Whole-genome Analyses Reveal Past Population Fluctuations and Low Genetic Diversities of the North Pacific Albatrosses.

Throughout the Plio-Pleistocene, climate change has impacted tropical marine ecosystems substantially, with even more severe impacts predicted in the Anthropocene. Although many studies have clarified demographic histories of seabirds in polar regions, the history of keystone seabirds of the tropics is unclear, despite the prominence of albatrosses (Diomedeidae, Procellariiformes) as the largest and most threatened group of oceanic seabirds. To understand the impact of climate change on tropical albatrosses, we investigated the evolutionary and demographic histories of all four North Pacific albatrosses and their prey using whole-genome analyses. We report a striking concordance in demographic histories among the four species, with a notable dip in effective population size at the beginning of the Pleistocene and a population expansion in the Last Glacial Period when sea levels were low, which resulted in increased potential coastal breeding sites. Abundance of the black-footed albatross dropped again during the Last Glacial Maximum, potentially linked to climate-driven loss of breeding sites and concordant genome-derived decreases in its major prey. We find very low genome-wide (π < 0.001) and adaptative genetic diversities across the albatrosses, with genes of the major histocompatibility complex close to monomorphic. We also identify recent selective sweeps at genes associated with hyperosmotic adaptation, longevity, and cognition and memory. Our study has shed light on the evolutionary and demographic histories of the largest tropical oceanic seabirds and provides evidence for their large population fluctuations and alarmingly low genetic diversities.

Intra-specific copy number variation of MHC class II genes in the Siamese fighting fish.

Duplicates of genes for major histocompatibility complex (MHC) molecules can be subjected to selection independently and vary markedly in their evolutionary rates, sequence polymorphism, and functional roles. Therefore, without a thorough understanding of their copy number variation (CNV) in the genome, the MHC-dependent fitness consequences within a species could be misinterpreted. Studying the intra-specific CNV of this highly polymorphic gene, however, has long been hindered by the difficulties in assigning alleles to loci and the lack of high-quality genomic data. Here, using the high-quality genome of the Siamese fighting fish (Betta splendens), a model for mate choice studies, and the whole-genome sequencing (WGS) data of 17 Betta species, we achieved locus-specific amplification of their three classical MHC class II genes - DAB1, DAB2, and DAB3. By performing quantitative PCR and depth-of-coverage analysis using the WGS data, we revealed intra-specific CNV at the DAB3 locus. We identified individuals that had two allelic copies (i.e., heterozygous or homozygous) or one allele (i.e., hemizygous) and individuals without this gene. The CNV was due to the deletion of a 20-kb-long genomic region harboring both the DAA3 and DAB3 genes. We further showed that the three DAB genes were under different modes of selection, which also applies to their corresponding DAA genes that share similar pattern of polymorphism. Our study demonstrates a combined approach to study CNV within a species, which is crucial for the understanding of multigene family evolution and the fitness consequences of CNV.

Development and characterization of microsatellite markers in Rosy-faced and other lovebirds (Agapornis spp.) using next-generation sequencing.

Agapornis are a group of small African parrots that are heavily traded around the world. They are invasive species in many places, but some of them are listed as Vulnerable or Near Threatened. However, the genetic tools for assessing inter-individual relationships, population structure, and genetic diversity of these birds are very limited. Therefore, we developed polymorphic microsatellite markers in A. roseicollis and tested the transferability on 5 lovebird species including A. personatus, A. nigrigenis, A. fischeri, A. pullarius, and A. canus, and two closely related outgroups (i.e. Bolbopsittacus lunulatus and Loriculus galgulus). We first performed whole-genome re-sequencing on five individuals of A. roseicollis to identify potential polymorphic loci. Out of 37 loci tested in 11 A. roseicollis, 27 loci were demonstrated to be polymorphic, with the number of the alleles ranging from 2 to 7 (mean = 3.963). The observed heterozygosity ranged from 0 to 0.875 (mean = 0.481) and expected heterozygosity ranged from 0.233 to 0.842 (mean = 0.642). Five loci (Agro-A13, p < 0.01; Agro-A15, p < 0.05; Agro-A43, p < 0.05, Agro-A65, p < 0.05; Agro-A67, p < 0.05) were detected to deviate from Hardy-Weinberg equilibrium, with the presence of null alleles suggested in locus Agro-A13 and Agro-A77. The exclusion powers for PE1 and PE2 are 0.997 and 0.999, respectively. The 27 novel polymorphic markers developed here will be useful for parentage and kinship assignment and population genetics study in Agapornis, and provide a tool for scientific research, captive breeding industry, and invasion and conservation management of these species.

