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Prader-Willi syndrome (PWS) is a rare genetic disorder caused by the loss of paternal genes on chromosome 15. The Aberrant Behavior Checklist (ABC) is a standardized rating scale for assessing problematic behaviors in persons with developmental disabilities. Our study aims to describe ABC scores in youth with PWS and track their change over time. The analysis included 69 patients. Mean ABC scores were compared in four age groups (5-8, 9-12, 13-16, and 17-22 years). A statistically significant difference was found only in the Irritability subscale, with lower scores in the 5-8 age group compared to the 9-12 age group. For change over time, scores for Irritability, Lethargy, Stereotypic Behavior, Hyperactivity subscales, and Total score were likely to decrease after age 12. Irritability subscale scores of males were predicted to increase more than those of females between ages of 5 and 12 . The Lethargy score in the nondeletion group had a greater reduction than the deletion group in the 12-20 year range. This study highlights the need for systematic collection and characterization of behavioral data given the burden of maladaptive behaviors that often persist for a lifetime., (© 2024 Wiley Periodicals LLC.)

Objectives: To evaluate temporal trends and identify patient characteristics associated with otitis media (OM) surgery., Methods: A retrospective cohort study performed using electronic health record data from seven large pediatric medical networks from January 1, 2009, to December 31, 2022. Children <6 months old cohort entrance time and OM history were included and followed longitudinally., Results: The database included 1,448,390 children entering at age <6 months of which 5.3% underwent tympanostomy tube insertion (TTI). Inclusion criteria was met by 454,924 children. Age at first OM was 1.6 years (standard deviation [SD]: 1.1), with mean follow-up of 6.3 years (SD 3.7), and 249,818 (54.9%) were male. Among children with OM 64,950 (14.3%) underwent only TTI, and 13,188 (2.9%) had TTI with adenoidectomy (TTI-A). Over time, TTI only rates exhibited seasonal fluctuations with a drop in 2020, TTI-A rates were flat. The following patient characteristics greatly increased TTI: sensorineural hearing loss (adjusted hazard ratio, aHR 4.0, [95% confidence interval, CI] 3.9-4.1), chronic adenoiditis (aHR 3.4 [95% CI 3.0-3.5]), and cleft palate (aHR 1.9 [95% CI 1.8-2.0]). Children 4-8 years old (aHR >11.7 [95% CI 10.6-16.4]), history of chronic adenoiditis (aHR 6.4 [95% CI 5.4-7.7]), or sleep disorders (aHR 4.9 [95% CI 4.7-5.2]) greatly increased TTI-A odds., Conclusions: Overall TTI rate was 5.3%, which increased to approximately 20% in children with OM. Aside from the COVID-19 pandemic, surgical rates have been stable. Though multiple characteristics increase the risk of TTI, sensorineural hearing loss for TTI only, and older age in the TTI-A subset carried the highest risk., Level of Evidence: 3 Laryngoscope, 2024., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Turner syndrome (TS) is defined by partial or complete absence of a sex chromosome. Little is known about the phenotype of individuals with TS mosaic with trisomy X (45,X/47,XXX or 45,X/46,XX/47,XXX) (~3% of TS). We compared the diagnostic, perinatal, medical, and neurodevelopmental comorbidities of mosaic 45,X/47,XXX (n = 35, 9.4%) with nonmosaic 45,X (n = 142) and mosaic 45,X/46,XX (n = 66). Females with 45,X/47,XXX had fewer neonatal concerns and lower prevalence of several TS-related diagnoses compared with 45,X; however the prevalence of neurodevelopmental and psychiatric diagnoses were not different. Compared to females with 45,X/46,XX, the 45,X/47,XXX group was significantly more likely to have structural renal anomalies (18% vs. 3%; p = 0.03). They were twice as likely to have congenital heart disease (32% vs. 15%, p = 0.08) and less likely to experience spontaneous menarche (46% vs. 75% of those over age 10, p = 0.06), although not statistically significant. Congenital anomalies, hypertension, and hearing loss were primarily attributable to a higher proportion of 45,X cells, while preserved ovarian function was most associated with a higher proportion of 46,XX cells. In this large TS cohort, 45,X/47,XXX was more common than previously reported, individuals were phenotypically less affected than those with 45,X, but did have trends for several more TS-related diagnoses than individuals with 45,X/46,XX., (© 2024 Wiley Periodicals LLC.)

Background: Current assessment techniques for determining whether a patient has normal interarytenoid anatomy, a deep interarytenoid notch, or a minor laryngeal cleft are highly variable. However, differentiating between these three entities is important, given it may distinguish whether a patient should be considered for surgical intervention. The Interarytenoid Assessment Protocol (IAAP) was developed to provide standardization of interarytenoid anatomy evaluations. We aimed to assess the reliability of the IAAP for assessment of interaytenoid mucosal height (IAMH) through a multi-institutional validation study., Methods: Reliability of the IAAP was assessed by 10 pediatric otolaryngologists all from different academic centers. 30 de-identified endoscopic videos of interarytenoid assessments were rated at two separate time points, 2 months apart. Intra-class correlation (ICC) coefficients with two-way models were used to evaluate inter- and intra-rater reliability., Results: Thirty endoscopic videos were collected for patients with a median (IQR) age of 4.9 years (59 months; range: 1 month to 20 years). On the first video assessment, inter-rater reliability was 0.74 (95% CI 0.63-0.84), and on the second video assessment, inter-rater reliability was 0.75 (95% CI 0.63-0.85) indicating strong inter-rater reliability. Overall intra-rater test-retest reliability was 0.75 (95% CI 0.69-0.79) indicating strong agreement. In almost half, 14 (46.6%) raters chose IAAP classification levels within 1 level of each other., Conclusions: Multi-institutional validation of the IAAP demonstrates strong inter- and intra-rater reliability for assessment of IAMH when evaluated through pictorial analysis. Standardization of anatomical evaluations may improve our ability to perform more reliable outcomes studies of pediatric pharyngeal dysphagia in the future., Level of Evidence: NA Laryngoscope, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Although the position of a pediatric cardiology chief is often seen as the apex of one's academic career, its roles, responsibilities, and qualifications are not well defined in the literature. This study was done to gain further insight of the role and attributes of a pediatric cardiology chief by surveying those who are currently serving the position across North American centers., Methods and Results: This was a mixed-methods study with a survey given to North American pediatric cardiology chiefs at programs with fellowship training programs. The survey was a semistructured questionnaire that was independently reviewed by 3 cardiologists. Smaller private practice groups and nonacademic programs were excluded. Survey inventory included items rated on a 5-point Likert scale, open-ended prompts, and targeted questions. A total of 40 of 65 (62%) pediatric cardiology chiefs responded to the survey. Respondents identified key chief attributes included communication skills, honesty/transparency, and conflict-resolution skills. Likert scale data demonstrated participants were satisfied with their position, although many reported growing concerns of increased demands from administration, faculty, and pressures of program performance in the current era. There is also a noted paucity of diversity among those serving in leadership positions within pediatric cardiology, which was acknowledged by survey respondents., Conclusions: We gathered information directly from current North American pediatric cardiology chiefs examining the current era of its role. There are resounding themes on the emphasis for communication, honesty, conflict resolution, and mentorship. Future studies should examine faculty perceptions and a global perspective of the role.

