A CpG island-encoded mechanism protects genes from premature transcription termination.

Transcription must be tightly controlled to regulate gene expression and development. However, our understanding of the molecular mechanisms that influence transcription and how these are coordinated in cells to ensure normal gene expression remains rudimentary. Here, by dissecting the function of the SET1 chromatin-modifying complexes that bind to CpG island-associated gene promoters, we discover that they play a specific and essential role in enabling the expression of low to moderately transcribed genes. Counterintuitively, this effect can occur independently of SET1 complex histone-modifying activity and instead relies on an interaction with the RNA Polymerase II-binding protein WDR82. Unexpectedly, we discover that SET1 complexes enable gene expression by antagonising premature transcription termination by the ZC3H4/WDR82 complex at CpG island-associated genes. In contrast, at extragenic sites of transcription, which typically lack CpG islands and SET1 complex occupancy, we show that the activity of ZC3H4/WDR82 is unopposed. Therefore, we reveal a gene regulatory mechanism whereby CpG islands are bound by a protein complex that specifically protects genic transcripts from premature termination, effectively distinguishing genic from extragenic transcription and enabling normal gene expression.

Postoperative Disposition Following Pediatric Sistrunk Procedures: A National Database Query.

OBJECTIVE/HYPOTHESIS: Variability exists in the postoperative disposition of children following Sistrunk procedures. Management options include discharge home versus overnight observation, with the latter allowing monitoring for immediate postoperative complications, presumably reducing the need for subsequent readmission. This study investigates the association between overnight observation and ambulatory management of children undergoing Sistrunk procedures and relevant postoperative complication and revisit rates to clarify best practice for these patients. METHODS: This was a retrospective database review using the Pediatric Health Information System database from 2007 to 2016. RESULTS: The cited dataset identified 6,434 qualifying patients, categorized into ambulatory versus overnight observation cohorts. The overall 30-day revisit rate was 4.9%; the revisit rate with overnight observation (6.1%) was higher than for ambulatory patients (3.8%, adjusted odds ratio (OR) 1.60; 95% confidence interval (CI): 1.21, 2.12). Revisit rates were significantly higher in patients 2 years of age or younger compared to older patients (6.7% vs. 4.3%). The rates of return to the operating room for the observation versus ambulatory groups were 1.8% and 0.5%, respectively. Cervical fluid collection and neck swelling were among the most common revisit indications in both groups, with a mean time to presentation of 9 days. CONCLUSIONS: This study demonstrates that ambulatory management following a Sistrunk procedure is not associated with increased rates of common postoperative complications, readmission, or need for secondary surgical intervention. A Sistrunk procedure may be safely performed on an ambulatory basis in select cases. LEVEL OF EVIDENCE: IV Laryngoscope, 131:E2352-E2355, 2021.

Understanding the interplay between CpG island-associated gene promoters and H3K4 methylation.

The precise regulation of gene transcription is required to establish and maintain cell type-specific gene expression programs during multicellular development. In addition to transcription factors, chromatin, and its chemical modification, play a central role in regulating gene expression. In vertebrates, DNA is pervasively methylated at CG dinucleotides, a modification that is repressive to transcription. However, approximately 70% of vertebrate gene promoters are associated with DNA elements called CpG islands (CGIs) that are refractory to DNA methylation. CGIs integrate the activity of a range of chromatin-regulating factors that can post-translationally modify histones and modulate gene expression. This is exemplified by the trimethylation of histone H3 at lysine 4 (H3K4me3), which is enriched at CGI-associated gene promoters and correlates with transcriptional activity. Through studying H3K4me3 at CGIs it has become clear that CGIs shape the distribution of H3K4me3 and, in turn, H3K4me3 influences the chromatin landscape at CGIs. Here we will discuss our understanding of the emerging relationship between CGIs, H3K4me3, and gene expression.

To drain or not to drain following a Sistrunk procedure: A dual institutional experience.