Management of Obstructive Sleep Apnea in the Infant and Newborn.

Obstructive sleep apnea in newborns and infants presents a unique challenge with distinct differences in sleep physiology, etiologies, and management compared to older children. The indications for and interpretation of polysomnography are less well defined in infants. There are also no broadly accepted clinical practice guidelines for treating sleep apnea in this age group. Etiologies include general causes of upper airway obstruction in infants such as laryngomalacia, micrognathia, and nasal obstruction in addition to adenotonsillar hypertrophy. Treatment strategies must be tailored to the specific anatomic features and comorbidities of the specific patients and often require a multidisciplinary approach.

Drug-Induced Sleep Endoscopy Predicts Subjective Outcomes of Adenotonsillectomy.

OBJECTIVES: Persistent obstructive sleep apnea (OSA) after adenotonsillectomy (AT) has been reported in 20%-30% of children. The aim of this study was to determine the predictive value of drug-induced sleep endoscopy (DISE) at the time of AT on subjective AT outcomes. METHODS: This was a prospective cohort study of children aged 2-18 years being treated with AT for sleep disordered breathing (SDB) with one or more risk factors for AT failure: age >7 years, obesity, severe baseline OSA, Black race. All underwent DISE at the time of AT. Potential predictors of subjective AT outcome included age, sex, obesity, and DISE patterns. Multivariable linear regression was used to model predictors of post-AT Pediatric Sleep Questionnaire (PSQ) and OSA-18 outcomes. RESULTS: Pre- and post-AT PSQ/OSA-18 responses were available from 194 children. Mean age was 9.3 ± 3.5 years, with 59% obese, 50% female, and 67% White. After AT, mean PSQ score decreased from 0.60 ± 0.19 to 0.28 ± 0.22, p < 0.001 and mean OSA-18 score decreased from 66 ± 21 to 37 ± 18, p < 0.001. The most frequent sites of obstruction were the tonsils (92%), nasal airway (77%), adenoids (64%), and velopharynx (65%). Multivariable regression modeling demonstrated worse outcomes with obesity, male gender, and multilevel obstruction that included the nasal airway and tongue base in addition to adenotonsillar obstruction. CONCLUSIONS: Persistent OSA and symptom burden after AT was common in this population. Obesity, male gender, and multilevel obstruction during DISE were all associated with worse subjective outcomes. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Zinc, copper, and blood pressure: Human population studies.

Copper and zinc are essential trace biometals that regulate cardiovascular homeostasis, and dysregulation of these metals has been linked to vascular diseases, including hypertension. In this article, we review recent human population studies concerning this topic, focusing on: 1) the relationship between blood pressure and levels of zinc and copper; 2) correlations between trace metals, the renin-angiotensin system, obesity, and hypertension; 3) the relationship between environmental metal pollution and the development of hypertension; and 4) methods commonly employed to assay zinc and copper in human specimens. Moreover, based on the findings of these studies, we suggest the following topics as the basis for future investigations: 1) the potential role of environmental metal pollution as a causal factor for hypertension; 2) metal profiles within specific pathogenic subsets of patients with hypertension; 3) standardizing the experimental design so that the results between different studies are more comparable; and 4) the requirement for animal experiments as complementary approaches to address mechanistic insight that cannot be studied in human populations.

Inflammatory mediator profiling reveals immune properties of chemotactic gradients and macrophage mediator production inhibition during thioglycollate elicited peritoneal inflammation.