This protocol describes the method for creating 3D-printed trachea models for use in high-fidelity simulation-based training and advanced surgical planning for pediatric patients undergoing slide tracheoplasty. The goal is to provide a template and methodology to allow for replicability and more widespread dissemination of these models to improve clinical training and patient care. Laryngoscope, 134:4409-4413, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Unilateral vocal fold immobility (VFI) is a known cause of morbidity amongst children following congenital heart surgery. Injection medialization (IM) provides medial distraction and improves glottic closure. Limited objective data is available for the effect of IM in young children (<2 years-old) with VFI., Methods: Retrospective case series of infants <2 who underwent IM for VFI after congenital cardiac surgery. Primary outcome was objective reduced risk of aspiration based on Dysphagia and Outcome Severity Scores (DOSS) on Video swallow study (VFSS) performed prior to and within 4 weeks following IM. Secondary analysis included perioperative complications and number of children who were able to avoid NG or G tube placement., Results: 17 children <2 years of age had unilateral VFI after congenital cardiac surgery and underwent IM. The median age at time of initial cardiac surgery was 6 days (IQR 3-7). There was no intraoperative or postoperative stridor or associated complications. All 17 patients had preoperative aspiration noted on VFSS. Average swallowing outcomes on VFSS improved after IM with an increase in DOSS score (preop score 3 (IQR 2-4) to postop score 6.5 (IQR 5-7) [P = 0.001]). At 2 months following IM, of the patients who had improvement in swallowing function, 50% (n = 6) were able to feed completely orally, 25% (n = 3) were fed orally with an NG wean, and 3 (25%) had a G tube placed., Conclusion: Initial results suggest that IM is safe and improves early objective swallowing outcomes in children <2 years old with VFI after congenital cardiac surgery., Level of Evidence: 4 Laryngoscope, 134:4396-4401, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Central nervous system (CNS) injury is common in sickle cell disease (SCD) and occurs early in life. Hydroxyurea is safe and efficacious for treatment of SCD, but high-quality evidence from randomized trials to estimate its neuroprotective effect is scant. HU Prevent was a randomized (1:1), double-blind, phase II feasibility/pilot trial of dose-escalated hydroxyurea vs. placebo for the primary prevention of CNS injury in children with HbSS or HbS-β 0 -thalassemia subtypes of SCD age 12-48 months with normal neurological examination, MRI of the brain, and cerebral blood flow velocity. We hypothesized that hydroxyurea would reduce by 50% the incidence of CNS injury. Two outcomes were compared: primary-a composite of silent cerebral infarction, elevated cerebral blood flow velocity, transient ischemic attack, or stroke; secondary-a weighted score estimating the risk of suffering the consequences of stroke (the Stroke Consequences Risk Score-SCRS), based on the same outcome events. Six participants were randomized to each group. One participant in the hydroxyurea group had a primary outcome vs. four in the placebo group (incidence rate ratio [90% CI] 0.216 [0.009, 1.66], p = .2914) (~80% reduction in the hydroxyurea group). The mean SCRS score was 0.078 (SD 0.174) in the hydroxyurea group, 0.312 (SD 0.174) in the placebo group, p = .072, below the p-value of .10 often used to justify subsequent phase III investigations. Serious adverse events related to study procedures occurred in 3/41 MRIs performed, all related to sedation. These results suggest that hydroxyurea may have profound neuroprotective effect in children with SCD and support a definitive phase III study to encourage the early use of hydroxyurea in all infants with SCD., (© 2024 Wiley Periodicals LLC.)

Adolescent transgender medicine is a growing clinical field. Gender-affirming medications for transgender youth may include gonadotropin-releasing hormone (GnRH) agonists, gender-affirming hormones or both. To evaluate the potential effects of GnRH agonists (puberty suppression) on pharmacokinetic processes for transgender youth, we searched PubMed from inception to May 2024 for publications on the effects of GnRH agonists on drug absorption, distribution, metabolism or excretion for transgender adolescents or effects on hormones (including gonadotropins, adrenal androgens, sex steroids) that are associated with changes in drug metabolism during puberty in the general adolescent population. No publications discussed the effects of GnRH agonist treatment on pharmacokinetic processes for adolescent transgender people. Sixteen publications observed marked decreases in gonadotropins and sex steroids for both adolescent transgender men and adolescent transgender women and slight effects on adrenal androgens. During GnRH agonist treatment, changes in body composition and body shape were greater for adolescent transgender people than for cisgender adolescent people. Further research is needed to better understand the effects of GnRH agonists on drug metabolism and other pharmacokinetic processes for transgender adolescents receiving GnRH agonists and other gender-affirming medications., (© 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

There is a shortage of clinical geneticists, even with concerted recruitment efforts. Previously, no data had been collected about why young career geneticists chose this specialty. To investigate this question, we carried out a survey of current and recent medical genetics and genomics residents. The goal of this survey was to understand their reasons for pursuing medical genetics and genomics as a specialty. Results demonstrate that, for most, interest in genetics begins in medical school and was largely influenced by mentorship. This suggests that placing greater focus on introducing medical genetics as a clinical specialty and fostering robust mentorship of students in preclinical years may increase recruitment into medical genetics residencies., (© 2024 Wiley Periodicals LLC.)

Objective: The objective of this study was to develop and assess multidisciplinary advanced surgical planning (ASP) sessions using three dimensional (3D) printed models for cervicothoracic slide tracheoplasty (CST). We hypothesized that these sessions would improve surgeon confidence, streamline intraoperative planning, and highlight the utility of 3D modeling., Methods: 3D-printed patient-specific trachea models were used in pre-operative ASP sessions consisting of a multidisciplinary case discussion and hands-on slide tracheoplasty simulation. Participants completed a survey rating realism, utility, impact on the final surgical plan, and pre- and post-session confidence. Statistical analysis was performed via Wilcoxon and Kruskal-Wallis tests., Results: Forty-eight surveys were collected across nine sessions and 27 different physicians. On a 5-point Likert scale, models were rated as "very realistic", "very useful" (both median of 4, IQR 3-4 and 4-5, respectively). Overall confidence increased by 1.4 points (+/- 0.7, p < 0.0001), with the largest change seen in those with minimal prior slide tracheoplasty experience (p = 0.005). Participants felt that the sessions "strongly" impacted their surgical plan or anticipated performance (median 4, IQR 4-5), regardless of training level or experience., Conclusion: 3D-printed patient-specific models were successfully implemented in ASP sessions for CST. Models were deemed very realistic and very useful by surgeons across multiple specialties and training levels. Surgical planning sessions also strongly impacted the final surgical plan and increased surgeon confidence for CST., Level of Evidence: 4 Laryngoscope, 134:3395-3401, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Anorectal malformations (ARMs) are congenital anomalies of the anorectum and the genitourinary system that result in a broad spectrum of hindgut anomalies. Despite surgical correction patients continue to have late postoperative genitourinary and colorectal dysfunction that have significant impact on quality of life., Aim: This paper will review the current evidence and discuss the evaluation and management of postoperative patients with ARMs who present with persistent defecation disorder., Methods: A literature search was conducted using PubMed/MEDLINE/EMBASE databases applying the following terms: ARMs, imperforate anus, constipation, faecal incontinence, neurogenic bowel, posterior sagittal anorectoplasty., Results: Patients who present with postoperative defecation disorders require timely diagnostic and surgical evaluation for anatomic abnormalities prior to initiation of bowel management. Goals of management are to avoid constipation in young children, achieve faecal continence in early childhood and facilitate independence in older children and adolescents. Treatment options vary from high dose stimulant laxatives to high-volume retrograde and antegrade enemas that facilitate mechanical colonic emptying., Conclusions: Appropriate diagnostic work-up and implementation of treatment can decrease long-term morbidity and improve quality of life in postoperative patients with ARMs who presents with defecation disorders., (© 2024 John Wiley & Sons Ltd.)