INTRODUCTION: A Sistrunk procedure is the standard operative management of patients with thyroglossal duct cysts. Drain placement is commonly employed with the goal of reducing postoperative complications. This study investigates the association between drain use and relevant postoperative complications following pediatric Sistrunk procedures. METHODS: Retrospective cohort study evaluating 295 pediatric patients treated between 2007 and 2016 at two tertiary care children's hospitals. RESULTS: The mean age of the study population was 5.6 years (SD 4.0). A drain was utilized in 234 cases (79.3%). The mean procedural duration was 108 min (SD 48), and significantly longer in patients receiving a drain. Early postoperative complications included seroma (5.8%), secondary infection (3.4%), wound breakdown (2.0%) and hematoma (0.3%). The risk of such complications did not significantly differ between patients without drain placement (9.8%) versus those who underwent surgical drain placement (12.0%) after accounting for age and history of preoperative infection (adjusted RR = 0.86; 95% CI: 0.37, 1.98; p = 0.72). In the subgroup analysis, findings were consistent across institutions, age category, history of infection, and primary versus secondary procedure. CONCLUSION: This dual institutional study found drain placement during a Sistrunk procedure may not reduce rates of common postoperative complications, even in longer duration cases in which a drain is more frequently placed. This data suggests a Sistrunk procedure may be safely performed without drain placement in select cases.

Teaching a tracheotomy handoff tool to pediatric first responders.

INTRODUCTION: The Critical Airway Risk Evaluation (CARE) system is an airway classification system we designed to improve handoffs between caregivers by describing the risk of a patient's airway above the tracheotomy tube, and therefore the correct resuscitation maneuvers in the event of an airway emergency. It is designed to quickly communicate 3 categories: 1-easily intubatable; 2-intubatable with specialized techniques or equipment; or 3-not intubatable. We have demonstrated previously that the system is easily taught to and used by pediatric otolaryngologists. For this system to be useful, it must be usable by a broader group, including first responders to a tracheostomy related airway emergency. The objective of this study is to analyze the reliability of teaching and ease of learning the CARE system among practicing otolaryngologists, otolaryngology residents, and pediatric residents. METHODS: A brief tutorial was designed to introduce the scale and was presented to practicing otolaryngologists, otolaryngology residents, and pediatrics residents. A 30-point questionnaire was administered in which patient's airways and airway management techniques were described. Participants were asked to classify each example according to the CARE system. Statistical analysis was performed using Student's t-test and Fleiss' kappa reliability. RESULTS: A total of 66 physicians participated in the study. The pediatric residents correctly identified the patients' airway class 89% of the time (26.6/30 ±â€¯SD = 2.9). Otolaryngology attendings and residents answered correctly 92% of the time (27.7/30 ±â€¯SD = 2.9), which was not statistically different (p = 0.23). Inter-rater reliability was also substantial among all groups, with a Fleiss' kappa greater than 0.7 for all groups. CONCLUSIONS: This study demonstrates that the system can be taught to pediatrics residents as effectively as it can be taught to otolaryngology residents and practicing otolaryngologists and, therefore, can be effectively utilized in inter-disciplinary handoffs to facilitate information transfer to potential first responders.

Appropriateness of Tympanostomy Tubes in the Boston Metropolitan Area: Are the AAO-HNSF Guidelines Being Met?

Introduction Otitis media (OM) is the most common reason children receive general anesthesia, with bilateral tympanostomy tube (TT) insertion the second most common surgery in children. Prior research suggests overuse of TT. As part of a project designed to improve appropriateness of OM referrals, we evaluated appropriateness of TT insertion in a patient cohort. Methods Patients younger than 9 years with initial otolaryngology (ORL) visits in academic and private office settings for OM from January 1, 2012, to August 31, 2013, were identified through claims database. A detailed retrospective chart review of patients undergoing TT insertion was performed to determine appropriateness of TT insertion per the 2013 American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF) guidelines. Results A total of 120 patients undergoing TT insertion were randomly chosen for detailed chart review; 32 patients were excluded. Sixty-six (75%) of 88 patients available for analysis met AAO-HNSF guidelines for TT. Recurrent acute OM with middle ear effusion was the most common indication (56%). Other indications included chronic OME and TT in at-risk patients with speech, learning, or behavioral delays. Of the 22 patients undergoing TT insertion not meeting AAO-HNSF guidelines, 11(50%) had abnormal exams, but were 1 to 2 infections short of meeting guidelines; 7 (33%) had normal exams but met criteria for number of infections. Discussion Contrary to prior publications, 75% of patients undergoing TT insertion had an appropriate indication per AAO-HNSF guidelines. In only 5% was TT insertion a substantial departure from guidelines. Implications for Practice The study outcomes suggest appropriate clinical decision making, improved guideline adherence, and better guideline applicability from the previously published 1994 and 2004 guidelines.