Understanding of spatiotemporal profiling of inflammatory mediators and their associations with MΦ accumulation is crucial to elucidate the complex immune properties. Here, we used murine thioglycollate elicited peritonitis to determine concentrations of 23 inflammatory mediators in peritoneal exudates and plasma before (day 0) and after (days 1 and 3) thioglycollate administration to peritoneal cavities; these mediators included TNF-α , FGF-9, IFN-γ , IP-10, RANTES, IL-1α , IL-6, IL-7, IL-10, IL-11, IL-12p70, IL-17A, lymphotactin, OSM, KC/GRO, SCF, MIP-1ß , MIP-2, TIMP-1, VEGF-A, MCP-1, MCP-3, and MCP-5. Our results showed that concentrations of most mediators in exudates and plasma reached peak levels on day 1 and were significantly reduced on day 3. Conversely, MΦ numbers started to increase on day 1 and reached peak levels on day 3. Moreover, LPS treatment in vitro significantly induced mediator productions in cell culture media and lysates from MΦ isolated on day 3. Our results also showed that on day 0, concentrations of many mediators in plasma were higher than those in exudates, whereas on day 1, the trend was reversed. Overall, the findings from thioglycollate elicited peritonitis reveal that reversible chemotactic gradients between peritoneal exudates and blood exist in basal and inflamed conditions and the inflammatory mediator production in vivo is disassociated with macrophage accumulation during inflammation resolution.

Drug-Induced Sleep Endoscopy Differences by Age in Surgically Naive Children With Sleep-Disordered Breathing.

Importance: Drug-induced sleep endoscopy (DISE) is increasingly used to guide treatment decisions in children with sleep-disordered breathing (SDB). Previous reports of DISE findings in children have typically included a broad age range, but it is unclear how these patterns of obstruction vary with age. Objective: To compare patterns of airway obstruction observed during DISE in 3 age groups of surgically naive children with SDB. Design, Setting, and Participants: This cross-sectional analysis of a prospective cohort of surgically naive nonsyndromic children with SDB or obstructive sleep apnea [OSA] at risk for residual disease after adenotonsillectomy (defined as having at least 1 of these criteria: severe OSA, older than 7 years, obesity, or Black race) who were recruited between May 1, 2015, and February 28, 2020, was conducted at a tertiary children's hospital. Data analysis was conducted from September 2021 to February 2022. Exposures: DISE. Main Outcomes and Measures: DISE findings were rated at 6 anatomic sites using the Sleep Endoscopy Rating Scale (SERS). The association between age and severity of obstruction at each anatomic site and overall were compared using correlation (Kendall τ) and ordinal logistic regression analysis. Results: Data from 288 children (144 girls [50%]; 20 American Indian/Alaska Native [7%], 4 Asian [1%], 19 Black [7%], 93 Hispanic [33%], 2 Middle Eastern [1%], 6 Native Hawaiian/Pacific Islander [2%], and 203 White [70%] individuals; median [IQR] age, 9.2 [7.0-11.7] years) were stratified by participant age into preschool (age 2-5 years; 27 [9%]), younger school-aged (age 5-10 years; 146 [51%]), and older school-aged (age 10-18 years; 115 [40%]). Among these subgroups, the prevalence of multilevel obstruction was 59%, 51%, and 30%, respectively. Increasing age was inversely correlated with obstruction of the nasal airway (τb, -0.19; 95% CI, -0.29 to -0.09), nasopharynx (τb, -0.20; 95% CI, -0.31 to -0.10), velopharynx (τb, -0.16; 95% CI, -0.26 to -0.06), and overall obstruction (SERS total score: τb, -0.24; 95% CI, -0.33 to -0.14). An adjusted analysis demonstrated an inverse association between age and nasopharyngeal obstruction (odds ratio [OR], 0.84; 95% CI, 0.76 to 0.92), SERS total score (OR, 0.83; 95% CI, 0.76 to 0.90), and the number of sites of complete obstruction (OR, 0.87; 95% CI, 0.87 to 0.95). Conclusions and Relevance: This cross-sectional analysis of data from a prospective cohort study of surgically naive children with SDB found that preschool-aged children had more frequent multilevel obstruction, more severe overall obstruction, and nasopharyngeal obstruction compared with older children. Understanding the most common sites of obstruction and expected changes with age could inform personalized treatment for children with SDB.

Both selection and drift drive the spatial pattern of adaptive genetic variation in a wild mammal.