Guidance on indications for, and types of, feeding tubes recommended in Prader-Willi syndrome (PWS) is needed. A Global PWS Registry survey was developed to investigate nasogastric (NG) and gastrostomy (G) tube use and associated complications. Of 346 participants, 242 (69.9%) had NG-tubes, 17 (4.9%) had G-tubes, and 87 (25.1%) had both NG- and G-tubes. Primary indication for placement was "feeding difficulties and/or poor weight gain" for both NG- (90.2%) and G-tubes (71.2%), while "aspiration/breathing difficulties" was the procedural indication for 6.4% of NG-tubes and 23.1% of G-tubes. NG-tubes were generally removed by age 6 months (NG Only: 82.9%; NG/G: 98.8%), while G-tubes were often removed by age 2 years (G Only: 85.7%; NG/G: 70.5%). The severe complication rate from G-tubes was 31.7% and from NG-tubes was 1.2%. Overall, caregivers indicated the presence of an NG- or G-tube had a positive effect on quality of life. Feeding difficulties in PWS are largely managed by NG-tube alone. The severe complication rate from G-tubes was about 25 times higher than from NG-tubes; yet, G-tube placement rates have generally increased. G-tube placement puts individuals with PWS at risk for anesthesia and surgery-related complications and should be considered judiciously by a multidisciplinary team., (© 2024 Wiley Periodicals LLC.)

Introduction: Vocal fold motion impairment (VFMI) is a known consequence after high-risk cardiac surgery. We implemented a universal laryngeal ultrasound (LUS) screening protocol for VFMI after the Norwood and aortic arch surgery. We hypothesized that LUS would accurately identify VFMI and predict postoperative aspiration., Methods: We implemented a screening algorithm with LUS for patients undergoing high-risk cardiac surgery at a tertiary care pediatric hospital. Positively screened patients underwent flexible nasolaryngoscopy (FNL). Patients with an abnormal FNL underwent a video-fluoroscopic swallow study (VFSS). Patient demographics, length of stay, and swallowing outcomes were assessed. Two-tailed chi square and Wilcoxon rank sum tests were used to assess for differences., Results: Sixty-seven patients underwent either Norwood or arch reconstruction over a 16-month period and underwent universal LUS. The average birth weight was 3.24 kg (SD 0.57). Of the 67 patients, VFMI was identified by LUS and 100% confirmed on FNL in 58.21% (n = 39/67) of patients. Aspiration and penetration on VFSS were higher in the group with VFMI as compared with those without VFMI (53.8% vs. 21.4%, p = 0.008). There was no difference in length of stay between patients who did not have a diagnosis of VFMI and those found to have VFMI (41.0 days vs 45.3 days p = 0.73)., Conclusions: Universal LUS screening for patients following high-risk cardiac surgery may lead to earlier identification of postoperative VFMI and aspiration. Recognition of VFMI through this universal screening program could lead to earlier interventions and possibly improved swallowing outcomes., Level of Evidence: 3 Laryngoscope, 134:1939-1944, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Turner syndrome (TS) is a genetic condition occurring in ~1 in 2000 females characterized by the complete or partial absence of the second sex chromosome. TS research faces similar challenges to many other pediatric rare disease conditions, with homogenous, single-center, underpowered studies. Secondary data analyses utilizing electronic health record (EHR) have the potential to address these limitations; however, an algorithm to accurately identify TS cases in EHR data is needed. We developed a computable phenotype to identify patients with TS using PEDSnet, a pediatric research network. This computable phenotype was validated through chart review; true positives and negatives and false positives and negatives were used to assess accuracy at both primary and external validation sites. The optimal algorithm consisted of the following criteria: female sex, ≥1 outpatient encounter, and ≥3 encounters with a diagnosis code that maps to TS, yielding an average sensitivity of 0.97, specificity of 0.88, and C-statistic of 0.93 across all sites. The accuracy of any estradiol prescriptions yielded an average C-statistic of 0.91 across sites and 0.80 for transdermal and oral formulations separately. PEDSnet and computable phenotyping are powerful tools in providing large, diverse samples to pragmatically study rare pediatric conditions like TS., (© 2023 Wiley Periodicals LLC.)

Background: We investigated how syndromic versus nonsyndromic forms of micrognathia impacted difficult intubation outcomes in children. Primary outcome was the first-attempt success rate of tracheal intubation, secondary outcomes were number of intubation attempts and complications. We hypothesized that syndromic micrognathia would be associated with lower first-attempt success rate., Methods: In micrognathic patients enrolled in the Pediatric Difficult Intubation Registry (08/2012-03/2019) we retrospectively compared demographic and clinical characteristics between children with nonsyndromic and syndromic micrognathia using standardized mean differences (SMD) and assessed the association of the presence of syndrome with the primary and secondary outcomes using propensity score matching analysis with and without matching for airway assessment findings., Results: Nonsyndromic patients (628) were less likely to have additional airway abnormalities. Syndromic patients (216) were less likely to have unanticipated difficult intubation (2% vs. 20%, SMD 0.59). First-attempt success rates of intubation were: 38% in the syndromic versus 34% in the nonsyndromic group (odds ratio [OR] 1.18; 95% confidence intervals [95% CI] 0.74, 1.89; p = .478), and 37% versus 37% (OR 0.99; 95% CI 0.66, 1.48; p = .959). Median number of intubation attempts were 2 (interquartile range [IQR]: 1, 3; range: 1, 8) versus 2 (IQR: 1, 3; range 1, 12) (median regression coefficient = 0; 95% CI: -0.7, 0.7; p = .999) and 2 (IQR: 1, 3; range: 1, 12) versus 2 (IQR: 1, 3; range 1, 8) (median regression coefficient = 0; 95% CI: -0.5, 0.5; p = .999). Complication rates were 14% versus 22% (OR 0.6; 95% CI 0.34, 1.04; p = .07) and 16% versus 21% (OR 0.71; 95% CI 0.43, 1.17; p = .185)., Conclusions: Presence of syndrome was not associated with lower first-attempt success rate on intubation, number of intubation attempts, or complication rate among micrognathic patients difficult to intubate, despite more associated craniofacial abnormalities. Nonsyndromic patients were more likely to have unanticipated difficult intubations, first attempt with direct laryngoscopy., (© 2024 Acta Anaesthesiologica Scandinavica Foundation.)

Objective: To review cases of congenital frontonasal dermoids to gain insight into the accuracy of preoperative computed tomography (CT) and magnetic resonance imaging (MRI) in predicting intracranial extension., Methods: This retrospective study included all patients who underwent primary excision of frontonasal dermoids at an academic children's hospital over a 23-year period. Preoperative presentation, imaging, and operative findings were reviewed. Receiver operating characteristic (ROC) statistics were generated to determine CT and MRI accuracy in detecting intracranial extension., Results: Search queries yielded 129 patients who underwent surgical removal of frontonasal dermoids over the study period with an average age of presentation of 12 months. Preoperative imaging was performed on 122 patients, with 19 patients receiving both CT and MRI. CT and MRI were concordant in the prediction of intracranial extension in 18 out of 19 patients. Intraoperatively, intracranial extension requiring craniotomy was seen in 11 patients (8.5%). CT was 87.5% sensitive and 97.4% specific for predicting intracranial extension with an ROC of 0.925 (95% CI [0.801, 1]), whereas MRI was 60.0% sensitive and 97.8% specific with an ROC of 0.789 (95% CI [0.627, 0.950])., Conclusion: This is the largest case series in the literature describing a single institution's experience with frontonasal dermoids. Intracranial extension is rare and few patients required craniotomy in our series. CT and MRI have comparable accuracy at detecting intracranial extension. Single-modality imaging is recommended preoperatively in the absence of other clinical indications., Level of Evidence: 4 Laryngoscope, 134:1961-1966, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: The complexity of congenital heart disease has been primarily stratified on the basis of surgical technical difficulty, specific diagnoses, and associated outcomes. We report on the refinement and validation of a pediatric echocardiography complexity (PEC) score., Methods and Results: The American College of Cardiology Quality Network assembled a panel from 12 centers to refine a previously published PEC score developed in a single institution. The panel refined complexity categories and included study modifiers to account for complexity related to performance of the echocardiogram. Each center submitted data using the PEC scoring tool on 15 consecutive inpatient and outpatient echocardiograms. Univariate and multivariate analyses were performed to assess for independent predictors of longer study duration. Among the 174 echocardiograms analyzed, 68.9% had underlying congenital heart disease; 44.8% were outpatient; 34.5% were performed in an intensive care setting; 61.5% were follow-up; 46.6% were initial or preoperative; and 9.8% were sedated. All studies had an assigned PEC score. In univariate analysis, longer study duration was associated with several patient and study variables (age <2 years, PEC 4 or 5, initial study, preoperative study, junior or trainee scanner, and need for additional imaging). In multivariable analysis, a higher PEC score of 4 or 5 was independently associated with longer study duration after controlling for study variables and center variation., Conclusions: The PEC scoring tool is feasible and applicable in a variety of clinical settings and can be used for correlation with diagnostic errors, allocation of resources, and assessment of physician and sonographer effort in performing, interpreting, and training in pediatric echocardiography.

