Citations

Abstract The molecular and functional diversity of regulatory T-cells (Tregs) in health and in disease remains unclear. We previously described in colorectal cancer (CRC) patients a subpopulation of RORγt+ Tregs with elevated expression of β-catenin and pro-inflammatory properties. Here we observed progressive expansion of RORγt+ Tregs in inflammatory bowel disease (IBD) patients during inflammation and early dysplasia. Activating Wnt/β-catenin signaling in human and murine Tregs was sufficient to recapitulate the disease-associated increase in frequencies of RORγt+ Tregs expressing IL-17, IFN-γ, and TNFa. We found that binding of the β-catenin interacting partner, TCF-1, to DNA overlapped with Foxp3 binding at enhancer sites of pro-inflammatory pathway genes. Sustained Wnt/β-catenin activation induced newly accessible chromatin sites in these genes and upregulated their expression. These findings indicate that TCF-1 and Foxp3 together limit the expression of pro-inflammatory genes in Tregs. Activation of ꞵ-catenin signaling interferes with this function and promotes the disease-associated RORγt+ Treg phenotype.

ABSTRACT: Objective: Postural orthostatic tachycardia syndrome (POTS) is estimated to occur in up to 1% of adolescents, with symptoms of dizziness, fatigue, and pain impacting daily functioning. However, many risk factors and symptoms for POTS overlap with those of youth with disordered eating, and adolescents with POTS may be at increased risk for developing eating disorders. Therefore, the present study sought to better understand this overlap. We hypothesized that patients with POTS would have higher than expected rates of weight change, restrictive eating patterns, and food sensitivities. Methods: We conducted a retrospective chart review of 96 adolescents and young adults diagnosed with POTS who were participating in a 3-week intensive interdisciplinary pain rehabilitation program. We conducted descriptive and correlational statistical analyses on data from self-report measures, biomarkers of nutritional status, and abstracted information about eating and weight concerns from medical notes. Results: Nearly 3 quarters of participants described engaging in restrictive eating, and more than half of them described experiencing weight loss. They also endorsed experiencing food allergies, celiac disease, and eating disorder at higher rates than would be expected in the general population. One-fifth of the sample had experienced invasive interventions to correct for nutritional imbalances, such as having a feeding tube. Conclusion: Weight and eating are clear areas of risk for patients with orthostatic intolerance. It is essential that treatment team members thoroughly screen for eating disturbances and make recommendations that support regular and balanced eating habits.

This combined American Neurotology Society, American Otological Society, and American Academy of Otolaryngology – Head and Neck Surgery Foundation document aims to provide guidance during the coronavirus disease of 2019 (COVID-19) on 1) “priority” of care for otologic and neurotologic patients in the office and operating room, and 2) optimal utilization of personal protective equipment. Given the paucity of evidence to inform otologic and neurotologic best practices during COVID-19, the recommendations herein are based on relevant peer-reviewed articles, the Centers for Disease Control and Prevention COVID-19 guidelines, United States and international hospital policies, and expert opinion. The suggestions presented here are not meant to be definitive, and best practices will undoubtedly change with increasing knowledge and high-quality data related to COVID-19. Interpretation of this guidance document is dependent on local factors including prevalence of COVID-19 in the surgeons’ local community. This is not intended to set a standard of care, and should not supersede the clinician's best judgement when managing specific clinical concerns and/or regional conditions. Access to otologic and neurotologic care during and after the COVID-19 pandemic is dependent upon adequate protection of physicians, audiologists, and ancillary support staff. Otolaryngologists and associated staff are at high risk for COVID-19 disease transmission based on close contact with mucosal surfaces of the upper aerodigestive tract during diagnostic evaluation and therapeutic procedures. While many otologic and neurotologic conditions are not imminently life threatening, they have a major impact on communication, daily functioning, and quality of life. In addition, progression of disease and delay in treatment can result in cranial nerve deficits, intracranial and life-threatening complications, and/or irreversible consequences. In this regard, many otologic and neurotologic conditions should rightfully be considered “urgent,” and almost all require timely attention to permit optimal outcomes. It is reasonable to proceed with otologic and neurotologic clinic visits and operative cases based on input from expert opinion of otologic care providers, clinic/hospital administration, infection prevention and control specialists, and local and state public health leaders. Significant regional variations in COVID-19 prevalence exist; therefore, physicians working with local municipalities are best suited to make determinations on the appropriateness and timing of otologic and neurotologic care.

The first documented case of COVID-19 in the United States occurred on January 30th, 2020. Soon after, a global pandemic was declared in March 2020 with each state issuing stay at home orders based on population, risk for community transmission and current number of positive cases. A priority for each region was to develop efficient systems for testing large patient volumes in a safe manner to reduce the risk of community transmission. A community based United States health care system in the upper mid-west implemented a drive through testing site in an attempt to divert suspected cases of COVID-19 away from larger patient areas while protecting staff and patients. This commentary outlines the planning, work flow and challenges of implementing this drive through testing site in a rural community setting.

In this article, we describe the long-term outcomes of children who were previously reported to have developed hypophosphatemic bone disease in association with elemental formula use. An extended chart review allowed for an updated report of 34 children with regard to severity/duration of bone disease, extent of recovery, and time to correction using radiology reports and biochemical data. After implementation of formula change and/or phosphate supplementation, we found that serum phosphorus concentration increased and serum alkaline phosphatase activity decreased in all patients, normalizing by 6.6 ± 4.0 (mean ± SD) months following diagnosis. The decrease in serum alkaline phosphatase from diagnosis to the time of correction was moderately correlated with the concurrent increase in serum phosphorus ( R = 0.48, P < .05). Age at diagnosis significantly correlated with time to resolution ( R = 0.51, P = .01). This study supports the earlier report that bone disease associated with hypophosphatemia during elemental formula use responds to formula change and/or phosphate supplementation.

Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease, stage, and pathologic findings guiding treatment decision-making. Treatment planning for H&N cancers involves a multidisciplinary team of experts. This article describes supportive care recommendations in the NCCN Guidelines for Head and Neck Cancers, as well as the rationale supporting a new section on imaging recommendations for patients with H&N cancers. This article also describes updates to treatment recommendations for patients with very advanced H&N cancers and salivary gland tumors, specifically systemic therapy recommendations.