The major histocompatibility complex (MHC) has been intensively studied for the relative effects of different evolutionary forces in recent decades. Pathogen-mediated balancing selection is generally thought to explain the high polymorphism observed in MHC genes, but it is still unclear to what extent MHC diversity is shaped by selection relative to neutral drift. In this study, we genotyped MHC class II DRB genes and 15 neutral microsatellite loci across 26 geographic populations of European badgers (Meles meles) covering most of their geographic range. By comparing variation of microsatellite and diversity of MHC at different levels, we demonstrate that both balancing selection and drift have shaped the evolution of MHC genes. When only MHC allelic identity was investigated, the spatial pattern of MHC variation was similar to that of microsatellites. By contrast, when functional aspects of the MHC diversity (e.g., immunological supertypes) were considered, balancing selection appears to decrease genetic structuring across populations. Our comprehensive sampling and analytical approach enable us to conclude that the likely mechanisms of selection are heterozygote advantage and/or rare-allele advantage. This study is a clear demonstration of how both balancing selection and genetic drift simultaneously affect the evolution of MHC genes in a widely distributed wild mammal.

Development and validation of the international pediatric sleep endoscopy scale (IPSES).

OBJECTIVES: To develop and validate a consensus international pediatric sleep endoscopy scale (IPSES) for pediatric drug-induced sleep endoscopy (DISE). METHODS: Existing published DISE ratings scales were reviewed in order to develop a consensus rating scale synthesizing the most common features and adding new elements to address areas of controversy. Samples of 30 de-identified DISE video recordings were reviewed to develop and refine the scale. After the consensus scale was defined, a separate sample of 25 de-identified DISE videos were scored with the new consensus scale by the development group and a panel of independent raters. A weighted kappa statistic was used to quantify the inter-rater and intra-rater reliability of the consensus scale at each anatomic level. RESULTS: Among all raters, intra-rater reliability was most variable for the nasal airway (kappa range 0.33-0.94) and best for the lateral oropharynx (kappa range 0.68-0.95). Inter-rater reliability ranged from 0.43 for the nasal airway to 0.57 at the soft palate. CONCLUSION: The IPSES is a reliable consensus scale that reflects the most common features of existing scales and can be adopted as a universal scoring scale for pediatric DISE.

International Pediatric Otolaryngology Group (IPOG) consensus on scoring of pediatric Drug Induced Sleep Endoscopy (DISE).

OBJECTIVES: To develop consensus statements for the scoring of pediatric drug induced sleep endoscopy in the diagnosis and management of pediatric obstructive sleep apnea. METHODS: The leadership group identified experts based on defined criteria and invited 18 panelists to participate in the consensus statement development group. A modified Delphi process was used to formally quantify consensus from opinion. A modified Delphi priori process was established, which included a literature review, submission of statements by panelists, and an iterative process of voting to determine consensus. Voting was based on a 9-point Likert scale. Statements achieving a mean score greater than 7 with one or fewer outliers were defined as reaching consensus. Statements achieving a mean score greater than 6.5 with two or fewer outliers were defined as near consensus. Statements with lower scores or more outliers were defined as no consensus. RESULTS: A total of 78 consensus statements were evaluated by the panelists at the first survey - 49 achieved consensus, 18 achieved near consensus, and 11 did not achieve consensus. In the second survey, 16 statements reached consensus and 5 reached near consensus. Regarding scoring, consensus was achieved on the utilization of a 3-point Likert scale for each anatomic site for maximal observed obstructions of <50% (Score 0, no-obstruction), ≥ 50% but <90% (Score 2, partial obstruction), and ≥ 90% (Score 3, complete obstruction). Anatomic sites to be scored during DISE that reached consensus or near-consensus were the nasal passages, adenoid pad, velum, lateral pharyngeal walls, tonsils (if present), tongue base, epiglottis, and arytenoids. CONCLUSION: This study developed consensus statements on the scoring of DISE in pediatric otolaryngology using a modified Delphi process. The use of a priori process, literature review, and iterative voting method allowed for the formal quantification of consensus from expert opinion. The results of this study may provide guidance for standardizing scoring of DISE in pediatric patients.

MRI of the pancreas: problem solving tool.

Advances in MR hardware and pulse sequence design over the years have improved the quality and robustness of MR imaging of the pancreas. Today, MRI is an indispensible tool for studying the pancreas and can provide useful information not attainable with other noninvasive or minimally invasive imaging techniques. In the present review, specific cases are reviewed where the strengths of MRI demonstrate the utility of this imaging modality as a problem solving tool.

Use of the Snoring, Trouble Breathing, Un-Refreshed questionnaire to predict perioperative respiratory adverse events in children.