Background: A previous multicenter study showed that longitudinal changes in standard cardiac functional parameters were associated with the development of cardiomyopathy in childhood cancer survivors (CCS). Evaluation of the relationship between global longitudinal strain (GLS) changes and cardiomyopathy risk was limited, largely due to lack of quality apical 2- and 3-chamber views in addition to 4-chamber view. We sought to determine whether apical 4-chamber longitudinal strain (A4LS) alone can serve as a suitable surrogate for GLS in this population., Methods: A4LS and GLS were measured in echocardiograms with acceptable apical 2-, 3-, and 4-chamber views. Correlation was evaluated using Pearson and Spearman coefficients, and agreement was evaluated with Bland-Altman plots. The ability of A4LS to identify normal and abnormal values compared to GLS as the reference was evaluated., Results: Among a total of 632 reviewed echocardiograms, we identified 130 echocardiograms from 56 patients with adequate views (38% female; mean age at cancer diagnosis 8.3 years; mean follow-up 9.4 years). Correlation coefficients between A4LS and GLS were .89 (Pearson) and .85 (Spearman), with Bland-Altman plot of GLS-A4LS showing a mean difference of -.71 ± 1.8. Compared with GLS as the gold standard, A4LS had a sensitivity of 86% (95% CI 79%-93%) and specificity of 82% (69%-95%) when using normal range cutoffs and 90% (82%-97%) and 70% (58%-81%) when using ±2 standard deviations., Conclusion: A4LS performs well when compared with GLS in this population. Given the more recent adoption of apical 2- and 3-chamber views in most pediatric echocardiography laboratories, A4LS is a reasonable stand-alone measurement in retrospective analyses of older study cohorts and echocardiogram biorepositories., (© 2024 Wiley Periodicals LLC.)

Background: Despite improvements in survival over time, the mortality rate for infants with single-ventricle heart disease remains high. Infants of low socioeconomic status (SES) are particularly vulnerable. We sought to determine whether use of a novel remote monitoring program, the Cardiac High Acuity Monitoring Program, mitigates differences in outcomes by SES., Methods and Results: Within the Cardiac High Acuity Monitoring Program, we identified 610 infants across 11 centers from 2014 to 2021. All enrolled families had access to a mobile application allowing for near-instantaneous transfer of patient information to the care team. Patients were divided into SES tertiles on the basis of 6 variables relating to SES. Hierarchical logistic regression, adjusted for potential confounding characteristics, was used to determine the association between SES and death or transplant listing during the interstage period. Of 610 infants, 39 (6.4%) died or were listed for transplant. In unadjusted analysis, the rate of reaching the primary outcome between SES tertiles was similar ( P =0.24). Even after multivariable adjustment, the odds of death or transplant listing were no different for those in the middle (odds ratio, 1.7 [95% CI, 0.73-3.94) or highest (odds ratio, 0.997 [95% CI, 0.30, 3.36]) SES tertile compared with patients in the lowest (overall P value 0.4)., Conclusions: In a large multicenter cohort of infants with single-ventricle heart disease enrolled in a digital remote monitoring program during the interstage period, we found no difference in outcomes based on SES. Our study suggests that this novel technology could help mitigate differences in outcomes for this fragile population of patients.

Objective: To achieve consensus on critical steps and create an assessment tool for actual and simulated pediatric tracheostomy emergencies that incorporates human and systems factors along with tracheostomy-specific steps., Methods: A modified Delphi method was used. Using REDCap software, an instrument comprising 29 potential items was circulated to 171 tracheostomy and simulation experts. Consensus criteria were determined a priori with a goal of consolidating and ordering 15 to 25 final items. In the first round, items were rated as "keep" or "remove". In the second and third rounds, experts were asked to rate the importance of each item on a 9-point Likert scale. Items were refined in subsequent iterations based on analysis of results and respondents' comments., Results: The response rates were 125/171 (73.1%) for the first round, 111/125 (88.8%) for the second round, and 109/125 (87.2%) for the third round. 133 comments were incorporated. Consensus (>60% participants scoring ≥8, or mean score >7.5) was reached on 22 items distributed across three domains. There were 12, 4, and 6 items in the domains of tracheostomy-specific steps, team and personnel factors, and equipment respectively., Conclusions: The resultant assessment tool can be used to assess both tracheostomy-specific steps as well as systems factors affecting hospital team response to simulated and clinical pediatric tracheostomy emergencies. The tool can also be used to guide debriefing discussions of both simulated and clinical emergencies, and to spur quality improvement initiatives., Level of Evidence: 5 Laryngoscope, 133:3588-3601, 2023., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Subdural hemorrhages (SDHs) in children are most often observed in abusive head trauma (AHT), a distinct form of traumatic brain injury, but they may occur in other conditions as well, typically with clear signs and symptoms of an alternative diagnosis. We present a case of an infant whose SDH initially raised the question of AHT, but multidisciplinary evaluation identified multiple abnormalities, including rash, macrocephaly, growth failure, and elevated inflammatory markers, which were all atypical for trauma. These, along with significant cerebral atrophy, ventriculomegaly, and an absence of other injuries, raised concerns for a genetic disorder, prompting genetic consultation. Clinical trio exome sequencing identified a de novo likely pathogenic variant in NLRP3, which is associated with chronic infantile neurological, cutaneous, and articular (CINCA) syndrome, also known as neonatal-onset multisystem inflammatory disease (NOMID). He was successfully treated with interleukin-1 blockade, highlighting the importance of prompt treatment in CINCA/NOMID patients. This case also illustrates how atraumatic cases of SDH can be readily distinguished from AHT with multidisciplinary collaboration and careful consideration of the clinical history and exam findings., (© 2023 Wiley Periodicals LLC.)

