and neonatal hypoglycemia. These results suggest that AMA pregnancies complicated by maternal obesity may benefit from earlier intervention and counseling.