STUDY OBJECTIVES: The Snoring, Trouble Breathing, Un-Refreshed (STBUR) screening questionnaire has been validated in identifying pediatric surgical patients with symptoms of sleep-disordered breathing who may be at risk of perioperative respiratory adverse events. We sought to assess the performance of the STBUR questionnaire when adjusting for potential confounders such as patient comorbidities or surgical service. METHODS: This was a retrospective cohort study of children aged 2-18 years undergoing elective procedures under general anesthesia over a 3-month period. Procedure specialties included general surgery, urology, orthopedic surgery, neurosurgery, plastic surgery, otolaryngology, dentistry, and gastroenterology. Preoperative STBUR questionnaire responses and perioperative respiratory adverse events were documented prospectively. Multivariate logistic regression was used to quantify associations between preoperative questionnaire responses, other potential risk factors (including age, sex, surgical specialty, comorbidities), and risk of perioperative respiratory adverse events. RESULTS: Of 555 children, 17% had a positive STBUR screen. The prevalence of perioperative respiratory adverse events with a positive questionnaire screen was significantly greater than with a negative screen (29% vs 9%, respectively; P < .001). A positive questionnaire screen was associated with a significantly increased risk of a perioperative respiratory adverse event (adjusted odds ratio 3.47 [95% confidence interval 1.53-7.84], P = .003). CONCLUSIONS: A positive screen on the STBUR questionnaire was associated with a 3.5-fold increased risk of perioperative respiratory adverse events in pediatric surgical patients. The STBUR questionnaire should be considered as a routine preoperative screening tool in children undergoing elective procedures. CITATION: Huerta J, Taleu H, Norton R, Gries H, Yun P, Lam D. Use of the Snoring, Trouble Breathing, Un-Refreshed questionnaire to predict perioperative respiratory adverse events in children. J Clin Sleep Med. 2022;18(3):695-701.

Novel Cluster AZ Arthrobacter phages Powerpuff, Lego, and YesChef exhibit close functional relationships with Microbacterium phages.

Bacteriophages exhibit a vast spectrum of relatedness and there is increasing evidence of close genomic relationships independent of host genus. The variability in phage similarity at the nucleotide, amino acid, and gene content levels confounds attempts at quantifying phage relatedness, especially as more novel phages are isolated. This study describes three highly similar novel Arthrobacter globiformis phages-Powerpuff, Lego, and YesChef-which were assigned to Cluster AZ using a nucleotide-based clustering parameter. Phages in Cluster AZ, Microbacterium Cluster EH, and the former Microbacterium singleton Zeta1847 exhibited low nucleotide similarity. However, their gene content similarity was in excess of the recently adopted Microbacterium clustering parameter, which ultimately resulted in the reassignment of Zeta1847 to Cluster EH. This finding further highlights the importance of using multiple metrics to capture phage relatedness. Additionally, Clusters AZ and EH phages encode a shared integrase indicative of a lysogenic life cycle. In the first experimental verification of a Cluster AZ phage's life cycle, we show that phage Powerpuff is a true temperate phage. It forms stable lysogens that exhibit immunity to superinfection by related phages, despite lacking identifiable repressors typically required for lysogenic maintenance and superinfection immunity. The ability of phage Powerpuff to undergo and maintain lysogeny suggests that other closely related phages may be temperate as well. Our findings provide additional evidence of significant shared phage genomic content spanning multiple actinobacterial host genera and demonstrate the continued need for verification and characterization of life cycles in newly isolated phages.

Drug-Induced Sleep Endoscopy Findings in Children With Obstructive Sleep Apnea With vs Without Obesity or Down Syndrome.