Objectives: To examine the otolaryngology residency selection process, including past experiences based on the medical literature and survey analysis of our present practices to generate recommendations for future selection system design., Methods: A mixed-methods study, including a scoping review and a cross-sectional survey, was completed. Four databases were assessed for articles on otolaryngology residency selection published from January 1, 2016 through December 31, 2020. A 36-question survey was developed and distributed to 114 otolaryngology program directors. Descriptive and thematic analysis was performed., Results: Ultimately, 67 of 168 articles underwent data abstraction and assessment. Three themes surfaced during the analysis: effectiveness, efficiency, and equity. Regarding the survey, there were 62 participants (54.4% response rate). The three most important goals for the selection process were: (1) to fit the program culture, (2) to make good colleagues, and (3) to contribute to the program's diversity. The three biggest 'pain points' were as follows: (1) Large volume of applications, (2) Lack of reliable information about personal characteristics, and (3) Lack of reliable information about a genuine interest in the program., Conclusions: Within this study, the depth and breadth of the literature on otolaryngology residency selection have been synthesized. Additionally, baseline data on selection practices within our specialty has been captured. With an informed understanding of our past and present, we can look to the future. Built upon the principles of person-environment fit theory, our proposed framework can guide research and policy discussions regarding the design of selection systems in otolaryngology, as we work to achieve more effective, efficient, and equitable outcomes., Level of Evidence: N/A Laryngoscope, 133:2929-2941, 2023., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Background Anthracycline-induced cardiomyopathy is a leading cause of premature death in childhood cancer survivors, presenting a need to understand the underlying pathogenesis. We sought to examine differential blood-based mRNA expression profiles in anthracycline-exposed childhood cancer survivors with and without cardiomyopathy. Methods and Results We designed a matched case-control study (Children's Oncology Group-ALTE03N1) with mRNA sequencing on total RNA from peripheral blood in 40 anthracycline-exposed survivors with cardiomyopathy (cases) and 64 matched survivors without (controls). DESeq2 identified differentially expressed genes. Ingenuity Pathway Analyses (IPA) and Gene Set Enrichment Analyses determined the potential roles of altered genes in biological pathways. Functional validation was performed by gene knockout in human-induced pluripotent stem cell-derived cardiomyocytes using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) technology. Median age at primary cancer diagnosis for cases and controls was 8.2 and 9.7 years, respectively. Thirty-six differentially expressed genes with fold change ≥±2 were identified; 35 were upregulated. IPA identified "hepatic fibrosis" and "iron homeostasis" pathways to be significantly modulated by differentially expressed genes, including toxicology functions of myocardial infarction, cardiac damage, and cardiac dilation. Leading edge analysis from Gene Set Enrichment Analyses identified lactate dehydrogenase A ( LDHA ) and cluster of differentiation 36 ( CD36 ) genes to be significantly upregulated in cases. Interleukin 1 receptor type 1, 2 ( IL1R1 , IL1R2 ), and matrix metalloproteinase 8, 9 ( MMP8, MMP9 ) appeared in multiple canonical pathways. LDHA -knockout human-induced pluripotent stem cell-derived cardiomyocytes showed increased sensitivity to doxorubicin. Conclusions We identified differential mRNA expression profiles in peripheral blood of anthracycline-exposed childhood cancer survivors with and without cardiomyopathy. Upregulation of LDHA and CD36 genes suggests metabolic perturbations in a failing heart. Dysregulation of proinflammatory cytokine receptors IL1R1 and IL1R2 and matrix metalloproteinases, MMP8 and MMP9 indicates structural remodeling that accompanies the clinical manifestation of symptomatic cardiotoxicity.

Objective: Patients with 22q11.2 deletion syndrome (22q11DelS) often present with velopharyngeal dysfunction (VPD). VPD in patients with 22q11DelS is multifactorial beyond velopharyngeal insufficiency (VPI) alone, and differences in surgical outcomes are poorly understood. Our objective was to determine whether patients with 22q11DelS have an increased risk for persistent VPI after sphincter pharyngoplasty compared to patients without 22q11DelS., Methods: We completed a retrospective cohort study of patients with 22q11DelS undergoing sphincter pharyngoplasty between 1995 and 2019 using a VPD clinic database. Patients with 22q11DelS were compared to a cohort of 2:1 frequency-matched (age, degree of velopharyngeal closure) patients without 22q11DelS. Variables included patient characteristics, surgical history, perceptual speech evaluation, and degree of closure on nasopharyngoscopic evaluations. Primary outcomes included postoperative VPI severity and hypernasality. Speech and nasopharyngoscopic characteristics were compared using Fisher's exact test. Postoperative VPI severity and hypernasality were compared between groups via relative risks (RR) from mixed effects Poisson regression models, with random effects of age and velopharyngeal closure., Results: 134 patients (51 22q11DelS, 83 matched) were included, with mean age of 7.3 years (standard deviation 3.0) and 50% male. Cohorts had similar preoperative speech characteristics and nasopharyngoscopic findings. Patients with 22q11DelS had similar postoperative VP function as patients without 22q11DelS (RR 0.85, CI 0.46-1.57 for VPI severity, RR 0.83, CI 0.45-1.53 for hypernasality). Even after adjusting by preoperative variables, no differences were seen between both groups., Conclusion: Matched for age and pre-operative velopharyngeal closure, patients with and without 22q11DelS and VPI had similar benefits after sphincter pharyngoplasty., Level of Evidence: Non-randomized controlled cohort study, 3 Laryngoscope, 133:2813-2820, 2023., (© 2023 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Racial, ethnic, and gender disparities in the otolaryngology-head and neck surgery (OHNS) match have been described individually, but not intersectionally. Intersectionality recognizes how multiple forms of discrimination (e.g., sexism, racism) can have a combined effect. The objective of this study was to analyze racial, ethnic, and gender disparities in the OHNS match using an intersectional approach., Methods: Cross-sectional evaluation of data from otolaryngology applicants from the Electronic Residency Application Service (ERAS) and of corresponding otolaryngology residents from the Accreditation Council for Graduate Medical Education (ACGME) from 2013 to 2019. Data were stratified by race, ethnicity, and gender. The Cochran-Armitage tests assessed trends over time in the proportions of applicants and corresponding residents. Chi-square tests with Yates' continuity correction were performed to evaluate differences between the aggregate proportions of applicants and corresponding residents., Results: The proportion of White men in the resident pool was increased compared to the applicant pool (ACGME 0.417, ERAS 0.375; Δ + 0.042; 95% CI 0.012 to 0.071; p = 0.03). This was also the case for White women (ACGME 0.206, ERAS 0.175; Δ + 0.031; 95% CI 0.007 to 0.055; p = 0.05). In contrast, there was a smaller proportion of residents compared to applicants among Multiracial men (ACGME 0.014, ERAS 0.047; Δ - 0.033; 95% CI -0.043 to -0.023; p < 0.001) and Multiracial women (ACGME 0.010, ERAS 0.026; Δ - 0.016; 95% CI -0.024 to -0.008; p < 0.001)., Conclusion: The findings of this study imply that White men have a persistent advantage, while several racial, ethnic, and gender minorities are disadvantaged in the OHNS match. Further research is necessary to examine why these differences exist in residency selection, including evaluation during the screening, reviewing, interviewing, and ranking stages. Laryngoscope, 133:2558-2563, 2023., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Isolated frontosphenoidal craniosynostosis (IFSC) is a rare congenital defect defined as premature fusion of the frontosphenoidal suture in the absence of other suture fusion. Until now, IFSC was regarded as a phenomenon with an unclear genetic etiology. We have identified three cases with IFSC with underlying syndromic diagnoses that were attributable to pathogenic mutations involving FGFR3 and MN1, as well as 22q11.2 deletion syndrome. These findings suggest a genetic predisposition to IFSC may exist, thereby justifying the recommendation for genetic evaluation and testing in this population. Furthermore, due to improved imaging resolution, cases of IFSC are now readily identified. With the identification of IFSC with underlying genetic diagnoses, in combination with significant improvements in imaging resolution, we recommend genetic evaluation in children with IFSC., (© 2023 Wiley Periodicals LLC.)

Objective: To assess the efficacy of interarytenoid injection augmentation (IAIA) and the ability of IAIA to predict response to interarytenoid suture augmentation (IASA) based on diet advancement on video fluoroscopic swallow studies (VFSS)., Methods: Retrospective cohort analysis of patients with persistent pharyngeal dysphagia at a tertiary children's hospital with VFSS pre- and post-IAIA were included between March 2011 and June 2019., Results: Median age of the 229 patients was 2.2 years (5.8 months-19 years). Interarytenoid mucosal height (IAMH) was found to be above the false vocal folds in 112 patients (53.4%) and at true vocal folds in 10 (4.9%) patients. On VFSS post-IAIA, 95 (41.5%) patients were successfully advanced in recommended diet consistency, 115 (50.2%) were stable, and 19 (8.3%) needed thicker consistency. Paired t-tests on pre- and post-operative consistency scores showed significant improvement, p-value of <0.0001, 95% confidence interval (CI; 0.50-0.85). Poisson regression found no covariates with significant association with improvement on IAIA. For IASA patients, 35/60 (58.3%) improved on post-op VFSS. Paired t-tests on pre- and post-operative consistency scores showed significant improvement, p-value of <0.0001, 95% CI (0.63-1.33). Positive predictive value for IAIA predicting response to IASA was 77% with positive likelihood ratio of 2.3. The response to IAIA versus no response to IAIA likelihood ratios were found to have a statistically significant difference (p < 0.05)., Conclusions: Our study suggests IAIA yields objective improvement in swallow function on VFSS in nearly half of our patients and may be a reliable diagnostic tool to predict response to IASA in patients with persistent pharyngeal dysphagia with or without a laryngeal cleft., Level of Evidence: 3 Laryngoscope, 133:1749-1756, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Study Objective: The immunosuppressant tacrolimus is a first-line agent to prevent graft rejection following pediatric heart transplant; however, it suffers from extensive inter-patient variability and a narrow therapeutic window. Personalized tacrolimus dosing may improve transplant outcomes by more efficiently achieving and maintaining therapeutic tacrolimus concentrations. We sought to externally validate a previously published population pharmacokinetic (PK) model that was constructed with data from a single site., Data Source: Data were collected from Seattle, Texas, and Boston Children's Hospitals, and assessed using standard population PK modeling techniques in NONMEMv7.2., Main Results: While the model was not successfully validated for use with external data, further covariate searching identified weight (p < 0.0001 on both volume and elimination rate) as a model-significant covariate. This refined model acceptably predicted future tacrolimus concentrations when guided by as few as three concentrations (median prediction error = 7%; median absolute prediction error = 27%)., Conclusion: These findings support the potential clinical utility of a population PK model to provide personalized tacrolimus dosing guidance., (© 2023 Pharmacotherapy Publications, Inc.)

Background Fetal diagnosis of congenitally corrected transposition of the great arteries (ccTGA) has been increasingly reported; however, predictors of clinical outcomes remain underexplored. We undertook a multicenter, retrospective study to investigate natural history, associated anomalies, and outcomes of fetal ccTGA. Methods and Results Fetuses with ccTGA diagnosed from January 2004 to July 2020 within 20 North American programs were included. Fetuses with severe ventricular hypoplasia thought to definitively preclude biventricular repair were excluded. We included 205 fetuses diagnosed with ccTGA at a median gestational age of 23 (interquartile range, 21-27) weeks. Genetic abnormalities were found in 5.9% tested, with extracardiac anomalies in 6.3%. Associated cardiac defects were diagnosed in 161 (78.5%), with atrioventricular block in 23 (11.3%). On serial fetal echocardiogram, 39% demonstrated a functional or anatomic change, most commonly increased tricuspid regurgitation (6.7%) or pulmonary outflow obstruction (11.1%). Of 194 fetuses with follow-up, 26 were terminated, 3 experienced fetal death (2 with atrioventricular block), and 165 were live-born. Of 158 with postnatal data (median follow-up 3.7 years), 10 (6.6%) had death/transplant before 1 year. On univariable analysis, fetal factors associated with fetal death or death/transplant by 1 year included ≥ mild tricuspid regurgitation, pulmonary atresia, aortic obstruction, fetal arrhythmia, and worsening hemodynamics on serial fetal echocardiogram (defined as worse right ventricular function, tricuspid regurgitation, or effusion). Conclusions Associated cardiac lesions and arrhythmias are common in fetal ccTGA, and functional changes commonly occur through gestation. Worse outcomes are associated with fetal tricuspid regurgitation (≥mild), any arrhythmia, pulmonary atresia, aortic obstruction, and worsening hemodynamics on serial echocardiograms. These findings can inform prenatal counseling and perinatal management planning.

Background: Complete and accurate documentation of surgical procedures is essential for optimizing patient care, yet significant variation in operative notes persists within and across institutions. We sought to reach consensus on the most important components of an operative note for pediatric microlaryngoscopy and bronchoscopy., Methods: A modified Delphi consensus process was used. A checklist for operative documentation, created by fellowship-trained pediatric otolaryngologists-head and neck surgeons, was sent to surgeons identified as experts in pediatric laryngoscopy and bronchoscopy. In the first round, items were rated as "keep" or "remove". In the second round, each item was rated on a 7-point Likert scale for importance. The mean score of each item was calculated to determine if consensus was reached., Results: Overall, 43/74 (58.1%) surgeons responded to our survey. After two rounds of editing, 28 components reached consensus, 24 were near consensus, and 26 did not reach consensus. Items that reached final consensus had mean (SD) ratings of 6.12 (0.94) (range, 5.31-6.72)., Conclusion: Pediatric otolaryngologists identified as bronchoscopy experts were able to create a checklist of essential components of an operative note for pediatric laryngoscopy and bronchoscopy using a Delphi method. Items reaching consensus included procedure name, description of breathing, grade of airway view, description of normal anatomic structures, grade of subglottic stenosis if present, presence and description of tracheobronchomalacia, presence of fistulae, cleft and rings, and several special cases including foreign body and tracheostomy management, as well as end of procedure disposition and complications., Level of Evidence: 5 Laryngoscope, 133:1234-1238, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Large (De Serres stage [IV-V]) head and neck lymphatic malformations (HNLMs) often have multiple, high-risk, invasive treatments (ITs) to address functional compromise. Logically reducing HNLM ITs should reduce treatment risk. We tested whether delaying HNLM ITs reduces total IT number., Materials: Consecutive HNLM patients (n = 199) between 2010 and 2017, aged 0-18 years., Methods: ITs (surgery or sclerotherapy) were offered for persistent or dysfunction causing HNLMs. Treatment effectiveness categorized by IT number: optimal (0-1), acceptable (2-5), or suboptimal (>5). Clinical data were summarized, and outcome associations tested (χ 2 ). Relative risk (RR) with a Poisson working model tested whether HNLM observation or IT delay (>6 months post-diagnosis) predicts treatment success (i.e., ≤1 IT)., Results: Median age at HNLM diagnosis was 1.3 months (interquartile range [IQR] 0-45 m) with 107/199(54%) male. HNLM were stage I-III (174 [88%]), IV-V (25 [13%]). Initial treatment was observation (70 [35%]), invasive (129 [65%]). Treatment outcomes were optimal (137 [69%]), acceptable (36 [18%]), and suboptimal (26 [13%]). Suboptimal outcome associations: EXIT procedure, stage IV-V, oral location, and tracheotomy (p < 0.001). Stage I-III HNLMs were initially observed compared with stage I-III having ITs within 6 months of HNLM diagnosis, had a 82% lower relative treatment failure risk ([i.e., >1 IT], RR = 0.09, 95% CI 0.02-0.36, p < 0.001). Stage I-III HNLMs with non-delayed ITs had reduced treatment failure risk compared with IV-V (RR = 0.47, 95% CI 0.33-0.66, p < 0.001)., Conclusion: Observation and delayed IT in stage I-III HNLM ("Grade 1") is safe and reduces IT (i.e., ≤1 IT). Stage IV-V HNLMs ("Grade 2") with early IT have a greater risk of multiple ITs., Level of Evidence: 4 Laryngoscope, 133:956-962, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Endoscopic laryngeal cleft repair (ELCR) with endolaryngeal suturing is an advanced surgical skill. This study objective was to assess the validity of 3-dimensionally (3D) printed laryngeal suturing simulator for ELCR., Study Design: Development and validation of a simulator for ELCR., Methods: An ELCR model was developed using 3D printed and readily available materials. Participants were surveyed before and after a simulation session using five-point Likert scale questions. Performance data was assessed using blinded expert video review and rated using a novel objective structured assessment of technical skills (OSATS) for endoscopic laryngeal suturing., Results: Twenty-one participants ranging from residents to attendings completed the simulation session. Survey respondents reported on a five-point Likert scale that the model was "easy to use" and "quite realistic" (both mean of 4). Confidence improved significantly in 86% of participants (p < 0.01). Overall OSATS scores (out of a total of 55) showed a median improvement in technical skills of 11.7 points (p = 0.004). OSATS demonstrated good intra-rater (κ = 0.689 and 0.677) and moderate inter-rater (κ = 0.573) reliability. Completion times improved from the first to the last suture by a median time of 512 to 350 s (decrease of 202 s, p = 0.002). Participants with no prior ELCR experience improved more than those with in vivo experience., Conclusion: This study demonstrates the validity of a simulator utilizing 3D printed larynges for ELCR. A novel OSATS for endoscopic laryngeal suturing was successfully implemented. Confidence, technical skills, and completion times improved with the use of the model across a variety of participants. Laryngoscope, 133:785-791, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Burkitt lymphoma arising in paediatric post-solid-organ transplantation-Burkitt lymphoma (PSOT-BL) is a clinically aggressive malignancy and a rare form of post-transplant lymphoproliferative disorder (PTLD). We evaluated 35 patients diagnosed with PSOT-BL at 14 paediatric medical centres in the United States. Median age at organ transplantation was 2.0 years (range: 0.1-14) and age at PSOT-BL diagnosis was 8.0 years (range: 1-17). All but one patient had late onset of PSOT-BL (≥2 years post-transplant), with a median interval from transplant to PSOT-BL diagnosis of 4.0 years (range: 0.4-12). Heart (n = 18 [51.4%]) and liver (n = 13 [37.1%]) were the most frequently transplanted organs. No patients had loss of graft or treatment-related mortality. A variety of treatment regimens were used, led by intensive Burkitt lymphoma-specific French-American-British/Lymphomes Malins B (FAB/LMB), n = 13 (37.1%), and a low-intensity regimen consisting of cyclophosphamide, prednisone and rituximab (CPR) n = 12 (34.3%). Median follow-up was 6.7 years (range: 0.5-17). Three-year event-free and overall survival were 66.2% and 88.0%, respectively. Outcomes of PSOT-BL patients receiving BL-specific intensive regimens are comparable to reported BL outcomes in immunocompetent children. Multi-institutional collaboration is feasible and provides the basis of prospective data collection to determine the optimal treatment regimen for PSOT-BL., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