Importance: Persistent obstructive sleep apnea after adenotonsillectomy is common in children with Down syndrome or obesity. Drug-induced sleep endoscopy could help to identify anatomic differences in these patients that might affect surgical decision-making. Objective: To assess drug-induced sleep endoscopy findings in surgically naive children with obstructive sleep apnea with obesity or Down syndrome and compare these findings with children without obesity or Down syndrome. Design, Setting, and Participants: This cross-sectional analysis of data from a prospective cohort study of patients enrolled between May 1, 2015, and December 31, 2019, was conducted at an academic tertiary care children's hospital and included a consecutive sample of surgically naive children (age 2-18 years) who underwent drug-induced sleep endoscopy at the time of adenotonsillectomy for sleep-disordered breathing. Indications for sleep endoscopy included severe sleep apnea, age older than 7 years, obesity, African American race, and Down syndrome. Exposures: Drug-induced sleep endoscopy. Main Outcomes and Measures: Sleep endoscopy findings were scored according to the Sleep Endoscopy Rating Scale. Ratings at 6 anatomic levels for children with obesity and those with Down syndrome were compared with controls without obesity or Down syndrome using several measures of effect size (Cohen d, Cramer V, and η2). Results: A total of 317 children (158 girls [50%]; 219 [69%] White, 20 [6%] Black, and 103 [34%] Hispanic; mean [95% CI] age, 9.6 [9.2-10.0] years) were included, of whom 115 (36%) were controls without obesity or Down syndrome, 179 (56%) had obesity without Down syndrome, and 23 (7%) had Down syndrome. The mean apnea-hypopnea index was 16 (95% CI, 13-19), and the mean minimum O2 saturation was 83% (95% CI, 81%-85%). Compared with controls without obesity or Down syndrome, children with Down syndrome demonstrated greater overall obstruction (mean sleep endoscopy rating scale total score of 5.6 vs 4.8; Cohen d, 0.46), and greater tonsillar (percentage of complete obstruction: 65% vs 54%), tongue base (percentage of complete obstruction: 26% vs 12%), and arytenoid obstruction (percentage of at least partial obstruction, 35% vs 6%). Children with obesity had greater tonsillar (percentage of complete obstruction, 74% vs 54%) and less base of tongue obstruction (percentage of complete obstruction, 2% vs 12%) compared with controls. Conclusions and Relevance: In this cohort study, surgically naive children with obesity with obstructive sleep apnea had predominantly tonsillar obstruction, whereas children with Down syndrome demonstrated greater obstruction of the tonsils, tongue base, and arytenoids compared with controls. Routine drug-induced sleep endoscopy should be considered in surgically naive children with Down syndrome to help inform the surgical plan.

Expert Consensus Statement: Pediatric Drug-Induced Sleep Endoscopy.

OBJECTIVE: To develop an expert consensus statement on pediatric drug-induced sleep endoscopy (DISE) that clarifies controversies and offers opportunities for quality improvement. Pediatric DISE was defined as flexible endoscopy to examine the upper airway of a child with obstructive sleep apnea who is sedated and asleep. METHODS: Development group members with expertise in pediatric DISE followed established guidelines for developing consensus statements. A search strategist systematically reviewed the literature, and the best available evidence was used to compose consensus statements regarding DISE in children 0 to 18 years old. Topics with significant practice variation and those that would improve the quality of patient care were prioritized. RESULTS: The development group identified 59 candidate consensus statements, based on 50 initial proposed topics, that focused on addressing the following high-yield topics: (1) indications and utility, (2) protocol, (3) optimal sedation, (4) grading and interpretation, (5) complications and safety, and (6) outcomes for DISE-directed surgery. After 2 iterations of the Delphi survey and removal of duplicative statements, 26 statements met the criteria for consensus; 11 statements were designated as no consensus. Several areas, such as the role of DISE at the time of adenotonsillectomy, were identified as needing further research. CONCLUSION: Expert consensus was achieved for 26 statements pertaining to indications, protocol, and outcomes for pediatric DISE. Clinicians can use these statements to improve quality of care, inform policy and protocols, and identify areas of uncertainty. Future research, ideally randomized controlled trials, is warranted to address additional controversies related to pediatric DISE.

Systemic Bevacizumab for Treatment of Respiratory Papillomatosis: International Consensus Statement.