The non-POU domain-containing octamer-binding (NONO) protein is involved in multiple steps of gene regulation such as RNA metabolism and DNA repair. Hemizygous pathogenic variants in the NONO gene were confirmed to cause a rare X-linked syndromic disorder. Through our in-house diagnostics and subsequent matchmaking, we identified six unrelated male individuals with pathogenic or likely pathogenic NONO variants. For a detailed comparison, we reviewed all published characterizations of the NONO-associated disorder. The combined cohort consists of 16 live-born males showing developmental delay, corpus callosum anomalies, non-compaction cardiomyopathy and relative macrocephaly as leading symptoms. Seven prenatal literature cases were characterized by cardiac malformations. In this study, we extend the phenotypic spectrum through two more cases with epilepsy as well as two more cases with hematologic anomalies. By RNA expression analysis and structural modeling of a new in-frame splice deletion, we reinforce loss-of-function as the pathomechanism for the NONO-associated syndromic disorder., (© 2022 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

A patient with a recurrent connection between their trachea and esophagus underwent an endoscopic repair (through the mouth with no incisions) with a graft secured via sutures, which is the first description of fully endoscopic graft placement for this pathology. Laryngoscope, 133:269-272, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Most pediatric patients show a decline in platelet counts while on extracorporeal life support (ECLS) and require multiple platelet transfusions. To better understand platelet loss during ECLS, this study estimated platelet loss rates due to diagnostic phlebotomy, platelet activation, bleeding and other causes., Methods: We collected data on 91 patients (1d-20y, 50 M, 41F). Platelet losses were estimated based on changes in platelet count, patient+circuit blood volume, and transfused platelet volumes. Platelet extracellular vesicles were measured by flow cytometry., Results: Median platelet loss was 2.8 × 10 9 /L/hr, more than twice the normal rate of platelet removal and equivalent to a 67 000/μl decrease in platelet count per day. While platelet loss was correlated with platelet transfusion (r 2  = 0.51), transfusion underestimated platelet loss in patients with large decreases in platelet count and over-estimated platelet loss in neonates where the circuit volume > patient blood volume. Patients with disseminated intravascular coagulation before or significant bleeding during ECLS have double the rate of platelet loss. Platelet activation accounted for ~32% of total platelet loss, bleeding ~36% and phlebotomy 4%, with the remaining one-third due to other causes. Annexin-negative platelet extracellular vesicle release, a measure of platelet damage, was increased 9-fold during ECLS., Conclusion: Our study is the first to quantitate total, phlebotomy and activation related platelet loss during ECLS. Platelet activation accounts for ~32% of total platelet loss, while bleeding doubles the platelet loss rate. The etiology of the remaining platelet loss is unknown., (© 2022 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

We report a neonate with severe Marfan syndrome (MS), prenatally identified to have persistent atrial tachycardia, biventricular dysfunction, and an unusual structure within the atria. Detailed postnatal echocardiographic evaluation and cross-sectional imaging confirmed congenital pseudoaneurysm of the mitral-aortic intervalvular fibrosa. Emergent testing by next-generation sequencing identified a FBN1 pathological variant, key to establishing goals of care. To our knowledge, this is the first reported case of a congenital pseudoaneurysm of the mitral-aortic intervalvular fibrosa in MS., (© 2022 Wiley Periodicals LLC.)

The aim of this scoping review initiated by the Education, Implementation and Teams Task Force of the International Liaison Committee on Resuscitation was to identify faculty development approaches to improve instructional competence in accredited life support courses. We searched PubMed, Ovid Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Central Register of Controlled Trials to identify studies published from January 1, 1966 to December 31, 2021 on approaches to improve faculty development for life support courses. Data on participant characteristics, interventions, design, and outcomes of included studies were extracted. Of the initially identified 10 310 studies, we included 20 studies (5 conference abstracts, 1 short communication, 14 full-length articles). Among them, 12 studies aimed to improve instructors/candidates' teaching ability in basic life support courses. A wide variety of interventions were identified. The interventions were categorized into 4 themes: instructor qualification/training (n=9), assessment tools (n=3), teaching skills enhancement (n=3), and additional courses for instructors (n=5). Most studies showed that these interventions improved specific teaching ability or confidence of the instructors and learning outcomes in different kinds of life support courses. However, no studies addressed clinical outcomes of patients. In conclusion, the faculty development approaches for instructors are generally associated with improved learning outcomes for participants, and also improved teaching ability and self-confidence of the instructors. It is encouraged that local organizations implement faculty development programs for their teaching staff of their accredited resuscitation courses. Further studies should explore the best ways to strengthen and maintain instructor competency, and define the cost-effectiveness of various different faculty development strategies.

Background: Hospitals quickly adapted perinatal care to mitigate SARS-CoV-2 transmission at the onset of the COVID-19 pandemic. The objective of this study was to estimate the impact of pandemic-related hospital policy changes on perinatal care and outcomes in one region of the United States., Methods: This interrupted time series analysis used retrospective data from consecutive singleton births at 15 hospitals in the Pacific Northwest from 2017 to 2020. The primary outcomes were those hypothesized to be affected by pandemic-related hospital policies and included labor induction, epidural use, oxytocin augmentation, mode of delivery, and early discharge (<48 hours after cesarean and <24 hours after vaginal births). Secondary outcomes included preterm birth, severe maternal morbidity, low 5-minute Apgar score, neonatal intensive care unit (NICU) admission, and 30-day readmission. Segmented Poisson regression models estimated the outcome level shift changes after the pandemic onset, controlling for underlying trends, seasonality, and stratifying by parity., Results: No statistically significant changes were detected in intrapartum interventions or mode of delivery after onset of the pandemic. Early discharge increased for all births following cesarean and vaginal birth. Newborn readmission rates increased but only among nulliparas (aRR: 1.49, 95%CI: 1.17, 1.91). Among multiparas, decreases were observed in preterm birth (aRR: 0.90, 95%CI: 0.84, 0.96), low 5-minute Apgar score (aRR: 0.75, 95%CI: 0.68, 0.81), and term NICU admission rates (aRR: 0.85, 95%CI: 0.80, 0.91)., Conclusions: Increases in early discharge and newborn readmission rates among nulliparas suggest a need for more postpartum support during the pandemic. Decreases in preterm birth and term NICU admission among multiparas may have implications beyond the pandemic and deserve further study., (© 2021 Wiley Periodicals LLC.)

Objectives/hypothesis: We hypothesized that the use of three-dimensional (3D) printed tracheal models to reproducibly simulate surgical technique variations in slide tracheoplasty would demonstrate the quantitative impact of surgical variables on postoperative tracheal dimensions., Study Design: Prospective analysis of three-dimensional printed surgical simulation models., Methods: Slide tracheoplasty was performed on 3D printed long segment tracheal stenosis models with combinations of tracheal transection incision angle (90°, 45° beveled superior to inferior, 45° beveled inferior to superior) and tracheal transection location relative to the stenosis (at midpoint, 2 mm each superior and inferior to midpoint). Postoperative computed tomography (CT) scans measured changes in tracheal length, volume, and cross-sectional area compared to controls. Statistical analysis was performed using one-way analysis of variance and unpaired two-tailed t-tests., Results: Slide tracheoplasty yielded 27 reconstructed tracheas. On average, slide tracheoplasty reduced total tracheal length by 36%. Beveled tracheal incisions yielded 9.5% longer final tracheas than straight transection incisions (P < .0001). Cross-sectional area at the stenosis midpoint increased from 9.0 mm 2 to 45 mm 2 but did not vary with technique (P > .05). Total tracheal luminal volume increased from 900 mm 3 to 1378 mm 3 overall and was largest with beveled incisions (P = .03). More material was discarded with straight incisions compared to beveled (89 mg vs. 19 mg, P < .0001)., Conclusions: Beveled tracheal transection incisions resulted in increased tracheal length, longer anastomotic segments, increased volume, and reduced tissue waste as compared to straight incisions. Offsetting the incision from the midpoint of stenosis did not significantly affect reconstructed tracheal morphology. Using 3D printed models for surgical simulation can be helpful for the quantitative study of the effect isolated surgical variables on technical outcomes., Level of Evidence: 3 Laryngoscope, 132:1306-1312, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Background There is limited information regarding the clinical use and effectiveness of IV sotalol in pediatric patients and patients with congenital heart disease, including those with severe myocardial dysfunction. A multicenter registry study was designed to evaluate the safety, efficacy, and dosing of IV sotalol. Methods and Results A total of 85 patients (age 1 day-36 years) received IV sotalol, of whom 45 (53%) had additional congenital cardiac diagnoses and 4 (5%) were greater than 18 years of age. In 79 patients (93%), IV sotalol was used to treat supraventricular tachycardia and 4 (5%) received it to treat ventricular arrhythmias. Severely decreased cardiac function by echocardiography was seen before IV sotalol in 7 (9%). The average dose was 1 mg/kg (range 0.5-1.8 mg/kg/dose) over a median of 60 minutes (range 30-300 minutes). Successful arrhythmia termination occurred in 31 patients (49%, 95% CI [37%-62%]) with improvement in rhythm control defined as rate reduction permitting overdrive pacing in an additional 18 patients (30%, 95% CI [19%-41%]). Eleven patients (16%) had significant QTc prolongation to >465 milliseconds after the infusion, with 3 (4%) to >500 milliseconds. There were 2 patients (2%) for whom the infusion was terminated early. Conclusions IV sotalol was safe and effective for termination or improvement of tachyarrhythmias in 79% of pediatric patients and patients with congenital heart disease, including those with severely depressed cardiac function. The most common dose, for both acute and maintenance dosing, was 1 mg/kg over ~60 minutes with rare serious complications.

Objectives/hypothesis: The diffuse sclerosing variant of papillary thyroid carcinoma (DSV) may be more aggressive than conventional well-differentiated non-DSV related papillary thyroid carcinomas (N-PTC)., Study Design: Retrospective chart review., Methods: Retrospective review of clinical outcomes for patients 21 years of age or younger who underwent initial surgery for PTC at a single institution from January 1, 2005 to April 1, 2020. Genomic analysis was performed using targeted next-generation sequencing. Data were analyzed using Fischer's exact test and Kaplan-Meier curve log-rank test., Results: Our cohort consisted of 72 patients, nine with DSV and 63 with N-PTC. Age at diagnosis was comparable (15.4 vs. 16.2 years, respectively, P = .46). DSV were more likely to be in the high-risk American Thyroid Academy pediatric risk group (100% vs. 41.3%, P = .004), to present with regional cervical lymph node metastases (100% vs. 60.3%, P = .036), and to present with distant metastases (67% vs. 22%, P = .005). No mortality seen in either group over 27.5 (interquartile range 14.8, 46.00) months average follow-up. Throughout the follow-up period, DSV were more likely to experience progression than N-PTC (hazard ratio = 5.7 [95% confidence interval 1.7-20.0; P = .0056]). In a subset of 19 patients with aggressive disease who had molecular testing as part of clinical care we detected RET fusions in nearly all DSV compared to a minority of N-PTC (83% vs. 15.4%, P = .0095)., Conclusions: Pediatric patients with DSV have more advanced disease at diagnosis and are more likely to experience progression of disease compared to patients with N-PTC. The prevalence of RET fusions in our cohort recapitulates the frequency of this alteration described in prior studies., Level of Evidence: 4 Laryngoscope, 132:1132-1138, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Racism has resulted in significant disproportionality and disparity in the US child welfare system. Being Black is not an inherent risk factor for child abuse and neglect yet Black children are almost twice as likely to be victims of substantiated abuse and neglect claims compared to other racial groups. Addressing the disproportionality within the child welfare system due to systemic racism falls squarely under the purview of bioethics. In this paper, we briefly review the impact of racism on child welfare. We then discuss some ethical considerations that mandatory healthcare reporters should think through when determining whether to report potential abuse and neglect. Specifically, we discuss the need for a broader consideration of what constitutes harm. We then present a hypothetical composite case to illuminate where and how bias can enter the process of referral to child protective services (CPS). We encourage thoughtful reporting with consideration of social and historical context and alternative explanations for worrisome findings. We recommend using evidence, avoiding assumptions by seeking clarification from families and ensuring internal consistency. When contemplating CPS referral, medical providers should feel empowered to ask questions if there is concern for potential bias. The ultimate goal is to protect children from harm. If there are clear safety concerns-they must be addressed. However, in the many cases where the safety concern is less tangible, we need to expand our considerations of the harms that can befall children, especially children of color., (© 2022 John Wiley & Sons Ltd.)

Justice is a core principle in bioethics, and a fair opportunity to achieve health is central to this principle. Racism and other forms of prejudice, discrimination, or bias directed against people on the basis of their membership in a particular racial or ethnic group are known contributors to health inequity, defined as unjust differences in health or access to care. Though hospital-based ethics committees and consultation services routinely address issues of justice that arise in the course of patient care, there is variability in whether and how racism and other causes of health inequities are addressed. In this paper, we describe a novel structure and process for addressing health equity within clinical ethics consultation. In addition, we discuss the barriers and challenges to its success, many of which are rooted in the identities, norms and assumptions that underlie traditional clinical ethics consultation. We offer pragmatic recommendations and conclude with unresolved questions that remain as we work to adapt the structure of a clinical ethics consultation service to improve attention to issues of health equity and promote anti-racism in patient care and institutional policy., (© 2022 John Wiley & Sons Ltd.)