OBJECTIVES/HYPOTHESIS: The purpose of this study is to develop consensus on key points that would support the use of systemic bevacizumab for the treatment of recurrent respiratory papillomatosis (RRP), and to provide preliminary guidance surrounding the use of this treatment modality. STUDY DESIGN: Delphi method-based survey series. METHODS: A multidisciplinary, multi-institutional panel of physicians with experience using systemic bevacizumab for the treatment of RRP was established. The Delphi method was used to identify and obtain consensus on characteristics associated with systemic bevacizumab use across five domains: 1) patient characteristics; 2) disease characteristics; 3) treating center characteristics; 4) prior treatment characteristics; and 5) prior work-up. RESULTS: The international panel was composed of 70 experts from 12 countries, representing pediatric and adult otolaryngology, hematology/oncology, infectious diseases, pediatric surgery, family medicine, and epidemiology. A total of 189 items were identified, of which consensus was achieved on Patient Characteristics (9), Disease Characteristics (10), Treatment Center Characteristics (22), and Prior Workup Characteristics (18). CONCLUSION: This consensus statement provides a useful starting point for clinicians and centers hoping to offer systemic bevacizumab for RRP and may serve as a framework to assess the components of practices and centers currently using this therapy. We hope to provide a strategy to offer the treatment and also to provide a springboard for bevacizumab's use in combination with other RRP treatment protocols. Standardized delivery systems may facilitate research efforts and provide dosing regimens to help shape best-practice applications of systemic bevacizumab for patients with early-onset or less-severe disease phenotypes. LEVEL OF EVIDENCE: 5 Laryngoscope, 131:E1941-E1949, 2021.

Competency-Based Assessment Tool for Pediatric Esophagoscopy: International Modified Delphi Consensus.

OBJECTIVES/HYPOTHESIS: Create a competency-based assessment tool for pediatric esophagoscopy with foreign body removal. STUDY DESIGN: Blinded modified Delphi consensus process. SETTING: Tertiary care center. METHODS: A list of 25 potential items was sent via the Research Electronic Data Capture database to 66 expert surgeons who perform pediatric esophagoscopy. In the first round, items were rated as "keep" or "remove" and comments were incorporated. In the second round, experts rated the importance of each item on a seven-point Likert scale. Consensus was determined with a goal of 7 to 25 final items. RESULTS: The response rate was 38/64 (59.4%) in the first round and returned questionnaires were 100% complete. Experts wanted to "keep" all items and 172 comments were incorporated. Twenty-four task-specific and 7 previously-validated global rating items were distributed in the second round, and the response rate was 53/64 (82.8%) with questionnaires returned 97.5% complete. Of the task-specific items, 9 reached consensus, 7 were near consensus, and 8 did not achieve consensus. For global rating items that were previously validated, 6 reached consensus and 1 was near consensus. CONCLUSIONS: It is possible to reach consensus about the important steps involved in rigid esophagoscopy with foreign body removal using a modified Delphi consensus technique. These items can now be considered when evaluating trainees during this procedure. This tool may allow trainees to focus on important steps of the procedure and help training programs standardize how trainees are evaluated. LEVEL OF EVIDENCE: 5. Laryngoscope, 131:1168-1174, 2021.

Impact of AAO-HNS Guideline on Obtaining Polysomnography Prior to Tonsillectomy for Pediatric Sleep-Disordered Breathing.

OBJECTIVE: To assess the impact of the 2011 American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) guideline on practice patterns in obtaining preadenotonsillectomy (AT) polysomnography (PSG) for pediatric sleep-disordered breathing (SDB). STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary children's hospital. SUBJECT AND METHODS: The study population included all patients referred to our pediatric otolaryngology clinic for consideration of AT for SDB during two 12-month time periods: before (2010-2011) and after (2015-2016) publication of the 2011 AAO-HNS guideline. Demographic, insurance, comorbidity, and Pediatric Sleep Questionnaire (PSQ) variables were assessed for association with pre-AT PSG using bivariate and multivariate logistic regression analysis. RESULTS: A greater percentage of patients underwent pre-AT PSG in 2015-2016 vs 2010-2011 (30% vs 22%, P = .001). On multivariate analysis, presence of neuromuscular disorder was the only predictor associated with pre-AT PSG in 2010 to 2011 (odds ratio [OR], 3.00; 95% CI, 1.10, 8.06; P = .03). Presence of neuromuscular disorder (OR, 2.54; 95% CI, 1.51, 4.29; P < .0001), craniofacial anomaly (OR, 2.32; 95% CI, 1.20, 4.50; P = .013), or Down syndrome (OR, 3.45; 95% CI, 1.54, 7.72; P = .003) was associated with pre-AT PSG in 2015 to 2016. Positive PSQ screen was significantly associated with decreased odds of pre-AT PSG in both time periods. CONCLUSION: After publication of the 2011 AAO-HNS guideline, there was a significant but modest increase in pre-AT PSG utilization in children with SDB and high-risk comorbidities at our institution, consistent with AAO-HNS guideline recommendations. However, overall guideline adherence remains low and may reflect limitations in PSG testing capacity.